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Journal: Heart
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Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure.
Schrage B, Lund LH, Benson L, Stolfo D, ... Ferreira JP, Savarese G
It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort.
Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating).
Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01).
In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Heart: 30 Jan 2021; 107:229-236
Heart: 30 Jan 2021; 107:229-236 | PMID: 32769169
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D-dimer and the incidence of heart failure and mortality after acute myocardial infarction.
Zhang X, Wang S, Liu J, Wang Y, ... Fang S, Yu B
D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.
We enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.
Over a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.
D-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.
Income level and outcomes in patients with heart failure with universal health coverage.
Hung CL, Chao TF, Su CH, Liao JN, ... Yeh HI, Chiang CE
We aimed to investigate the influence of income level on guideline-directed medical therapy (GDMT) prescription rates and prognosis of patients with heart failure (HF) following implementation of a nationwide health insurance programme.
A total of 633 098 hospitalised patients with HF from 1996 to 2013 were identified from Taiwan National Health Insurance Research Database. Participants were classified into low-income, median-income and high-income groups. GDMT utilisation, in-hospital mortality and postdischarge HF readmission, and mortality rates were compared.
The low-income group had a higher comorbidity burden and was less likely to receive GDMT than the other two groups. The in-hospital mortality rate in the low-income group (5.07%) was higher than in the median-income (2.47%) and high-income (2.51%) groups. Compared with the high-income group, the low-income group had a significantly higher risk of postdischarge HF readmission (adjusted HR (aHR): 1.29, 95% CI 1.27 to 1.31), all-cause mortality (aHR: 1.98, 95% CI 1.95 to 2.02) and composite HF readmission/all-cause mortality (aHR: 1.54, 95% CI 1.52 to 1.56). These results were generally consistent among the population after propensity matching (low vs high: HR=2.08 for mortality and 1.36 for HF readmission; median vs high: HR=1.23 for mortality and 1.12 for HF readmission; all p<0.001) and after inverse probability of treatment weighting (low-income vs high-income group: HR: 2.19 for mortality and 1.16 for HF readmission; median-income vs high-income group: HR: 1.53 for mortality and 1.09 for HF readmission; all p<0.001). Lower utilisation of GDMT and poorer prognosis in lower-income hospitalised patients with HF appeared to mitigate over time.
Low-income patients with HF had nearly a twofold increase in the risk of in-hospital mortality and postdischarge events compared with the high-income group, partly due to lower GDMT utilisation. The differences between postdischarge HF outcomes among various income groups appeared to mitigate over time following the implementation of nationwide universal health coverage.
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Long-term survival benefit of ramipril in patients with acute myocardial infarction complicated by heart failure.
Wu J, Hall AS, Gale CP, AIREX Study Investigators
ACE inhibition reduces mortality and morbidity in patients with heart failure after acute myocardial infarction (AMI). However, there are limited randomised data about the long-term survival benefits of ACE inhibition in this population.
In 1993, the Acute Infarction Ramipril Efficacy (AIRE) study randomly allocated patients with AMI and clinical heart failure to ramipril or placebo. The duration of masked trial therapy in the UK cohort (603 patients, mean age=64.7 years, 455 male patients) was 12.4 and 13.4 months for ramipril (n=302) and placebo (n=301), respectively. We estimated life expectancy and extensions of life (difference in median survival times) according to duration of follow-up (range 0-29.6 years).
By 9 April 2019, death from all causes occurred in 266 (88.4%) patients in placebo arm and 275 (91.1%) patients in ramipril arm. The extension of life between ramipril and placebo groups was 14.5 months (95% CI 13.2 to 15.8). Ramipril increased life expectancy more for patients with than without diabetes (life expectancy difference 32.1 vs 5.0 months), previous AMI (20.1 vs 4.9 months), previous heart failure (19.5 vs 4.9 months), hypertension (16.6 vs 8.3 months), angina (16.2 vs 5.0 months) and age >65 years (11.3 vs 5.7 months). Given potential treatment switching, the true absolute treatment effect could be underestimated by 28%.
For patients with clinically defined heart failure following AMI, ramipril results in a sustained survival benefit, and is associated with an extension of life of up to 14.5 months for, on average, 13 months treatment duration.
Heart: 14 Jan 2021; epub ahead of print
Heart: 14 Jan 2021; epub ahead of print | PMID: 33452123
Effusive-constrictive pericarditis in the spectrum of pericardial compressive syndromes.
Janus SE, Hoit BD
When pericardial fluid accumulates and exceed the reserve volume of the pericardium or when the pericardium becomes scarred and inelastic, one of three pericardial compressive syndromes may ensue, namely, cardiac tamponade (CT), characterised by the accumulation of pericardial fluid under pressure; constrictive pericarditis (CP), the result of scarring and loss of the normal elasticity of the pericardial sac; and effusive-constrictive pericarditis (ECP), characterised by the concurrence of a tense pericardial effusion and constriction of the heart by the visceral pericardium. Although relatively uncommon, prevalence estimates vary widely and depend on the nature of the cohorts studied, the methods used to diagnose ECP and the manner in which ECP is defined. Most cases of ECP are idiopathic, reflecting the frequency of idiopathic pericardial disease in general, and other causes include radiation, malignancy, chemotherapy, infection and postsurgical/iatrogenic pericardial disease. The diagnosis of ECP often becomes apparent when pericardiocentesis fails to decrease the right atrial pressure by 50% or to a level below 10 mm Hg. Important non-invasive diagnostic modalities include echocardiography, cardiac magnetic resonance and, to a lesser extent, cardiac CT. In cases with clear evidence of pericardial inflammation, a trial of an anti-inflammatory regimen is warranted. A complete pericardiectomy should be reserved for refractory symptoms or clinical evidence of chronic CP.
Sacubitril/valsartan in the treatment of systemic right ventricular failure.
Zandstra TE, Nederend M, Jongbloed MRM, Kiès P, ... Schalij MJ, Egorova AD
Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients.
Data on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment.
Six-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950-358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%-22%, p<0.001 and -11% to -13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively).
We describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
Risk of out-of-hospital cardiac arrest in patients with bipolar disorder or schizophrenia.
Barcella CA, Mohr G, Kragholm K, Christensen D, ... Gislason GH, Bach Søndergaard K
Patients with bipolar disorder and schizophrenia are at high cardiovascular risk; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared with the general population remains scarcely investigated.
We conducted a nested case-control study using Cox regression to assess the association of bipolar disorder and schizophrenia with the HRs of OHCA of presumed cardiac cause (2001-2015). Reported are the HRs with 95% CIs overall and in subgroups defined by established cardiac disease, cardiovascular risk factors and psychotropic drugs.
We included 35 017 OHCA cases and 175 085 age-matched and sex-matched controls (median age 72 years and 66.9% male). Patients with bipolar disorder or schizophrenia had overall higher rates of OHCA compared with the general population: HR 2.74 (95% CI 2.41 to 3.13) and 4.49 (95% CI 4.00 to 5.10), respectively. The association persisted in patients with both cardiac disease and cardiovascular risk factors at baseline (bipolar disorder HR 2.14 (95% CI 1.72 to 2.66), schizophrenia 2.84 (95% CI 2.20 to 3.67)) and among patients without known risk factors (bipolar disorder HR 2.14 (95% CI 1.09 to 4.21), schizophrenia HR 5.16 (95% CI 3.17 to 8.39)). The results were confirmed in subanalyses only including OHCAs presenting with shockable rhythm or receiving an autopsy. Antipsychotics-but not antidepressants, lithium or antiepileptics (the last two only tested in bipolar disorder)-increased OHCA hazard compared with no use in both disorders.
Patients with bipolar disorder or schizophrenia have a higher rate of OHCA compared with the general population. Cardiac disease, cardiovascular risk factors and antipsychotics represent important underlying mechanisms.
Socioeconomic status and cardiovascular health in the COVID-19 pandemic.
Naylor-Wardle J, Rowland B, Kunadian V
The goals of this review are to evaluate the impact of socioeconomic (SE) status on the general health and cardiovascular health of individuals during the COVID-19 pandemic and also discuss the measures to address disparity. SE status is a strong predictor of premature morbidity and mortality within general health. A lower SE status also has implications of increased cardiovascular disease (CVD) mortality and poorer CVD risk factor profiles. CVD comorbidity is associated with a higher case severity and mortality rate from COVID-19, with both CVD and COVID-19 sharing important risk factors. The COVID-19 pandemic has adversely affected people of a lower SE status and of ethnic minority group, who in the most deprived regions are suffering double the mortality rate of the least deprived. The acute stress, economic recession and quarantine restrictions in the wake of COVID-19 are also predicted to cause a decline in mental health. This could pose substantial increase to CVD incidence, particularly with acute pathologies such as stroke, acute coronary syndrome and cardiogenic shock among lower SE status individuals and vulnerable elderly populations. Efforts to tackle SE status and CVD may aid in reducing avoidable deaths. The implementation of \'upstream\' interventions and policies demonstrates promise in achieving the greatest population impact, aiming to protect and empower individuals. Specific measures may involve risk factor targeting restrictions on the availability and advertisement of tobacco, alcohol and high-fat and salt content food, and targeting SE disparity with healthy and secure workplaces.
Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial.
Maznyczka AM, McCartney P, Duklas P, McEntegart M, ... Berry C, T-TIME (Trial of low-dose adjunctive alTeplase during primary PCI) investigators
Persistently impaired culprit artery flow (
In T-TIME (trial of low-dose adjunctive alTeplase during primary PCI), patients ≤6 hours from onset of ST-elevation myocardial infarction (STEMI) were randomised to placebo, alteplase 10 mg or alteplase 20 mg, administered by infusion into the culprit artery, pre-stenting. In this prespecified, secondary analysis, coronary flow was assessed angiographically at the point immediately before drug administration. Microvascular obstruction, myocardial haemorrhage and infarct size were assessed by cardiovascular magnetic resonance (CMR) at 2-7 days and 3 months.
TIMI flow was assessed after first treatment (balloon angioplasty/aspiration thrombectomy), immediately pre-drug administration, in 421 participants (mean age 61±10 years, 85% male) and was 3, 2 or 1 in 267, 134 and 19 participants respectively. In patients with TIMI flow ≤2 pre-drug, there was higher incidence of microvascular obstruction with alteplase (alteplase 20 mg (53.1%) and 10 mg (59.5%) combined versus placebo (34.1%); OR=2.47 (95% CI 1.16 to 5.22, p=0.018) interaction p=0.005) and higher incidence of myocardial haemorrhage (alteplase 20 mg (53.1%) and 10 mg (57.9%) combined vs placebo (27.5%); OR=3.26 (95% CI 1.44 to 7.36, p=0.004) interaction p=0.001). These effects were not observed in participants with TIMI 3 flow pre-drug. There were no interactions between TIMI flow pre-drug, alteplase and 3-month CMR findings.
In patients with impaired culprit artery flow (
Trial registration number
NCT02257294.
Coronary revascularisation in patients with ischaemic cardiomyopathy.
Ryan M, Morgan H, Petrie MC, Perera D
Heart failure resulting from ischaemic heart disease is associated with a poor prognosis despite optimal medical treatment. Despite this, patients with ischaemic cardiomyopathy have been largely excluded from randomised trials of revascularisation in stable coronary artery disease. Revascularisation has multiple potential mechanisms of benefit, including the reversal of myocardial hibernation, suppression of ventricular arrhythmias and prevention of spontaneous myocardial infarction. Coronary artery bypass grafting is considered the first-line mode of revascularisation in these patients; however, evidence from the Surgical Treatment of Ischaemic Heart Failure (STICH) trial showed a reduction in mortality, though this only became apparent with extended follow-up due to an excess of early adverse events in the surgical arm. There is currently no randomised controlled trial evidence for percutaneous coronary intervention in patients with ischaemic cardiomyopathy; however, the REVIVED-BCIS2 trial has recently completed recruitment and will address this gap in the evidence. Future directions include (1) clinical trials of revascularisation in patients hospitalised with heart failure, (2) defining the role of viability and ischaemia testing in heart failure, (3) studies to enhance the understanding of the mechanistic effects of revascularisation and (4) generating models to refine pre- and post-revascularisation risk prediction.
Single high-sensitivity troponin levels to assess patients with potential acute coronary syndromes.
Barnes C, Fatovich DM, Macdonald SPJ, Alcock RF, ... Schultz CJ, Hillis GS
We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement.
This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in <3 hours. Secondary outcomes included the duration of observation and death or acute myocardial infarction in the next 30 days.
The study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (p<0.001). The median duration of observation was 4.3 (IQR 3.3-7.1) hours in the standard cohort and 3.6 (2.6-5.4) hours in the STAT cohort (p<0.001), with 21% and 38% discharged in <3 hours, respectively (p<0.001). No patients discharged directly from the emergency department died or suffered an acute myocardial infarction within 30 days in either cohort.
Among low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe.
ACTRN12618000797279.
Remote monitoring in heart failure: current and emerging technologies in the context of the pandemic.
Mohebali D, Kittleson MM
The incidence of heart failure (HF) remains high and patients with HF are at risk for frequent hospitalisations. Remote monitoring technologies may provide early indications of HF decompensation and potentially allow for optimisation of therapy to prevent HF hospitalisations. The need for reliable remote monitoring technology has never been greater as the COVID-19 pandemic has led to the rapid expansion of a new mode of healthcare delivery: the virtual visit. With the convergence of remote monitoring technologies and reliable method of remote healthcare delivery, an understanding of the role of both in the management of patients with HF is critical. In this review, we outline the evidence on current remote monitoring technologies in patients with HF and highlight how these advances may benefit patients in the context of the current pandemic.
Sex differences in heart failure hospitalisation risk following acute myocardial infarction.
Yandrapalli S, Malik A, Pemmasani G, Aronow W, ... Frishman W, Panza J
We evaluated the sex differences in 6-month heart failure (HF) hospitalisation risk in acute myocardial infarction (AMI) survivors.
For this retrospective cohort analysis, adult survivors of an AMI between January and June 2014 were identified from the US Nationwide Readmissions Database. The primary outcome was a HF hospitalisation within 6 months. Secondary outcomes were fatal HF hospitalisation and the composite of index in-hospital HF or 6-month HF hospitalisation.
Of 237 549 AMI survivors, females (37.9%) were older (70±14 years vs 65±13 years; p<0.001), had a higher prevalence of cardiac comorbidities and a lower revascularisation rate compared with males. The primary outcome occurred in 12 934 patients (5.4%), at a 49% higher rate in females (6.8% vs 4.6% in males, p<0.001), which was attenuated to a 19% higher risk after multivariable adjustment. Findings were consistent across subgroups of age, AMI type and major risk factors. In the propensity-matched time-to-event analysis, female sex was associated with a 13% higher risk for 6-month HF readmission (6.4% vs 5.8% in males; HR 1.13, 95% CI 1.05 to 1.21, p<0.001), and the increased risk was evident early on after the AMI. Fatal HF rate was similar between groups (4.7% vs 4.6%, p=0.936), but females had a higher rate of the composite HF outcome (36.2% vs 27.5%, p<0.001).
In a large all-comers AMI survivors\' cohort, females had a higher HF hospitalisation risk that persisted after adjustment for baseline risk differences. This was consistent across several clinically relevant subgroups and was evident early on after the AMI.
Survival and risk of recurrence of takotsubo syndrome.
Lau C, Chiu S, Nayak R, Lin B, Lee MS
The goal of this study is to evaluate the long-term outcomes of patients with takotsubo syndrome and assess factors associated with death or recurrence.
This is a retrospective population-based cohort study of consecutive patients who presented to an integrated health system in Southern California with takotsubo syndrome between 2006 and 2016. Medical records were manually reviewed to confirm diagnosis and to identify predisposing factors, medication treatment and long-term outcomes. Factors associated with death or recurrent takotsubo syndrome were tested using Cox regression models.
Between 2006 and 2016, there were 519 patients with a confirmed diagnosis of takotsubo syndrome. Patients were followed for 5.2 years (IQR 3.0-7.2). During the follow-up period, 39 (7.5%) had recurrent takotsubo syndrome and 84 (16.2%) died. In multivariate modelling, factors associated with higher risk of recurrence or death were age (HR 1.56 per 10-year increase, 95% CI 1.29 to 1.87), male sex (HR 2.52, 95% CI 1.38 to 4.60), diabetes (HR 1.6, 95% CI 1.06 to 2.43), pulmonary disease (HR 2.0, 95% CI 1.37 to 2.91) and chronic kidney disease (HR 1.58, 95% CI 1.01 to 2.47). Treatment with beta-blockers were associated with lower risk of recurrence or death (HR 0.46, 95% CI 0.29 to 0.72). No association was observed between treatment with ACE inhibitors or angiotensin-receptor blockers and recurrence or death (HR 0.92, 95% CI 0.59 to 1.42).
Recurrent takotsubo syndrome occurred in a minor subset of patients. Treatment with beta-blocker was associated with higher event-free survival.
Socioeconomic disparities in prehospital factors and survival after out-of-hospital cardiac arrest.
Møller S, Wissenberg M, Starkopf L, Kragholm K, ... Torp-Pedersen C, Gerds TA
It remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival.
From the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001-2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders.
We included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in private unwitnessed arrests (OR 1.74, 95% CI 1.47 to 2.05). For 30-day survival, the biggest differences were in public witnessed arrests with 26.0% (95% CI 22.4% to 29.7%) higher survival in highest income compared with lowest income patients. Had bystander CPR been the same for lowest income as for highest income patients, then survival would be 25.3% (95% CI 21.5% to 29.0%) higher in highest income compared with lowest income patients, resulting in elimination of 0.79% (95% CI 0.08% to 1.50%) of the income disparity in survival. Similar trends but smaller were observed in low and high-income patients, the other three subgroups and with education instead of income. From 2002 to 2014, increases were observed in both CPR and survival in all income groups.
Overall, lower socioeconomic status was associated with poorer prehospital factors and survival after OHCA that was not explained by patient or cardiac arrest-related factors.
Transcatheter tricuspid valve replacement in patients with severe tricuspid regurgitation.
Lu FL, An Z, Ma Y, Song ZG, ... Qiao F, Xu ZY
Tricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR.
This was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients\' data at baseline, before discharge, 30 days and 6 months after the procedure were collected.
All patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.0 (1.0, 4.0) days. 6-month mortality was 17.4%. Device migration occurred in one patient (2.4%) during follow-up. Transthoracic echocardiography at 6 months after operation showed TR was significantly reduced (none/trivial in 33, mild in 4 and moderate in 1) and the primary safety end point was achieved in 38 cases (82.6%). Patients suffered from peripheral oedema and ascites decreased from 100.0% and 47.8% at baseline to 2.6% and 0.0% at 6 months.
The present study showed TTVR was feasible, safe and with low complication rates in patients with severe TR.
Tyrosine kinase inhibitors in chronic myeloid leukaemia and emergent cardiovascular disease.
Leong D, Aghel N, Hillis C, Siegal D, ... Pond G, Seow H
(1) Describe how the risk of major adverse cardiovascular events (MACE) in individuals with chronic myeloid leukaemia (CML) has evolved; (2) evaluate the risk of MACE associated with the prescription of different CML tyrosine kinase inhibitors (TKI).
A population-based retrospective study including all patients (n=4238) diagnosed with CML in Ontario, Canada between 1986 and 2017 and and age-matched and sex-matched individuals who received healthcare but who did not have CML (controls: n=42 380). The cohort was divided into those entering before 2001 vs from 2001 onwards (when TKIs were introduced). We developed competing risks models to compare time-to-event in CML cases versus controls. We adjusted for baseline comorbidities and present subdistribution HRs and 95% CIs. The relationship between TKI use and MACE was assessed by logistic regression.
Before 2001 and from 2001 on, patients with CML had a higher crude incidence of MACE than patients without CML (19.8 vs 15.3 and 20.3 vs 12.6 per 1000 person-years, respectively). After adjustment for cardiovascular risk factors, patients with CML had a lower subdistribution hazard for MACE (0.59, 95% CI 0.46 to 0.76) before 2001; but from 2001, the adjusted subdistribution HR for MACE (1.27, 95% CI 0.96 to 1.43) was similar to age-matched and sex-matched patients. The incidence (9.3 vs 13.8 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.43, 95% CI 0.36 to 0.52) were lower in patients with CML than controls before 2001. From 2001 on, the incidence (6.3 vs 5.4 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.99, 95% CI 0.84 to 1.18) were similar to age-matched and sex-matched patients without CML with a higher risk of cerebrovascular events (8.6 vs 5.6 per 1000 person-years; 1.35, 95% CI 1.00 to 1.83) and peripheral arterial events (6.9 vs 3.0 per 1000 person-years; 1.66 95% CI, 1.15 to 2.39) in patients with CML than patients without CML. Compared with imatinib, there was no difference in the risk of MACE among those prescribed dasatinib (OR 0.67, 95% CI 0.41 to 1.10) or nilotinib (OR 1.22, 95% CI 0.70 to 1.97).
In a contemporary CML population, the risk of MACE and cardiovascular death is at least as high as among age-matched and sex-matched patients without CML and may be higher for cerebrovascular and peripheral arterial events. No difference in the risk of MACE between imatinib, dasatinib and nilotinib was observed.
The new role of diagnostic angiography in coronary physiological assessment.
Ghobrial M, Haley HA, Gosling R, Rammohan V, ... Gunn JP, Morris PD
The role of \'stand-alone\' coronary angiography (CAG) in the management of patients with chronic coronary syndromes is the subject of debate, with arguments for its replacement with CT angiography on the one hand and its confinement to the interventional cardiac catheter laboratory on the other. Nevertheless, it remains the standard of care in most centres. Recently, computational methods have been developed in which the laws of fluid dynamics can be applied to angiographic images to yield \'virtual\' (computed) measures of blood flow, such as fractional flow reserve. Together with the CAG itself, this technology can provide an \'all-in-one\' anatomical and functional investigation, which is particularly useful in the case of borderline lesions. It can add to the diagnostic value of CAG by providing increased precision and reduce the need for further non-invasive and functional tests of ischaemia, at minimal cost. In this paper, we place this technology in context, with emphasis on its potential to become established in the diagnostic workup of patients with suspected coronary artery disease, particularly in the non-interventional setting. We discuss the derivation and reliability of angiographically derived fractional flow reserve (CAG-FFR) as well as its limitations and how CAG-FFR could be integrated within existing national guidance. The assessment of coronary physiology may no longer be the preserve of the interventional cardiologist.
Incidence and predictors of stroke in patients with rheumatic heart disease.
Vasconcelos M, Vasconcelos L, Ribeiro V, Campos C, ... Teixeira AL, Nunes MCP
Ischaemic stroke is a severe complication of rheumatic heart disease (RHD), which may result in permanent disability and death. This study aimed to assess the incidence and predictors of stroke in patients with RHD in the current era of evidence-based recommendations for prevention.
Consecutive patients with RHD diagnosed by clinical and echocardiographic criteria were selected. A structured clinical and neurological assessment was performed to determine the aetiology and classification of stroke at enrolment. The primary endpoint was an ischaemic cerebrovascular event, which included fatal or non-fatal stroke. Risk of stroke was estimated accounting for competing risks.
A total of 515 patients were enrolled, 438 women (85%), 46±12 years of age. The most frequent valve lesion was mixed mitral (80%). At the time of enrolment, 92 patients (18%) had a prior stroke, with anterior circulation infarction being the most frequent topography (72%). During the mean follow-up of 3.9 years, 27 patients (5.2%) had stroke with the overall incidence of 1.47 strokes per 100 patient-years. Predictors of stroke by the Cox model were prior stroke (adjusted HR 5.395, 95% CI 2.272 to 12.811), age (HR 1.591, 95% CI 1.116 to 2.269) and atrial fibrillation (AF) at baseline (HR 2.945, 95% CI 1.083 to 8.007). By considering death as a competing risk, the effect of AF on stroke risk was attenuated (HR 2.287, 95% CI 0.962 to 5.441).
In this large cohort of patients with RHD, stroke occurred in 5.2% of the patients, which was predicted by age, AF and prior stroke. The effect of AF on stroke risk estimation was influenced by death as competing risk.
Improvement in left ventricular mechanics following medical treatment of constrictive pericarditis.
Sato K, Ayache A, Kumar A, Cremer PC, ... Johnston D, Klein AL
Patients with constrictive pericarditis (CP) with active inflammation may show resolution with anti-inflammatory therapy. We aimed to investigate the impact of anti-inflammatory medications on constrictive pathophysiology using echocardiography in patients with CP.
We identified 35 patients with CP who were treated with anti-inflammatory medications (colchicine, prednisone, non-steroidal anti-inflammatory drugs) after diagnosis of CP (mean age 58±13; 80% male). Clinical resolution of CP (transient CP) was defined as improvement in New York Heart Association class during follow-up. We assessed constrictive pathophysiology using regional myocardial mechanics by the ratio of peak early diastolic tissue velocity (e\') at the lateral and septal mitral annulus by tissue Doppler imaging (lateral/septal e\') or the ratio of the left ventricular lateral and septal wall longitudinal strain (LS/LS) by two-dimensional speckle-tracking echocardiography. Longitudinal data were analysed using a mixed effects model.
During a median follow-up of 323 days, 20 patients had transient CP, whereas 15 patients had persistent CP. Transient CP had higher baseline erythrocyte sedimentation rates (ESR) (p=0.003) compared with persistent CP. There were no significant differences in LS/LS and lateral/septal e\'. During follow-up, only transient CP showed improvement in lateral/septal e\' (p<0.001) and LS/LS (p=0.003), and recovery of inflammatory markers was similar between the two groups. In the logistic model, higher baseline ESR and greater improvement in lateral/septal e\' and LS/LS were associated with clinical resolution of CP using anti-inflammatory therapy.
Improvement of constrictive physiology detected by lateral/septal e\' and LS/LS was associated with resolution of clinical symptoms after anti-inflammatory treatment. Serial monitoring of these markers could be used to identify transient CP.
Cardiovascular magnetic resonance imaging: emerging techniques and applications.
Chowdhary A, Garg P, Das A, Nazir MS, Plein S
This review gives examples of emerging cardiovascular magnetic resonance (CMR) techniques and applications that have the potential to transition from research to clinical application in the near future. Four-dimensional flow CMR (4D-flow CMR) allows time-resolved three-directional, three-dimensional (3D) velocity-encoded phase-contrast imaging for 3D visualisation and quantification of valvular or intracavity flow. Acquisition times of under 10 min are achievable for a whole heart multidirectional data set and commercial software packages are now available for data analysis, making 4D-flow CMR feasible for inclusion in clinical imaging protocols. Diffusion tensor imaging (DTI) is based on the measurement of molecular water diffusion and uses contrasting behaviour in the presence and absence of boundaries to infer tissue structure. Cardiac DTI is capable of non-invasively phenotyping the 3D micro-architecture within a few minutes, facilitating transition of the method to clinical protocols. Hybrid positron emission tomography-magnetic resonance (PET-MR) provides quantitative PET measures of biological and pathological processes of the heart combined with anatomical, morphological and functional CMR imaging. Cardiac PET-MR offers opportunities in ischaemic, inflammatory and infiltrative heart disease.
Cardiovascular or mortality risk of controlled hypertension and importance of physical activity.
Park S, Han K, Lee S, Kim Y, ... Kim YS, Kim DK
To investigate the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death of patients with controlled hypertension and suggest the benefits of physical activity in their prognosis.
People aged 40-69 years from the prospective UK Biobank cohort (UKB, n=220 026) and the retrospective Korean National Health Insurance Service cohort (KNHIS, n=3 593 202) were included in this observational cohort study, excluding those with previous cerebrocardiovascular diseases or hypertension without treatment. The study groups were stratified into normotension, controlled hypertension (patients with hypertension with systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg) and uncontrolled hypertension groups. The outcomes were MACCEs and all-cause mortality, analysed by Cox regression analysis.
We included 161 405/18 844/39 777 and 3 122 890/383 828/86 484 individuals with normotension/controlled hypertension/uncontrolled hypertension state from the UKB and KNHIS cohorts, respectively. The controlled hypertension group showed significantly higher risk of MACCEs (UKB: adjusted HR 1.73 (95% CI 1.55 to 1.92); KNHIS: 1.46 (95% CI 1.43 to 1.49)) and all-cause mortality (UKB: adjusted HR 1.28 (95% CI 1.18 to 1.39); KNHIS: 1.29 (95% CI 1.26 to 1.32)) than individuals with normotension. The controlled hypertension group not involved in any moderate or moderate-to-vigorous physical activity showed high risk of adverse outcomes, which was comparable with or even higher than the risk of patients with uncontrolled hypertension who were engaged in physical activity.
Controlled hypertension is associated with residual risks of adverse outcomes. Clinicians may encourage physical activity for patients with controlled hypertension, not being reassured by their achieved target blood pressure values.
Prognostic role of PET/MRI hybrid imaging in patients with pulmonary arterial hypertension.
Kazimierczyk R, Szumowski P, Nekolla SG, Blaszczak P, ... Musial WJ, Kaminski KA
Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). Metabolic alterations may precede haemodynamic and clinical deterioration. Increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) was recently associated with progressive RV dysfunction in MRI, but the prognostic value of their combination has not been established.
Twenty-six clinically stable patients with PAH (49.9±15.2 years) and 12 healthy subjects (control group, 44.7±13.5 years) had simultaneous PET/MRI scans. FDG uptake was quantified as mean standardised uptake value (SUV) for both left ventricle (LV) and RV. Mean follow-up time of this study was 14.2±7.3 months and the clinical end point was defined as death or clinical deterioration.
Median SUV/SUV ratio was 1.02 (IQR 0.42-1.21) in PAH group and 0.16 (0.13-0.25) in controls, p<0.001. In PAH group, SUV/SUV significantly correlated with RV haemodynamic deterioration. In comparison to the stable ones, 12 patients who experienced clinical end point had significantly higher baseline SUV/SUV ratio (1.21 (IQR 0.87-1.95) vs 0.53 (0.24-1.08), p=0.01) and lower RV ejection fraction (RVEF) (37.9±5.2 vs 46.8±5.7, p=0.03). Cox regression revealed that SUV/SUV ratio was significantly associated with the time to clinical end point. Kaplan-Meier analysis showed that combination of RVEF from MRI and SUV/SUV assessment may help to predict prognosis.
Increased RV glucose uptake in PET and decreased RVEF identify patients with PAH with worse prognosis. Combining parameters from PET and MRI may help to identify patients at higher risk who potentially benefit from therapy escalation, but this hypothesis requires prospective validation.
Heart: 30 Dec 2020; 107:54-60
Heart: 30 Dec 2020; 107:54-60 | PMID: 32522819
Predicting sudden cardiac death in adults with congenital heart disease.
Oliver JM, Gallego P, Gonzalez AE, Avila P, ... Bermejo J,
To develop, calibrate, test and validate a logistic regression model for accurate risk prediction of sudden cardiac death (SCD) and non-fatal sudden cardiac arrest (SCA) in adults with congenital heart disease (ACHD), based on baseline lesion-specific risk stratification and individual\'s characteristics, to guide primary prevention strategies.
We combined data from a single-centre cohort of 3311 consecutive ACHD patients (50% male) at 25-year follow-up with 71 events (53 SCD and 18 non-fatal SCA) and a multicentre case-control group with 207 cases (110 SCD and 97 non-fatal SCA) and 2287 consecutive controls (50% males). Cumulative incidences of events up to 20 years for specific lesions were determined in the prospective cohort. Risk model and its 5-year risk predictions were derived by logistic regression modelling, using separate development (18 centres: 144 cases and 1501 controls) and validation (two centres: 63 cases and 786 controls) datasets.
According to the combined SCD/SCA cumulative 20 years incidence, a lesion-specific stratification into four clusters-very-low (<1%), low (1%-4%), moderate (4%-12%) and high (>12%)-was built. Multivariable predictors were lesion-specific cluster, young age, male sex, unexplained syncope, ischaemic heart disease, non-life threatening ventricular arrhythmias, QRS duration and ventricular systolic dysfunction or hypertrophy. The model very accurately discriminated (C-index 0.91; 95% CI 0.88 to 0.94) and calibrated (p=0.3 for observed vs expected proportions) in the validation dataset. Compared with current guidelines approach, sensitivity increases 29% with less than 1% change in specificity.
Predicting the risk of SCD/SCA in ACHD can be significantly improved using a baseline lesion-specific stratification and simple clinical variables.
Cardiovascular outcomes of pregnancy in Turner syndrome.
Grewal J, Valente AM, Egbe AC, Wu FM, ... Roos-Hesselink JW,
Women with Turner syndrome (TS) are frequently counselled against pregnancy due to lack of data and unclear aortic dissection risk. However, with advances in fertility therapy, more women with TS are contemplating pregnancy. This study compared rates of adverse cardiovascular (CV) outcomes among: (1) pregnant and non-pregnant women with TS and (2) pregnant women with TS with/without structural heart disease.
Retrospective analysis of pregnant and age-matched non-pregnant controls with TS (2005-2017) across 10 CV centres was done. Data were collected at initial evaluation in pregnancy and outcomes were assessed to 6 months postpartum. Adverse CV events were defined as CV death, aortic dissection/rupture and/or aortic intervention. Non-pregnant age-matched controls were followed over the same time period.
Sixty-eight pregnancies were included (60 women, mean age 33 years, 48% primigravid, 49% fertility therapy, 80% structurally normal heart, 25% XO karyotype). Based on American Society of Reproductive Medicine criteria, 10 pregnancies occurred in women stratified to high-risk category. There were no CV events in the pregnant women or in the non-pregnant women with TS. Obstetric events complicated 12 (18%) pregnancies with 9 (13%) attributed to hypertensive disorder of pregnancy. Fetal events included small for gestational age neonates (18%), preterm delivery (15%) and fetal death (3%).
This study helps to refine the approach to pregnancy in women with TS. Among women with TS without structural heart disease, pregnancy does not impose an increased risk of CV outcomes. Among women with TS with structural heart disease, the risk of pregnancy is not as prohibitive as previously described but does require ongoing evaluation.
A novel method to interpret early phase trials shows how the narrowing of the coronary sinus concordantly improves symptoms, functional status and quality of life in refractory angina.
Jolicoeur EM, Verheye S, Henry TD, Joseph L, ... Edelman E, Banai S
Reduction of the coronary sinus was shown to improve angina in patients unsuitable for revascularisation. We assessed whether a percutaneous device that reduces the diameter of the coronary sinus improved outcomes across multiple endpoints in a phase II trial.
We conducted a novel analysis performed as a post hoc efficacy analysis of the COSIRA (ronary nus educer for Treatment of Refractory ngina) trial, which enrolled patients with Canadian Cardiovascular Society (CCS) class 3-4 refractory angina. We used four domains: symptoms (CCS Angina Scale), functionality (total exercise duration), ischaemia (imaging) and health-related quality of life. For all domains, we specified a meaningful threshold for change. The primary endpoint was defined as a probability of ≥80% that the reducer exceeded the meaningful threshold on two or more domains (group-level analysis) or that the average efficacy score in the reducer group exceeded the sham control group by at least two points (patient-level analysis).
We randomised 104 participants to either a device that narrows to coronary sinus (n=52) or a sham implantation (n=52). The reducer group met the prespecified criteria for concordance at the group level and demonstrated improvement in symptoms (0.59 CCS grade, 95% credible interval (CrI)=0.22 to 0.95), total exercise duration (+27.9%, 95% CrI=2.8% to 59.8%) and quality of life (stability +11.2 points, 95% CrI=3.3 to 19.1; perception +11.0, 95% CrI=3.3 to 18.7).
The reducer concordantly improved symptoms, functionality and quality of life compared with a sham intervention in patients with angina unsuitable for coronary revascularisation. Concordant analysis such as this one can help interpret early phase trials and guide the decision to pursue a clinical programme into a larger confirmatory trial.
Trail registration number
ClinicalTrials.gov identifier: NCT01205893.
Multimodality imaging assessment of mitral annular disjunction in mitral valve prolapse.
Mantegazza V, Volpato V, Gripari P, Ghulam Ali S, ... Tamborini G, Pepi M
Mitral annular disjunction (MAD) is an abnormality linked to mitral valve prolapse (MVP), possibly associated with malignant ventricular arrhythmias. We assessed the agreement among different imaging techniques for MAD identification and measurement.
131 patients with MVP and significant mitral regurgitation undergoing transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were retrospectively enrolled. Transoesophageal echocardiography (TOE) was available in 106 patients. MAD was evaluated in standard long-axis views (four-chamber, two-chamber, three-chamber) by each technique.
Considering any-length MAD, MAD prevalence was 17.3%, 25.5%, 42.0% by TTE, TOE and CMR, respectively (p<0.05). The agreement on MAD identification was moderate between TTE and CMR (κ=0.54, 95% CI 0.49 to 0.59) and good between TOE and CMR (κ=0.79, 95% CI 0.74 to 0.84). Assuming CMR as reference and according to different cut-off values for MAD (≥2 mm, ≥4 mm, ≥6 mm), specificity (95% CI) of TTE and TOE was 99.6 (99.0 to 100.0)% and 98.7 (97.4 to 100.0)%; 99.3 (98.4 to 100.0)% and 97.6 (95.8 to 99.4)%; 97.8 (96.2 to 99.3)% and 93.2 (90.3 to 96.1)%, respectively; sensitivity (95% CI) was 43.1 (37.8 to 48.4)% and 74.5 (69.4 to 79.5)%; 54.0 (48.7 to 59.3)% and 88.9 (85.2 to 92.5)%; 88.0 (84.5 to 91.5)% and 100.0 (100.0 to 100.0)%, respectively. MAD length was 8.0 (7.0-10.0), 7.0 (5.0-8.0], 5.0 (4.0-7.0) mm, respectively by TTE, TOE and CMR. Agreement on MAD measurement was moderate between TTE and CMR (ρ=0.73) and strong between TOE and CMR (ρ=0.86).
An integrated imaging approach could be necessary for a comprehensive assessment of patients with MVP and symptoms suggestive for arrhythmias. If echocardiography is fundamental for the anatomic and haemodynamic characterisation of the MV disease, CMR may better identify small length MAD as well as myocardial fibrosis.
Augmentation of pulmonary blood flow and cardiac output by non-invasive external ventilation late after Fontan palliation.
Charla P, Karur GR, Yamamura K, Yoo SJ, ... Hanneman K, Wald RM
Although a life-preserving surgery for children with single ventricle physiology, the Fontan palliation is associated with striking morbidity and mortality with advancing age. Our primary objective was to evaluate the impact of non-invasive, external, thoraco-abdominal ventilation on pulmonary blood flow (PBF) and cardiac output (CO) as measured by cardiovascular magnetic resonance (CMR) imaging in adult Fontan subjects.
Adults with a dominant left ventricle post-Fontan palliation (lateral tunnel or extracardiac connections) and healthy controls matched by sex and age were studied. We evaluated vascular flows using phase-contrast CMR imaging during unassisted breathing, negative pressure ventilation (NPV) and biphasic ventilation (BPV). Measurements were made within target vessels (aorta, pulmonary arteries, vena cavae and Fontan circuit) at baseline and during each ventilation mode.
Ten Fontan subjects (50% male, 24.5 years (IQR 20.8-34.0)) and 10 matched controls were studied. Changes in PBF and CO, respectively, were greater following BPV as compared with NPV. In subjects during NPV, PBF increased by 8% (Δ0.20 L/min/m (0.10-0.53), p=0.011) while CO did not change significantly (Δ0.17 L/min/m (-0.11-0.23), p=0.432); during BPV, PBF increased by 25% (Δ0.61 L/min/m (0.20-0.84), p=0.002) and CO increased by 16% (Δ0.47 L/min/m (0.21-0.71), p=0.010). Following BPV, change in PBF and CO were both significantly higher in subjects versus controls (0.61 L/min/m (0.2-0.84) vs -0.27 L/min/m (-0.55-0.13), p=0.001; and 0.47 L/min/m (0.21-0.71) vs 0.07 L/min/m (-0.47-0.33), p=0.034, respectively).
External ventilation acutely augments PBF and CO in adult Fontan subjects. Confirmation of these findings in larger populations with longer duration of ventilation and extended follow-up will be required to determine sustainability of haemodynamic effects.
Heart: 30 Dec 2020; 107:142-149
Heart: 30 Dec 2020; 107:142-149 | PMID: 32748799
Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis.
Rizos EC, Markozannes G, Tsapas A, Mantzoros CS, Ntzani EE
Omega-3 supplements are popular for cardiovascular disease (CVD) prevention. We aimed to assess the association between dose-specific omega-3 supplementation and CVD outcomes.
We included double-blind randomised clinical trials with duration ≥1 year assessing omega-3 supplementation and estimated the relative risk (RR) for all-cause mortality, cardiac death, sudden death, myocardial infarction and stroke. Primary analysis was a stratified random-effects meta-analysis by omega-3 dose in 4 a priori defined categories (<1, 1, 2, ≥3 of 1 g capsules/day). Complementary approaches were trial sequential analysis and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid, sample size, statin use, study duration.
Seventeen studies (n=83 617) were included. Omega-3 supplementation as ≤1 capsule/day was not associated with any outcome under study; futility boundaries were crossed for all-cause mortality and cardiac death. For two capsules/day, we observed a statistically significant reduction of cardiac death (n=3, RR 0.55, 95% CI 0.33 to 0.90, I=0%); for ≥3 capsules/day we observed a statistically significant reduction of cardiac death (n=3, RR 0.82, 95% CI 0.68 to 0.99, I=0%), sudden death (n=1, RR 0.70, 95% CI 0.51 to 0.97) and stroke (n=2, RR 0.74, 95% CI 0.57 to 0.95, I=0%).
Omega-3 supplementation at <2 1 g capsules/day showed no association with CVD outcomes; this seems unlikely to change from future research. Compared with the robust scientific evidence available for low doses, the evidence for higher doses (2-4 1 g capsules/day) is weak. The emerging postulated benefit from high-dose supplementation needs replication and further evaluation as to the precise formulation and indication.
Evaluation of indicators supporting reproducibility and transparency within cardiology literature.
Anderson JM, Wright B, Rauh S, Tritz D, ... Cook S, Vassar M
It has been suggested that biomedical research is facing a reproducibility issue, yet the extent of reproducible research within the cardiology literature remains unclear. Thus, our main objective was to assess the quality of research published in cardiology journals by assessing for the presence of eight indicators of reproducibility and transparency.
Using a cross-sectional study design, we conducted an advanced search of the National Library of Medicine catalogue for publications in cardiology journals. We included publications published between 1 January 2014 and 31 December 2019. After the initial list of eligible cardiology publications was generated, we searched for full-text PDF versions using Open Access, Google Scholar and PubMed. Using a pilot-tested Google Form, a random sample of 532 publications were assessed for the presence of eight indicators of reproducibility and transparency.
A total of 232 eligible publications were included in our final analysis. The majority of publications (224/232, 96.6%) did not provide access to complete and unmodified data sets, all 229/232 (98.7%) failed to provide step-by-step analysis scripts and 228/232 (98.3%) did not provide access to complete study protocols.
The presentation of studies published in cardiology journals would make reproducing study outcomes challenging, at best. Solutions to increase the reproducibility and transparency of publications in cardiology journals is needed. Moving forward, addressing inadequate sharing of materials, raw data and key methodological details might help to better the landscape of reproducible research within the field.
Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study.
Feijen EAM, van Dalen EC, van der Pal HJH, Reulen RC, ... Kremer LCM,
In this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study.
Eight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3-5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors.
Overall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14-30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)).
In this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.
Place and causes of acute cardiovascular mortality during the COVID-19 pandemic.
Wu J, Mamas MA, Mohamed MO, Kwok CS, ... Deanfield JE, Gale CP
To describe the place and causes of acute cardiovascular death during the COVID-19 pandemic.
Retrospective cohort of adult (age ≥18 years) acute cardiovascular deaths (n=5 87 225) in England and Wales, from 1 January 2014 to 30 June 2020. The exposure was the COVID-19 pandemic (from onset of the first COVID-19 death in England, 2 March 2020). The main outcome was acute cardiovascular events directly contributing to death.
After 2 March 2020, there were 28 969 acute cardiovascular deaths of which 5.1% related to COVID-19, and an excess acute cardiovascular mortality of 2085 (+8%). Deaths in the community accounted for nearly half of all deaths during this period. Death at home had the greatest excess acute cardiovascular deaths (2279, +35%), followed by deaths at care homes and hospices (1095, +32%) and in hospital (50, +0%). The most frequent cause of acute cardiovascular death during this period was stroke (10 318, 35.6%), followed by acute coronary syndrome (ACS) (7 098, 24.5%), heart failure (6 770, 23.4%), pulmonary embolism (2 689, 9.3%) and cardiac arrest (1 328, 4.6%). The greatest cause of excess cardiovascular death in care homes and hospices was stroke (715, +39%), compared with ACS (768, +41%) at home and cardiogenic shock (55, +15%) in hospital.
and relevance
The COVID-19 pandemic has resulted in an inflation in acute cardiovascular deaths, nearly half of which occurred in the community and most did not relate to COVID-19 infection suggesting there were delays to seeking help or likely the result of undiagnosed COVID-19.
Prevalence and clinical outcomes of triglyceride deposit cardiomyovasculopathy among haemodialysis patients.
Onishi T, Nakano Y, Hirano KI, Nagasawa Y, ... Takashima H, Amano T
To evaluate the effect of triglyceride deposit cardiomyovasculopathy (TGCV) on the cardiovascular outcomes in haemodialysis (HD) patients with suspected coronary artery disease (CAD).
This retrospective single-centre observational study included data from the cardiac catheter database of Narita Memorial Hospital between April 2011 and March 2017. Among 654 consecutive patients on HD, the data for 83 patients with suspected CAD who underwent both [I]-β-methyl-iodophenyl-pentadecanoic acid scintigraphy and coronary angiography were analysed. Patients were divided into three groups: definite TGCV (17 patients), probable TGCV (22 patients) and non-TGCV control group (44 patients). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke assessed for up to 5 years of follow-up.
The prevalence of definite TGCV was approximately 20% and 2.6% among consecutive HD patients with suspected CAD and among all HD patients, respectively. At the end of the median follow-up period of 4.7 years, the primary endpoint was achieved in 52.9% of the definite TGCV patients (HR, 7.45; 95% CI: 2.28 to 24.3; p<0.001) and 27.3% of the probable TGCV patients (HR, 3.28; 95% CI: 0.93 to 11.6; p=0.066), compared with that in 9.1% of the non-TGCV control patients. Definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes among HD patients in all multivariate models.
TGCV is not uncommon in HD patients and is associated with an increased risk of cardiovascular events including cardiovascular death. Thus, TGCV might be a potential therapeutic target.
Infective endocarditis at a tertiary care hospital in South Korea.
Kim JH, Lee HJ, Ku NS, Lee SH, ... Choi JY, Yeom JS
The treatment of infective endocarditis (IE) has become more complex with the current myriad healthcare-associated factors and the regional differences in causative organisms. We aimed to investigate the overall trends, microbiological features, and outcomes of IE in South Korea.
A 12-year retrospective cohort study was performed. Poisson regression was used to estimate the time trends of IE incidence and mortality rate. Risk factors for in-hospital mortality were identified with multivariable logistic regression, and model comparison was performed to evaluate the predictive performance of notable risk factors. Kaplan-Meier survival analysis and Cox regression were performed to assess long-term prognosis.
We included 419 patients with IE, the incidence of which showed an increasing trend (relative risk 1.06, p=0.005), whereas mortality demonstrated a decreasing trend (incidence rate ratio 0.93, p=0.020). The in-hospital mortality rate was 14.6%. On multivariable logistic regression analysis, aortic valve endocarditis (OR 3.18, p=0.001), IE caused by(OR 2.32, p=0.026), neurological complications (OR 1.98, p=0.031), high Sequential Organ Failure Assessment score (OR 1.22, p=0.023) and high Charlson Comorbidity Index (OR 1.11, p=0.019) were predictors of in-hospital mortality. Surgical intervention for IE was a protective factor against in-hospital mortality (OR 0.25, p<0.001) and was associated with improved long-term prognosis compared with medical treatment only (p<0.001).
The incidence of IE is increasing in South Korea. Although the mortality rate has slightly decreased, it remains high. Surgery has a protective effect with respect to both in-hospital mortality and long-term prognosis in patients with IE.
Evaluation and treatment of premature ventricular contractions in heart failure with reduced ejection fraction.
Mulder BA, Rienstra M, Blaauw Y
Premature ventricular complexes (PVCs) are often observed in patients presenting with heart failure with a reduced ejection fraction (HFrEF). PVCs may in some patients be considered to be the cause of heart failure, while in others it may be the consequence of heart failure. PVCs are important prognostic markers in HFrEF. The uncertainty whether PVCs are the cause or effect in HFrEF impacts clinical decision making. In this review, we discuss the complexity of the cause-effect relationship between PVCs and HFrEF. We demonstrate a workflow with the use of a trial period of amiodarone that may discover whether the reduced LVEF is reversible, the symptoms are due to PVCs and whether biventricular pacing can be increased by the reduction of PVCs. The use of non-invasive and invasive (high-density) mapping techniques may help to improve accuracy and efficacy in the treatment of PVC, which will be demonstrated. With these results in mind, we conclude this review highlighting the future directions for PVC research and treatment.
Contrast echocardiography: current status and future directions.
Lindner JR
Contrast echocardiography is a family of ultrasound-based procedures, whereby acoustic enhancing agents, usually microbubbles, are administered by intravenous route and detected in order to improve diagnostic performance. This review describes: (1) the agents that have been designed for diagnostic imaging, (2) current clinical applications where either left ventricular opacification or microvascular perfusion imaging with myocardial contrast echocardiography have been demonstrated to provide incremental information to non-contrast echocardiography and (3) future diagnostic and therapeutic applications of contrast ultrasound that rely on unique compositional design of ultrasound-enhancing agents.
Clinical and budget impacts of changes in oral anticoagulation prescribing for atrial fibrillation.
Orlowski A, Gale CP, Ashton R, Petrungaro B, ... Smith W, Wu J
To assess temporal clinical and budget impacts of changes in atrial fibrillation (AF)-related prescribing in England.
Data on AF prevalence, AF-related stroke incidence and prescribing for all National Health Service general practices, hospitals and registered patients with hospitalised AF-related stroke in England were obtained from national databases. Stroke care costs were based on published data. We compared changes in oral anticoagulation prescribing (warfarin or direct oral anticoagulants (DOACs)), incidence of hospitalised AF-related stroke, and associated overall and per-patient costs in the periods January 2011-June 2014 and July 2014-December 2017.
Between 2011-2014 and 2014-2017, recipients of oral anticoagulation for AF increased by 86.5% from 1 381 170 to 2 575 669. The number of patients prescribed warfarin grew by 16.1% from 1 313 544 to 1 525 674 and those taking DOACs by 1452.7% from 67 626 to 1 049 995. Prescribed items increased by 5.9% for warfarin (95% CI 2.9% to 8.9%) but by 2004.8% for DOACs (95% CI 1848.8% to 2160.7%). Oral anticoagulation prescription cost rose overall by 781.2%, from £87 313 310 to £769 444 028, (£733,466,204 with warfarin monitoring) and per patient by 50.7%, from £293 to £442, giving an incremental cost of £149. Nevertheless, as AF-related stroke incidence fell by 11.3% (95% CI -11.5% to -11.1%) from 86 467 in 2011-2014 to 76 730 in 2014-2017 with adjustment for AF prevalence, the overall per-patient cost reduced from £1129 to £840, giving an incremental per-patient saving of £289.
Despite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke led to incremental savings at the national level.
N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy.
Wu G, Liu J, Wang S, Yu S, ... Wang J, Song L
Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.
The study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell\'s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson\'s staining was analysed.
During follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson\'s trichrome staining in the myocardium (r=0.198, p<0.05).
NT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.
Heart: 23 Dec 2020; epub ahead of print
Heart: 23 Dec 2020; epub ahead of print | PMID: 33361398
Prognostic value of electrocardiographic abnormalities in adults from the Brazilian longitudinal study of adults\' health.
Pinto-Filho MM, Brant LC, Dos Reis RP, Giatti L, ... Barreto SM, Ribeiro ALP
Cardiovascular diseases (CVDs) are highly preventable non-communicable diseases. ECG is a potential tool for risk stratification with respect to CVD. Our aim was to evaluate ECG\'s role in all-cause and cardiovascular mortality prediction.
Participants from the Brazilian Longitudinal Study of Adult Health, free of known CVD at baseline were included. A 12-lead ECG was obtained at baseline (2008-2010). Participants were followed up to 2018 by annual interviews. Deaths were independently reviewed. Cox as well as Fine and Grey multivariable regression models were applied to evaluate if the presence of any major electrocardiographic abnormality (MEA), defined according to the Minnesota Code system, would predict total and cardiovascular deaths. We also evaluated the Net Reclassification Index of adding MEA to the Systematic Coronary Risk Evaluation (SCORE).
The 13 428 participants (median age 51 years, 45% men) were followed up for 8±1 years. All-cause and cardiovascular mortality occurred in 2.8% and 1.2% of the population, respectively. Prevalent MEA was an independent predictor of overall (HR=2.3, 95% CI 1.7 to 2.9) and cardiovascular mortality (HR=4.6, 95% CI 3.0 to 7.0) after adjustments for age, race, education and traditional cardiovascular risk factors. Adding MEA to the SCORE resulted in 9% mis-reclassification in the non-event subgroup and 33% correct reclassification in those with a fatal cardiovascular event.
Presence of MEA was an independent predictor of overall and cardiovascular mortality. ECG may have a role in risk prediction of cardiovascular mortality in primary care.
Prognostic value of electrocardiographic abnormalities in adults from the Brazilian longitudinal study of adults' health.
Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II.
Blacher M, Zimerman A, Engster PHB, Grespan E, ... Biolo A, Rohde LE
New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the(ReBIC)-1 Trial.
The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient\'s self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100).
Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14).
Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.
Greater admissions, mortality and cost of heart failure in adults with congenital heart disease.
Burstein DS, Rossano JW, Griffis H, Zhang X, ... Edelson JB, Menachem JN
Limited contemporary data exist regarding outcomes and resource use among adults with congenital heart disease and heart failure (ACHD-HF). This study compared outcomes, emergency department (ED) and hospital resource use, and advanced heart failure (HF) therapies in ACHD-HF versus non-ACHD with HF (HF-non-ACHD).
The Nationwide Emergency Department Sample and Nationwide Inpatient Sample were used to analyse outcomes and resource use among ACHD-HF ED visits and hospitalisations from 2006 to 2016. ACHD-HF was stratified by single-ventricle (SV) and two-ventricle (2V) disease.
A total of 76 557 ACHD-HF visits (3.6% SV physiology) and 31 137 414 HF-non-ACHD visits were analysed. ACHD-HFs were younger (SV 33 years (IQR 25-44), 2V 62 years (IQR 45-76); HF-non-ACHD 74 years (IQR 63-83); p<0.001). ACHD-HFs had higher ED admissions (78% vs 70%, p<0.001), longer hospital length of stay (5 days (IQR 2-8) vs 4 days (IQR 2-7), p<0.001) and greater hospital costs ($49K (IQR 2K-121K) vs $32K (17K-66K), p<0.001). Mortality was significantly higher among ACHD-HFs with SV physiology (6.6%; OR 1.6, 95% CI 1.1 to 2.3) or 2V physiology (6.3%; OR 1.4, 95% CI 1.3 to 1.5) versus HF-non-ACHD (5.5%). ACHF-HF hospitalisations increased more (46% vs 6% HF-non-ACHD) over a 10-year period, but the proportion receiving ventricular assist device (VAD) (ACHD-HF -2% vs HF-non-ACHD 294%) or transplant (ACHD-HF -37% vs HF-non-ACHD 73%) decreased.
ACHD-HFs have significant ED and hospital resource use that has increased over the past 10 years. However, advanced HF therapies (VAD and transplantation) are less commonly used compared with those without adult congenital heart disease.
Multimodality imaging anatomy of interatrial septum and mitral annulus.
Faletra FF, Leo LA, Paiocchi V, Schlossbauer S, Narula J, Ho SY
The detailed anatomy of the interatrial septum (IAS) and mitral annulus (MA) as observed on cardiac magnetic resonance, computed tomography and two-dimensional/three-dimensional transthoracic and transesophageal echocardiography is reviewed. The IAS comprises of two components: the septum primum that is membrane-like forming the floor of the fossa ovalis (FO) and the septum secundum that is a muscular rim that surrounds the FO. The latter is an enfolding of atrial wall forming an interatrial groove. Named Waterston\'s groove, it is filled with adipose tissue on the epicardial side. Thus, the safest area for transseptal puncture (TSP) is within the limits of the FO floor, which provides direct interatrial access. While crossing an intact septum is a well-established procedure, TSP is a more complex and time-consuming procedure in the presence of patent foramen ovalis, aneurysmal FO or atrial septal defect closure devices. MA comprises two distinctive segments: an anterior-straight and a posterior-curved segment. The posterior MA is a thin, discontinuous fibrous \'string\', interspersed with adipose tissue, where four components converge: the atrial and ventricular musculature, epicardial adipose tissue and the leaflet\'s hinge line. In parts of where this fibrous string is deficient or absent, the posterior leaflet is inserted directly on ventricular and atrial myocardium rendering the MA less robust and producing an \'asymmetric\' dilation. The marked vulnerability of posterior MA to calcifications might be due to its insertion on the crest of ventricular myocardium being subject to friction injury due to the contraction and relaxation of LV.
Impact of cardiovascular disease and risk factors on fatal outcomes in patients with COVID-19 according to age: a systematic review and meta-analysis.
Bae S, Kim SR, Kim MN, Shim WJ, Park SM
Previous studies that evaluated cardiovascular risk factors considered age as a potential confounder. We aimed to investigate the impact of cardiovascular disease (CVD) and its risk factors on fatal outcomes according to age in patients with COVID-19.
A systematic literature review and meta-analysis was performed on data collected from PubMed and Embase databases up to 11 June 2020. All observational studies (case series or cohort studies) that assessed in-hospital patients were included, except those involving the paediatric population. Prevalence rates of comorbid diseases and clinical outcomes were stratified by mean patient age in each study (ranges: <50 years, 50-60 years and ≥60 years). The primary outcome measure was a composite fatal outcome of severe COVID-19 or death.
We included 51 studies with a total of 48 317 patients with confirmed COVID-19 infection. Overall, the relative risk of developing severe COVID-19 or death was significantly higher in patients with risk factors for CVD (hypertension: OR 2.50, 95% CI 2.15 to 2.90; diabetes: 2.25, 95% CI 1.89 to 2.69) and CVD (3.11, 95% 2.55 to 3.79). Younger patients had a lower prevalence of hypertension, diabetes and CVD compared with older patients; however, the relative risk of fatal outcomes was higher among the former.
The results of the meta-analysis suggest that CVD and its risk factors (hypertension and diabetes) were closely related to fatal outcomes in COVID-19 for patients across all ages. Although young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients.
Prospero registration number
CRD42020198152.
Cardiogenetics: genetic testing in the diagnosis and management of patients with aortic disease.
Thakker PD, Braverman AC
Thoracic aortic aneurysm and aortic dissection have a potent genetic underpinning with 20% of individuals having an affected relative. Heritable thoracic aortic diseases (HTAD) may be classified as syndromic (including Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome and others) or non-syndromic (without recognisable phenotypes) and relate to pathogenic variants in multiple genes affecting extracellular matrix proteins, transforming growth factor-beta (TGF-β) signalling and smooth muscle contractile function. Clinical and imaging characteristics may heighten likelihood of an underlying HTAD. HTAD should be investigated in individuals with thoracic aortic aneurysm or aortic dissection, especially when occurring in younger individuals, in those with phenotypic features and in those with a family history of aneurysm disease. Screening family members for aneurysm disease is important. Consultation with a medical geneticist and genetic testing of individuals at increased risk for HTAD is recommended. Medical management and prophylactic aortic surgical thresholds are informed by an accurate clinical and molecular diagnosis.
Effect of the COVID-19 pandemic on mortality of patients with STEMI: a systematic review and meta-analysis.
Rattka M, Dreyhaupt J, Winsauer C, Stuhler L, ... Rottbauer W, Imhof A
Since the beginning of the SARS-CoV-2 outbreak, hospitals reported declining numbers of patients admitted with ST-segment elevation myocardial infarction (STEMI), indicating that the pandemic might keep patients from seeking urgent medical treatment. However, data on outcomes and mortality rates are inconsistent between studies.
A literature search and meta-analysis were performed on studies reporting the mortality of patients with STEMI admitted before and during the COVID-19 pandemic using PubMed, Embase and Web of Science. Additionally, prehospital and intrahospital delay times were evaluated.
Outcomes of a total of 50 123 patients from 10 studies were assessed. Our study revealed that, despite a significant reduction in overall admission rates of patients with STEMI during the COVID-19 pandemic (incidence rate ratio=0.789, 95% CI 0.730 to 0.852, I=77%, p<0.01), there was no significant difference in hospital mortality (OR=1.178, 95% CI 0.926 to 1.498, I=57%, p=0.01) compared with patients with STEMI admitted before the outbreak. Time from the onset of symptoms to first medical contact was similar (mean difference (MD)=33.4 min, 95% CI -10.2 to 77.1, I=88%, p<0.01) while door-to-balloon time was significantly prolonged in those presenting during the pandemic (MD=7.3 min, 95% CI 3.0 to 11.7, I=95%, p<0.01).
The significant reduction in admission of patients with STEMI was not associated with a significant increase of hospital mortality rates. The causes for reduced incidence rates remain speculative. However, the analysed data indicate that acute and timely medical care of these patients has been maintained during the pandemic in most countries. Long-term data on mortality have yet to be determined.
Variations in knowledge, awareness and treatment of hypertension and stroke risk by country income level.
O\' Donnell M, Hankey GJ, Rangarajan S, Chin SL, ... Nilanont Y, Yusuf S
Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke.
We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension.
Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46).
Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.
O' Donnell M, Hankey GJ, Rangarajan S, Chin SL, ... Nilanont Y, Yusuf S
Prognostic value of automated longitudinal strain measurements in asymptomatic aortic stenosis.
Kitano T, Nabeshima Y, Negishi K, Takeuchi M
Two-dimensional (2D) longitudinal strain (LS) predicts cardiac events in aortic stenosis (AS). However, it requires manual editing, which affects its accuracy and reliability. We investigated whether left ventricular (LV), left atrial (LA) and right ventricular (RV) LSs using fully automated 2D strain software provide useful prognostic information in asymptomatic AS.
We performed LS analyses in 340 asymptomatic patients with AS using novel, fully automated 2D strain analytical software (AutoStrain, Philips) to obtain LV global LS (LVGLS), LALS, RV free wall LS and RVLS. The primary end point was a composite of cardiac events, including cardiac death, heart failure hospitalisation, myocardial infarction or ventricular tachyarrhythmia.
During a median of 24 months follow-up, 46 patients reached a primary end point. 62 patients had aortic valve surgery. All four LSs were significantly associated with the primary end point using univariate analysis (HR 0.821 to 0.951, p<0.05). Multivariate analysis revealed that LVGLS (HR 0.873 to 0.888, p<0.05) remained significantly associated with cardiac events, even after adjusting haemodynamic measures of AS severity and LV ejection fraction. Kaplan-Meier survival curve showed median values of both LVGLS (cut-off: 15.1%) and LALS (cut-off: 22.3%) provide a significant difference in cardiac event rate (3-year event-free rate; LVGLS: 89% vs 76%, p=0.002; LALS: 89% vs 76%, p=0.001). Classification and regression-tree analysis, including four LSs, clinical characteristics and traditional echocardiographic parameters, selected LVGLS and E/ε\' for stratifying a high-risk group of patients with cardiac events.
Fully automated 2D LS analysis, especially LVGLS provides useful prognostic information in asymptomatic AS.
Discontinuation of oral anticoagulation in atrial fibrillation and risk of ischaemic stroke.
García Rodríguez LA, Cea Soriano L, Munk Hald S, Hallas J, ... Sharma M, Gaist D
To evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF).
We undertook a population-based cohort study with nested case-control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked registries from the Region of Southern Denmark (RSD). Patients with AF (76 882 UK, 41 526 RSD) were followed to identify incident IS cases during 2016-2018. Incident IS cases were matched by age and sex to controls. Adjusted ORs for OAC discontinuation (vs current OAC use) were calculated using logistic regression.
We identified 616 incident IS cases in the UK and 643 in the RSD. ORs for IS with any OAC discontinuation were 2.99 (95% CI 2.31 to 3.86, UK) and 2.30 (95% CI 1.79 to 2.95, RSD), for vitamin K antagonist discontinuation they were 2.38 (95% CI 1.72 to 3.30, UK) and 1.83 (95% CI 1.34 to 2.49, RSD), and for non-vitamin K antagonist oral anticoagulant discontinuation they were 4.59 (95% CI 2.97 to 7.08, UK) and 3.37 (95% CI 2.35 to 4.85, RSD). ORs were unaffected by time since discontinuation and duration of use. Annually, up to 987 IS cases in the UK and 132 in Denmark could be preventable if OAC therapy is not discontinued.
Our results suggest that patients with AF who discontinue OAC therapy have a significant twofold to threefold higher risk of IS compared with those who continue therapy. Addressing OAC discontinuation could potentially result in a significant reduction in AF-attributed IS.
Translational applications of computational modelling for patients with cardiac arrhythmias.
Bifulco SF, Akoum N, Boyle PM
Cardiac arrhythmia is associated with high morbidity, and its underlying mechanisms are poorly understood. Computational modelling and simulation approaches have the potential to improve standard-of-care therapy for these disorders, offering deeper understanding of complex disease processes and sophisticated translational tools for planning clinical procedures. This review provides a clinician-friendly summary of recent advancements in computational cardiology. Organ-scale models automatically generated from clinical-grade imaging data are used to custom tailor our understanding of arrhythmia drivers, estimate future arrhythmogenic risk and personalise treatment plans. Recent mechanistic insights derived from atrial and ventricular arrhythmia simulations are highlighted, and the potential avenues to patient care (eg, by revealing new antiarrhythmic drug targets) are covered. Computational approaches geared towards improving outcomes in resynchronisation therapy have used simulations to elucidate optimal patient selection and lead location. Technology to personalise catheter ablation procedures are also covered, specifically preliminary outcomes form early-stage or pilot clinical studies. To conclude, future developments in computational cardiology are discussed, including improving the representation of patient-specific fibre orientations and fibrotic remodelling characterisation and how these might improve understanding of arrhythmia mechanisms and provide transformative tools for patient-specific therapy.
Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation.
Hanon O, Vidal JS, Pisica-Donose G, Orvoën G, ... Boureau AS,
Direct oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.
We performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.
Major bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score-matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score-matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.
Our study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.
Heart: 30 Nov 2020; epub ahead of print
Heart: 30 Nov 2020; epub ahead of print | PMID: 33262185
Associations of symptoms and quality of life with outcomes in patients with atrial fibrillation.
Krisai P, Blum S, Aeschbacher S, Beer JH, ... Conen D,
We aimed to investigate changes in atrial fibrillation (AF)-related symptoms and quality of life (QoL) over time, and their impact on prognosis.
We prospectively followed 3836 patients with known AF for a mean of 3.7 years. Information on AF-related symptoms and QoL was obtained yearly. The primary end point was a composite of stroke or systemic embolism. Main secondary end points included stroke subtypes, all-cause mortality, cardiovascular death, hospitalisation for congestive heart failure (CHF), myocardial infarction and major bleeding. We assessed associations using multivariable, time-updated Cox proportional hazards models.
Mean age was 72 years, 72% were male. Patients with AF-related symptoms (66%) were younger (70 vs 74 years, p<0.0001), more often had paroxysmal AF (56% vs 37%, p<0.0001) and had lower QoL (71 vs 72 points, p=0.009). The incidence of the primary end point was 1.05 and 1.02 per 100 person-years in patients with and without symptoms, respectively. The multivariable adjusted HR (aHR) (95% CIs) for the primary end point was 1.11 (0.77 to 1.59; p=0.56) for AF-related symptoms. AF-related symptoms were not associated with any of the secondary end points. QoL was not significantly related to the primary end point (aHR per 5-point increase 0.98 (0.94 to 1.03; p=0.37)), but was significantly related to CHF hospitalisations (0.92 (0.90 to 0.94; p<0.0001)), cardiovascular death (0.90 (0.86 to 0.95; p<0.0001)) and all-cause mortality (0.88 (0.86 to 0.90; p<0.0001)).
AF-related symptoms were not associated with adverse outcomes and should therefore not be the basis for prognostic treatment decisions. QoL was strongly associated with CHF, cardiovascular death and all-cause mortality.
Heart: 29 Nov 2020; 106:1847-1852
Heart: 29 Nov 2020; 106:1847-1852 | PMID: 32234819
Maternal cardiovascular risk after hypertensive disorder of pregnancy.
Arnott C, Nelson M, Alfaro Ramirez M, Hyett J, ... Taylor L, Woodward M
and objective
Hypertensive disorders of pregnancy (HDPs) affect 5%-10% of pregnancies and have been associated with excess maternal cardiovascular disease (CVD) risk. The primary aim of this study was to reliably estimate absolute and relative risks of CVD after HDP.
A retrospective cohort of women who had singleton pregnancies in New South Wales, Australia, between 2002 and 2016 and identified using linked population health administrative databases. The primary exposure was new-onset HDP (pre-eclampsia/eclampsia and gestational hypertension), and the endpoint was hospitalisation or death due to ischaemic or hypertensive heart disease, or stroke. Kaplan-Meier analysis estimated risks among mothers following their first birth, and multivariable time-dependent Cox regression estimated the association between HDP and CVD.
Among 528 106 women, 10.3% experienced HDP in their first pregnancy. The 10-year estimated risk of CVD was 2.1 per 1000 if no HDP and 5.5 per 1000 following HDP. Adjusting for demographics, gestational diabetes, small for gestational age and preterm birth, we found that there was an interaction between smoking and HDP, and a larger effect of early-onset (<34 weeks) HDP, compared with late-onset HDP. The HR for women with early-onset HDP who did not smoke was 4.90 (95% CI 3.00 to 7.80) and the HR for those who did smoke was 23.5 (95% CI 13.5 to 40.5), each compared with women without HDP who did not smoke.
In this nationally representative Australian cohort, HDP, especially early onset, conferred a clear increase in the risk of CVD, with amplification by smoking. Targeted preventive health, during and after pregnancy, could prevent a substantial burden of CVD among childbearing women.
Sex-based impact of carotid plaque in patients with chest pain undergoing stress echocardiography.
Ahmadvazir S, Pradhan J, Khattar RS, Senior R
Women with suspected angina without history of coronary artery disease (CAD) less frequently have flow-limiting stenosis (FL-CAD) and more often have microvascular disease, affecting predictive accuracy of stress echocardiography (SE) for detection of FL-CAD. We postulated that carotid plaque burden (CPB) assessment would improve detection of FL-CAD and risk stratification.
Consecutive consenting patients assessed by SE on clinical grounds for new-onset chest pain also underwent simultaneous carotid ultrasound. Patients were followed for major adverse events (MAE): all-cause mortality, non-fatal myocardial infarction and unplanned revascularisation. Carotid plaque presence and burden (CPB) were assessed.
After a mean of 2617±469 days (range 17-3740), of 591 recruited patients, 573 (97%) outcome data (314 females) were obtainable. Despite lower pretest probability of CAD in females versus males (14.9±0.8 vs 20.5±1.3, respectively, p<0.0001), prevalence of myocardial ischaemia was similar (p=0.08). Females also had lower prevalence of both carotid plaque (p<0.0001) and FL-CAD (p<0.05). CPB improved the positive predictive value of SE for detection of FL-CAD (from 34.5% to 60%) in females but not in males. Absence of CPB in females with myocardial ischaemia ruled out FL-CAD in 93% versus 57% in males. CPB was the only independent predictor of MAE (p=0.012) in females, whereas in males both SE (p<0.0001) and CPB (p=0.003) remained significant.
In females with new-onset stable angina without a history of cardiovascular disease, CPB improved the predictive accuracy of myocardial ischaemia for flow-limiting CAD. However, CPB provided incremental risk stratification in both sexes.
Spondylodiscitis complicating infective endocarditis.
Carbone A, Lieu A, Mouhat B, Santelli F, ... Tribouilloy C, Habib G
The primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS.
Prospective case-control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded.
Patients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p<0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4-L5. Neurological symptoms were observed in 59% of patients. Enterococci andwere more frequent (24% vs 12% and 24% vs 11%; p<0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS.
PS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal orIE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.
Lung ultrasound-guided therapy reduces acute decompensation events in chronic heart failure.
Marini C, Fragasso G, Italia L, Sisakian H, ... Margonato A, Agricola E
Pulmonary congestion is the main cause of hospital admission in patients with heart failure (HF). Lung ultrasound (LUS) is a useful tool to identify subclinical pulmonary congestion. We evaluated the usefulness of LUS in addition to physical examination (PE) in the management of outpatients with HF.
In this randomised multicentre unblinded study, patients with chronic HF and optimised medical therapy were randomised in two groups: \'PE+LUS\' group undergoing PE and LUS and \'PE only\' group. Diuretic therapy was modified according to LUS findings and PE, respectively. The primary endpoint was the reduction in hospitalisation rate for acute decompensated heart failure (ADHF) at 90-day follow-up. Secondary endpoints were reduction in NT-proBNP, quality-of-life test (QLT) and cardiac mortality at 90-day follow-up.
A total of 244 patients with chronic HF and optimised medical therapy were enrolled and randomised in \'PE+LUS\' group undergoing PE and LUS, and in \'PE only\' group. Thirty-seven primary outcome events occurred. The hospitalisation for ADHF at 90 day was significantly reduced in \'PE+LUS\' group (9.4% vs 21.4% in \'PE only\' group; relative risk=0.44; 95% CI 0.23 to 0.84; p=0.01), with a reduction of risk for hospitalisation for ADHF by 56% (p=0.01) and a number needed to treat of 8.4 patients (95% CI 4.8 to 34.3). At day 90, NT-proBNP and QLT score were significantly reduced in \'PE+LUS\' group, whereas in \'PE only\' group both were increased. There were no differences in mortality between the two groups.
LUS-guided management reduces hospitalisation for ADHF at mid-term follow-up in outpatients with chronic HF.
Prediction of cardiovascular health by non-exercise estimated cardiorespiratory fitness.
Cabanas-Sánchez V, Artero EG, Lavie CJ, Higueras-Fresnillo S, ... Rodríguez-Artalejo F, Martínez-Gómez D
To estimate the incidence of major biological cardiovascular disease (CVD) risk factors in adults using non-exercise estimated cardiorespiratory fitness (eCRF).
200 039 healthy people (99 957 women), aged ≥18 years (38.5±12.1 years) from the Taiwan MJ Cohort. eCRF was estimated with validated algorithms. Biological CVD risk factors, including hypertension (HTN), hypercholesterolemia, atherogenic dyslipidaemia, type 2 diabetes mellitus (T2DM) and systemic inflammation, were assessed by standardised physical examinations and laboratory tests.
In a basic model, baseline eCRF was inversely associated with the incidence of each CVD risk factor in both men and women (HR per 1 metabolic equivalent (MET) increase in eCRF ranged from 0.53 for T2DM in women to 0.96 for hypercholesterolemia in women). In full adjusted models, the associations were attenuated but remained statistically significant, with the exception of hypercholesterolemia in women. In a subcohort of 116 313 individuals with two repeated exposure measurements, an increase in eCRF was associated in both sexes with a subsequent lower incidence of CVD risk factors (HR per 1-MET increase ranged from 0.58 to 0.91 in models adjusted for age, year of examination and baseline eCRF). Comparisons of predictive performance showed that the addition of eCRF to values of traditional CVD risk factors had relevant improvements in risk discrimination (C-index increased from 0.1% to 3.2%), mainly for HTN and T2DM risk prediction.
eCRF and its changes predict the incidence of biological CVD risk factors, especially HTN and T2DM. Routine assessment of eCRF in clinical settings is technically feasible and might be useful for CVD prevention.
The \'wait for symptoms\' strategy in asymptomatic severe aortic stenosis.
San Román JA, Vilacosta I, Antunes MJ, Iung B, Lopez J, Schäfers HJ
Calcific aortic stenosis is a prevalent and worrisome healthcare problem. The therapeutic approach in asymptomatic aortic stenosis is not well established. We argue that the natural history of this disease is based on old incomplete studies with many limitations. Likewise, studies suggesting that replacement, either surgical or percutaneous, improves prognosis in asymptomatic patients with severe aortic stenosis have important drawbacks and do not support this strategy as the treatment of choice. Despite the lack of evidence, some groups recommend early valve replacement in patients with severe asymptomatic aortic stenosis. There are five ongoing randomised trials which will shed light on this topic. Our conclusion is that unless a randomised study changes the evidence, valve replacement cannot be recommended in asymptomatic patients with severe aortic stenosis.
The 'wait for symptoms' strategy in asymptomatic severe aortic stenosis.
Pathogen influence on epidemiology, diagnostic evaluation and management of infective endocarditis.
Talha KM, DeSimone DC, Sohail MR, Baddour LM
Infective endocarditis (IE) is uncommon and has, in the past, been most often caused by viridans group streptococci (VGS). Due to the indolent nature of these organisms, the phrase \'subacute bacterial endocarditis\', so-called \'SBE\', was routinely used as it characterised the clinical course of most patients that extended for weeks to months. However, in more recent years, there has been a significant shift in the microbiology of IE with the emergence of staphylococci as the most frequent pathogens, and for IE due to , the clinical course is acute and can be associated with sepsis. Moreover, increases in IE due to enterococci have occurred and have been characterised by treatment-related complications and worse outcomes. These changes in pathogen distribution have been attributed to a diversification in the target population at risk of IE. While prosthetic valve endocarditis and history of IE remain at highest risk of IE, the rise in prevalence of injection drug use, intracardiac device implantations and other healthcare exposures have heavily contributed to the existing pool of at-risk patients. This review focuses on common IE pathogens and their impact on the clinical profile of IE.
Right ventricle in heart failure with preserved ejection fraction.
Berglund F, Piña P, Herrera CJ
Heart failure with preserved ejection fraction (HFpEF) affects half of all patients with heart failure. While previously neglected, the right ventricle (RV) has sparked interest in recent years as a means for better understanding this condition and as a potential therapeutic target.Right ventricular dysfunction (RVD) is present in 4%-50% of patients with HFpEF. The RV is intimately connected to the pulmonary circulation, and pulmonary hypertension is commonly implicated in the pathophysiology of RVD. The development of RVD in HFpEF may also be driven by comorbidities, such as chronic obstructive pulmonary disease, obesity, obstructive sleep apnoea and atrial fibrillation. The evaluation of RVD is particularly challenging due to anatomical and structural factors, as well as unique physiological characteristics of this chamber like load and interventricular dependency. Fractional area change, tricuspid annular plane systolic excursion and tricuspid annular systolic velocity are commonly used measurements of RV function. Speckle tracking echocardiography and cardiac magnetic resonance (CMR) are also gaining attention as important tools for the assessment of RV structure, fibre deformation and systolic performance. Further research is needed to confirm the utility and prognostic significance of RV [F]fluorodeoxyglucose (FDG) positron emission tomography imaging as FDG accumulation is suggested to increase with progressive RVD. Targeted pharmacotherapy with phosphodiesterase inhibitors, guanylate-cyclase stimulators, nitrates and inhaled inorganic nitrites have yet to demonstrate improvement in RVD, compelling the need for evaluation and discovery of novel pharmacological interventions for this entity.
Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis.
Lee S, Lee SA, Choi B, Kim YJ, ... Kang DH, Song JK
To evaluate whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors and their cardiac tissue distribution profile and anticalcification abilities are associated with risk of aortic stenosis (AS) progression.
Out of the five different classes of DPP-4 inhibitors, two had relatively favourable heart to plasma concentration ratios and anticalcification ability in murine and in vitro experiments and were thus categorised as \'favourable\'. We reviewed the medical records of 212 patients (72±8 years, 111 men) with diabetes and mild-to-moderate AS who underwent echocardiographic follow-up and classified them into those who received favourable DPP-4 inhibitors (n=28, 13%), unfavourable DPP-4 inhibitors (n=69, 33%) and those who did not receive DPP-4 inhibitors (n=115, 54%).
Maximal transaortic velocity (Vmax) increased from 2.9±0.3 to 3.5±0.7 m/s during follow-up (median, 3.7 years), and the changes were not different between DPP-4 users as a whole and non-users (p=0.143). However, the favourable group showed significantly lower Vmax increase than the unfavourable or non-user group (p=0.018). Severe AS progression was less frequent in the favourable group (7.1%) than in the unfavourable (29.0%; p=0.03) or the non-user (29.6%; p=0.01) group. In Cox regression analysis after adjusting for age, baseline renal function and AS severity, the favourable group showed a significantly lower risk of severe AS progression (HR 0.116, 95% CI 0.024 to 0.551, p=0.007).
DPP-4 inhibitors with favourable pharmacokinetic and pharmacodynamic properties were associated with lower risk of AS progression. These results should be considered in the preparation of randomised clinical trials on the repositioning of DPP-4 inhibitors.
Computed tomography aortic valve calcium scoring for the assessment of aortic stenosis progression.
Doris MK, Jenkins W, Robson P, Pawade T, ... Newby DE, Dweck MR
CT quantification of aortic valve calcification (CT-AVC) is useful in the assessment of aortic stenosis severity. Our objective was to assess its ability to track aortic stenosis progression compared with echocardiography.
Subjects were recruited in two cohorts: (1) awhere patients underwent repeat CT-AVC or echocardiography within 4 weeks and (2) awhere patients underwent annual CT-AVC and/or echocardiography. Cohen\'s d-statistic () was computed from the ratio of annualised progression and measurement repeatability and used to estimate group sizes required to detect annualised changes in CT-AVC and echocardiography.
A total of 33 (age 71±8) and 81 participants (age 72±8) were recruited to the reproducibility and progression cohorts, respectively. Ten CT scans (16%) were excluded from the progression cohort due to non-diagnostic image quality. Scan-rescan reproducibility was excellent for CT-AVC (limits of agreement -12% to 10 %, intraclass correlation (ICC) 0.99), peak velocity (-7% to +17%; ICC 0.92) mean gradient (-25% to 27%, ICC 0.96) and dimensionless index (-11% to +15%; ICC 0.98). Repeat measurements of aortic valve area (AVA) were less reliable (-44% to +28%, ICC 0.85).CT-AVC progressed by 152 (65-375) AU/year. For echocardiography, the median annual change in peak velocity was 0.1 (0.0-0.3) m/s/year, mean gradient 2 (0-4) mm Hg/year and AVA -0.1 (-0.2-0.0) cm/year. Cohen\'s d-statistic was more than double for CT-AVC (=3.12) than each echocardiographic measure (peak velocity =0.71 ; mean gradient =0.66; AVA =0.59, dimensionless index =1.41).
CT-AVC is reproducible and demonstrates larger increases over time normalised to measurement repeatability compared with echocardiographic measures.
Novel bradycardia pacing strategies.
Heckman L, Vijayaraman P, Luermans J, Stipdonk AMW, ... Prinzen FW, Vernooy K
The adverse effects of ventricular dyssynchrony induced by right ventricular (RV) pacing has led to alternative pacing strategies, such as biventricular, His bundle (HBP), LV septal (LVSP) and left bundle branch pacing (LBBP). Given the overlap, LVSP and LBBP are also collectively referred to as left bundle branch area pacing (LBBAP). Although among these alternative pacing sites HBP is theoretically the ideal strategy as it maintains a physiological ventricular activation, its application requires more skills and is associated with the most complications. LBBAP, where the ventricular pacing lead is advanced through the interventricular septum to its left side, creates ventricular activation that is only slightly more dyssynchronous. Preliminary studies have shown that LBBAP is feasible, safe and encounters less limitations than HBP. Further studies are needed to differentiate between LVSP and LBBP with regard to acute functional and long-term clinical outcome.
Changes in quality of life, cognition and functional status following catheter ablation of atrial fibrillation.
Piccini JP, Todd DM, Massaro T, Lougee A, ... Di Biase L, Kirchhof P
To investigate changes in quality of life (QoL), cognition and functional status according to arrhythmia recurrence after atrial fibrillation (AF) ablation.
We compared QoL, cognition and functional status in patients with recurrent atrial tachycardia (AT)/AF versus those without recurrent AT/AF in the AXAFA-AFNET 5 clinical trial. We also sought to identify factors associated with improvement in QoL and functional status following AF ablation by overall change scores with and without analysis of covariance (ANCOVA).
Among 518 patients who underwent AF ablation, 154 (29.7%) experienced recurrent AT/AF at 3 months. Patients with recurrent AT/AF had higher mean CHADS-VASc scores (2.8 vs 2.3, p<0.001) and more persistent forms of AF (51 vs 39%, p=0.012). Median changes in the SF-12 physical (3 (25th, 75th: -1, 8) vs 1 (-5, 8), p=0.026) and mental scores (2 (-3, 9) vs 0 (-4, 5), p=0.004), EQ-5D (0 (0,2) vs 0 (-0.1, 0.1), p=0.027) and Karnofsky functional status scores (10 (0, 10) vs 0 (0, 10), p=0.001) were more favourable in patients without recurrent AT/AF. In the overall cohort, the proportion with at least mild cognitive impairment (Montreal Cognitive Assessment <26) declined from 30.3% (n=157) at baseline to 21.8% (n=113) at follow-up. ANCOVA identified greater improvement in Karnofsky functional status (p<0.001) but not SF-12 physical (p=0.238) or mental scores (p=0.065) in those without recurrent AT/AF compared with patients with recurrent AT/AF.
Patients without recurrent AT/AF appear to experience greater improvement in functional status but similar QoL as those with recurrent AT/AF after AF ablation.
Risk for cardiovascular events following \'microsize\' versus usual myocardial infarctions.
Almarzooq ZI, Colantonio LD, Okin PM, Richman JS, ... Bryan J, Safford MM
Microsize myocardial infarction (MI) is a recently described phenomenon that meets rigorous criteria for MI with very low peak troponin elevations. We aim to compare the risk for cardiovascular events and mortality following microsize versus usual MIs.
Methods and results
Prospective cohort analysis of REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a history of coronary heart disease (CHD) who had an incident MI between 2003 and 2015. Incident MIs were classified as microsize MI (peak troponin <0.5 ng/mL) or usual MI (peak troponin ≥0.5 ng/mL). Participants were followed for a composite of cardiovascular events that included recurrent MI, coronary revascularisation, fatal CHD and heart failure, and all-cause mortality. Overall, 1024 participants with an incident MI were included in the analysis (328 with microsize MI and 696 with usual MI). Participants with microsize MI were more likely to be older and black. The multivariable-adjusted adjustment HR for cardiovascular events among participants with microsize versus usual MI after a median follow-up of 1.7 years was 1.11 (95% CI 0.86 to 1.44). The multivariable-adjusted HR for all-cause mortality after 28 days from incident MI among participants with microsize versus usual MI after a median follow-up of 3.6 years was 1.09 (95% CI 0.81 to 1.45).
Microsize MIs have a prognostic value for future cardiovascular events and mortality comparable to usual MIs. These findings should encourage clinicians to initiate secondary prevention strategies in patients with microsize MI until this emerging clinical entity is better understood.
Risk for cardiovascular events following 'microsize' versus usual myocardial infarctions.
Disproportionate secondary mitral regurgitation: myths, misconceptions and clinical implications.
Grayburn PA, Packer M, Sannino A, Stone GW
Secondary (functional) mitral regurgitation (SMR) most commonly arises secondary to left ventricular (LV) dilation/dysfunction. The concept of disproportionately severe SMR was proposed to help explain the different results of two randomised trials of transcatheter edge-to-edge mitral valve repair (TEER) versus medical therapy. This concept is based on the fact that effective regurgitant orifice area (EROA) depends on LV end-diastolic volume (LVEDV), ejection fraction, regurgitant fraction and the velocity-time integral of SMR. This review focuses on the haemodynamic framework underlying the concept and the myths and misconceptions arising from it. Each component of EROA/LVEDV is prone to measurement error which can result in misclassification of individual patients. Moreover, EROA is typically measured at peak systole rather than its mean value over the duration of MR. This can result in physiologically impossible values of EROA or regurgitant volume. Although the EROA/LVEDV ratio (1) emphasises that grading MR severity needs to consider LV size and function and (2) helps explain the different outcomes between COAPT and MITRAFR, there are important factors that are not included. Among these are left atrial compliance, LV pressure and ejection fraction, pulmonary hypertension, right ventricular function and tricuspid regurgitation. Because medical therapy can reduce LV volumes and improve both LV function and SMR severity, the key to patient selection is forced titration of neurohormonal antagonists to the target doses that have been proven in clinical trials (along with cardiac resynchronisation when appropriate). Patients who continue to have symptomatic severe SMR after doing so should be considered for TEER.
Bleeding and thrombotic risk in pregnant women with Fontan physiology.
Girnius A, Zentner D, Valente AM, Pieper PG, ... Mulder BJM, Veldtman GR
Background/objectives
Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.
We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.
We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096).
Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.
Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial.
Klein AL, Lin D, Cremer PC, Nasir S, ... Fang F, Paolini JF
Recurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.
This multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).
Outcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients.
Secondary outcomes
health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.
Rilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.
Path ahead for \'low risk\' adolescents living with a Fontan circulation.
Baker DW, Dennis MR, Zannino D, Schilling C, ... Celermajer DS, Cordina R
A high risk of morbidity and mortality is well documented in adults with a Fontan circulation. The difference in outcomes between those with and without significant morbidity at the time of transition to adult care has not been well characterised.
We analysed clinical outcomes in patients enrolled in the Australian and New Zealand Fontan Registry ≥16 years of age. Low risk (LR) Fontan patients were defined as those without history of sustained arrhythmia, thromboembolic event, transplantation, Fontan conversion, protein-losing enteropathy, plastic bronchitis, New York Heart Association class III/IV and/or moderate/severe atrioventricular valve regurgitation or ventricular dysfunction. Increased risk (IR) patients had one or more risk factor.
Inclusion criteria were met in 822 patients; mean age 26±8 years, median follow-up from age 16 was 9 years, 203 had atriopulmonary connection (APC) and 619 had total cavopulmonary connection (TCPC). Survival at 30 years was higher in the LR versus IR; 94% versus 82% (p=0.005), 89% versus 77% (p=0.07) for APC and 96% versus 89% (p=0.05) for TCPC. LR patients experienced less Fontan failure (HR 0.34, 95% CI 0.23 to 0.49, p<0.001) and ventricular dysfunction (HR 0.46, 95% CI 0.29 to 0.71, p=0.001) compared with IR patients. For LR TCPC patients, modelled survival projections at 60 years were 49%-67%.
Clinical outcomes for adolescents LR at transition to adult care are markedly superior to those who have established risk factors for Fontan failure, which is an important consideration when formulating individualised long-term risk estimates and counselling patients.
Path ahead for 'low risk' adolescents living with a Fontan circulation.
Comorbidity burden in patients undergoing left atrial appendage closure.
Sanjoy S, Choi YH, Holmes D, Herrman H, ... Mamas M, Bagur R
To estimate the risk of in-hospital complications after left atrial appendage closure (LAAC) in relationship with comorbidity burden.
Cohort-based observational study using the US National Inpatient Sample database, 1 October 2015 to 31 December 2017. The main outcome of interest was the occurrence of in-hospital major adverse events (MAE) defined as the composite of bleeding complications, acute kidney injury, vascular complications, cardiac complications and postprocedural stroke. Comorbidity burden and thromboembolic risk were assessed by the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Score (ECS) and CHADS-VASc score. MAE were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. The associations of comorbidity with in-hospital MAE were evaluated using logistic regression models.
A total of 3294 hospitalisations were identified, among these, the mean age was 75.7±8.2 years, 60% were male and 86% whites. The mean CHADS-VASc score was 4.3±1.5 and 29.5% of the patients had previous stroke or transient ischaemic attack. The mean CCI and ECS were 2.2±1.9 and 9.7±5.8, respectively. The overall composite rate of in-hospital MAE after LAAC was 4.6%. Females and non-whites had about 1.5 higher odds of in-hospital AEs as well participants with higher CCI (adjusted OR (aOR): 1.19, 95% CI: 1.13 to 1.24, p<0.001), ECS (aOR: 1.06, 95% CI: 1.05 to 1.08, p<0.001) and CHADS-VASc score (aOR: 1.08, 95% CI: 1.02 to 1.15, p=0.01) were significantly associated with in-hospital MAE.
In this large cohort of LAAC patients, the majority of them had significant comorbidity burden. In-hospital MAE occurred in 4.6% and female patients, non-whites and those with higher burden of comorbidities were at higher risk of in-hospital MAE after LAAC.
The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial.
Tsaban G, Yaskolka Meir A, Rinott E, Zelicha H, ... Stampfer MJ, Shai I
A Mediterranean diet is favourable for cardiometabolic risk.
To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk.
For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3-4 cups/day) and a(Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state.
Participants (n=294; age 51 years; body mass index 31.3 kg/m; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean -6.2 kg; Mediterranean -5.4 kg) vs the HDG group -1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (-8.6 cm) than the Mediterranean (-6.8 cm; p=0.033) and HDG (-4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean -6.1 mg/dL (-3.7%), -2.3 (-0.8%), HDG -0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean -7.2 mm Hg, Mediterranean -5.2 mm Hg, HDG -3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean -0.77, Mediterranean -0.46, HDG -0.27; p=0.020 between extreme groups). The LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio decline was greater in the green Mediterranean group (-0.38) than in the Mediterranean (-0.21; p=0.021) and HDG (-0.14; p<0.001) groups. High-sensitivity C-reactive protein reduction was greater in the green Mediterranean group (-0.52 mg/L) than in the Mediterranean (-0.24 mg/L; p=0.023) and HDG (-0.15 mg/L; p=0.044) groups. The green Mediterranean group achieved a better improvement (-3.7% absolute risk reduction) in the 10-year Framingham Risk Score (Mediterranean-2.3%; p0.073, HDG-1.4%; p<0.001).
The green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet.
This study is registered under ClinicalTrials.gov Identifier no NCT03020186.
Prognostic significance of natriuretic peptide levels in atrial fibrillation without heart failure.
Hamatani Y, Iguchi M, Ueno K, Aono Y, ... Morita S, Akao M
Natriuretic peptides are an important prognostic marker in patients with heart failure (HF). However, little is known regarding their prognostic significance in patients with atrial fibrillation (AF) without HF and natriuretic peptides levels are underused in these patients in daily practice.
The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We investigated patients with AF without HF (defined as prior HF hospitalisation, New York Heart Association functional class≥2 or left ventricular ejection fraction<40%) using the data of B-type natriuretic peptide (BNP, n=388) or N-terminal pro-B-type natriuretic peptide (NT-proBNP, n=771) at enrolment. BNPs were converted to NT-proBNP using a conversion formula. We divided the patients according to quartiles of NT-proBNP levels and compared the backgrounds and outcomes.
Of 1159 patients (mean age: 72.1±10.2 years, median CHADS-VASc score: 3 and oral anticoagulant (OAC) prescription: 671 (56%)), the median NT-proBNP level was 488 (IQR 169-1015) ng/L. Patients with high NT-proBNP levels were older, had higher CHADS-VASc scores and had more OAC prescription (all p<0.001). Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of stroke/systemic embolism, all-cause death and HF hospitalisation during a median follow-up period of 5.0 years (log rank, all p<0.001). Multivariable Cox regression analyses revealed that NT-proBNP levels were an independent predictor of adverse outcomes even after adjustment by various confounders.
NT-proBNP levels are a significant prognostic marker for adverse outcomes in patients with AF without HF and may have clinical value.
UMIN000005834.
Long-term outcomes of adult out-of-hospital cardiac arrest in Queensland, Australia (2002-2014): incidence and temporal trends.
Pemberton K, Franklin RC, Bosley E, Watt K
To describe annual incidence and temporal trends (2002-2014) in incidence of long-term outcomes of adult out-of-hospital cardiac arrest (OHCA) of presumed cardiac aetiology attended by Queensland Ambulance Service (QAS) paramedics, by age, gender, geographical remoteness and socioeconomic status (SES).
This is a retrospective cohort study. Cases were identified using the QAS OHCA Registry and were linked with entries in the Queensland Hospital Admitted Patient Data Collection and the Queensland Registrar General Death Registry. Population data were obtained from the Australian Bureau of Statistics to calculate incidence. Inclusion criteria were adult (18+ years) residents of Queensland who suffered OHCA of presumed cardiac aetiology and survived to hospital admission. Analyses were undertaken by three mutually exclusive outcomes: (1) survival to less than 30 days (Surv<30 days); (2) survival from 30 to 364 days (Surv30-364 days); and (3) survival to 365 days or more (Surv365+ days). Incidence rates were calculated for each year by gender, age, remoteness and SES. Temporal trends were analysed.
Over the 13 years there were 4393 cases for analyses. The incidence of total admitted events (9.72-10.13; p<0.01), Surv30-364 days (0.18-0.42; p<0.05) and Surv365+ days (1.94-4.02; p<0.001) increased significantly over time; no trends were observed for Surv<30 days. An increase in Surv365+ days over time was observed in all remoteness categories and most SES categories.
Evidence suggests that implemented strategies to improve outcomes from OHCA have been successful and penetrated groups living in more remote locations and the lower socioeconomic groups. These populations still require focus. Ongoing reporting of long-term outcomes from OHCA should be undertaken using population-based incidence.
Role of echocardiography in screening and evaluation of athletes.
Niederseer D, Rossi VA, Kissel C, Scherr J, ... Bohm P, Schmied C
The term athlete\'s heart describes structural, functional and electrical adaptations of the cardiovascular system due to repetitive intense exercise. Physiological cardiac adaptations in athletes, however, may mimic features of cardiac diseases and therefore make it difficult to distinguish physiological adaptions from disease. Furthermore, regular exercise may also lead to pathological adaptions that can promote or worsen cardiac disease (eg, atrial dilation/atrial fibrillation, aortic dilation/aortic dissection and rhythm disorders). Sudden cardiac death (SCD) is a major concern in sports cardiology, and preparticipation screening (PPS) has demonstrated to be effective in identifying athletes at risk for SCD. In Europe, PPS is advocated to include personal and family history, physical examination and ECG, with further workup including echocardiography only if the initial screening investigations show abnormal findings. We review the current available evidence for echocardiography as a screening tool for conditions associated with SCD in recreational and professional athletes and advocate to include screening echocardiography to be performed at least twice in an athlete\'s career. We recommend that the first echocardiography is performed during adolescence to rule out structural heart conditions associated with SCD that cannot be detected by ECG, especially mitral valve prolapse, coronary artery anomalies, bicuspid aortic valve and dilatation of the aorta. A second echocardiography could be performed from the age of 30-35 years, when athletes age and become master athletes, to especially evaluate pathological cardiac remodelling to exercise (eg, atrial and/or right ventricular dilation), late onset cardiomyopathies and wall motion abnormalities due to myocarditis or coronary artery disease.
Predictors of low exercise cardiac output in patients with severe pulmonic regurgitation.
Karsenty C, Khraiche D, Jais JP, Raimondi F, ... Iserin L, Legendre A
and objectives
Chronic pulmonic regurgitation (PR) following repair of congenital heart disease (CHD) impairs right ventricular function that impacts peak exercise cardiac index (pCI). We aimed to estimate in a non-invasive way pCI and peak oxygen consumption (pVO) and to evaluate predictors of low pCI in patients with significant residual pulmonic regurgitation after CHD repair.
We included 82 patients (median age 19 years (range 10-54 years)) with residual pulmonic regurgitation fraction >40%. All underwent cardiac MRI and cardiopulmonary testing with measurement of pCI by thoracic impedancemetry. Low pCI was defined <7 L/min/m.
Low pCI was found in 18/82 patients. Peak indexed stroke volume (pSVi) tended to compensate chronotropic insufficiency only in patients with normal pCI (r=-0.31, p=0.01). Below 20 years of age, only 5/45 patients had low pCI but near-normal (≥6.5 L/min/m). pVO (mL/kg/min) was correlated with pCI (r=0.58, p=0.0002) only in patients aged >20 years. Left ventricular stroke volume in MRI correlated with pSVi only in the group of patients with low pCI (r=0.54, p=0.02). No MRI measurements predicted low pCI. In multivariable analysis, only age predicted a low pCI (OR=1.082, 95% CI 1.035 to 1.131, p=0.001) with continuous increase of risk with age.
In patients with severe PR, pVO is a partial reflection of pCI. Risk of low pCI increases with age. No resting MRI measurement predicts low haemodynamic response to exercise. Probably more suitable to detect ventricular dysfunction, pCI measurement could be an additional parameter to take into account when considering pulmonic valve replacement.
Effect of blood pressure lowering drugs and antibiotics on abdominal aortic aneurysm growth: a systematic review and meta-analysis.
Golledge J, Singh TP
There is currently no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. The aim of this systematic review and meta-analysis was to pool data from previous randomised controlled trials assessing the efficacy of blood pressure-lowering and antibiotic medications in limiting AAA growth and AAA-related events, that is, rupture or repair.
A systematic literature search was performed to identify randomised controlled trials that examined the efficacy of blood pressure-lowering medications or antibiotics in reducing AAA growth and AAA-related events. AAA growth (mm/year) was measured by ultrasound or computed tomography imaging. Meta-analyses were performed using random effects models. A subanalysis was conducted including trials that investigated tetracycline or macrolide antibiotics.
Ten randomised controlled trials including 2045 participants with an asymptomatic AAA were included. Follow-up was between 18 and 63 months. Neither blood pressure-lowering medications (mean growth±SD 2.0±2.4 vs 2.3±2.7 mm/year; standardised mean difference (SMD) -0.07, 95% CI -0.19 to 0.06; p=0.288) or antibiotics (mean growth±SD 2.6±2.1 vs 2.6±2.5 mm/year; SMD -0.11, 95% CI -0.38 to 0.16; p=0.418) reduced AAA growth or AAA-related events (blood pressure-lowering medications: 92 vs 95 events; risk ratio (RR) 0.86, 95% CI 0.66 to 1.11; p=0.244; and antibiotics: 69 vs 73 events; RR 0.93, 95% CI 0.69 to 1.25; p=0.614). The subanalysis of antibiotics showed similar results.
This meta-analysis suggests that neither blood pressure-lowering medications or antibiotics limit growth or clinically relevant events in people with AAAs.
What is the normal composition of pericardial fluid?
Buoro S, Tombetti E, Ceriotti F, Simon C, ... Imazio M, Brucato A
Biochemical and cytological pericardial fluid (PF) analysis is essentially based on the knowledge of pleural fluid composition. The aim of the present study is to identify reference intervals (RIs) for PF according to state-of-art methodological standards.
We prospectively collected and analysed the PF and venous blood of consecutive subjects undergoing elective open-heart surgery from July 2017 to October 2018. Exclusion criteria for study enrolment were evidence of pericardial diseases at preoperatory workup or at intraoperatory assessment, or any other condition that could affect PF analysis.
The final study sample included 120 patients (median age 69 years, 83 men, 69.1%). The main findings were (1) High levels of proteins, albumin and lactate dehydrogenase (LDH), but not of glucose and cholesterol (2) High cellularity, mainly represented by mesothelial cells. RIs for pericardial biochemistry were: protein content 1.7-4.6 g/dL PF/serum protein ratio 0.29-0.83, albumin 1.19-3.06 g/dL, pericardium-to-serum albumin gradient 0.18-2.37 g/dL, LDH 141-2613 U/L, PF/serum LDH ratio 0.40-2.99, glucose 80-134 mg/dL, total cholesterol 12-69 mg/dL, PF/serum cholesterol ratio 0.07-0.51. RIs for pericardial cells by optic microscopy were: 278-5608 × 10 nucleated cells/L, 40-3790 × 10 mesothelial cells/L, 35-2210 × 10 leucocytes/L, 19-1634 × 10 lymphocytes/L.
PF is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Physicians should stop to interpret PF as exudate or transudate according to tools not validated for this setting.
Endocrine therapy use and cardiovascular risk in postmenopausal breast cancer survivors.
Matthews AA, Peacock Hinton S, Stanway S, Lyon AR, ... Lund JL, Bhaskaran K
Examine the effect of tamoxifen and aromatase inhibitors (AIs) on the risk of 12 clinically relevant cardiovascular outcomes in postmenopausal female breast cancer survivors.
We carried out two prospective cohort studies among postmenopausal women with breast cancer in UK primary care and hospital data (2002-2016) and US Surveillance, Epidemiology and End Results-Medicare data (2008-2013). Using Cox adjusted proportional hazards models, we compared cardiovascular risks between AI and tamoxifen users; and in the USA, between users of both drug classes and women receiving no endocrine therapy.
10 005 (UK) and 22 027 (USA) women with postmenopausal breast cancer were included. In both countries, there were higher coronary artery disease risks in AI compared with tamoxifen users (UK age-standardised incidence rate: 10.17 vs 7.51 per 1000 person-years, HR: 1.29, 95% CI 0.94 to 1.76; US age-standardised incidence rate: 36.82 vs 26.02 per 1000 person-years, HR: 1.29, 95% C I1.06 to 1.55). However, comparisons with those receiving no endocrine therapy (US data) showed no higher risk for either drug class and a lower risk in tamoxifen users (age-standardised incidence rate tamoxifen vs unexposed: 26.02 vs 35.19 per 1000 person-years, HR: 0.74, 95% 0.60 to 0.92; age-standardised incidence rate AI vs unexposed: 36.82 vs 35.19, HR: 0.96, 95% CI 0.83 to 1.10). Similar patterns were seen for other cardiovascular outcomes (arrhythmia, heart failure and valvular heart disease). As expected, there was more venous thromboembolism in tamoxifen compared with both AI users and those unexposed.
Higher risks of several cardiovascular outcomes among AI compared with tamoxifen users appeared to be driven by protective effects of tamoxifen, rather than cardiotoxic effects of AIs.
Cardiovascular genetics: the role of genetic testing in diagnosis and management of patients with hypertrophic cardiomyopathy.
Ahluwalia M, Ho CY
Genetic testing in hypertrophic cardiomyopathy (HCM) is a valuable tool to manage patients and their families. Genetic testing can help inform diagnosis and differentiate HCM from other disorders that also result in increased left ventricular wall thickness, thereby directly impacting treatment. Moreover, genetic testing can definitively identify at-risk relatives and focus family management. Pathogenic variants in sarcomere and sarcomere-related genes have been implicated in causing HCM, and targeted gene panel testing is recommended for patients once a clinical diagnosis has been established. If a pathogenic or likely pathogenic variant is identified in a patient with HCM, predictive genetic testing is recommended for their at-risk relatives to determine who is at risk and to guide longitudinal screening and risk stratification. However, there are important challenges and considerations to implementing genetic testing in clinical practice. Genetic testing results can have psychological and other implications for patients and their families, emphasising the importance of genetic counselling before and after genetic testing. Determining the clinical relevance of genetic testing results is also complex and requires expertise in understanding of human genetic variation and clinical manifestations of the disease. In this review, we discuss the genetics of HCM and how to integrate genetic testing in clinical practice.
Obstructive sleep apnoea, intermittent hypoxia and heart failure with a preserved ejection fraction.
Sanderson JE, Fang F, Lu M, Ma CY, Wei YX
Obstructive sleep apnoea (OSA) is recognised to be a potent risk factor for hypertension, coronary heart disease, strokes and heart failure with a reduced ejection fraction. However, the association between OSA and heart failure with a preserved ejection fraction (HFpEF) is less well recognised. Both conditions are very common globally.It appears that there are many similarities between the pathological effects of OSA and other known aetiologies of HFpEF and its postulated pathophysiology. Intermittent hypoxia induced by OSA leads to widespread stimulation of the sympathetic nervous system, renin-angiotensin-aldosterone system and more importantly a systemic inflammatory state associated with oxidative stress. This is similar to the consequences of hypertension, diabetes, obesity and ageing that are the common precursors to HFpEF. The final common pathway is probably via the development of myocardial fibrosis and structural changes in collagen and myocardial titin that cause myocardial stiffening. Thus, considering the pathophysiology of OSA and HFpEF, OSA is likely to be a significant risk factor for HFpEF and further trials of preventive treatment should be considered.
Association of heart failure and its comorbidities with loss of life expectancy.
Drozd M, Relton SD, Walker AMN, Slater TA, ... Kearney MT, Cubbon RM
Estimating survival can aid care planning, but the use of absolute survival projections can be challenging for patients and clinicians to contextualise. We aimed to define how heart failure and its major comorbidities contribute to loss of actuarially predicted life expectancy.
We conducted an observational cohort study of 1794 adults with stable chronic heart failure and reduced left ventricular ejection fraction, recruited from cardiology outpatient departments of four UK hospitals. Data from an 11-year maximum (5-year median) follow-up period (999 deaths) were used to define how heart failure and its major comorbidities impact on survival, relative to an age-sex matched control UK population, using a relative survival framework.
After 10 years, mortality in the reference control population was 29%. In people with heart failure, this increased by an additional 37% (95% CI 34% to 40%), equating to an additional 2.2 years of lost life or a 2.4-fold (2.2-2.5) excess loss of life. This excess was greater in men than women (2.4 years (2.2-2.7) vs 1.6 years (1.2-2.0); p<0.001). In patients without major comorbidity, men still experienced excess loss of life, while women experienced less and were non-significantly different from the reference population (1 year (0.6-1.5) vs 0.4 years (-0.3 to 1); p<0.001). Accrual of comorbidity was associated with substantial increases in excess lost life, particularly for diabetes, chronic kidney and lung disease.
Comorbidity accounts for the majority of lost life expectancy in people with heart failure. Women, but not men, without comorbidity experience survival close to reference controls.
Trends of global burden of atrial fibrillation/flutter from Global Burden of Disease Study 2017.
Wang L, Ze F, Li J, Mi L, ... Niu H, Zhao N
This study aimed to estimate the global burden of atrial fibrillation/atrial flutter (AF/AFL).
We retrieved data from the Global Health Data Exchange query tool and estimated the age-standardised rates (ASRs) of prevalence, incidence and disability-adjusted life-years (DALYs) of AF/AFL, as well as the population attributable fraction (PAF) of risk factors contributing to DALYs. ASRs and sociodemographic index (SDI) were assessed using Pearson\'s correlation coefficients.
In 2017, there were 37.6 million (95% uncertainty interval (UI) 32.5 to 42.6 million) individuals with AF/AFL globally. The prevalence rates increased with increased SDI values in most regions for all years. Men had a higher prevalence than women across all regions except for China. From 1990 to 2017, global prevalence rate decreased by 5.08% (95% UI -6.24% to -3.82%), with the largest decrease noted in the region with high SDI values. The global DALYs rate declined by 2.53% (95% UI -4.16 to -0.29). PAF of elevated systolic blood pressure for attributable DALYs accounted for the highest percentage, followed by high body mass index, alcohol use, high-sodium diet, smoking and lead exposure.
Although the ASRs of prevalence, incidence and DALYs decreased from 1990 to 2017, the absolute number of patients with AF/AFL, annual number of new AF/AFL cases and DALYs lost due to AF/AFL increased. This indicates that the burden of AF/AFL is likely to remain high. Systematic surveillance is needed to better identify and manage AF/AFL so as to prevent its various risk factors and complications.
Determinants of clinical outcomes of surgery for isolated severe tricuspid regurgitation.
Park SJ, Oh JK, Kim SO, Lee SA, ... Kim DH, Kim JB
Although the incidence of patients with isolated tricuspid regurgitation (TR) is increasing, data regarding the clinical outcomes of isolated TR surgery are limited. This study sought to investigate the prognostic implications according to procedural types, and to identify preoperative predictors of clinical outcomes after isolated TR surgery.
Among consecutive 2610 patients receiving tricuspid valve (TV) procedure, we analysed 238 patients (age, 59.6 years; 143 females) who underwent stand-alone TV surgery (repair, 132; replacement, 106) for severe TR. Primary outcome was the composite of all-cause mortality and heart transplantation. Clinical outcomes between the repair and the replacement groups were compared after adjusting with the inverse probability of treatment weighting (IPTW) method.
During follow-up (median, 4.1 years), 53 patients died and 4 received heart transplantation. Multivariable analysis revealed that age (p=0.001), haemoglobin level (p=0.003), total bilirubin (p=0.040), TR jet area (p=0.005) and right atrial (RA) pressure (p=0.022) were independent predictors of the primary outcome. After IPTW adjustment, there were no significant intergroup differences in the risk of primary outcome (HR 1.01; 95% CI 0.55 to 1.87). In the subgroup analysis, tricuspid annular diameter was identified as a significant effect modifier (p=0.012) in the comparison between repair versus replacement, showing a trend favouring replacement in patients with annular diameter >44 mm.
The outcomes of stand-alone severe TR surgery were independently associated with the severity of TR and RA pressure. In selected patients with severe annular dilation >44 mm, replacement may become a feasible option.
Association between right ventricular strain and outcomes in patients with dilated cardiomyopathy.
Liu T, Gao Y, Wang H, Zhou Z, ... Dong J, Xu L
To explore the association between three-dimensional (3D) cardiac magnetic resonance (CMR) feature tracking (FT) right ventricular peak global longitudinal strain (RVpGLS) and major adverse cardiovascular events (MACEs) in patients with stage C or D heart failure (HF) with non-ischaemic dilated cardiomyopathy (NIDCM) but without atrial fibrillation (AF).
Patients with dilated cardiomyopathy were enrolled in this prospective cohort study. Comprehensive clinical and biochemical analysis and CMR imaging were performed. All patients were followed up for MACEs.
A total of 192 patients (age 53±14 years) were eligible for this study. A combination of cardiovascular death and cardiac transplantation occurred in 18 subjects during the median follow-up of 567 (311, 920) days. Brain natriuretic peptide, creatinine, left ventricular (LV) end-diastolic volume, LV end-systolic volume, right ventricular (RV) end-diastolic volume and RVpGLS from CMR were associated with the outcomes. The multivariate Cox regression model adjusting for traditional risk factors and CMR variables detected a significant association between RVpGLS and MACEs in patients with stage C or D HF with NIDCM without AF. Kaplan-Meier analysis based on RVpGLS cut-off value revealed that patients with RVpGLS <-8.5% showed more favourable clinical outcomes than those with RVpGLS ≥-8.5% (p=0.0037). Subanalysis found that this association remained unchanged.
RVpGLS-derived from 3D CMR FT is associated with a significant prognostic impact in patients with NIDCM with stage C or D HF and without AF.
Comparison of incidence rates and risk factors of heart failure between two male cohorts born 30 years apart.
Ergatoudes C, Hansson PO, Svärdsudd K, Rosengren A, ... Pivodic A, Fu M
To compare two cohorts of middle-aged men from the general population born 30 years apart for incidence and predictors of heart failure (HF).
Two population samples of men, born in 1913 (n=855) and in 1943 (n=797), were examined at 50 years of age and followed up for 21 years (1963-1994 and 1993-2014). Cox regression analysis was used to examine the impact of different factors on the risk of developing HF.
Eighty men born in 1913 (9.4%) and 42 men born in 1943 (5.3%) developed HF during follow-up; adjusted HRs comparing the two cohorts (born 1943 vs 1913) were: 0.46 (95% CI 0.28 to 0.74, p=0.002). In both cohorts, higher body mass index, higher diastolic blood pressure, treatment for hypertension, onset of either atrial fibrillation (AF), ischaemic heart disease and diabetes mellitus were associated with higher risk of HF. Higher heart rate was associated with an increased risk only in men born in 1913, whereas higher systolic blood pressure (SBP), smoking, higher glucose, higher cholesterol and physical inactivity were associated with an increased risk in men born in 1943. AF contributed higher risk of incident HF, whereas SBP and physical inactivity contributed lower risk in men born in 1943 compared with men born in 1913.
Men born in 1943 had half the risk of HF after their 50s than those born 30 years earlier. AF, obesity, ischaemic heart disease, diabetes and hypertension remain important precursors of HF.
Heart: 30 Oct 2020; 106:1672-1678
Heart: 30 Oct 2020; 106:1672-1678 | PMID: 32114518
Exercise intervention improves quality of life in older adults after myocardial infarction: randomised clinical trial.
Campo G, Tonet E, Chiaranda G, Sella G, ... Myers J, Grazzi G
To establish the benefits of an early, tailored and low-cost exercise intervention in older patients hospitalised for acute coronary syndrome (ACS).
The study was a multicentre, randomised assessment of an exercise intervention in patients with ACS ≥70 years with reduced physical performance (as defined by the short physical performance battery (SPPB), value 4-9). The exercise intervention included four supervised sessions (1, 2, 3, 4 months after discharge) and home-based exercises. The control group attended a health education programme only. The outcomes were the 6-month and 1-year effects on physical performance, daily activities, anxiety/depression and quality of life. Finally, 1-year occurrence of adverse events was recorded.
Overall, 235 patients with ACS (median age 76 (73-81) years) were randomised 1 month after ACS. Exercise and control groups were well balanced. Exercise intervention improved 6-month and 1-year grip strength and gait speed. Exercise intervention was associated with a better quality of life (as measured by EuroQol-visual analogue scale at 6 months 80 (70-90) vs 70 (50-80) points, p<0.001 and at 1 year 75 (70-87) vs 65 (50-80) points, p<0.001) and with a reduced perception of anxiety and/or depression (6 months: 21% vs 42%, p=0.001; 1 year 32% vs 47%, p=0.03). The occurrence of cardiac death and hospitalisation for cardiac cause was lower in the intervention group (7.5% vs 17%, p=0.04).
The proposed early, tailored, low-cost exercise intervention improves mobility, daily activities, quality of life and outcomes in older patients with ACS. Larger studies are needed to confirm the clinical benefit.
Association of household income and adverse outcomes in patients with atrial fibrillation.
LaRosa AR, Claxton J, O\'Neal WT, Lutsey PL, ... Alonso A, Magnani JW
Social determinants of health are relevant to cardiovascular outcomes but have had limited examination in atrial fibrillation (AF).
The purpose of this study was to examine the association of annual household income and cardiovascular outcomes in individuals with AF.
We analysed administrative claims for individuals with AF from 2009 to 2015 captured by a health claims database. We categorised estimates of annual household income as <$40 000; $40-$59 999; $60-$74 999; $75-$99 999; and ≥$100 000. Covariates included demographics, education, cardiovascular disease risk factors, comorbid conditions and anticoagulation. We examined event rates by income category and in multivariable-adjusted models in reference to the highest income category (≥$100 000).
Our analysis included 336 736 individuals (age 72.7±11.9 years; 44.5% women; 82.6% white, 8.4% black, 7.0% Hispanic and 2.1% Asian) with AF followed for median (25th and 75th percentile) of 1.5 (95% CI 0.6 to 3.0) years. We observed an inverse association between income and heart failure and myocardial infarction (MI) with evidence of progressive risk across decreased income categories. Individuals with household income <$40 000 had the greatest risk for heart failure (HR 1.17; 95% CI 1.05 to 1.30) and MI (HR 1.18; 95% CI 0.98 to 1.41) compared with those with income ≥$100 000.
We identified an association between lower household income and adverse outcomes in a large cohort of individuals with AF. Our findings support consideration of income in the evaluation of cardiovascular risk in individuals with AF.
LaRosa AR, Claxton J, O'Neal WT, Lutsey PL, ... Alonso A, Magnani JW
Animation-supported consent for urgent angiography and angioplasty: a service improvement initiative.
Wald DS, Casey-Gillman O, Comer K, Mansell JS, ... McCaughan V, Polenio N
Patient understanding of angiography and angioplasty is often incomplete at the time of consent. Language barriers and time constraints are significant obstacles, particularly in the urgent setting. We introduced digital animations to support consent and assessed the effect on patient understanding.
Multi-language animations explaining angiography and angioplasty (www.explainmyprocedure.com/heart) were introduced at nine district hospitals for patients with acute coronary syndrome before urgent transfer to a cardiac centre for their procedure. Reported understanding of the reason for transfer, the procedure, its benefits and risks in 100 consecutive patients were recorded before introduction of the animations into practice (no animation group) and in 100 consecutive patients after their introduction (animation group). Patient understanding in the two groups was compared.
Following introduction, 83/100 patients reported they had watched the animation before inter-hospital transfer (3 declined and 14 were overlooked). The proportions of patients who understood the reason for transfer, the procedure, its benefits and risks in the no animation group were 58%, 38%, 25% and 7% and in the animation group, 85%, 81%, 73% and 61%, respectively. The relative improvement (ratio of proportions) was 1.5 (95% CI 1.2 to 1.8), 2.1 (1.6 to 2.8), 2.9 (2.0 to 4.2) and 8.7 (4.2 to 18.1), respectively (p<0.001 for all comparisons).
Use of animations explaining angiography and angioplasty is feasible before urgent inter-hospital transfer and was associated with substantial improvement in reported understanding of the procedure, its risks and its benefits. The approach is not limited to cardiology and has the potential to be applied to all specialties in medicine.
Cardiovascular risk factors and the risk of major adverse limb events in patients with symptomatic cardiovascular disease.
Hageman SHJ, de Borst GJ, Dorresteijn JAN, Bots ML, ... Visseren FLJ,
To determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease.
Patients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (1996-2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb.
In 8139 patients (median follow-up 7.8 years, IQR 4.0-11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1 mmol/L non-HDL-c (HR 1.14, 95% CI 1.01 to 1.29). Per 10 mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95% CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95% CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95% CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95% CI 3.99 to 12.57).
The risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease.
Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction.
Saijo Y, Kusunose K, Okushi Y, Yamada H, Toba H, Sata M
The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up.
We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up.
LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015).
Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.
Cerebrovascular events after transcatheter mitral valve interventions: a systematic review and meta-analysis.
Châteauneuf G, Nazif TM, Beaupré F, Kodali S, Rodés-Cabau J, Paradis JM
Current guidelines support the use of transcatheter mitral valve interventions to treat some selected high-risk patients with significant mitral valvulopathy. As with any other interventional cardiac procedure, concerns have been raised about cerebrovascular event. The aim of this systematic review and meta-analysis was to determine the incidence of cerebrovascular events following (1) transcatheter mitral valve edge-to-edge repair with mitral valve clip and (2) transcatheter mitral valve replacement (TMVR).
We conducted a systematic review of studies reporting the cerebrovascular adverse events after transcatheter mitral valve edge-to-edge repair and TMVR procedures. The primary endpoint was the incidence of cerebrovascular events as defined by the Mitral Valve Academic Research Consortium. An event that occurred within 30 days or during index hospitalisation was defined as periprocedural; otherwise it was defined as non-periprocedural. This study was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Aggregated study-level data were pooled using a random effect model. The quality of each study was appraised with the Hawker checklist, a method of systematically reviewing research from different paradigms.
Sixty studies totalling 28 155 patients undergoing edge-to-edge repair with mitral valve clip were included in the analysis. Periprocedural stroke and non-periprocedural stroke rates were 0.9% (95% CI 0.6 to 1.1) and 2.4% (95% CI 1.6 to 3.2), respectively. For TMVR procedures, 26 studies including 1910 patients were analysed. The estimated periprocedural stroke incidence was 1% (95% CI 0.5 to 1.8) compared with 7% (95% CI 0.8 to 18.5) for non-periprocedural stroke.
Transcatheter mitral valve interventions are associated with low rates of cerebrovascular events. The exact mechanisms of these complications are still poorly understood given the relative paucity of good quality data.
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