295 CHAPTER 18.5 NSTEMI Early invasive vs conservative therapy Cardiac catheterization may be undertaken in patient s pre- senting with symptoms suggestive of unstable coronary syndromes for one of several r easons: to assist with risk strati \201 cation, as a prelude to revascularization and to e xclude signi \201 cant epicardial coronary stenosis as a cause of symptoms when the diagno sis is uncertain. An early invasive approach has now been compared with a conservative appr oach in several prospective studies. Two earlier trials, the TIMI IIIb study and the VANQWI SH trial, both performed before use of coronary stenting and plate- let glycoprotein IIb/II Ia inhibitors was widespread, were negative. More recently, several trials, including a sub study of FRISC II, TACTICS TIMI-18 and RITA-3 found a signi \201 - cant reduction in the c ombined end-point of death, MI or recurrent angina with invasive management. The most recen t comparison, the ICTUS study, found no difference in a composite of death, MI or rehospita lization for angina at 1yr between a group assigned to early invasive manage- ment and anot her assigned to selectively invasive manage- ment. As >40% of patients in the selectively i nvasive group were revascularized in the \201 rst month, this trial probably argues not s o much against an early invasive strategy as for selection of those patients most likely to benefit. Alternatively (or in parallel), improved adjunctive antiplate- let, antithrombin and lipid-lowering therapy may have nar- rowed the difference between strategies. Further reading ACC guidelines UA/NSTEMI http://content.onlinejacc. org/cgi/reprint/50/7/e1 Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guide- lines for the management of pa tients with unstable angina/ non-ST-elevation myocardial infarction \200\224executive summa ry. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction). Circulation 2007; 1 16: 803 \200\22377. Bavry AA, Kumbhani DJ, Rassi AN, et al. Bene \201 t of early invasive therapy in acute cor onary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Card iol 2006; 48: 1319 \200\22325. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus mod- erate lipid lowering with s tatins after acute coronary syndromes. N Engl J Med 2004; 350: 1495 \200\223504. Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinic al evidence of improved patient out- comes. Part II: clinical trial evidence (acute coronar y syndromes through renal disease) and future directions. Circulation 2006; 114: 2871 \200 \22391. The TIMI Study Group http://www.timi.org Yusuf S, Zhao F, Mehta SR, et al. Effects of clopi dogrel in addition to aspirin in patients with acute coronary syndromes without st-segment elevation. N Engl J Med 2001; 345: 494 \200\223502. 296 D TARDITI & S HOLLENBERG STEMI In conjunction with \201 brinolytic therapy, IV B-blockers reduce the incidence of subseq uent non-fatal re-infarction and recurrent ischaemia. A key to prevention of recurrent isch aemia is judicious but aggressive titration of B-block- ade to achieve both heart rate and blood pressure control (heart rate \211 60 beats/min and blood pressure \211 120/80. B-Bl ockers should not be administered acutely to patients with sigini \201 cant bradycardia, S BP <100mm Hg, moderate \200\223 severe heart failure, AV block or reactive airway disease/ active wheezing. Many of these patients will tolerate B-blockers when started later. Import ant update regarding IV b-bockers: Based on results of the COMMIT-CCS2 trial, it seems rea- sonable to defer IV B-blockers in patients who are haemo- dynamically compromised, as mort ality may be increased in such patients. Risk strati \201 cation \200\224before reperfusion Risk strati \201 cation in STEMI can b e based on initial history, physical examination, ECG and CXR. High risk features include a dvanced age, low blood pressure, tachycardia, heart failure and anterior MI. Killip class ( I = no congestive heart failure, II = rales, S3, congestion on CXR, III pulmo- nary oedema, IV cardiogenic shock) can be used for clinical strati \201 cation. A TIMI risk score for STEMI includes 8 predictors: \200 Age \211 75 years \200\2243 points; 65 \200\22374 year s \200\2242 points \200 History of diabetes, hypertension or angina \200\2241 point \200 Systolic blood pressure <100mm Hg \200\2243 points \200 Heart rate >100 beats/min \200 \2242 points \200 Killip class II \200\223IV \200\2242 points \200 Weight <76kg \200 \2241 point \200 Anterior ST elevation or LBBB \200\2241 point \200 Time to reperfusion therapy >4h \200\2241 point Reperfusion therapy Rapid reperfusion is the most important objective in treatment of patie nts with STEMI. A decision must be made as soon as possible regarding primary PCI vs throm- bolysis. While door to balloon time is the standard of care measurement, with a goal door to needle time (thrombol- ysis) <30min, and goal door to balloon (primary PCI) <90min, the decision should be make by assessing time and risk. Reperfusion therapy, particularly \201 brinolytics, is most effec- tive when instituted with the first 3h. Unfortunately, pat ients with STEMI present at a mean of 3 \200\2234h after symp- tom onset. In addition, achi eving prompt reperfusion when transfer to another hospital is required is challenging. In t he NRMI 4 registry, only 5.3% of patients transferred for pri- mary PCI had a door to ballo on time \211 90min. All patients with cardiogenic shock or Killip class \211 3 should rec eive primary PCI. In addition, patients with contraindi- cations to fibrinolysis should be reperfused with PCI. Absolute contraindications to fibrinolysis in STEMI include: \200 \200 The TIMI risk score for STEMI has been validated in pre- dicting in-hospital mortality. The re is a continuous relation- ship between the score and 30 day and 1yr mortality regardless of reperfusion strategy. The location of the MI in STEMI by ECG can predict out- comes. Th e greater the number of leads with ST elevation, lack of ST resolution at 90 \200\223180min after thrombolysis, presence of Q waves, or anterior compared with inferior infarcts. Therapy Initial management The initial goals when the diagnosis of STEMI is made include: \200 \200 \200 Relief of ischaemic pain Assessment of haemodynamic state Initiation of reperfusion therapy (primary PCI or throm- bolysis) Antithrombotic therapy to prevent rethrombosis or subtotal stenosis at the site of ruptured plaque Any prior intracranial hemorrhage (ICH) Known structural cerebral vascular lesion (e.g. AV mal- formation) Known malignant intracranial neoplasm Ischaemic stroke within 3 months EXCE PT acute ischae- mic stroke within 3h Suspected aortic dissection Active bleeding or bleedi ng diathesis (excluding men- ses) Signi \201 cant closed-head or facial trauma within 3 mo nths In the emergency department, initial management includes oxygen, ASA, B-blockers, analgesia , GTN, and anticoagula- tion with heparin. \200 Acute therapy Reperfusion therapy should be accomplished with either primary PCI or thrombo lysis as discussed below. Antiplatelet therapy should include ASA, clopidogrel and, in pati ents undergoing PCI, glycoprotein IIb/IIIa inhibitors (tiro \201 ban, epti \201 batide or abciximab). IV GTN should be used in patients with heart failure, hypertension or persiste nt chest pain after three sublingual GTN tablets. B-Blockers should be administered to all patients without contraindications who experience STEMI. \200 Primary PCI vs thrombolytics Treatment with primary PCI, if timely, high quality at a high volume center, is the treatment of choice, with multiple randomized trials demonstrating im proved survival com- pared with thrombolysis, with a lower risk of ICH and recurrent MI. Fi brinolysis is successful in achieving reperfusion in 75 \200\22385% of patients. As many as 1/2 to 2/3 of patients presenting with AMI may be ineligible for lytic therapy, however. T he major advantages of primary PCI over thrombolytic ther- apy include a higher rate of nor mal (TIMI grade 3) \202 ow, lower risk of ICH and the ability to stratify risk based on t he severity and distribution of CAD. b-Blockers These medications appear to reduce the magnitude of inf- arction, complications, rate of re-infarction and frequency of ventricular tachyarrhythmias. These bene \201 ts a re medi- ated by reducing heart rate, systemic arterial pressure and myocardial contractili ty, thereby decreasing myocardial oxygen demand. In ISIS-1, >16 000 patients given atenolol had reduced mortality at 7 days (4.3% vs 3.7%, P < 0.02). 297 CHAPTER 18.6 STEMI A meta-analysis of 23 trials (n = 7739) by Keeley et al. dem- onstrated a 2% absolute morta lity reduction at 4 \200\2236 weeks (P = 0.0002). However, this analysis has some limitatio ns: \200 ACC guidelines state that it is reasonable to start abcixi- mab in patients undergoing prim ary PCI (with or without stenting). The data supporting this treatment are limited to small er studies with composite end-points driven primarily by decreased urgent target vessel rev ascularization, rather than mortality or re-infarction. Use of tiro \201 ban or epti \201 batide is also considered reasona- ble, but there are fewer data than with abciximab to su p- port their use in STEMI undergoing primary PCI. Time from symptom onset to treatment (<6h in nine of the trials, <12h in 13 of the trials) Small size of studies (15/23 trials had <500 patients) Variable de \201 nition of end-poin ts (e.g. re-infarction) Use of both \201 brin-speci \201 c and non-speci \201 c \201 brinolytic agents \200 \200 In both the VIENNA and PRAGUE-2 trials, comparing streptokinase vs transfer for primary PCI , patients who had symptom onset to treatment <3h had no difference in 30 day mortality. Wh en primary PCI is compared with tPA and the SHOCK trial is excluded, mortality rate is not statistically signi \201 - cantly reduced, P = 0.081. The Achilles heel of thrombolysis is that 5 \200\22315% of patients with successful thrombolysis will reocclude. Patients who p resent with STEMI should receive reper- fusion based on the time from symptom onset (<3h, e ither strategy is acceptable), mortality risk (age, heart rate, BP, Killip class and locati on of MI), risk of bleeding (>75yrs old and female sex have highest risk of ICH) and time f or trans- fer to a skilled PCI laboratory. If the patient presents within 3h, and there is no delay to an invasive strategy, either \201 bri- nolysis or primary PCI is acceptable. If the patient presents within 3h, is not high risk and the expected door to balloon time e xceeds the door to needle time by >60min, \201 bri- nolysis is generally preferred. If a skilled PCI lab is available with surgical back-up and a door to balloon time <90min, if th e patients is at high risk or if presentation is >3h from symptom onset, an invasive strate gy is generally preferred. Risk strati \201 cation \200\224discharge and beyond The importance of post-infarct risk s trati \201 cation is to iden- tify patients at increased risk for arrhythmic and non- arrh ythmic cardiac death. Stress testing Pre-discharge stress testing is usually performed to detect residual ischaem ia in patients with more than one coro- nary lesion or those who received successful thromb olytic reperfusion. It is not performed in patients who have been fully revascu- larized (P CI or CABG) unless as part of a cardiac rehabili- tation program. Low level stress testing appears to be safe in appropriate patients: \200 \200 \200 Patient has undergone in-hospital cardiac rehabilitation ECG stable for 48 \200\22372h No s ymptoms of recurrent angina or heart failure Complications Ventricular free wall rupture Ventricular free wall rupture typically occurs during the first week after infarction. The classic patient is elderly, female and hyperten sive. Early use of \201 brinolytic therapy reduces the incidence of cardiac rupture, but late use may actually increase the risk. Free wall rupture presents as a catastrophic event with shock and electro- mechanical dissociation. Salvage is possible with prompt recogniti on, pericardiocentesis to relieve acute tamponade and thoracotomy with repair. Emergent ech ocardiography or pulmonary artery catheterization can help make the diagnosis. Other medical therapy Patients with STEMI should be treated with ASA, clopidog- rel, B-bloc kers, ACE inhibitors and high dose statins. Anticoagulation Heparin Patients undergoing rep erfusion should receive UFH or LMWH. These agents should be used after STEMI in patients wh o are at high risk for systemic emboli (large or anterior MI, AF, previous embolus, known L V thrombus or cardiogenic shock). For patients receiving thrombolytic therapy rather than p rimary PCI, the EXTRACT-TIMI 25 trial demonstrated that enoxaparin administered for the dur ation of the hospi- talization was associated with a 17% relative risk reduction in death o r MI at 30 days compared with UFH for 48h. The OASIS-6 study, compared fondaparinux (2.5mg daily for up to 8 days) vs control (placebo in stratum 1 and UFH in stratum 2). This compli cated trial demonstrated a 14% relative risk reduction in death/MI at 30 days compared with control driven mainly by the reduction in stratum 1 (UFH not indicated, 11.2% vs 14 %). Th ere was no differ- ence in stratum 2 (UFH indicated, 8.3% vs 8.7%). There was a concerning increased rate of guiding catheter thrombosis in the primary PCI cohort on fondaparinux (n = 22 vs n = 0, P <0.001). This drug requires further studies before rou- tine use can be re commended. Ventricular septal rupture Septal rupture presents as severe heart failure or cardio- genic shock, with a pansystolic murmur and parasternal thrill. The hallmark \201 nding is a le ft-to-right intracardiac shunt ( \200\230step-up \200\231 in oxygen saturation from right a trium to right ventricle), and surgical treatment has been controver- sial, but most author ities now suggest that repair should be undertaken early, within 48h of the rupture. Papillary muscle rupture Papillary muscle rupture typically occurs in association with infe rior MI, and presents dramatically with pulmonary oedema, hypotension and cardiogenic shock . A murmur of acute mitral regurgitation may be soft or inaudible, espe- cially when cardia c output is low. Echocardiography, either transthoracic or transesophageal, usually makes d iagnosis. Haemodynamic monitoring with pulmonary artery catheterization may also be helpful . Management includes afterload reduction with nitroprus- side and intra-aortic balloon pum ping as temporizing measures. Inotropic or vasopressor therapy may also be needed to suppor t cardiac output and blood pressure. De \201 nitive therapy, however, is surgical valve re pair or replacement, which should be undertaken as soon as pos- sible since clinical deteri oration can be sudden. Glycoprotein IIb/IIIa inhibitors Studies comparing use of abciximab with half-dose \201 b rino- lytic with full-dose lytic have shown no difference in 30 day mortality, although the re is a decrease in non-fatal re-inf- arction. 298 D TARDITI & S HOLLENBERG discharged on ASA, B-blockers, ACE inhibitor or ARB, and statins unless contraindicated. Ep lerenone may be given when indicated, and nitrates used as needed. The optimal duration of dual antiplatelet therapy is controversial, and depends on the type of reperfusion strategy ( \201 brinolytic or PCI) and the type of stent (bare metal or drug-eluting). For patient s who undergo mechanical reperfusion, clopidogrel and ASA should be continued for at least 9 \200\22312 months. The greatest risk for very late stent thrombosis with drug- eluting st ents is premature discontinuation of dual antiplatelet therapy. Right ventricular infarction RV infarction occurs in up to 30% of patients with inferior in farction and is clinically signi \201 cant in 10%. The combina- tion of a clear CXR with j ugular venous distention in a patient with an inferior wall MI should lead to the suspicion of a co-existing RV infarct. The diagnosis is substantiated by demonstration of ST-segment elevation in the right precor- dial leads (V3R \200\223V5R) or by characteristic haemodyna mic \201 ndings (elevated RA and RV end-diastolic pressures with normal to low wedge pres sure and low cardiac output). Echocardiography can demonstrate depressed RV contrac- tility . RV preload should be maintained with \202 uid administration, but overdilation of the R V can compromise LV \201 lling and cardiac output, and so inotropic therapy with dobutami ne may be more effective in some patients. Maintenance of AV synchrony is also important to optimize RV \201 lling. For patients with continued haemodynamic instability, intra- aor tic balloon pumping may be useful to decrease RV wall stress and increase right coronary pe rfusion pressure. Reperfusion of the occluded coronary artery is also cru- cial. Patients w ith cardiogenic shock on the basis of RV inf- arction have a better prognosis than those wi th left-sided pump failure. This may be due in part to the fact that RV function tends to r eturn to normal over time with sup- portive therapy, although such therapy may need to be p rolonged. Further reading ACC guidelines STEMI http://www.acc.org/qualityand- science/clinical/guidel ines/stemi/Guideline1/ index.pdf Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction \200\224executive summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circul ation 2004; 110: 588 \200\223636. Boersma E, Mercado N, Poldermans D, et al. Acute myocardial inf- arction. Lancet 2003; 361: 847 \200\22358. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral meto- prolol in 45,852 patient s with acute myocardial infarction: Randomized placebo-controlled trial. Lancet 2005; 366: 1622 \200\22332. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intrave- nous t hrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomized trials. Lancet 2003; 361: 13 \200\22320. Discharge regimen Secondary prevention with therapeutic lifestyle modi \201 ca- tion, smok ing cessation, blood pressure control (<130/80mm Hg) weight loss, exercise, control of diab etes (goal HgA1c <7%) should be provided to all patients at the time of discharge. Explanat ion of bene \201 ts and side effects of medications prescribed, as well as those to avoid (sildena \201 l, etc.) should be given. All patients should be National Registry of Myocardial Infarction http://www.nrmi. org/index.html Van de Werf F, Ardissino D, Betriu A, et al. Management of acute myocardial infarction in p atients presenting with ST-segment elevation. The task force on the management of acute myo cardial infarction of the European Society of Cardiology. Eur Heart J 2003; 24: 28 \200\223 66. This page intentionally left blank 300 M TAVARES, A EL GHORCH, & A MEBAZAA Acute heart failure: assessment Table 18.7.2 Aetiologies of AHF De \201 nition Acute heart failure (AHF) is de \201 ned as rapid onset or change in heart failure (HF) signs and symptoms resulting in the need for urgent therapy. AHF may occur wi th or without previous cardiac disease. The cardiac dysfunction can be related to systolic or diastolic dysfunction, to abnor- malities in cardiac rhythm or to preload and afterload mis- match. This is a heterogeneous syndrome that has many different aetiologies and, as su ch, it is the result of diverse pathophysiological processes and encompasses a large spectr um of patients. Most of our knowledge about AHF comes from studies made with in-hospital HF patients, but several recent pub- lications challenged some of the traditional views by lo ok- ing at admission data (Table 18.7.1) Decompensation of pre-existing chronic heart failure (CAD, myopathic, valvular) Acute coronary syndromes MI/UA with large extent of ischaemia and ischaemic dysfunction Mec hanical complication of AMI Right ventricular infarction Hypertensive crisis Acute arrhythmia Ventricular tachycardia, ventricular \201 brillation Atrial \201 brill ation or \202 utter Other supraventricular tachycardia Valvular regurgitation Endocarditis Rupture of chordae tendinae Worsening of pre-existing v alvular regurgitation Epidemiology and incidence In the USA, each year, HF is the primary diagnosis of 1 mil- lio n admissions within 3 million admissions with primary or secondary diagnosis of HF per year . It is a disease with a huge burden, with an in-hospital all-cause mortality of 10 \200 \223 16%, and a readmission rate of 20 \200\22325% at 90 days that goes up to 50% by 6 mont hs; survival ranges from 80% at 2yrs for patients rendered free of congestion to <50% at 6 months for patients with refractory symptoms, and 75% of US HF annual expenditure is spent during the recurrent hospitalizations. Its incidence increases with age, and at >75yrs this incidence increases more steeply. Severe aortic valve stenosis Acute severe myocarditis Cardiac tamponade Aortic dissection Post-partum cardiomyopathy High output syndromes Septicaemia Thyroid storm Severe anemia Shunt syndromes Table 18.7.1 Patient characteristics in major AHF registries OPTIMIZE, n = 48 612 EHFS-II, n = 3580 EFICA, n = 599 Italian AHFS n = 2807 ADHERE, n = 163 447 History and examination HF symptoms and signs are usually dominated by those related to con gestion, due to elevated \201 lling pressures. High left-sided filling pressures cause lu ng congestion noticeable as dyspnoea, orthopnoea or paroxistical noc- turnal dyspnoea, lung rales, noticeable S3 or loud P2. Elevated right-sided \201 lling pressures cause anorexi a, early satiety, abdominal fullness, discomfort when bending, high jugular venous pressure (JVP), oedema in pending regions or ascites, related to venous congestion in the liver, ki dney, intestine, jugular veins or lower extremities. Symptoms and signs attributable to low resting cardiac output are less common and usually include prostration or fatigue, low blo od pressure, narrow pulse pressure, ACE inhibitor-related symptomatic hypotension, cold ext remi- ties, sleepiness, pulsus alternans or low urine output. Usually low resting cardiac o utput symptoms appear in an advanced stage of chronic HF. Mean age 75 73 70 73 73 Women % 52 52 39 41 39 New onset HF % 25 13 37 34 44 Preserved LVEF 34% (<45%) 27% (<45%) 50,4 % 49% 34 HF aetiologies The Acute Decompensated Heart Failure National Registry (ADHERE) showed that the major reasons for HF hospi- talizations in the USA are worsening chronic HF (70%), de novo AHF (25%) and advanced/end-stage HF (5%). In this series of the most common co-morbid conditions were hypertension (73%), CAD (57%) and diabetes (44%). Almost 2/3 of AHF patient s have a history of CAD, and >30% of these patients had prior myocardial ischaemia. Interes tingly, several continental differences exist. More patients in the USA have hypertension ( 72% vs 53%), diabe- tes (44% vs 27%) and renal insuf \201 ciency (30% vs 17%), with fewer having AF (31% vs 43%) than in Europe. Women admitted with AHF appear to have less CAD and more hypertension than men, but a similar rate of AF (30%), diabetes (40%) and anemia (35%) . 40% of men and 30% of women have an intraventricular conduction delay (QRS >120ms), and a pproximately 20% have decreased serum sodium (less than 136 mEq/L). ESC/ESICM classi \201 cation In 2005, the ESC and the ESICM proposed a new classi \201 ca - tion for AHF syndromes in the above-mentioned guide- lines. In this classi \201 cation, AHF is presented in 6 distinct clinical conditions: 1 Acute decompensated HF de novo or dec ompensa- tion of chronic HF: signs and symptoms of AHF, which are mild and do not ful \201 l criteria for cardiogenic shock, pulmonary oedema or hypertensive HF. 2 Hypertensive AHF: signs and symptoms of HF accom- panied by high blood pressure and relat ively preserved LV function with signs and symptoms of congestion. 301 CHAPTER 18.7 Acute heart failure: assessment and/or radiographic) but some may have minimal pulmo- nary congestion. 3 Pulmonary oedema: AHF accompanied by severe res- piratory distress and usually SpO2 <90% on room air prior to treatment. Hypotensive AHF A small percentage of patients with AHF present with low SBP (2 \200\2238% of patients); typically presents with low cardiac output and signs of organ hypoperfusion, clinical pulmo- nary oedema (3% of patients) or cardiogenic shock (<1% of patients). 4 Cardiogenic shock: cardiogenic shock de \201 ned as evi- dence of tissue hypoperfusion i nduced by HF after cor- rection of preload. It is characterized by reduced blood pressure ( SBP <90mm Hg or a drop of MAP >30mm Hg) and/or low urine output (<0.5ml/kg/h) with a pulse rate >60 bpm with or without evidence of organ congestion. 5 High output failure characteri zed by high heart rate with warm periphery, pulmonary congestion and some- times with low B P, i.e. in septic shock. HF with preserved LVEF In the major recent AHF registries, 30 \200\22350% of AHF patients s howed preserved EF (Table 18.7.1). Hypertension-induced LV diastolic dysfunction often occu rs in the ICU or emer- gency room. In the emergency room, Ghandi et al. com- pared the echo cardiographic \201 ndings at admission and after 2 \200\2233 days of treatment in patient s presenting for an acute pulmonary oedema in the context of severe arterial hypertension. The authors found no difference in LVEF between the acute episode and after 24 and 72h of a de- quate treatment. Furthermore, 50% of the patients admit- ted with an acute pulmonary oe dema had preserved EF, and 89% of the patients who had a preserved EF after treatment also had no sign of systolic dysfunction during the acute episode. In addition, the authors sugg ested that acute diastolic failure might also be the major mechanism of decompensation in p atients with baseline systolic dys- function. Similar \201 ndings can be observed in the ICU. Of note, myocardial ischaemia is an important mechanism of LV diastolic dysfunction. S everal factors including pain- induced sympathetic activation (tachycardia, hypertension), shivering, anemia, hypovolaemia and hypoxia, may alter myocardial oxygen balance, leading t o impaired ventricular relaxation and abnormal compliance. 6 Right HF characterized by low output syndrome with increased JVP, increased liver size and hypotension. Clinical classi \201 cation of 3580 patients hospitalized for AHF in 30 European countries according to these guidelines in the EHS-II divided AHF patients into decompensated HF (65 %), pulmonary oedema (16%), HF and hypertension (11%), cardiogenic shock (4%) and right HF (3%). Coronary heart disease, hypertension and AF were the most common underlying condition s. In the Italian survey on AHF in 2807 patients, the clinical pro \201 les according to t he above-mentioned ESC guidelines were acute pulmo- nary oedema in 49.6% of patients, worse ned NYHA func- tional class in 42.7% and cardiogenic shock in 7.7% of cases. More than half (56%) had worsening chronic HF, and an EF >40% was found in 34% of cases. Classi \201 cation based on SBP at admission In the USA, in-hospital outcomes of 48 612 ad ult patients with HF showed that most patients with AHF present with speci \201 c sets of symptoms that can be classi \201 ed into 3 main types of HF according to the patient \200 \231s blood pressure at the time of presentation. This classi \201 cation is mostly based on the recent evidence that a strong inverse relationship was noted between SBP and short- and long-term out- come: the higher the SBP at admission, the lower are short- and long-ter m morbidity and mortality. In addition, these subgroups have different clinical signs at ad mission and need different therapeutic targets: Renal function and HF Impaired renal function was shown to be a stronger pre- dictor of mor tality than impaired LVEF or NYHA class in advanced HF, and it is associated with increased plasma lev- els of natriuretic peptides. In these patients, impaired renal function is not related to LVEF. Even mild or moderate decreases in renal function have been shown to corr elate with signi \201 cant morbidity and mortality in patients with asymptomatic and sympt omatic congestive HF. In Europe, nearly 1/3 of patients hospitalized for decom- pensated HF develop worsening renal function during hos- pitalization, excluding patients who have a m ajor in-hospital complication likely to compromise renal function. Such patients have longe r duration of admissions, but a similar mortality and re-hospitalization rate, to those wit hout worsening renal function (if patients experiencing a major in-hospital complication ar e excluded). The risk of worsen- ing renal function in these patients is associated with se rum creatinine levels on admission, pulmonary oedema and a history of AF. Hypertensive AHF Most patients admitted to hospital with AHF have a nor- mal-to-high SBP. T he elevated blood pressure may develop rapidly and is possibly related to increased sympath etic tone. It results in neurohormonal activation and increased LV afterload with impairmen t of cardiac function. Because symptoms may develop abruptly, these patients tend to be euv olaemic or mildly hypovolaemic, and present with pul- monary rather than systemic congestio n (e.g. peripheral oedema). In these patients, with often preserved LV systo- lic function, pulmonary oedema is not caused by \202 uid accu- mulation but rather \202 uid redistri bution that is directed into the lungs because of AHF. These patients are older, more likel y to be women and have a higher incidence of hyper- tension, LV hypertrophy and diabetes th an patients admit- ted with AHF and systolic dysfunction. Diagnosis \200\224immediate questions Does this patient has HF? The diagnosis of AHF is bas ed on the symptoms and clini- cal \201 ndings, supported by appropriate investigations su ch as ECG, CXR, biomarkers and Doppler echocardiography. Up to 75% of AHF patients will hav e at presentation a pre- vious diagnosis of HF, and the available information may help the clinician. Dyspnoea is a common presenting symp- tom in patients with AHF syndromes. Normotensive AHF The other common type of AHF is characterized by a nor- mal SBP, usually w ith a history of progressive or chronic HF. In these patients, symptoms and signs develop g radually, over days or weeks, and pulmonary and systemic conges- tion (jugular venous diste nsion, pulmonary rales and peripheral oedema) are usually present. They usually have a redu ced EF. Despite high LV \201 lling pressures they may present several degrees of pulmonar y congestion (clinical 302 M TAVARES, A EL GHORCH, & A MEBAZAA Dyspnoea is the primary reason that patients present for medical care with AHF. In the ADHE RE (n = 163 447) and OPTIMIZE-HF (n = 48 612) registries, 89 and 90% of patientsm respectiv ely, initially presented with a complaint of dyspnoea. Dyspnoea on exertion is the most sen sitive symptom (neg- ative likelihood ratio 0.45, 95% CI 0.35 \200\2230.67), whereas par- o xysmal nocturnal dyspnoea is the most speci \201 c (positive likelihood ratio 2.6, 95% CI 1.5 \200\2234.5). Elevated JVP is the best indicator for identifying acute decompensated he art failure (positive likelihood ratio 5.1, 95% CI 3.2 \200\2237.9, nega- tive likelihood r atio 0.66, 95% CI 0.57 \200\2230.77), although measurement of JVP by clinicians is notoriou sly inaccurate. A murmur may point to a new valvular disease or a compli- cation of a previ ously known heart disease. An auscultated S3 gallop is not only diagnostic for AHF but pred icts an increased risk of subsequent adverse events. Both ven- tricular gallops and jugular venous distension are limited by interobserver variation and low sensitivity. In the emerg ency department, rapid measurement of brain natriuretic peptide (BNP) used in conjunction w ith other clinical information is useful in establishing or excluding the diagnosis of cong estive HF in patients with acute dyspnoea, and improves the evaluation and treatment of pat ients with acute dyspnoea, thereby reducing the time to dis- charge and the total cost of t reatment. In patients with acute shortness of breath, HF patients have higher mean levels o f both BNP or NT-proBNP blood levels (see car- diac peptides below). Although the pulmonary artery catheter may provide a good measure of \201 lling pressures and an estimate of ca rdiac output in the patient in shock, therapy to reduce volume overload during hospitalizat ion for heart failure led to marked improve- ment in signs and symptoms of elevated \201 lling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitaliza tion. Are there other conditions/co-morbidities that may contribute to the picture? Patients with AHF also have signi \201 cant cardiac and non- cardiac underlying conditions that may not be the main etiology but may contribute to the pathogenesis of AHF, including CAD (ischaem ia, hibernating myocardium and endothelial dysfunction), hypertension, AF and type II dia- betes mellitus. Many patients have other complications of atherosclerosis, hypertension or diabetes, while other con- ditions share a common etiology such as smoking-related chronic pulmonary disease or renal vascular disease. Some co-morbidities are complications of HF or the combination of HF, its underlying etiology and advanced age, such as renal impairment, stroke, and atrial and ventricular arrhyth- mias. Patients with renal failure are less lik ely to be pre- scribed ef \201 cacious therapies, but have better outcomes if they receive these medications. The importance of certain co-morbidities as independent predictors of p oor outcome showed the importance of considering them as potential therapeutic targets, suc h as anemia or obstructive sleep apnoea. Troponin, worsening renal function, hyponatraemia, lung con- gestion persistence after initial treatment and low SBP have all been described as the main prognostic factors in AHF. Hypertensive, normotensive or hypotensive? Most patients with AHF present with either norma l SBP or elevated blood pressure. Patients who present with ele- vated SBP usually have pul monary congestion and a rela- tively preserved LVEF, and have symptoms that typically devel op abruptly, with severe lung congestion and minimal weight gain often being seen in elderl y women. Their response to therapy is usually rapid. Patients with normal SBP presenting wi th systemic congestion and reduced LVEF are usually younger, with a history of chronic HF, and have symptoms that develop gradually over days or weeks. Usually they present signi \201 cant weight gain with oedema, liver and renal dysfunction, and hyponatraemia. Their lu ng congestion may not be so evident and, although they may improve with initial therapy, th ey will continue to have sys- temic congestion during the next days. What is the etiology? The HF etiology is the next question to answer as it may imply speci \201 c management. Systolic dysfunction or preserved EF? The patient should be classi \201 ed as soon as poss ible accord- ing to previously described criteria for systolic and/or pre- served dysfuncti on, and by the characteristics of left or right HF. Are there any precipitating factors? The presence of any precipitating factors should be so ught as its correction may be of most importance to stabilize the patient, such as a hypert ensive emergency, anemia, dysrhythmia or infection (Table 18.7.3). Investigations ECG Besides signs of heart disease, the ECG may provide important aetiologic al information such as ACS or rhythm disturbances. Table 18.7.3 AHF precipitating factors Lack of compliance with medical treatment Acute arrhythmia Hypertensive crisis Volume overl oad Infection, particularly sepsis Severe brain insult Major surgery Reduction in renal fun ction Asthma New medications (excess B-blockade) Alcohol abuse Drug abuse Phaeochromocytoma Chest X-ray Although chest radiography is routine in the evaluation of patients with shortn ess of breath and a quick and inexpen- sive examination, 1 of every 5 patients admitted fr om the emergency department with AHF have no signs of conges- tion on chest radiography, an d patients lacking signs of con- gestion on emergency department chest radiography were mor e likely to have an emergency department non-HF diagnosis than patients with signs of conge stion in the ADHERE registry. Cardiac peptides When the heart muscle cell is stretched, as in HF, the car- diac peptide, NT-proBNP, is released into the bloodstream. 303 CHAPTER 18.7 Acute heart failure: assessment the heart, echocardiography, is widely accepted as an objective diagnostic tool in characte rizing cardiac dysfunc- tion. Besides ventricular function, evaluation echocardiog- raphy m ay provide early aetiological information, such as ischaemic regional motion abnormalities that could not yet be seen in the ECG, signs of muscular, valvular or pericar- dial disease . It should be done in every patient as soon as possible. Limited emergency echocardiograph y to evaluate wall motion and EF performed by emergency physicians has been shown to correl ate well with de \201 nitive testing.