Complex coronary angioplasty Chronic total occlusion A chronic total occlusion (CTO) is de \201 ned as a total coronary arterial occlusion known to be greater than 3 months old. Rec ent data suggest that nearly half of patients with signi \201 cant coronary artery disease on a coronary angiogram have at least one CTO. Despite this high incidence, only about 10 % of percutaneous interventions are performed for CTO, with the majority of patients being referred for coronary artery bypass graft surgery (CABG), which remains the \200\230gold s tandard \200\231 in CTO revascu- larization. The main reason that percutaneous intervention s to CTOs fail is that a wire cannot be passed through the point of occlusion. Why should w e treat CTO? \200 Relief of anginal symptoms \200 Improved LV function \200 Reduced n eed for CABG \200 Successful intervention confers a survival advantage. Who should treat CTO? \200 Procedural success improves with operator experience. Lower- volume centers may wish to participate in CTO clubs and invite guest operators, and dedicat ed CTO days can be implemented at institutions committed to learning advanced CTO-PCI techn iques. The following factors have been shown to improve procedural success : \200 experienced op erator(s) \200 specialist equipment such as \200\230CTO wires \200\231 hydrophilic wires, can slip through the occlusion \200 tapered-tip guide wires: Cross-IT, Conquest, Miracle \200 \200\230heavy duty \200\231 wires with stiff tips, e.g. Con \201 anza \200 procedural planning using non-invasive imaging such as multislice computed tomography (MSCT) the use of micro-catheters to allow support of the wire and improve manipulation. Predictors of procedural failure include: \200 longer length of occlusion \200 longer d uration of occlusion \200 presence of calci \201 cation \200 presence of bridging coll aterals \200 \200\230blunt \200\231 (as opposed to tapered) stump at point of occlusion \200 presence of a side branch at the point of occlusion \200 vessel tortuosity. What m akes angioplasty complex? \200 Increased risk of procedural failure \200 Suboptimal res ult likely \200 Complication rate higher \200 Worse long-term outcome (death, MI, repea t procedure) COMPLEX CORONARY ANGIOPLASTY 349 Patient characteristics: clinical presentation \200\224 acute vs. stable \200 diabetes \200 body habitus \200 signi \201 cant co-morbidity \200 access problems \200\224 peripheral vascular disease Lesion characteristics: e.g. long, calci \201 ed, bifurcation, left main stem, chronic total occlusions Dif \201 cult anatomy. Potential complications of CTO intervention These procedures may be long, involve signi \201 cant X-ray exposure, and considerable contrast load; thus, compl ications are not infrequent, and this must be considered when taking consent. Complications may include: \200 impairment of collateral \202 ow \200 retrograde dissection \200 perforation \200 guide-wire entrapment \200 subacute vessel reocclusion \200 extensi ve contrast use, resulting in contrast-induced nephropathy \200 increased radiation expos ure. The use of stents in CTO intervention The implantation of a stent improves the outcome of CTO intervention when compared to balloon angioplasty alone. However, the long-term out come of CTO intervention is hindered by a relatively high rate of restenosis. This has been somewhat ameliorated by the use of DESs, with improved ef \201 cacy of DESs demonstrated in several randomized controlled trials (RCTs). Approaches to CTO percutaneous intervention \200 A normal approach to CTO PCI involves a planned, progressive escalation in the equi pment chosen to tackle the occlusion. A femoral approach, using 8 Fr guiding catheters is often chosen \200\224 such that guide catheter support can be optimized. Most operators will begin with softer wires, such that the occlusion may be \200\230probed \200\231 \200\224 before moving on to more stiff wires that may all ow the cap of the occlusion to be penetrated. Over-the-wire balloons, and micro-catheters m ay increase the chances of successful wire penetration. If the occlusion is crossed, the oc clusion can be dilated, and treated with stent implantation in a conventional manner. Several new wiring techniques and devices have evolved to treat CTO, further details on the se can be found in the reference at the end of this section. These include: \200 side-bra nch technique Fig 6.17 \200 parallel wire technique Fig 6.18 \200 subintimal re-entry t echnique \200 IVUS-guided recanalization technique Fig. 6.19 \200 retrograde approach \200 an approach that relies on access via collateral branches from the contralateral artery to gain access to the point of occlusion \200\230see-saw \200\231 wiring technique. 350 CHAPTER 6 Cardiac catheterization & intervention (a) (b) (c) (d) (e) (f) Fig. 6.17 Side-branch technique. Reproduced with permission from Y www.summitmd.com . COMPLEX CORONARY ANGIOPLASTY 351 Fig. 6.18 Parallel wire technique. Reproduced with permission from Y www.summitmd.com . False lumen Guide wire True lumen Fig. 6.19 IVUS-guided technique. Reproduced with permission from Y www.summitmd.com . 352 CHAPTER 6 Cardiac catheterization & intervention Adjunctive tools \200 FrontRunner \204 catheter controlled blunt micro-dissection Optical coherence re \202 ectometry (OCR) SafeSteer \204 system Forward-looking guidance system using OCR to determine tissue types (plaque vs. arterial wa ll) navigates through total occlusion Flow Cardia Crosser \204 system \200 High-frequency ultrasound recanalization \200 Bi ological approach \200 Prolonged pharmacological lysis infusion \200 Collagenase plaque digestion. Further reading Further information on CTO treatment can be found in: Di Mario C et al . ( 2007 ). European perspective in the recanalisation of Chronic Total Occlusions (CTO): consensus document from the EuroCTO Club . EuroInterv 3 : 30 \200\223 43 . Bifurcation lesions \200 The prescence of atheromatous narrowings involving a coronary bifurcation present unique problems to the interventional cardiologist. As a subset of coro nary artery narrowings, bifurcations are associated with higher rates of restenosis when co mpared to non-bifurcation lesions. A simple de \201 nition of bifurcation lesions can be the involvement of a side branch wit h a reference diameter greater than 2 mm in the stenosis. IVUS studies show that plaque in the main vessel almost invariably extends some distance into side branches that arise withi n the plaque. Furthermore, angioplasty to a plaque will often cause plaque-shift (the so-ca lled \200\230snowplow \200\231 effect) into the daughter vessel. The Medina classi \201 cation of bifurcation lesions, based on the presence or abscence of atheroma in the proximal main branch, distal main branch and side branch, is shown in Fig. 6.20 . Several strategies exist for the treatment of bifurcation lesions. These are broadly classi \201 ed into single-stent (or provisional) techniques, and double-stent techniques. The m ajority of operators adopt a \200\230simple \200\231 provisional strategy, in which the ma in branch stent is implanted, and the side branch only treated in the event of its occlusio n or dissection. The two-stent techniques have names such as \200\230T \200\231 stent, \200\230cullotte \200\231, \200\230crush \200\231, mini-crush \200\231, and \200\230shotg un \200\231, and are described in more detail in the reference at the end of this section. 1 Unless \202 ow in the side branch was severely impaired, or the ostium severely narrowed, during the treatment of the main vessel, a single- stent technique is preferable to the us e of two stents. This is the so-called \200\230provisional T-stenting \200\231 technique. Dilating with a balloon through the stents of a strut carries the risk of deforming the dis tal parts of the stent and failure of adequate apposition of the stent to the vessel wall. This carries a high risk of thrombosis and restenosis, and thus a \201 nal \200\230kissi ng \200\231 balloon should be employed. COMPLEX CORONARY ANGIOPLASTY 353 Recent data regarding the use of a sirolimus-coated stent in the treatment of bifurcations suggests that implantation of a SES reduces the restenosis and re intervention rates after bifurcation lesion treatment. \200 Poor results of bifurcation s tenting have led to the development of dedicated bifurcation stents, although complexity of delivery has been a limiting factor. O ne example of a bifurcation stent that is currently undergoing investigation is the Tryton Stent \204 (Tryton Medical, USA), which is a balloon-expandable side-branch-speci \201 c stent that can be wed to any standard stent. The stent is initially deployed from the main vessel into the side branch, see Fig. 6.20 . 0/1 MB distal MB (proximal) SB 0/1 0/1 0.1.1 1.1.1 1.1.0 1.0.1 1.0.0 0.1.0 0.0.1 Fig. 6.20 The Medina classi \201 cation, Reproduced with permission from Touch cardiology \200\224see. Y http://www.touchcardiology.com/articles/percutaneous- coronary-intervention- de-novo-bifurcation-lesions. 1 Stankovic G, Darremont O, Ferenc M, et al ( 2009 ). Percutaneous coronary intervention fo r bifurcation lesions: 2008 consensus document from the fourth meeting of the European Bifu rcation Club . EuroIntervention 5 ( 1 ): 39 \200\223 49 . 354 CHAPTER 6 Cardiac catheterization & intervention Angioplasty in multivessel disease Previous studies in the bare metal stent era showed PCI with BMS was inferior to CABG for multivessel disease (MVD) in terms of relieving angina an d freedom from repeat procedures. Generally, these studies had included lower-risk patients with less complex disease and better LV function. SYNTAX (Synergy between Percutaneousn Coronary Intervention with TAXUS and Coronary Surgery ) is the largest prospective, randomized multicentre trial including \200\230all-comers \200\231 with complex MVD (left main stem/ complex 3VD (three-vessel disease)). A total of 1800 patients from Europe and US were randomized to multivessel PCI with TAXUS \204 DES o r CABG, based on the revascularization strategy decision of a \200\230heart team \200\231, including an interventional cardiologist and surgeon. The only exclusion criteria were pri or revascularization, acute MI, or need for concomitant cardiac surgery. The SYNTAX scoring system was developed as a composite of estab- lished coronary disease ri sk-scoring systems and is now available as an online tool ( Y www.syntaxscore.com ). It sho uld be used to risk stratify patients and help decision making for complex revascularizatio n cases. \200 At one year there was an excess of repeat revascularizations in the PCI gro up (13.5 % vs. 5.9 % ); however, rates of clinically signi \201 cant graft or stent closur e were remarkably similar. There was a statistically signi \201 cant excess of strokes in the CABG group (2.2 % vs. 0.6 % ). Overall MACE rates favor PCI for \200\230simple \200\231 MVD with less complex anatomy and CABG for complex or left main stem disease. Left main stem (LMS) subgroup analysis \200 There was no difference in all-cause deaths b etween PCI and CABG groups (4.2 % vs. 4.4 % ) and MI (4.3 % vs 4.1 % ). As before, there was an excess of strokes in the CABG group and reduction in repeat procedures. Longer-term results of LMS PCI are awaited. 2-year MACE rates remained signi \201 cantly higher for PCI than CABG, mainly driven by hi gher repeat revascularization in the PCI arm. MACE rates at 2 years were not signi \201 cantly different for patients with a low (0 \200 \22322) or intermediate (23 \200\22332) baseline SYNTAX score treated with either PCI or CA BG. For patients with high SYNTAX scores ( \211 33), MACE continued to be increased at 2 years in patients treated with PCI compared with CABG. \200 In the prede \201 ned subgroups of patients with either 3VD or LM disease: \200 in the LM group, safet y outcomes and MACE rates were similar for PCI and CABG, but the 2-year revascularization r ate was lower in the CABG group safety outcomes (death/CVA/MI) in the 3VD group were similar for PCI and CABG, but the 2-ye ar revascularization and MACE rates favored CABG. SYNTAX SCORE 355 SYNTAX score Segments: RCA proximal 1 RCA RCA mid 2 RCA distal 3 Left main 5 LM LAD proximal 6 LAD LAD mid 7 LAD apical 8 First diagonal 9 Add. \201 rst diagonal 9a Second diagonal 10 Add. second diagonal 10a Proximal circum \202 ex 11 LCX Intermediate/anterolateral 12 Obtuse marginal 12a Obtuse marginal 12b Distal circum \202 ex 13 Left posterolateral 14 Left posterolateral 14a Left posterolateral 14b Posterior descending 15 Lesions are then graded depending on the presence of the following features, and a cumulati ve score derived: \200 total occlusion \200 trifurcation \200 bifurcation \200 seve re tortuosity \200 length > 20 mm \200 heavy calci \201 cation \200 thrombus \200 diffuse disease/small vessels. Patients are classi \201 ed as low (0 \200\22322), intermed iate (23 \200\22332), or high ( > 33) risk, with a higher score favoring CABG. 356 CHAPTER 6 Cardiac catheterization & intervention Left main stem angioplasty NICE guidelines had suggested that patients with stenosis of the LMCA should be offered bypass graft surgery. However, the emergence of reg- istry data for both BMSs and, more recently, DESs has suggested that PCI to the LMS in patients with suit able LMS anatomy achieves acceptable results with low rates of procedural complication, and long-term vessel patency. The advent of DESs, and the reality of lower rates of in-stent r estenosis compared to PCI with BMS, has further changed the approach of many interventional cardiologists to this previously taboo subset. In patients treated electively for LMS sten osis, reference vessel size and LV function appear to be the strongest predictors of favora ble outcome. Patient groups in whom LMS PCI may be appropriate \200 Emergency LMS PCI: bailout PCI after complications involving the LMS Elective LMS PCI: patients refused CABG, but with continuing angina \200 patients who refuse surgery \200 younger patients with favorable LMS anatomy (i.e. not ostial disease, not short LMS). Optimization of results of LMS PCI Nothing less than an excellent angiographic result shoul d be accepted. Intravascular ultrasound may be utilized both pre-procedure to ascertain the true vessel diameter, and post-procedure to ensure that stents have been adequately deploy ed. LMS bifurcations may be approached using the techniques described before. There is emerging evidence that the use of DESs in the LMS bifurcation results in improved clinical outcomes . Most operators routinely re-examine the LMS by angiography 2 \200\2234 months after PCI, to look for restenosis. This page intentionally left blank 358 CHAPTER 6 Cardiac catheterization & intervention Adjunctive therapy for angioplasty and stenting Aspirin The bene \201 cial effect of aspir in during PCI has been shown in the Montreal Heart Study, in which treatment with aspirin a nd dipyridamole was superior to placebo in the prevention of peri-procedural Q-wave MI. Sub sequent studies showed that dipyridamole added nothing to the bene \201 cial effects provi ded by aspirin. Low-dose aspirin (usually 75 mg once daily), initiated at least 24 h prior to procedure, is recommended in patients undergoing PCI. Thienopyridines Clopidogrel and ticlopidine are thienopyridine derivatives that inhibit pla telet function independently of aspirin, by interference with the platelet adenosine diphos phate (ADP) receptor. Early studies showed that a dual antiplatelet therapy with aspirin an d ticlopidine was superior to aspirin alone. The use of ticlopidine was limited by potentia lly severe neutropenia. Clopidogrel, a newer thienopyridine, has a safer side-effect pro \201 le, and has thus become the agent of choice. The PCI-CURE (PCI \200\224 Clopidogrel i n Unstable Angina to prevent Recurrent Events) study showed that pre- treatment with clopid ogrel (300 mg loading dose, followed by 75 mg daily) in addition to aspirin for a median of 10 days before PCI, compared with aspirin alone, reduced the composite of cardiovascular d eath, MI, or urgent target vessel revascularization by 30 % after 1 month. Most centers hav e adopted the policy of high-loading-dose clopidogrel (600 mg 2 \200\2234 hours pre-PCI) if the patient has not been preloaded. Prasugrel is the newest oral antiplatelet agent to be reviewed by NICE. Its active metaboli te binds irreversibly with the P2Y 12 class of ADP receptors on platelets. Data from TRITON TIMI 38 demonstrated that prasugrel therapy was associated with signi \201 cantly reduced rates of ischaemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding in ACS patients treated with PCI. Overall mortality did not differ signi \201 cantly between treatment groups. It has therefore been recommended for use in conjunction with aspirin for acute coronary syndrome (ACS) patients being treate d with PCI in the following contexts: \200 STEMI \200 previous stent thrombosis with cl opidogrel \200 patient with diabetes. After a loading dose of 60 mg, maintenance of 10 mg should be continued for one year. Prasugrel should be used with caution in those at increased risk of bleeding, particularly those over 75 years, with a history of bleeding, or body weight <60 kg. ADJUNCTIVE THERAPY FOR ANGIOPLASTY AND STENTING 359 Heparin Although there is general agreement that patients undergoing PCI should receive hep arin before the intervention, there remains controversy regarding the issue of optimal hepa rin dosage. An inverse relation between the level of anticoagulation (measured by ACT) and the occurrence of acute ischaemic complications has been observed; however, longer ACTs are associated with higher bleeding risks. At present, an ACT > 300 s is recommended for patie nts undergoing PCI. Low molecular weight heparin (LMWH, enoxaparin) has been shown to be ef fective in PCI; however, it has not as yet replaced unfractionated heparin (UFH) in routine use. Glycoprotein IIb/IIIa inhibitors The \201 nal common pathway for platelet aggregation is mediated by the platelet GPIIb/IIIa receptor. Trials in both diabetic and non-diabetic pati ents undergoing PTCA have found that the combination of stent and a GPIIb/IIIa inhibitor re duces cardiovascular morbidity and mortality compared with stent plus placebo. Bivalirudin Bivalirudin is a direct thrombin inhibitor that exerts its activity by speci \201 - cally and reversibly interacting with circulating (inactive) and clot-bound (active) thrombin. Clinical trials of bivalirudin in PCI have demonstrated similar bene \201 ts to the combination of abciximab and heparin, with a reduced risk of clinically signi \201 ca nt blood loss. NICE guidelines on use of GPIIb/IIIa inhibitors \200\230 it is recommended that a GP IIb/IIIa inhibitor is considered an adjunct to P CI to all patients with diabetes undergoing elective PCI, and for those patients undergoing complex procedures. \200\231 \200\230If PCI is indicated as part of the early management of unstable angina or NSTEMI, but is delayed beyond the early management phase, then the use of a IIb/IIIa inhibitor is r ecommended as an adjunct to PCI \200\231 360 CHAPTER 6 Cardiac catheterization & intervention Embolic protection devices The distal embolization of particulate matter that lodges in the microcir- culation (e.g. plaque debris, thrombus, and \201 brin) during balloon in \202 ation and stent deployment is becoming increasingly recognized as a cause of suboptimal re sults after PCI. Vein grafts, and thrombotic lesions are now recognized as being particular ly prone to complications arising from distal embolization, such as the \200\230no-re \202 ow \200\231 phenomenon, which is seen in up to 30 % of vein grafts that contain thromb us at the time of PCI. Hence, the use of distal protection devices should be considered in these angioplasty subsets. Devices for distal protection Devices can be broadly split into those that occlude the cond uit distally and then allow aspiration of debris, or distal \201 lters that capture debri s downstream. Balloon occlusion devices (Fig. 6.21) \200 PercuSurge GuardWire: this consi sts of three parts: (1) the GuardWire temporary occlusion catheter, which is place distally in the vessel to allow occlusion; (2) the MicroSeal adapter that allows control over the i n \202 ation and de \202 ation of the balloon; (3) the Export aspiration catheter, which allows collected debris to be aspirated into a 20 mL syringe. One of the main disadvantages of this system is that the target vessel is temporarily occlu ded, and thus the distal myocardium may be rendered ischaemic. Filter devices \200 AngioG uard: this device consists of an angioplasty guide wire with an expandable \201 lter at the distal tip. The \201 lter can be expanded once the target l esion has been crossed. Anterograde blood \202 ow in the vessel is maintained, and displa ced debris should theoretically be collected in the \201 lter. The \201 lter is then co llapsed and withdrawn into the retrieving catheter. FilterWireEX (Fig. 6.22): this device consists of a \200\230 \201 shmouth \200\231 openin g distal \201 lter, mounted on an angioplasty guide wire. The \200\230mouth \200\231 of th e \201 lter in theory expands to \201 ll the entire lumen of the vessel. The \201 lte r is deployed by withdrawing a delivery sheath, and collected into a retrieval sheath. Limitations of distal protection devices \200 Crossing pro \201 le may cause distal embo lization \200 Incomplete \201 lter apposition, or incomplete conduit occlusion \200 L ack of protection of side branches \200 Distal ischaemia in balloon occlusion devices. EMBOLIC PROTECTION DEVICES 361 Fig. 6.21 Balloon occlusion device for distal protection. Fig. 6.22 Filterwire. Reproduced with permission from Boston Scienti \201 c. 362 CHAPTER 6 Cardiac catheterization & intervention Special techniques Complex lesions that are unsuitable for routine angioplasty continue to pose a signi \201 cant problem. A number of alternative devices have been developed, in an attempt to facilitate treatment of resistant stenoses, including laser, rotational, and di rectional atherectomy catheters and cutting balloons. A number of evolving clinical indicat ions have been described in the clinical literature, including angioplasty-resistant stenos es (particularly heavily calci \201 ed lesions), in-stent restenosis, ostial lesions, and small-vessel disease. Rotational atherectomy (rotablation) Rotational atherectomy catheters have irrigated diamon d-tipped burrs that rotate at up to 200 000 rpm and preferentially remove hard tissue, thus preparing a lesion for subsequent stenting. When conventional PCI is feasible, rotablation confers no additional bene \201 ts, and is associated with a higher risk of vessel dissec tion and perforation, spasm, and occlusion. It does, however, have a role in the management of some complex coronary lesions but is limited by cost and technical complexity, meaning additional operator and assistant training is required. Cutting balloon Cutting balloons are similar to conventional angioplasty balloons with the addition of three (2.0 and 2.5 mm balloon) or four ( \211 3.0 mm balloon) atherotomes, wh ich are microsurgical blades, 0.010" in height, and bonded longitudinally to the balloon su rface. The balloon is folded to shield the blades and protect the vessel wall as the cathet er is passed to and from the lesion. As the cutting balloon is in \202 ated, the atherotom es expand radially and incise the plaque, facilitating maximum dilatation of the target les ion with the least amount of force, and resulting in controlled injury, in contrast to the irregular and unpredictable intimal injury associated with regular balloon angioplasty. Add itional care must be taken to avoid dissection and vessel occlusion. This page intentionally left blank 364 CHAPTER 6 Cardiac catheterization & intervention Mitral valvuloplasty (Fig. 6.23 ) In carefully selected patients with mitral stenosis, perc utaneous balloon mitral valvuloplasty (PMV) is now the treatment of choice. In fact the Ame rican Heart Association and American College of Cardiology states: \200\230 In centers with skilled, experienced operators, PMV should be considered the init ial procedure of choice for symptomatic patients with moderate to severe mitral stenosis wh o have favorable valve morphology in the absence of signi \201 cant mitral regurgitation o r left atrial thrombus. In asymptomatic patients with favorable valve morphology, PMV may b e considered if there is evidence of a haemodynamic effect on left atrial pressure (new-ons et atrial \201 brillation) or pulmonary circulation (pulmonary artery pressure > 50 mmHg at rest or 60 mmHg with exercise). \200\231 Case selection Careful case selection is paramount. The factors that must be considered inc lude: \200 age : older patients seem to have poorer outcomes in PMV. However, this is likely to be related to valve morphology in this group as opposed to age per se . I n patients in whom surgery to the mitral valve is contraindicated, e.g. extreme age, and si gni \201 cant co-morbidity), adequate results can be obtained even in the presence of subo ptimal valve morphology. valve morphology : a valve scoring system (ECHO based) is used to assess the valve \200\231s suitability for PMV. Studies have shown that patients with a val ve score of less than or equal to eight consistently achieve superior and more sustained re sults from the procedure than patients with scores above eight. mitral regurgitation : the presence of signi \201 cant mitral regurgitation is a contraindication to PMV. left atrial thrombus : this is a contraindication to PMV. Patients in AF should have been fully anticoagulated for a period of 4 \200\2236 weeks prior to the proced ure. p regnancy : PMV can be performed in pregnancy. Radiation risk to the fetus is reduced after 14 weeks. Complications of mitral valvuloplasty \200 Mitral regurgitation \200 Pericardial tampon ade \200 Thromboembolic events \200 Iatrogenic ASD. MITRAL VALVULOPLASTY 365 Fig. 6.23 Balloon mitral valvuloplasty: the upper panel shows the balloon partly in \202 a ted across the mitral valve, demonstrating the typical dumb-bell shape. As the in \202 ati on pressure and volume are increased, the stenosed valve dilates (lower panel). Adapted wit h permission from Braunwald E (ed) (2001). Heart disease: a textbook of cardiovascular medi cine . 5th ed. WB Saunders: Philadelphia. This page intentionally left blank 367 Chapter 7 Heart failure Introduction 368 Forms of heart failure 370 Causes and precipitants 372 Signs and symptoms 374 Investigations 378 Management of heart failure 382 Diuretics in heart failure 386 Angio tensin-converting enzyme inhibitors for heart failure 390 Angiotensin II receptor antagonis ts for heart failure 392 Beta-blockers for heart failure 394 Aldosterone receptor antagonis ts in heart failure 398 Cardiac glycosides (digoxin) in heart failure 400 Hydralazine and i sosorbide dinitrate in heart failure 401 Vasodilators in acute heart failure 401 Other phar macological treatments used in heart failure 402 Device therapy for heart failure 404 Surge ry for heart failure 406 Heart failure with normal ejection fraction (HFNEF)/diastolic heart failure (DHF) 408 Diagnosis and treatment of HFNEF 410 Common co-morbidities in patients with heart failure 4 12 Palliative care for heart failure 414 Worsening heart failure 414 High-output heart fail ure 416 368 CHAPTER 7 Heart failure Introduction De \201 nition Heart failure is a complex clinical syndrome in which the hear t fails to meet the metabolic demands of the body. It can result from any struc- tural or f unctional cardiac disorder that impairs the ability of the ventricle to \201 ll with or e ject blood. A diagnosis of heart failure is based on the presence of a triad of typical sym ptoms (shortness of breath on exertion and at rest, fatigue), signs (tachycardia, tachypnoe a, raised jugular venous pressure, peripheral oedema, and pulmonary congestion), and object ive evidence of a structural or functional cardiac abnormality (cardiomegaly, abnormal echo cardiogram, raised natriuretic peptide concentration). A clinical response to treatment dir ected at heart failure alone (e.g. diuretic use) may be a useful adjunct but is not suf \201 cient to establish the diagnosis. Epidemiology and prognosis Heart failure is the fastest-growing cardiovascular disease, aff ecting 2 \200\2233 % of the overall population. The prevalence rises with age, affecting be tween 10 % and 20 % of the population aged over 70 years. Although recent epi- demiological studies indicate improved survival, the overall prognosis remains poor, with mortality exc eeding 50 % at 5 years. The primary causes of death are either progressive pump failure or sudden cardiac death sec- ondary to ventricular arrhythmia. Morbidity also remains poor, wi th a high rate of rehospitalization (up to 50 % in a year), placing a signi \201 cant burd en on national healthcare systems. Pathophysiology The origin of symptoms in heart failure is poorly understood. An initial ev ent (infarction, in \202 ammation, pressure/volume overload) causes myocardial damage, res ulting in an increase in myocardial wall stress. This is followed by the activation of mult iple neuroendocrine systems including the renin \200\223 angiotensin \200\223aldosterone sy stem, the sympathetic nervous system, and the release of cytokines such as tumor necrosis f actor (TNF). Neuroendocrine activation is also accompanied by structural and metabolic chan ges in the peripheral skeletal muscle and by abnormalities in cardiopulmonary re \202 ex f unction such as the barore \202 ex and chemore \202 ex. These produce further wall stress , perpetuating this vicious cycle (see Fig. 7.1 ). INTRODUCTION 369 Stroke volume Arterial perfusion Neuroendocrine activation Starling effect Wall stress Remodeling Compensated Normalized wall stress Restoration of stroke volume Limited volume/shape change Limited in LVEF Non-compensated Persistent in wall stress Persistent neuroendocrine activation LV volume LV EF HEART FAILURE Fig. 7.1 Pathophysiology of heart failure. LV = left ventricle; LVEF = left ventricular eje ction fraction. 370 CHAPTER 7 Heart failure Forms of heart failure Acute vs. chronic heart failure The clinical manifestations depend o n the speed with which the syn- drome develops. Acute heart failure is often used to descri be the patient with acute-onset dyspnoea and pulmonary oedema, but can also apply to cardio genic shock where the patient is hypotensive and oliguric. Compensatory mechanisms have not yet become operative. Acute dete- rioration may be a consequence of myocardial infarction (MI), arrhythmia, or acute valve dysfunction (e.g. endocarditis). See b Acute pulmonary oed ema: assessment, p. 724. Systolic vs. diastolic heart failure Most patients with heart failure have evidence of both systolic (failure of the ventricle to eject blood) and diastolic (failure of the ventricle to relax and \201 ll with blood) dysfunction. Patients with diastolic heart failure have symptoms and signs of heart failure with a preserved LVEF. Current studies indicate that m ore than 50 % of heart failure patients have a normal or near-normal ejection fraction (EF) , and their prognosis appears to be similar to that of those with systolic heart failure. T he terms diastolic heart failure, heart failure with normal ejection fraction (HFNEF), and heart failure with preserved ejection fraction are used interchangeably. Right vs. left heart failure Right and left heart failure refers to whether the patient has either pre- dominantly systemic venous congestion (swollen ankles, hepatomegaly) or pulmon ary venous congestion (pulmonary oedema). These terms do not necessarily indicate which ven tricle is most seriously affected. Fluid retention in heart failure is due to a combination of factors: reduced glomerular \201 ltration rate (GFR), and activation of the renin \200\223 angiotensin \200\223aldoster one system, and sympathetic system. However, remember there are causes for swollen ankles o ther than heart failure (gravitational disorder, e.g. immobility, venous thrombosis or obst ruction, varicose veins, hypoproteinaemia, e.g. nephrotic syndrome or liver disease, lympha tic obstruction). High-output vs. low-output heart failure A variety of high-output states may lead to heart failure, e.g. thyrotoxicosis, Paget \200\231s disease, beri-beri, and anemia. This is chara cterized by warm extremities and normal or widened pulse pressure. The arterial \200\223mix ed venous oxygen saturation (a marker of the ability of the heart to deliver oxygen to the metabolizing tissues) is typically normal or even low in high- output heart failure. In con trast, low-output states are characterized by cool pale extremities, cyanosis due to system ic vasoconstriction, and low pulse volume. The arterial \200\223mixed venous oxygen saturat ion is typically abnormally high in low-output states. This page intentionally left blank 372 CHAPTER 7 Heart failure Causes and precipitants In all patients with heart failure, it is important to carefully co nsider the underlying etiology, as there may be speci \201 c exacerbating factors or other diseases that in \202 uence the patients \200\231 management. A non-exhaustive list is gi ven below. Etiology of heart failure \200 Ischaemic heart disease Alcoholic cardiomyopathy \200 Post viral \200 Peripartum cardiomyopathy \200 In \201 ltrative disease (amyloidosis, (accounting for 70 % of patients with heart failure in the developed world) Idiopathic dilated cardiomyopathy (unknown etiology, up to 50 % may be familial) sarcoidosis) Connective tissue disease \200 Iatrogenic (chemotherapy, Valve disease (accounting for 10 % of patients with heart failure) radiotherapy) Infections (Chagas \200\231 disease, human immunode \201 ciency virus (HIV)) \200 Thyroi d disease (severe hypo- or Hypertension (the primary cause of heart failure in patients of African-Caribbean descent) hyperthyroidism) \200 Haemochromatosis \200 Nutritional (beri-beri) Patients with compensated heart failure have a high rate of readmission to hospital with ac ute exacerbations. A number of studies have demon- strated that a precipitating cause for e mergency admission to hospital with heart failure can be identi \201 ed in up to two-third s of patients. \200 Inappropriate reduction in therapy: self-discontinuation or iatrogeni c withdrawal of diuretics, angiotensin-converting enzyme inhibitor (ACE-I), digoxin, as wel l as dietary excess of salt are recognized precipitants. Education of the patient/family is important. Cardiac arrhythmias: most commonly atrial \201 brillation (AF), but any tachyarrhythmia will further reduce LV \201 lling and stroke volume, and may exacerbate i schaemia. Marked bradycardia reduces cardiac output, especially if stroke volume cannot inc rease any further. Myocardial ischaemia or infarction: exacerbates LV dysfunction, and may worsen mitral regur gitation (MR) due to ischaemia of papillary muscles. Infection: respiratory infections are more common, but any systemic sepsis can precipitate heart failure due to a combination of factors such as direct myocard ial depression from in \202 ammatory cytokines, sinus tachycardia, fever, etc. Anemia: this causes a high-output state that may precipitate acute heart failure, and may exacerbate underlying ischaemia. Concomitant drug therapy: drugs that directly depress myocardial function (e.g. calcium ant agonists \200\224 verapamil, diltiazem; many antiarrhythmics, anesthetics, over-enthusiast ic initiation of B -blockers, etc.), as well as drugs causing salt and water retention (e.g . non-steroidal anti- in \202 ammatory drugs (NSAIDs), oestrogens, steroids, COX-2 antagon ists) may precipitate heart failure. CAUSES AND PRECIPITANTS 373 Alcohol: this is directly toxic and, in excess, can depress myocardial function as well as predispose to arrhythmias. Pulmonary embolism: the risk increases in the immobile patient with low-output state and AF. It is very important to look for precipitating causes in all patients with heart failure. O nce the precipitant has been identi \201 ed and treated, appropriate measures (patient and family/education, adjustment of therapy, etc) should be put into place to prevent recurren ce. See Table 7.1. Table 7.1 Population-attributable risk of heart failure related to various risk factors a Risk factor Attributable risk ( % ) Coronary disease 61.6 Cigarette smoking 17.1 Hypertension 10.1 Physical inactivity 9.2 Male sex 8.9 <High school education 8.9 Overweight 80 Diabetes 3.1 Valvular heart disease 2.2 a He, J, Ogden LG, Bazzano LA, et al (2001). Risk factors for congestive heart failure in U S men and women: NHANES 1 Epidemiologic follow-up study. Arch Intern Med 161 : 996. Conditions mimicking heart failure \200 Obesity \200 Chest disease \200\224 including lung, Intrinsic renal disease \200 Intrinsic hepatic disease \200 Pulmonary embolic disease \200 Depression and/or anxiety diaphragm, or chest wall Venous insuf \201 ciency in lower limbs. \200 Drug-induced ankle swelling (e.g. dihydrop yridine calcium blockers) disorders Severe anemia \200 Thyroid disease \200 Bilateral renal artery stenosis Drug-induced \202 uid retention (e.g. NSAIDs) \200 Hypoalbuminaemia 374 CHAPTER 7 Heart failure Signs and symptoms The evaluation of a heart failure patient should start with a comprehens ive history and clinical examination. Primary symptoms can be attributed to either reduced cardiac output or \202 uid accumulation, and include: \200 fatigue \200 dyspnoea (on exertion or at palpitations (tachycardia) \200 hypotension \200 raised jugular venous pressure (JVP) \200 displaced apex beat \200 gallop rhythm (3rd heart sound) \200 cahexia. rest) orthopnoea \200 paroxysmal noctural dyspnoea \200 peripheral oedema \200 chest pain It is important to remember that heart failure is a multisystem disorder affecting every si ngle aspect of a patient \200\231s body. It is not unusual for patients to present with: \200 gastrointestinal symptoms secondary to congestive hepatomegaly, ascites, reduced bowel perfusion, and oedema (abdominal distension and pain, anorexia, bloa ting, nausea, constipation, jaundice) \200 genitourinary symptoms secondary to impaired r enal perfusion (oliguria/anuria, urinary frequency, nocturia) cerebrovascular symptoms secondary to cerebral hypoperfusion and associated electrolyte abn ormalities (confusion, memory impairment, anxiety, headaches, insomnia, bad dreams or night mares, psychosis with disorientation, delirium, or hallucinations) musculoskeletal symptoms (gout, carpal tunnel syndrome, muscle cramps). Many of these signs can be dif \201 cult to elicit particularly in a noisy emer- gency or outpatient clinic. Even in study conditions, the reproducibility and inter-observer agreement of the presence of signs is low. Despite this, a clinical diagnosis of heart failure can be made with some