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INTRODUCTION syndromes resulting in more patients alive albeit with an impaired cardiac function, and the genOver the years, heart failure has become one of eral population getting older and, hence, at the most dramatic developments in medicine, higher cardiovascular risk result in a high prevaexemplified by fast increasing incidence world-lence of heart failure, particularly in the elderly. wide, its debilitating nature, enormous cost To cope with a situation such as this requires aspects, and a mortality rate which surpasses full awareness of size and severity of the probmany other diseases, including most cancers. lem, not only by the doctor or nurse directly
Changing lifestyles leading to more cardio-involved in heart failure care, but also by the vascular disease, a better treatment of ischemic health-care authorities who sanction the means for improved care and research into better forms of treatment, as well as the patient, his family, and indeed the general public, who may force health-care authorities into this.
Accordingly, heart failure management encompasses far more than the prescription of the correct medication or performing the appropriate diagnostic techniques, important as they are.
Extensive educational programs for the public, health-care officials, paramedical personnel, primary care physicians, and specialists involved in heart failure patient care form an integral part when it comes to improving heart failure management.
In addition, a better understanding of the need for primary and secondary preventive measures, the importance of screening programs, structured HF management pathways, including nurse-led outpatient and home care and HF clinics, and the role of nonpharmacological therapies, for example, devices and exercise programs, is mandatory if we want to contain this major medical problem.
Obviously, the doctor, whether primary care physician, internist, geriatrician, or cardiologist, has a pivotal position in the management of heart failure patients and should be well educated about how to provide appropriate care. Guidelines on diagnosis and treatment of heart failure exist in many countries worldwide and do provide the intellectual means to optimize HF management in the individual patient.
This chapter aims, with a view on the most recent HF guidelines, at painting a picture of how, with currently available information, optimal HF care may be achieved.1–3
HOW TO DETECT HEART FAILURE
The characteristic signs and symptoms of heart failure are by no means specific. Although orthopnea and nocturnal dyspnea may suggest a high likelihood of heart failure, the more common symptoms such as dyspnea on effort and tiredness are less specific, certainly in the elderly. Also, typical signs of heart failure like ankle edema or rales can often be explained by other causes, particularly in women or the elderly, whereas other, potentially more specific signs such as a third heart sound or an elevated jugular pressure demand a certain level of diagnostic experience.
Nevertheless, these signs and symptoms should alert the physician, and when presenting in clinically meaningful combination and/or against the background of cardiovascular disease, should prompt additional investigations including an electrocardiogram (ECG), chest x-ray, and, if available, B-type natriuretic peptide (BNP) or NTproBNP. An abnormal ECG is common in heart failure, but does not have much predictive value. In contrast, a normal ECG makes heart failure unlikely. A chest x-ray should always be part of the initial workup and may suggest heart failure when cardiomegaly or pulmonary congestion is present, particularly when typical signs and symptoms and an abnormal ECG are present. On its own, its predictive value is too low and should not be considered sufficient for the diagnosis.
There is accumulating evidence that natriuretic peptides have strong prognostic value in heart failure.4 Their potential to monitor treatment is questionable, though. In particular, the effect of b -blockade is not consistently reflected by reductions in natriuretic peptide levels. In the CARMEN study, carvedilol alone significantly reversed cardiac remodeling, but this was not accompanied by decreased BNP levels.5 In contrast, whereas enalapril alone did not decrease cardiac volumes in that study, it did lead to a significant reduction in BNP. Natriuretic pep-tides are particularly useful to exclude heart failure, as in untreated patients a normal value strongly suggests the absence of heart failure.6 In particular, if the ECG and natriuretic peptides are normal, it is unlikely that heart failure is present, and the doctor is well advised to consider other explanations for the patient’s complaints.
In all other cases, however, cardiac function needs to be evaluated. Heart failure should never be diagnosed based on clinical signs and symptoms alone. Unfortunately, this is still practiced by many primary care physicians, as indicated by the SHAPE study.7 In this survey carried out in 2003 of more than 4000 primary care physicians in nine European countries, 75% would still diagnose heart failure based on signs and symptoms alone and 22% believed the response to diuretics necessary to confirm the diagnosis. Only a minority would request an echocardiogram to ascertain cardiac dysfunction.
Echocardiography is the preferred method for the assessment of cardiac function, allowing for the measurement of both systolic and diastolic function noninvasively. The most important measurement here is the left ventricular (LV) ejection fraction to distinguish patients with LV systolic dysfunction from those with preserved LV systolic function. The latter is not equivalent to diastolic LV dysfunction. To diagnose heart failure due to diastolic LV dysfunction in patients with typical signs and symptoms of heart failure and a (near) normal LV ejection fraction, relaxation abnormalities, diastolic distensibility, or diastolic stiffness needs to be present.
The combined assessment of mitral annular velocities and transmitral blood flow velocities may allow one to assess different filling patterns inherent with mild, moderate, and severe diastolic dysfunction, that is, impaired relaxation, pseudonormal filling, and restrictive filling, respectively.8,9
How important the diagnosis of diastolic heart failure really is, is uncertain as prospective data in controlled studies are lacking. Most heart failure patients have a certain degree of diastolic dysfunction together with systolic dysfunction, and the management of both conditions does not differ much (see the following paragraphs).
In cases where echocardiography cannot be performed, LV function may be determined by nuclear angiography, contrast angiography, or cardiac magnetic resonance imaging (MRI). The latter provides well-reproducible information on cardiac volumes, size, wall motion, and myocardial mass, but is not readily available in many places worldwide.
Other investigations may be useful to detect underlying causes of heart failure or suggest alternative diagnoses, but are not really necessary to define whether heart failure is present or not. Thus, exercise testing should not routinely be performed to diagnose heart failure, although exercise capacity is likely to be reduced in heart failure. It may be useful, though, like stress echocardiography or scintigraphy, to detect myocardial ischemia. Similarly, coronary angiography should not be performed routinely when angina is not present, but may be considered when, in acute or worsening heart failure, patients do not react sufficiently to therapy to detect significant, treatable coronary disease. Similarly, cardiac catheterization, including angiography, should be considered when treatment effect is inappropriate and the underlying cause is unclear and to consider the need for valve repair in severe mitral or aortic disease.
Essential hematological and biochemical evaluations during diagnosis include hemoglobin, hematocrit, renal function tests (creatinine clearance, serum urea), electrolytes, liver function tests, serum glucose, and urine analysis. Anemia and renal dysfunction are important prognostic indicators, which may cause or contribute to worsening heart failure, and are targets of specific therapies (see Chap. 10). Severe renal dysfunction and electrolyte disorders may be limiting factors in therapies such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, and aldosterone antagonists. The presence of diabetes should be evaluated routinely, but thyroid function on indication only. A flowchart of diagnostic steps and necessary or supporting components of heart failure diagnosis are given in Fig. 22-1 and Tables 22-1 and 22-2, respectively.
HEART FAILURE THERAPY— WHAT IS AVAILABLE
ACE Inhibitors
Irrespective of the severity of heart failure, patients should receive an ACE inhibitor. This includes asymptomatic left ventricular dysfunction. Patients usually tolerate ACE inhibition well and there are few absolute contraindications (bilateral renal artery stenosis and angioedema during previous ACE inhibitor use). Relative contraindications may include severe renal dysfunction, severe hypotension, and persistent hyperkalemia despite non-potassium-sparing diuretic therapy. If there are no signs of fluid overload, ACE inhibitors are to be administered before diuretic therapy, with fluid overload together with diuretics.1 Whereas ACE inhibitors should be uptitrated starting with low dosages, it is important to continue until the dosages have been reached, which when used in large randomized controlled trials (RCT) have been shown to improve mortality and morbidity. All too often, ACE inhibitor uptitration is stopped too early at insufficient dose levels, that is, those that were not studied in RCTs and for which there is no indication of efficacy. A survey of European primary care physician (PCP) practices in 1999 indicated that overall doses prescribed were approximately 50% of the target dose levels of ACE inhibitors suggested by available European guidelines on heart failure treatment.10,11 A recent survey, also amongst European PCPs, did not indicate any improvement in PCP prescription practice, as less than 50% of the PCPs would reach target doses.7 One contributing reason for undertreatment may be that many PCPs overestimate the risk of side effects with ACE inhibitors and this overestimation may undermine doctors’ accurate assessment of the benefit-risk ratio, potentially increasing the likelihood of not starting or inappropriately stopping treatment.10 Changes in blood pressure and increases in serum creatinine are usually small with ACE inhibition in normotensive patients without severe heart failure, and symptomatic hypotension is uncommon. This overestimation of the risk of side effects with ACE inhibitors very likely contributes to the PCPs’ preference of diuretics as first-line treatment of heart failure, also in patients without overt signs of fluid overload.
The recent SHAPE survey found that 39% of European PCPs would start treatment with a diuretic and only 43% would always (in >90% of their patients) use an ACE inhibitor for the treatment of heart failure.5 In contrast, 64% of European internists and geriatricians and 82% of European cardiologists would always prescribe an ACE inhibitor for heart failure.12
Diuretics
Diuretics are obviously essential for symptomatic treatment when fluid overload is clinically manifest as peripheral edema or pulmonary congestion, as they may quickly diminish symptoms such as dyspnea and improve exercise tolerance.
However, there are no RCTs with diuretics with regard to their effect on mortality and, indeed, symptoms. As diuretic treatment may lead to adverse effects such as neurohormonal activation, renal dysfunction, and hyponatremia, diuretics should be used in a flexible way as adjunctive therapy to ACE inhibition, b-blockade, and possibly low-dose aldosterone antagonists and angiotensin receptor blockade (ARB).3 Nevertheless, diuretics are used as first-line therapy without ACE inhibition by a sizeable percentage of PCPs (39%) and by 18% of internists and geriatricians in Europe.7,12 If a patient’s symptoms improve following diuretic treatment, its use should always be reconsidered and reduced or even stopped as patients are apparently free of fluid overload and free of symptoms.
b-Blockade in Heart Failure
The greatest recent advance in heart failure therapeutics is the finding that b-blockers further reduce morbidity and mortality when added to an ACE inhibitor. This evidence became apparent from 1996 onwards and international guidelines produced since then clearly mandate the use of b-blockade in addition to ACE inhibitors and diuretics in all symptomatic heart failure patients.1,2,13–16 b-Blockers are also indicated in asymptomatic LV dysfunction after a myocardial infarction (MI).17
Nevertheless, uptake of b -blockade for the treatment of heart failure by the medical community has been slow and hesitant, particularly by noncardiologists. Whereas in a survey carried out in 1998 amongst PCPs. b-blocker use was as low as 6%, the recent SHAPE survey indicated that still only 5% of European PCPs would always (in >90% of patients) and 35% (in >50%) prescribe a b-blocker, whereas 11% of PCPs would never prescribe a b-blocker.7,10 Overall, 35% would not prescribe a b-blocker to a patient who had mild symptoms on treatment with an ACE inhibitor and a diuretic. The main risks of treatment with b-blockers were thought to be bronchospasm, heart block, cold extremities, worsening of heart failure, and hypotension, which were also given as a reason for stopping b-blocker therapy by 66%, 58%, 18%, 31%, and 25%, respectively. Most PCPs said they would not prescribe a b -blocker for patients with a bradycardia or asthma/chronic obstructive pulmonary disease. Overall, 35% said they would not prescribe a b-blocker to a patient who had mild symptoms on treatment with an ACE inhibitor.
Of interest, this is not much better among internists and geriatricians. In the same SHAPE survey, only 39% would prescribe a b -blocker in >50% of their patients, compared to 73% of cardiologists.12
Which b-Blocker? At present, four b-blocking drugs have been shown to improve survival and/or lead to clinical benefit, at least including a reduction in cardiovascular hospitalizations: bisoprolol, metoprolol succinate, carvedilol, and nebivolol.13–16,18 Bisoprolol and metoprolol succinate are b1 selective blockers without and nebivolol with vasodilating properties. Carvedilol, on the other hand, has a more profound antiadrenergic effect, including b1 and a2 and b1 antagonistic properties. Moreover, it has antioxidative and antiendothelin effects. Together, these properties suggest a better therapeutic profile in heart failure. Indeed, in the only head-to-head comparison with another b -blocker, metoprolol tartrate, carvedilol displayed a more profound improvement in survival and reduced the occurrence of death and hospitalizations for heart failure more than metoprolol during long-term treatment.19 As it also had a significant effect on all vascular modes of death (Fig. 22-2) and on myocardial infarction and stroke, a vascular component in its mode of action seems likely, possibly the result of its alpha-1 blocking properties. Suggestions that the better effect of carvedilol was due to a more profound effect on heart rate and blood pressure and/or to dose differences were recently shown unfounded.22
b-Blockade or ACE Inhibition in Mild Heart Failure–Which One First?
All large b-blocker trials were conducted on top of ACE inhibition. As a consequence, guidelines would advocate the use of ACE inhibitors as a first step (with or without a diuretic), followed by b-blockade if symptoms persist; that is, as patients would become asymptomatic b-blockade would not be advocated in conditions where chronic heart failure was not caused by an MI. Typically based on historical grounds (the ACE inhibitor being the first to be explored in heart failure), one may wonder whether this assumption is correct. In view of its pharmacological profile in relation to early mechanisms in cardiac remodeling and heart failure, a b-blocker such as carvedilol may well be as good or possibly better than an ACE inhibitor. The CARMEN study indicated that carvedilol alone had a better long-term effect on remodeling in mild heart failure than enalapril alone, although the combination proved to be superior (Fig. 22-3).5 In the latter arm of the study, carvedilol was uptitrated first and appeared well tolerated. The results of CARMEN suggest that in cases where ACE inhibition is contraindicated carvedilol is a good alternative, but that, whenever possible, both drugs should be combined from the start of treatment to achieve the best effect on remodeling. Sliwa et al. subsequently reported in a smaller, single-center study that the order of administration favored carvedilol.23 Both CARMEN and the study of Sliwa et al indicate that b-blockade (with carvedilol) may be the first rather than the second step, particularly in patients with an elevated heart rate.24 CIBIS III examined the effect of bisoprolol as first-line treatment as compared to enalapril and determined that it was as safe and efficacious to start bisoprolol first.
Aldosterone Antagonists
Aldosterone plays a pivotal role in the pathophysiology of several cardiovascular syndromes, including heart failure. Aldosterone synthase and the mineralocorticoid receptor are produced in close proximity in organs such as
CARMEN primary endpoint: Comparison of LVESVI between treatments
LVESVI (biplane) [ml/m2]
Baseline Month 6 Month 12 Month 18
LVESVI = Left Ventricular Endsystolic Volume Index
the heart, vascular tissue, and the brain. As such, aldosterone acts not only as an endocrine hormone following suprarenal production, but also as a paracrine neurohormone. Of importance, its production is greatly stimulated in the cardiovascular system following an acute myocardial infarction and in the failing heart.25 Among its multiple actions are fibrosis of the heart and vessels, myocardial hypertrophy, cytokine activation, endothelial dysfunction, vascular inflammation, increased cardiac norepinephrine uptake, sodium reabsorption, and potassium and magnesium excretion, which together may lead to hypertension, ischemia, arrhythmias, and heart failure. As many other stimuli than angiotensin II result in aldosterone activation, ACE inhibition or angiotensin II receptor blockade (ARB) do not suppress aldosterone production. To block the untoward effects of the neurohormone, aldosterone receptor antagonists are required. Spironolactone binds to mineralocorticoid receptors, but also to glucocorticoid receptors and has progestational and antiandrogenic actions. Eplerenone has a greater specificity for mineralocorticoid receptors and fewer progestational and antiandrogenic actions. Both drugs have clear antiremodeling effects in postinfarct and heart failure models, reduce oxyradicals formation, improve endothelial function, and prevent cardiovascular fibrosis. Spironolactone significantly improved survival in advanced heart failure in addition to ACE inhibition and b-blockade, and reduced cardiovascular and heart failure hospitalizations in the RALES study.26 In EPHESUS, eplerenone had similar effects on mortality in postinfarct heart failure patients with LVSD, and reduced sudden death in particular (Fig. 22-4).27 Again, effects were present, and in fact better, when administered in addition to ACE inhibition and b-blockade, a clear demonstration of the importance to block the 3 major neurohormonal systems simultaneously with combined targeted therapy. Of importance, this combined therapy was generally well tolerated, hypotension not being a major issue. Hyperkalemia did occur in both RALES and EPHESUS in patients receiving aldosterone antagonists in addition to ACE inhibition, as to be expected. However, serious hyperkalemia was not an issue in RALES and occurred in 1.6% of eplerenone patients in EPHESUS, but not leading to excess deaths. This small increase in serious hyperkalemia was offset by a 4.7% absolute decrease in serious hypokalemia in these patients, very likely having contributed to the reduction in sudden death in patients treated with eplerenone. Although hyperkalemia was not a major issue in RALES and EPHESUS due to adherence to a strict titration scheme, an increase in hospitalizations for hyperkalemia due to a surge in spironolactone use following publication of the RALES results was recently reported.28 Most likely this is due to a less careful approach in spironolactone administration and patient selection in usual clinical care as compared to controlled study conditions. Based on the trial results, aldosterone antagonists are recommended in patients with heart failure post-MI and in advanced heart failure in addition to ACE inhibition and b-blockade. Although it is very likely that these agents will be beneficial in patients with mild heart failure, this will be clarified in an upcoming large multinational study in patients with New York Heart Association (NYHA) Class II heart failure (EMPHASIS-HF).
Angiotensin Receptor Blockers
ARBs are advocated in patients who are intolerant to ACE inhibitors.1–3 In the CHARM–Alternative study, candesartan significantly reduced cardiovascular death or hospitalizations for heart failure.30 Whereas this makes sense and is not very surprising, there are seemingly good reasons to expect a better effect from an ARB than an ACE inhibitor in heart failure treatment. Studies have indicated that during long-term ACE inhibition the initial decrease in circulating angiotensin II levels diminishes over time, possibly the result of alternative pathways to form angiotensin II from its precursor, for example, by way of chymases. However, and in contrast to the consistent beneficial effects of ACE inhibitors, b -blockers, and aldosterone antagonists in heart failure, the potential positive effects of ARBs in chronic heart failure have been more difficult to demonstrate. In ELITE 2, the first large controlled study in heart failure, which compared ACE inhibition (captopril) head to head with an ARB (losartan), monotherapy with the ARB did not prove better than the ACE inhibitor.31 If anything, there was a tendency to a worse outcome with losartan, although side effects were less. Subsequent meta-analyses also including smaller studies indicated equal efficacy in terms of survival and reduced morbidity.32 Nevertheless, in post-MI patients with LV systolic dysfunction or heart failure, again a diverse pattern emerged with less efficacy of the ARB as compared to ACE inhibition in one and no inferiority in another study.33,34
Further studies concentrated on a combined ACE inhibitor and ARB effect, comparing this combination to ACE inhibition alone. The obvious idea behind this is that the combination would take care of a possible ACE inhibitor escape effect on angiotensin II levels, at the same time preserving the effect of ACE inhibition on bradykinin, an essential modulator of cardiac remodeling and a strong vasodilator. The Val-HeFT study compared the ARB valsartan plus ACE inhibition to ACE inhibition alone.35 The first primary endpoint, survival, did not improve with the combination, but there were fewer heart failure hospitalizations. In contrast, in the CHARM–Added study, candesartan plus ACE inhibition significantly reduced the combination of cardiovascular death or heart failure hospitalizations by 15% compared to ACE inhibition alone and reduced LV function.36 However, in both Val-HeFT and CHARM–Added there was a higher rate of discontinuation due to renal impairment, hyperkalemia, and hypotension in the combination arms, indicating a need for careful monitoring. In heart failure or LV dysfunction post-MI, there was similar efficacy in the combination and single component arms, but again a higher incidence of side effects.34 Despite a lack of homogeneous efficacy in the above studies, possibly caused by relatively low dosages in several studies, the most recent guidelines are relatively mild, suggesting that ARBs are used as an alternative to ACE inhibitors, if intolerant, or can be considered in combination with ACE inhibitors in patients who remain symptomatic despite accepted therapy including ACE inhibitors and b-blockers.3,31,33 Concerns regarding a negative interaction with b-blockade raised by earlier studies could not be confirmed in later trials.
Digitalis Glycosides
Digitalis glycosides are prescribed less and less, although they are still favored by PCPs and in Eastern European countries. Their use is primarily in atrial fibrillation (preferably together with b-blockade) for heart rate control, and in more advanced heart failure in patients with sinus rhythm for symptom control. The DIG study did not indicate a positive effect on survival, but hospitalizations and heart failure hospitalizations were reduced.37 This study, performed before the introduction of b -blockade and aldosterone antagonism for the treatment of heart failure, leaves much doubt about the efficacy of glycosides in the presence of these drugs. Both efficacy and adverse effects may be less when plasma levels are relatively low.38
Vasodilators
With the exception of African Americans, there is no specific role for direct-acting vasodilators in heart failure. The combination of nitrates and hydralazine, better than placebo, is less effective than ACE inhibition in the overall population, although a recent study indicated a significant better effect in African Americans.39–41 Other vasodilators, including nitrates and long-acting calcium antagonists such as amlodipine and felodipine, which do not lead to beneficial effects but also are not harmful in the setting of heart failure, may be considered for concomitant treatment of angina and hypertension.42
Antiarrhythmic Agents or Implantable Cardioverter Defibrillators
In terms of antiarrhythmic agents, only b-blockers (class II drugs) have been shown to reduce sudden death in heart failure. Amiodarone may be effective against supraventricular and ventricular arrhythmias; it does not affect death in heart failure, at least not in mild-moderate chronic heart failure. In the SCD-HeFT study, amiodarone was not better than placebo in NYHA II patients on ACE inhibition and b-blockade (approximately 70%) but relatively low numbers on aldosterone antagonists, but was significantly better in NYHA Class III patients.43 Conversely, simple shock-only implantable cardioverter defibrillator (ICD) prevented death better in mild heart failure, but not in NYHA Class III compared to placebo. Nevertheless, if the overall population was considered, amiodarone proved no better than placebo, but ICD did. The place of amiodarone in death prevention is unclear and there appears no reason for routine use in chronic heart failure. However, the agent may be effective in restoring sinus rhythm in atrial fibrillation (with or without electrical cardioversion) and has the advantage of not being negatively inotropic. Besides SCD-HeFT, other data from large controlled studies supported by meta-analyses including smaller studies indicate an important role of ICDs in symptomatic heart failure patients due to significant LV dysfunction, despite optimal background therapy including b-blockade, in order to reduce the occurrence of sudden death.43,44 Also, ICD is effective in post-MI patients with LV systolic dysfunction, but not necessarily symptomatic heart failure.45 Thus far, the efficacy has not been well established in NYHA Class IV chronic heart failure. Moreover, a greater use of aldosterone antagonists, effective against sudden death, may impact on the efficacy of ICD. Which patient is a good candidate for ICD needs further evaluation, also in light of cost.
Pacemaker therapy for CHF—The Role of Cardiac Resynchronization Therapy
Cardiac dyssynchrony is a common feature in heart failure, particularly advanced cases. Resynchronization with multiple-lead biventricular pacing improves cardiac function, symptoms, and exercise capacity in the course of several months.46,47 An important part of symptomatic improvement may relate to reduction of mitral insufficiency as contraction sequence improves. Two large trials have focused on the long-term effect of cardiac resynchronization therapy (CRT) on mortality and morbidity. COMPANION selected patients with NYHA Class III–IV heart failure, LV ejection fraction ≤35%, and a QRS width 120 msec to optimal pharmacological therapy only, CRT, or CRT with ICD.48 Both CRT arms significantly reduced the primary endpoint (time to death or all-cause hospitalization) compared to placebo, although there was no difference between the arms. All cause death was only significantly reduced by the CRT–ICD combination.
In CARE-HF, patients with similar entry criteria, and also LV end diastolic dimension ≥30 mm, were randomized to medical therapy alone or with CRT.49 There was a significant 37% relative risk reduction in the primary endpoint (all-cause death or cardiovascular hospitalization) and a 36% relative risk reduction in all-cause death in the CRT arm. These significant clinical effects were supported by hemodynamic improvement, less mitral insufficiency, and a reduction in LV end-diastolic volume. Based on the results of COMPANION and CARE-HF, the new European Society of Cardiology (ESC) guidelines indicate that CRT can be considered in patients with NYHA Class III–IV with reduced LV function and ventricular dyssynchrony (QRS width ≥120 msec), who remain symptomatic despite optimal medical therapy.3
Devices and Surgery
The surgical approaches to chronic heart failure can be divided into revascularization procedures, mitral valve surgery, LV restoration procedures, and heart transplantation.
Although symptomatic relief is observed in individual patients with symptomatic ischemic heart disease, the lack of prospective data from large controlled trials does not allow the use of bypass surgery in the average heart failure patient, also as heart failure patients have a considerably increased operative mortality risk.
Mitral valve surgery may significantly improve symptoms, particularly in patients with large ventricles and severe mitral insufficiency. Whether survival improves is unknown, however.
Left ventricular restoration attempts to reduce wall stress by reducing cardiac volumes or restricting further dilatation. Thus far, aneurysmectomy can be advocated in patients with sufficiently large aneurysms. In contrast, results of other procedures including cardiomyoplasty or the so-called Batista procedures have been disappointing and are not to be recommended as yet.
In addition to these procedures, several new techniques have been developed, including the myosplint and the Acorn external cardiac support device, both of which aim at reducing wall stress by restricting enlargement of the left ventricle.50,51 Initial data are encouraging, but the outcomes of larger prospective trials are awaited.
Heart transplantation has gradually become a successful mode of treatment in end-stage cardiac failure despite optimal medical treatment, with a 5-year survival of approximately 75%. The main problems are shortage of donor hearts, early rejection, long-term consequences of immunosuppressive therapy, and new progressive coronary disease.
Although novel pharmacological therapies have resulted in patients improving to such an extent that they can be removed from the transplant list, bridging with ventricular assist devices or artificial hearts is often considered necessary. Despite the fact that at present assist devices are still external and prone to complications such as infections, they are often used for relatively long periods due to the scarcity of donor hearts.52 Studies with fully implantable devices are currently in progress.
WHEN TO TREAT AND HOW
Heart Failure Due to LV Systolic Dysfunction
Attention should be paid to treatable underlying causes of heart failure and to reasons for heart failure worsening.
In asymptomatic patients, ACE inhibition, and in post-MI patients, a b-blocker added to ACE inhibition, is mandatory. In mild symptomatic heart failure without signs of fluid retention, ACE inhibitors and b-blockers suffice, but diuretics should be added when fluid retention is present. It is important not to leave a time delay between, prescribing the ACE inhibitor and the b-blocker; the sequence of administration depends on the individual patient. If patients are intolerant to ACE inhibitors an ARB should be given. Patients with heart failure post-MI should receive an aldosterone antagonist in addition to ACE inhibitors and b-blockade. In other cases, an ARB may be added when patients remain symptomatic or worsen. However, in NYHA Class III patients who have improved from NYHA Class IV, an aldosterone antagonist would be the first choice and the addition of an ARB may be considered if symptoms persist. Potassium-sparing diuretics are usually not necessary, particularly when low-dose spironolactone may already be part of the treatment package. Digoxin should be considered in atrial fibrillation and continued in sinus rhythm if patients do improve from severe-tomilder heart failure. In worsening patients, it may be useful to prescribe a combination of different diuretics, that is, loop diuretics and thiazides, if increasing doses of a loop diuretic are not sufficient. At this stage, the usefulness of mitral valve operation may be considered, or cardiac transplantation. The latter should always be considered in end-stage heart disease with or without bridging procedures such as assist devices or interim support with intravenous inotropic agents. Figure 22-5 displays the use of pharmacological therapy as proposed by the ESC.3
Heart Failure with Preserved LV Systolic Function or Diastolic Dysfunction
Currently there are few data from controlled studies indicating how heart failure due to diastolic dysfunction or with preserved LV systolic function should be treated. Basically, suggested therapies conform to those of patients with systolic LV dysfunction. Of importance is to detect and correct underlying mechanisms, for example, ischemia (b-blockers, nitrates, calcium antagonists), to reduce heart rate to lengthen the diastolic period and improve diastolic coronary perfusion (b-blockers, verapamil-type calcium antagonists), and to correct hypertension if present and reduce cardiac hypertrophy (ACE inhibitors, ARB, and possibly dihydropyridine type calcium antagonists). ACE inhibitors directly improve relaxation and cardiac distensibility. Verapamil has shown improvement in hypertrophic cardiomyopathy and ARB reduced hospitalization for heart failure in CHARM–Preserved.53,54 Of importance, although it may often be necessary to prescribe diuretics as pulmonary fluid retention occurs easily in rigid hypertrophied hearts, they may reduce preload extensively and lead to hypotension.
THE ROAD TO OPTIMAL HEART FAILURE MANAGEMENT AND CARE
In the last few decades, significant improvements in heart failure diagnosis and, particularly, therapy have been achieved. Nevertheless, many patients are undermanaged, and many heart failure patients may even be undetected. Particularly nonspecialist doctors are insufficiently aware of the seriousness of heart failure and the necessity for early detection and management. Education is clearly needed. However, even with fast improvements in this respect and appropriate perception of optimal heart failure management of all caregivers involved, there are also important logistical aspects to be taken care of. The heart failure patient typically is an example of a chronically disabled patient with the potential to quickly change from a stable to an unstable condition, leading to (repeat) hospitalizations or (sudden) death.
To prevent this, continuous control by a specialized heart failure team is necessary. There are ample examples in the literature showing that a well-structured system of supervision and patient care may significantly reduce hospitalization frequency.55,56 Which of the different models used is the best is unclear. However, a system employing specialized heart failure nurses would appear to be effective and cost-efficient. The extent to which this form of care is set up depends on whether all patients or only selected patient groups are involved and the availability of the necessary funds. In this respect, the awareness and perception of heart failure in all its aspects should not only be a matter for health-care providers, be it doctors, nurses, or other paramedical personnel and patients, but also for the general public and, in particular, the health-care authorities.57
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