Feature Article
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Congestive Heart Failure in the Elderly Population: Some Common Questions Congestive Heart Failure in the Elderly Population: Some Common Questions
Subrato Ghosh, MD, and Krishan Gupta, MD
Dr. Ghosh is a Clinical Fellow and Dr. Gupta is Program Director at the Division of Geriatrics, Department of Medicine, New York Medical College, Valhalla, NY. Address for correspondence: Subrato Ghosh, MD, 101 Monarch Dr, Amherst, NY 14226. E-mail: subughosh@yahoo.com.
The prevalence of congestive heart failure (CHF) increases with age. It is important to recognize that diastolic dysfunction is more common in the elderly population than in younger adults. The presentation and management of diastolic dysfunction is different from systolic dysfunction. The use of neurohormonal antagonists such as angiotensin-converting enzyme inhibitors and beta-blockers is associated with significant reduction of morbidity and mortality in patients with CHF. This article addresses several important common questions about pathophysiology and management of CHF. (Annals of Long-Term Care: Clinical Care and Aging 2002;10[12]:29-39)
Introduction
An estimated 4.7 million Americans suffer from congestive heart failure, and the prevalence doubles with each decade after the fourth decade.1 Seventy-five percent of these patients are older than 65 years, and one half-million new cases are diagnosed every year. CHF accounts for 700,000 hospital admissions and is the most common discharge diagnosis in patients older than 65 years. About 78% of men and 85% of women hospitalized with CHF are older than 65 years. CHF is the second most common (after hypertension) reason for outpatient consultations, accounting for 12 million office visits per year. Approximately $40 billion is spent annually on the management of CHF in the elderly population.2
Intensive research in the last two decades has helped better the understanding of the pathophysiology of CHF, which has led to improvement in the management of CHF. Several landmark trials using different classes of pharmacologic agents have convincingly shown to improve survival and quality of life in patients with CHF. 3-10 Even though the overall mortality and morbidity from coronary and cerebrovascular disease has decreased, the number of deaths from CHF is gradually rising. This fact stimulates the need to pursue the ongoing research and trials using several experimental agents to improve the mortality and quality of life indicators in patients with CHF.
What is CHF?
Congestive heart failure is a clinical syndrome characterized by inadequate tissue perfusion and/or signs and symptoms of volume overload. Though it is usually caused by a defect in myocardial contraction in younger adults, more than 50% of patients older than 80 years with CHF have normal or near normal systolic function.11 The rate of myocardial contraction and relaxation is prolonged in older adults. Several adaptive mechanisms, including the Frank-Starling mechanism, activation of neurohormonal system (norepinephrine, renin-angiotensin-aldosterone), and myocardial remodeling set in to maintain the pumping function of the myocardium.1 Heart failure in the presence of normal myocardial function is usually due to sudden mechanical loading that exceeds its functional capacity, such as rupture of aortic cusps, acute hypertensive crises, or massive pulmonary embolism. Inadequate tissue perfusion is manifested as fatigue and decreased exercise tolerance. Symptoms and signs of volume overload include shortness of breath, rales, increased jugular venous pressure, peripheral edema, and diastolic gallop (S3).
It is important to recognize and distinguish between underlying and precipitating causes of heart failure. Several precipitating causes (anemia, infection, arrhythmias, thyrotoxicosis, pregnancy, hypertension, myocardial ischemia, myocarditis, infective endocarditis) can lead to clinical manifestations of heart failure in patients with chronically overburdened myocardium. Every newly diagnosed patient with CHF should be screened for precipitating causes, as early detection and treatment of these causal factors can significantly improve prognosis.
What Are the Recent Epidemiologic Trends in Patients Diagnosed With CHF?
The primary and secondary prevention of coronary artery disease (CAD), better treatment of hypertension, and myocardial salvage by aggressive treatment of myocardial infarction are expected to decrease the incidence of CHF. However, data from death certificates have shown an increase in CHF incidence in the U.S. population. Similarly, the number of hospital discharges for CHF in the United States has also increased.1,2 The progressive increase in life expectancy due to better treatment of CAD, hypertension, and hyperlipidemia also increases the chances of development of CHF in the aging population. A study done to evaluate the effect of recent advances in diagnosis and management of CHF failed to show appreciable difference in the incidence and survival of patients with CHF between two subsets of patients over a 10 year period—1981 to 1991.12
What Are the Different Etiologic Factors and Pathophysiologic Types of CHF?
CHF can be due to systolic and/or diastolic dysfunction.13-15 Systolic dysfunction is characterized by decreased left ventricular ejection fraction and accounts for most cases of CHF. The common causes of systolic dysfunction include coronary artery disease, idiopathic dilated cardiomyopathy, valvular heart disease with left ventricular (LV) dilatation and dysfunction, and end-stage hypertensive heart disease. Most of the therapeutic trials have been done in patients with systolic dysfunction. The prevalence of diastolic dysfunction increases with age. One study has shown that diastolic dysfunction is present in 30-50% of patients with CHF.11 Diastolic dysfunction is characterized by increased left ventricular stiffness and abnormal left ventricular relaxation. Table I illustrates major factors causing impaired ventricular relaxation and decreased ventricular compliance. Structural remodeling and other factors, such as myocardial ischemia, left ventricular hypertrophy, increased heart rate, and abnormal calcium flux, can impair diastolic function and cause an increase in left ventricular filling pressure.14 Ischemia impairs left ventricular relaxation by restricting supply of high-energy phosphate required for rapid removal of calcium from the cytoplasm. Hypertrophy interferes with left ventricular relaxation by slowing the rate of myosin-actin dissociation. Hypertrophy and collagen deposition impair left ventricular compliance. Similarly, tachycardia interferes with diastolic function by reducing the duration of the diastolic phase. Other known causes of diastolic dysfunction include coronary artery disease, hypertensive cardiomyopathy, restrictive cardiomyopathies, hypertrophic cardiomyopathy, constrictive pericarditis, diabetes mellitus, obesity, and aortic stenosis.
What Are the Common Clinical Manifestations of CHF in the Elderly Population?
About 20-40% of patients with decreased ejection fraction may remain asymptomatic. Fatigue, impaired exercise tolerance, and dyspnea on exertion are the earliest but nonspecific indicators of congestive heart failure. Paroxysmal nocturnal dyspnea and orthopnea are more specific symptoms of CHF. Peripheral edema, ascites, and pleural effusion are also seen in patients with CHF, but are not very specific. Acute CHF leading to pulmonary edema is usually secondary to ischemic heart disease, arrythmias, and/or papillary muscle dysfunction.
The important physical signs include increased jugular venous pressure, S3, and rales. Table II shows the common symptoms and signs of CHF, and Table III shows the Framingham criteria for the diagnosis of CHF.16 In the elderly, these signs and symptoms may be very subtle, as these patients have lower levels of activity and decreased functional capacity. A high index of suspicion is needed to make a diagnosis and manage appropriately. Clinical estimation of severity of CHF is done using the functional capacity classification of the New York Heart Association (NYHA) that comprises four classes.17
How Is the Diagnosis of CHF Confirmed?
A careful history and a meticulous physical examination are required for clinical diagnosis of CHF. Due to high incidence of diastolic dysfunction, typical chest x-ray findings (such as cardiomegaly) are often absent. Transthoracic, two- dimensional, aní Doppler echocardiography helps in the evaluation of left ventricular function and estimation of size and thickness of ventricular wall. Diastolic dysfunction in the elderly population can be assessed by pulsed Doppler echocardiography.18 It also helps to exclude any valvular abnormality, pericardial disease, or presence of thrombus. Aortic valve disease is very common in the elderly and ranges from calcific sclerosis to severe critical stenosis. Gated pool scintigraphy using technetium-99m (Tc-99m) allows quantitative assessment of both systolic and diastolic functions.
Electrocardiogram commonly shows sinus tachycardia, atrial and ventricular tachyarrythmias, intraventricular conduction defects, and left ventricular hypertrophy. Invasive studies of cardiac catheterization and angiography are helpful in patients with suspected coronary artery disease and valvular disease.
How Is Systolic Dysfunction Distinguished From Diastolic Dysfunction?
Third heart sound, jugular venous distension, cardiomegaly, and decreased ejection fraction favors systolic dysfunction. Fourth heart sound and normal jugular pressure, heart size, and ejection fraction points to diastolic dysfunction.13-15 Echocardiography shows a dilated hypokinetic LV in patients with systolic dysfunction, whereas patients with diastolic dysfunction have hypertrophied LV with a preserved ejection fraction.18 Echocardiography also shows delayed LV diastolic filling in patients with diastolic dysfunction. Abnormal diastolic properties may be detected on the Doppler studies by a prolonged isovolumic relaxation time (time from aortic closure to mitral valve opening) or a prolonged or shortened deceleration time (time from highest velocity of flow across the mitral or tricuspid valve to return to baseline in early diastole). Table IV illustrates the important points in distinguishing systolic and diastolic dysfunctions.
What Are the Cornerstones in the Management of CHF?
General measures include avoidance of alcohol and nicotine, a low-salt diet, adequate rest, exercise within limits of tolerance, and fluid restriction in patients with hyponatremia. Replacement of severely stenosed aortic valve or regurgitant mitral valve may also significantly improve the symptoms of CHF. Several classes of pharmacologic agents have been shown to improve the symptoms and survival of patients with CHF.
Most of the large randomized trials have been done in patients with systolic dysfunction.3 Several trials have proved the efficacy and survival benefit of angiotensin-converting enzyme (ACE) inhibitors in the management of patients with systolic dysfunction (Table V).4,19-24 Unlike other vasodilators, ACE inhibitors exert their vasodilatory effect by interfering with endogenous neurohormonal mechanisms (block enzymatic conversion of endogenous angiotensin I to active angiotensin II). ACE inhibitors also improve LV relaxation and stiffness by reducing afterload in patients with diastolic dysfunction. Angiotensin II receptor blockers (ARB) were thought to provide all the benefits of ACE inhibitors without all the side effects from kinin accumulation. However, «ecent studies (ELITE-II, RESOLVD, Val-HeFT) using ARB alone or in combination with ACE inhibitors did not result in better outcomes when compared to ACE inhibitors alone.3-6�Presently, angiotensin II receptor blockers are recommended only in patients who are intolerant (cough, rash, angioedema) to ACE inhibitors.
Several studies have shown that beta blocker therapy in patients with systolic dysfunction is associated with improvement of exercise tolerance and prolonged survival.2,7,8 Table VI shows the results of the landmark trials using beta-blockers (carvedilol, metoprolol, and bisoprolol).9,25-27 The beneficial effect of beta-blockers in heart failure is due to their ability to block the beta-receptors and neutralize the deleterious effect of circulating catecholamines on already depressed myocardium.1 Most studies8,9 have shown an increase in ejection fraction and decrease in pulmonary capillary wedge pressure with beta-blocker therapy. One study showed that addition of carvedilol to standard therapy was associated with 65% reduction in mortality and 27% reduction in hospital admission rates compared to placebo.9 The use of beta-blockers is associated with lower heart rates and increased diastolic phase. The improved diastolic filling phase, better control of blood pressure (BP), and regression of left ventricular hypertrophy accounts for the role of beta-blockers in patients with diastolic dysfunction.7 However, the use of beta-blockers in elderly patients is associated with increased incidence of both serious (hypotension and bradycardia due to coexistent conduction system disease) and common (fatigue, sexual dysfunction, and depression) side effects and needs careful supervision during therapy.
Calcium channel blockers (verapamil, diltiazem) are reported to improve diastolic function by attenuating calcium homeostasis, lowering BP, and slowing heart rate and regression of left ventricular hypertrophy in patients with diastolic dysfunction. Second-generation vascular selective calcium channel blockers, such as felodipine and amlodipine, did not worsen the symptoms or mortality.28,29 Newer calcium channel blockers active against T-channels like mibefradil showed lack of efficacy in patients with heart failure.30 The role of calcium channel blockers in patients with systolic dysfunction is less clear and presently not indicated. However, these drugs are a useful adjunct for treatment of associated angina and/or hypertension.
Diuretics play an important role in the management of acute exacerbations of CHF. Judicious use of diuretics is recommended, since overuse can lead to prerenal azotemia, as they are dependent on preload to maintain a satisfactory cardiac output. Diuretics can cause hyponatremia, hypokalemia, hypomagnesemia, prerenal azotemia, activation of renin-angiotensin system, and thirst leading to increasing fluid intake and development of refractory edema. Spironolactone (aldosterone antagonist) in conjunction with ACE inhibitors, digoxin, and/or loop diuretics have been shown to decrease the morbidity and risk of death from progressive heart failure and sudden cardiac death.10
Maintenance of sinus rhythm is important, as atrial systole contributes significantly to diastolic filling in patients with diastolic dysfunction. Routine use of antiarrhythmics for treatment of asymptomatic ventricular arrythmias is not recommended because of low efficacy, pro-arrhythmogenic potential, negative inotropic effect, and increased cardiotoxicity due to altered drug pharmacokinetics. The DIAMOND study, carried out in patients with heart failure and recent myocardial infarction with left ventricular systolic dysfunction using dolfetilide (class III antiarrythmic), was associated with neutral effect on mortality and a 25% reduction in the frequency of heart failure hospitalizations.31 One recent study supported the use of automatic cardioverter defibrillator (AICD) in patients with nonischemic dilated cardiomyopathy presenting with recurrent syncope.32 Routine electrophysiologic testing has limited utility.
Digoxin inhibits the activation of the sympathetic nervous system, rennin release, and increases cardiac contractility. The Digitalis Investigation Group trial concluded that digoxin was well-tolerated, improved quality of life, and did not increase mortality.33 Two similar trials demonstrated that withdrawal of digoxin from standard treatment regimens of patients with heart failure increased congestive symptoms and frequency of hospitalizations.34,35 Intermittent, low-dose dobutamine reduced the frequency of hospitalizations but did not affect the functional class or mortality.36 The studies using phosphodiesterase inhibitors failed to show any survival benefit.37
Anticoagulants are indicated in patients with high risk of systemic or pulmonary embolism like patients with history of thromboembolism, established or paroxysmal atrial fibrillation, severe left ventricular dysfunction, and echocardiographic evidence of thrombus.38
CHF remains the common indication for cardiac transplantation, which is the only known definitive therapy. Postoperative survival figures of 82% at one year and 74% at five years have been reported in properly selected patients.39
What Is the Prognosis of CHF in the Elderly Population?
There is a high rate of readmission among older CHF patients. One study showed that 34% of CHF patients were discharged from the hospital without a prescription of ACE inhibitor with no contraindication to such use.40 The other common causes of readmission include noncompliance with medical therapy, excessive salt intake, fluid overload in patients with renal failure, and infection.41 One randomized, prospective trial of multidisciplinary team use in order to increase patient counseling and compliance with diet and medications was shown to reduce the 90-day readmission rate of elderly patients with CHF from 42.1% to 28.9%.42 The intervention arm included intensive follow-up after discharge, frequent home visits, and telephonic contact.
The mortality from advanced-stage CHF is 30% or more at one year in the elderly population. The mortality rate increases exponentially after age 65 years. Age more than 55 years, advanced stage heart failure (NYHA class III/IV),17 cardiac enlargement, decreased ejection fraction, and histological evidence of myofilaments loss are poor prognostic factors. The mortality from CHF due to systolic dysfunction is three to four times that from diastolic dysfunction. The Framingham study reported that survival remained unchanged during 40 years of follow-up after onset of CHF.16
Which Pharmacotherapeutic Agents and Experimental Surgical Modalities Are Being Studied for CHF Therapy?
Several trials of different classes of agents have been done in the past, and several are still continuing in an effort to find the ideal pharmacotherapeutic agent. Most were conducted with young and middle-aged adult populations.
Neutral Endopeptidase Inhibitors
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in patients with CHF, which is related to increased plasma rennin activity and epinephrine.43 Resistance to natriuretic action of ANP in CHF has been proposed to be due to upregulation of Renin-Angiotensin-Aldosterone System (RAAS), downregulation of natriuretic peptide receptors, or an increase in renal endopeptidase activity. Inhibition of ANP metabolism using ecadotril (a neutral endopeptidase inhibitor) has shown to improve the hemodynamics in small series of patients. The recently concluded VA sodilation in the management of acute CHF (VAMC) trial, using nesiritide (analogue of BNP) in patients with acute decompensated CHF, showed more rapid reduction of dyspnea and pulmonary capillary wedge pressure (PCWP) when compared to nitroglycerine and placebo.44
Endothelin Receptor Antagonist
Elevated levels of endothelin (potent vasoconstrictor) have been observed in patients with CHF and are inversely related to left ventricular ejection fraction and cardiac index. The endothelin receptor antagonist of interest includes darusentan, sitaxsentan, tezosentan, and bosentan. A prospective, randomized, double-blind, placebo-controlled, multicenter study using intravenous tezosentan in patients with acute decompensated heart failure showed significant improvement of cardiac index and PCWP.45 A recent study with darusentan showed similar results.46 Research on Endothelin Antagonism in Chronic Heart failure (REACH-1) using oral bosentan was prematurely stopped due to high incidence of liver toxicity.47
Calcium Sensitizers
Calcium sensitizers alter interactions between troponin and contractile protein and increase the contractility at a given calcium concentration.48 They also have vasodilator properties (Inodilator). Pimobendan improved exercise capacity, peak oxygen consumption, and quality of life.49 VEsnarinone Survival Trial (VEST) was prematurely stopped due to excess mortality.50 One recent trial using levosimendan showed improvement in symptoms and hemodynamics in patients with decompensated heart failure.51
Miscellaneous Agents
Growth Hormone. Small trials using growth hormone in patients with CHF showed improvement in quality of life, exercise capacity, left ventricular dimensions, and ejection fraction.52 Proposed mechanism of action includes activation of cardiac cell growth and physiologic ventricular remodeling, which results in enhanced contractility.
Thyroid Hormone. One trial showed improved hemodynamics and exercise capacity (possibly due to upregulation of beta-1 receptors) in patients with heart failure.53
Coenzyme Q10. A long-term, multicenter, randomized study in patients with CHF using coenzyme Q10 showed improvement of NYHA functional class possibly by improving myocardial energetics.54
Thiamine. Several small studies using thiamine reported improvement in functional class and left ventricular ejection fraction in patients with CHF.55
Intravenous Immune Globulin. Immune modulation of viral or autoimmune pathogenic mechanism in patients with myocarditis and cardiomyopathy using immunoglobulin is associated with favorable effect on NYHA class and left ventricular hemodynamics.56
Cardiac Synchronization Therapy
Cardiac synchronization therapy (CRT) has been shown to be useful in patients with CHF and ventricular dysynchrony (intraventricular conduction delay). A trial conducted in heart failure patients showed improvement of exercise capacity (distance of six-minute walk), quality of life score, left ventricular ejection fraction, and NYHA class.57 Another trial studying CRT using biventricular pacing showed similarly encouraging results whether or not the patient was in atrial fibrillation.58 Presently, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend that pacing should be done in patients with CHF with an ACC/AHA class I indication only if they have another class I indication (such as symptomatic sinus node dysfunction or atrioventricular block) for pacing.59
Experimental Surgical Therapy
Experimental surgical therapy includes dynamic cardiomyoplasty60 using autologous paced Latissimus dorsi wrapped around ventricles, battery-powered ventricular assist devices,61 surgical ventricular remodeling (partial ventriculectomy), and xenografting.62
Conclusion
In summary, diastolic heart failure is common in the elderly population and characterized by normal or near normal ejection fraction. Diuretics and beta-blockers are first-line therapy for diastolic heart failure, followed by ACE inhibitors and calcium channel blockers. Digoxin should be avoided in patients with diastolic heart failure and sinus rhythm. For patients with systolic heart failure, diuretics, ACE inhibitors, and beta-blockers are first-line therapy. Spironolactone should be considered in severe systolic heart failure, and digoxin can be added if CHF persists after initiating first-line treatment. Calcium channel blockers should be avoided in systolic heart failure. Despite overwhelming evidence of benefits of ACE inhibitors and beta-blockers, they are underutilized in the therapy of CHF. Beta-blockers should be started at very low doses and increased gradually, since higher doses can worsen symptoms at the initiation of therapy. Diuretics should be judiciously used to reduce congestive symptoms, since higher doses frequently lead to hypovolumia, prerenal azotemia, and electrolyte disturbance and fall. Regular clinical assessments of patients and their medications can significantly help avoid undesirable side effects and increase compliance with medical therapy. The rising incidence and associated economic burden of CHF continue to stimulate research with newer agents.
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