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■ REVIEW ARTICLE CONGESTIVE HEART FAILURE IN THE ELDERLY Chiung-Zuan Chiu1,2, Jun-Jack Cheng1,2,3* 1 School of Medicine, Fu Jen Catholic University, 2Division of Cardiology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, and 3School of Medicine, Taipei Medical University, Taipei, Taiwan. SUMMARY Over the past 30 years, the prevalence and incidence of heart failure (HF) have increased markedly with age, with increases of approximately fivefold from the age of 40 to 70 years. HF is predominantly a disorder of the elderly, and over 70% of HF patients are over 65 years old. The most important factor in the increasing prevalence and incidence of HF is the growing proportion of elderly with new-onset diastolic HF resulting from chronic hypertension and coronary heart disease. Other predictors of HF include diabetes, prior stroke, atrial fibrillation, renal dysfunction, reduced ankle-brachial index, increased C-reactive protein, left ventricular hypertrophy, reduced forced expiratory volume, and obesity. At least half of all elderly HF patients have preserved left ventricular systolic function, and they are classified as diastolic HF. There was a strong female predominance (67%) in diastolic HF when compared with male HF patients. The morbidity and mortality of older HF patients are the highest of any chronic cardiovascular disorder. Mortality increases markedly with age. Mortality from diastolic HF is about half of that reported for systolic HF. There are some comorbidities in older HF patients, including renal dysfunction, chronic lung disease, cognitive dysfunction, depression, postural hypotension, urine incontinence, sensory deprivation, nutritional disorders, polypharmacy and frailty, which may precipitate and exacerbate the underlying HF symptoms. Clinical diagnosis of HF may be more difficult in the elderly because of frequently inadequate history taking, less evident HF symptoms for reduced daily activity, and similar symptoms to other frequent disorders. The treatment goals in older HF patients resemble those for any chronic disorder and include relief of symptoms, improvement in functional status, exercise tolerance, quality of life, prevention of acute exacerbation, and finally, prolongation of long-term survival. [International Journal of Gerontology 2007; 1(4): 143–152] Key Words: chronic hypertension, coronary artery disease, diastolic heart failure, elderly, heart failure Epidemiology and Predictors Over the past 30 years, mortality rates for cardiovascular disease have declined dramatically. However, the prevalence and incidence of heart failure (HF) have increased markedly with age over this period1. In the Framingham Heart Study, the incidence of HF increased approximately fivefold from the age of 40 to 70 years2. HF is predominantly a disease of the elderly; over 70% of HF patients are aged 65 years or older. The most *Correspondence to: Dr Jun-Jack Cheng, Division of Cardiology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, 95, Wen-Chan Road, Shih-Lin, Taipei, Taiwan. E-mail: [email protected] Accepted: July 15, 2007 International Journal of Gerontology | December 2007 | Vol 1 | No 4 © 2007 Elsevier. important factor in the increasing prevalence and incidence of HF is the growing proportion of elderly (> 50%) with new-onset diastolic HF resulting from chronic hypertension and coronary heart disease. Recent studies in older population have found that pulse pressure, an index of arterial stiffness, is the strongest blood pressure predictor of HF3,4. Coronary heart disease, especially prior myocardial infarction, and degenerative aortic stenosis are also potent predictors of HF in the elderly. Male sex, obesity, and diabetes mellitus were independent predictors of HF in the Cardiovascular Health Study5. Additional predictors of HF in this study were prior stroke, atrial fibrillation, renal dysfunction, reduced ankle-brachial index, increased Creactive protein, left ventricular (LV) hypertrophy, and reduced forced expiratory volume5. 143 ■ C.Z. Chiu, J.J. Cheng Clinical Outcomes The morbidity and mortality of older HF patients are perhaps the highest of any chronic cardiovascular disorder. Mortality of HF increases markedly with age. In community-based individuals of 65 to 74 years of age, the 10-year mortality was 50% in women and > 70% in men6. Among elderly persons hospitalized for HF, the prognosis is even worse, with a 5-year mortality of > 70%. The mortality from diastolic HF is about half of that reported for systolic HF; in the Framingham Study, the respective annual mortality rates were 8.9% and 19.6%7. However, survival appears similar in elderly patients hospitalized with diastolic versus systolic HF8–10. The morbidity from HF is also very high in the elderly. Between 30% and 50% of older patients hospitalized for HF will be rehospitalized within 3 to 6 months11–13. In contrast to mortality, the readmission rates for HF patients with preserved systolic function appear to be the same as those for patients with impaired systolic function. Pathophysiology—Higher Prevalence of Diastolic HF in the Elderly The pathophysiology of HF in the elderly differs from that in younger patients because of multiple age-associated changes in cardiovascular and non-cardiovascular function and structure and multiple morbid disorders accompanied by aging. The most evident difference is the higher prevalence of HF with preserved systolic LV function (diastolic HF) in the older patients. Aging is associated with a concentric hypertrophy of the LV myocardium and reduced early diastolic relaxation and filling rates14,15. Both of these may result in age-associated increase in arterial stiffness16. These findings are similar to those seen in younger hypertensive patients and provide a condition more prone to development of diastolic HF. A recent community study indicated that advancing age and female gender are associated with increases in vascular and ventricular systolic and diastolic stiffness, even in the absence of cardiovascular disease17. This combined ventricular–vascular stiffening may contribute to the increased prevalence of diastolic HF in elderly persons, particularly in elderly women. In addition, reduced chronotropic, inotropic and vasodilator responses to beta-adrenergic stimulation occur with aging18–20. Several non-cardiovascular aging changes, including reduced ventilatory capacity, reduced glomerular 144 ■ filtration rate (GFR) and impaired central nervous system autoregulation, also contribute to the susceptibility to HF in the elderly. Many morbidities of elderly HF patients, including systolic hypertension, LV hypertrophy, renal dysfunction and chronic lung disease, are exaggerations of these age-associated physiologic changes. A reduced heart rate and increased systemic vascular resistance at rest and a reduced heart rate response to exercise in older patients could be seen in a previous study21. Plasma norepinephrine also increased with age without consistent age trends seen for plasma renin activity or urine aldosterone. A reduction of GFR and increases in renal vascular resistance and serum creatinine levels were seen at older ages. Echocardiography studies in the elderly showed smaller ventricles, higher fractional shortening, higher Doppler A wave velocity, lower ratio of early transmitral flow velocity to atrial flow velocity, and longer deceleration time than in the younger group22, which reflected a better systolic function and an impaired diastolic function in the elderly. Wong et al. indicated that about 30% of the older group had atrial fibrillation, which may further impair LV function in the elderly23. Exercise intolerance, manifested as fatigue and exertional dyspnea, is the primary symptom in chronic HF with either a reduced or a preserved ejection fraction. Previous studies have demonstrated that diastolic HF patients have severely reduced exercise capacity as measured by peak VO2 during exercise, and their exercise intolerance is as severe as that of age-matched systolic HF patients24–26. Invasive cardiopulmonary exercise testing showed that diastolic HF patients have a reduced ability to increase stroke volume via the Frank-Starling law despite severely increased LV filling pressure, indicative of diastolic dysfunction24. This resulted in severely reduced exercise cardiac output and early lactate formation and was a significant independent contributor to the severely reduced exercise capacity and associated chronic exertional symptoms24. These findings indicate that diastolic HF also plays a very important role in the pathogenesis of HF in the elderly. One study indicated that decreased aortic distensibility, due to the combined effects of aging and hypertension-induced thickening and remolding of the thoracic aortic wall, is an important contributor to exercise intolerance in chronic diastolic HF. Patients with diastolic HF had increased pulse pressure and thoracic aortic wall thickening and markedly decreased aortic distensibility, which correlated with their severely International Journal of Gerontology | December 2007 | Vol 1 | No 4 ■ ■ Congestive Heart Failure in the Elderly decreased peak exercise VO225. It is very likely that systolic hypertension plays an important role in the genesis of diastolic HF in the elderly. In animal models, diastolic dysfunction develops early in systemic hypertension, and LV diastolic relaxation is very sensitive to increased afterload. Increased afterload impairs LV relaxation, leading to increased LV filling pressures, decreased stroke volume, and symptoms of congestion and dyspnea27,28. Most diastolic HF patients (88%) have a history of chronic systemic hypertension29. Although the role of ischemia in diastolic HF is uncertain, it is likely to be a significant contributor in some patients. It has been hypothesized that patients with a normal ejection fraction following an episode of chronic HF may have transiently reduced systolic function and/or ischemia at the time of acute exacerbation. However, the more likely hypothesis indicated that acute pulmonary edema and/or chronic HF due to acute exacerbation of diastolic dysfunction caused by severe systolic hypertension or marked elevation of blood pressure rather than by ischemia may play the real role of diastolic HF in the elderly with normal systolic function30. Neurohormonal activation is thought to play an important role in the pathogenesis of systolic HF. In a group of patients with diastolic HF, a study showed that atrial natriuretic peptide and brain natriuretic peptide were increased, and there was an exaggerated response during exercise31. Another study showed that older patients with diastolic HF have markedly increased norepinephrine levels, equivalent to those seen in systolic HF, and had levels of atrial natriuretic peptide and brain natriuretic peptide that were increased tenfold compared with age-matched normal people. Predisposing Factors for HF in the Elderly Rare studies have reported the predisposing factors of HF in the elderly. In a series of 154 HF patients aged 75 ± 8 years admitted to the hospital, 71% had coronary artery disease, 45% had hypertension, and 32% had valvular heart disease32. Factors precipitating HF included atrial fibrillation (16%), poor drug compliance (10%), renal failure (8%), fever (7%), and anemia (6%). Multiple studies also showed the important role of atrial fibrillation in the development of HF in the elderly patients. In the EPESE community-based cohort, myocardial infarction was the precipitant of HF in 49 of 173 cases (28%)4. Acute elevation of blood pressure International Journal of Gerontology | December 2007 | Vol 1 | No 4 appears to be responsible for a significant portion of patients presenting with acute pulmonary edema30. The episode of acute pulmonary edema may be primarily due to elevation of blood pressure or secondary to an elevation of sympathetic tone. Challenges in Diagnosing Elderly HF Patients The diagnosis of HF in the elderly is challenging for several reasons. First, many symptoms and signs of HF in the elderly are similar to other chronic systemic disorders. Second, many elderly patients reduce their daily activity because of various causes, which may mask the two cardinal symptoms of fatigue and exertional dyspnea. Third, many elderly patients cannot provide an adequate history taking because of dementia, or cognitive or sensory impairments. Fourth, elderly patients with HF often present with nonspecific symptoms such as weakness, fatigue, confusion, and disorientation. Finally, the frequent occurrence of a normal LV ejection fraction in older HF patients (diastolic HF) may lead the clinicians to exclude the diagnosis of HF. The many different diagnosis criteria for HF may cause diversity in the diagnosis of HF in the elderly. McKee et al. proposed simplified criteria for the diagnosis of HF in the elderly33. There is a history of acute pulmonary edema or the occurrence of at least two of the following with no other identifiable cause and with improvement following diuretic therapy: exertional dyspnea, paroxysmal nocturnal dyspnea, orthopnea, bilateral lower extremity edema or exertional fatigue. Echocardiography is the preferred imaging study for initial diagnosis of HF, because it can detect some important disorders, such as valvular heart disease, hypertrophic cardiomyopathy, cardiac amyloidosis or pericardial effusion. An echocardiography that reveals an LV ejection fraction of < 45% to 50% represents reduced systolic function and evidence of systolic HF. Diastolic HF is always manifested as typical clinical symptoms/signs of HF, hypertension and/or concentric LV hypertrophy, and diastolic dysfunction as noted by echocardiography. General Considerations in Treatment of HF The treatment goals of older HF patients include relief of symptoms, improvement in functional status and quality of life, prevention of acute exacerbation and 145 ■ C.Z. Chiu, J.J. Cheng hospitalization, and finally, prolongation of long-term survival. A systematic management plan should pay much attention to diet, exercise and physical activity, and other life style factors, avoidance of aggravating conditions, and careful titration of medications and frequent follow-up. Adequate education of patient and family can also gain some benefits. The management team might involve the attending physician, nurse, dietitian, pharmacist, social worker, and physical therapist. Other strategies, such as cessation of smoking and drinking, administration of influenza and pneumococcal vaccines, minimal use of sodium-retaining medications or foods and use of cardiac rehabilitation, should be advocated. Common HF precipitants, such as atrial fibrillation, renal failure, anemia and pulmonary infections, should be treated aggressively. During the past decade, the value of multidisciplinary HF management programs has been repeatedly demonstrated by reductions in HF exacerbations, rehospitalizations and costs, and improvement in the quality of life11,34–36. Diet Excessive intake of sodium is a common cause of acute exacerbation of HF. Moderate sodium restriction (2 g/ day) is adequate to prevent weight gain in most stable patients. More severe sodium restriction may allow for a reduction in diuretic dose. Water restriction is necessary when significant hyponatremia is present. The ageassociated reduction in GFR in HF patients adds to the difficulty in maintaining sodium balance in the elderly. Physical activity Exercise intolerance in elderly HF patients may improve after exercise and aerobic training programs. Although limited number of patients were enrolled, several prospective trials demonstrated increases in peak VO2, cardiac output, and other physiologic parameters in older patients with systolic HF37,38. A representative large, multicenter, randomized trial (HF-ACTION) involving 2 years of aerobic exercise training in 3,000 systolic HF patients with LV ejection fraction of 35% will provide the outcome of aerobic exercise training in improving functional class in elderly patients with HF. ■ enzyme (ACE) inhibitors, beta-blockers, digitalis, angiotensin-receptor blockers (ARBs), and vasodilators in patients with systolic HF. More recent trials also reported the effect of these drugs in older patients with systolic HF. Diuretics Diuretics provide rapid symptomatic relief and control of pulmonary edema and peripheral edema in most HF patients. Diuretics, especially in the elderly, should be titrated to the lowest effective dose for preventing renal function deterioration, electrolyte imbalance, and hyperactivity of the renin–angiotensin system. Thiazide may be effective in patients with mild HF, but most patients with HF need loop diuretics to achieve the target effect. Patients with severe fluid retention and/or renal dysfunction may require the addition of metolazone. In patients with nocturnal congestive symptoms, a twice-daily regimen may be necessary. Fluid restriction may be needed if hyponatremia occurs. Careful monitoring of fluid status, renal function, electrolytes, and body weight should be undertaken, especially in the elderly, during the administration of intravenous diuretic agents. In past studies, only spironolactone has been shown to reduce HF mortality (27%) in patients with New York Heart Association (NYHA) Class III–IV HF39. ACE inhibitors Numerous studies have established the effect of ACE inhibitors as important in the drug therapy for systolic HF. In the first CONSENSUS trial, enalapril (10 to 20 mg twice daily) reduced the 6-month mortality from 48% to 29% in older patients with NYHA Class IV systolic HF despite the use of digoxin and diuretics40. Subsequent studies also showed that ACE inhibitors had effects on reducing mortality and improving quality of life in the elderly and that they should be used in older patients if there is no contraindication. Patients with HF benefited from ACE inhibitors by the suppression of the renin–angiotensin system and inhibition of progressive LV dilatation and remodeling41,42. The effect is especially evident in myocardial infarction patients with severe systolic dysfunction (LV ejection fraction, < 35%)41. ARBs Pharmacologic Treatment of Systolic HF Over the past 20 years, a large number of clinical trials reported on the efficacy of angiotensin-converting 146 In recent trials, ARBs have not been definitely proven to be as effective as ACE inhibitors in reducing morbidity and mortality in HF of any age. Although the ELITE-I study suggested a survival advantage of ARB losartan International Journal of Gerontology | December 2007 | Vol 1 | No 4 ■ Congestive Heart Failure in the Elderly over the ACE inhibitor captopril in patients ≥ 65 years of age43, the larger ELITE-II study failed to confirm this finding44. So, ACE inhibitors remain the preferred initial treatment in the elderly with systolic HF. An advantage of ARBs over ACE inhibitors is the lower incidence of cough, so ARBs could be used in patients with intolerance to ACE inhibitors. However, the ELITE-I study demonstrated that the incidence of renal dysfunction and other side effects with ARBs was not lower than with ACE inhibitors. The addition of ARBs in patients who remain symptomatic despite maximal doses of ACE inhibitors may improve symptoms and exercise tolerance45. In the RESOLVD trial, the combination of ARBs and ACE inhibitors was associated with more LV remodeling than either agent alone46. However, in the Valsartan in Heart Failure Trial (Val-HeFT) trial, the combination of ARBs and ACE inhibitors did not reduce the all-cause mortality but showed a 28% reduction in hospitalization and improved quality of life47. In the Val-HeFT trial, the small subgroup with an older mean age of 67 years that was not given ACE inhibitors at baseline showed a 45% reduction in all-cause mortality, confirming ARBs as an alternative treatment in patients who are intolerant to ACE inhibitors. In the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) study, candesartan significantly reduced all-cause mortality, cardiovascular death, and HF hospitalizations in patients with chronic HF and LV ejection fraction of ≤ 40% when added to standard therapies, including ACE inhibitors, beta-blockers, and an aldosterone antagonist. A recent study also showed that plasma brain natriuretic peptide concentration, 123I-meta-iodobenzylguanidine images, and echocardiographic parameter improved significantly in systolic HF patients treated with valsartan and implied that valsartan can improve cardiac sympathetic nerve activity and LV performance in patients with systolic HF48. Digoxin In the multicenter Digitalis Investigation Group study in which nearly 8,000 HF patients with sinus rhythm and LV ejection fraction of ≤ 45% and given ACE inhibitors and diuretics were randomized to receive digoxin or placebo, digoxin had no effect on mortality but reduced HF symptoms and hospitalizations49. Digoxin was also as effective in patients who were ≥ 80 years old in this study50. So, digoxin is recommended in patients who remain symptomatic despite the use International Journal of Gerontology | December 2007 | Vol 1 | No 4 ■ of ACE inhibitors and diuretics. Digoxin is especially effective in HF patients with atrial fibrillation, because it can help in controlling ventricular rate. Beta adrenergic blockers Several large randomized trials have shown that betaadrenergic blockers reduce all-cause mortality and hospitalization and improve symptoms in the elderly with systolic HF51,52. However, relative contraindications to beta-blockade, such as bradycardia, conduction disturbance, chronic obstructive lung disease or peripheral arterial disease, may limit the use of beta-blockade in the elderly. So, beta-blocker should be started at very low doses (carvedilol 3.125 mg twice daily) in elderly clinically stable HF patients receiving appropriate doses of ACE inhibitors and diuretics. Synthetic catecholamines Synthetic catecholamines, such as dobutamine and dopamine, have been used successfully in elderly patients with refractory systolic HF53, though randomized controlled trials are lacking. In a small study by Rich et al., dobutamine infusion gave rise to lesser increases in cardiac output in patients who were > 80 years old than in younger patients54, compatible with the age-associated decreased sensitivity to catecholamines that occurs in normal population. Low dose dopamine, as a renal vasodilator, also improved GFR and urine output in the elderly HF patients when added to intravenous diuretics55. Biventricular pacing and automatic intracardiac defibrillator Recent trials have shown that atrial-synchronized biventricular pacing can improve LV function and enhance functional status and quality of life in HF patients with QRS prolongation of > 120 ms. The MIRACLE study also demonstrated a 40% reduction in death or hospitalization of severe HF patients after biventricular pacing in a randomized double-blind trial56. Although no age-specific analysis was performed, the mean age of 64 years and the absence of an upper age limit make these findings relevant to the elderly. The MADIT-II study showed that prophylactic implantation of defibrillator in patients with a prior myocardial infarction and ejection fraction of ≤ 30% reduced all-cause mortality from 20% to 14% over a mean follow-up of 20 months57. The benefit in older patients (≥ 70 years) was similar to that in younger individuals. 147 ■ C.Z. Chiu, J.J. Cheng In addition to the above treatments, aortic valve replacement in elderly HF patients with degenerative aortic stenosis may also relieve the symptoms of HF with low surgical mortality (< 10%) in octogenarians58,59. Coronary artery revascularization in older HF patients could improve myocardial ischemia and HF symptoms60. In myocardial infarction with systolic HF and LV aneurysm, LV aneurysmectomy and partial left ventriculectomy may relieve HF symptoms by reducing LV size and improving LV function. Treatment of Diastolic HF In contrast to systolic HF, treatment of diastolic HF has been according to evidence-based medicine for the past 30 years. There were rare, large, randomized, multicenter trials on diastolic HF treatment in the past61,62. Advances in therapy of diastolic HF have been hindered by lack of standard definition, absence of a reliable test to quantify diastolic function, and insufficient understanding of the real pathophysiology of diastolic HF61. As we know, there is no single pattern of diastolic HF treatment in the elderly. General principle The general approaches for patients with systolic HF are the same as those with diastolic HF62. Diuretics could also be used as an initial treatment of pulmonary congestion and peripheral edema. Primary etiology, such as hypertension, of diastolic HF should be investigated and treated. Most patients may have hypertension62 which should be controlled aggressively. Chronic hypertension causes LV hypertrophy and fibrosis which impair diastolic function and ventricular compliance. Acute elevation of blood pressure or poor blood pressure control further impairs LV diastolic function and may induce HF symptoms and acute lung edema. A recent trial indicated that progressively abnormal diastolic function is associated with reduced arterial compliance in hypertensive patients with exertional dyspnea63. So, arterial compliance is an independent predictor of diastolic dysfunction in patients with hypertensive heart disease and should be considered a potential target for intervention in diastolic HF. The STOP-2 trial favored the use of ACE inhibitors to control blood pressure and prevent HF simultaneously in the elderly (70–84 years)64. The ALLHAT study showed that diuretics were superior to alpha-blockade and 148 ■ were at least equivalent to ACE inhibitors and calcium antagonists for prevention of HF in older hypertensive patients65,66. A noninvasive survey for coronary artery disease should be done in patients with chest pain and/or abrupt onset of pulmonary edema, because ischemia is a therapeutic goal for diastolic HF. Some patients with hypertrophic cardiomyopathy, valvular heart disease, amyloidosis or pericardial illness could be diagnosed by echocardiographic examination67–69. Sinus rhythm and/or rate control should be achieved and maintained in patients with atrial fibrillation in order to restore atrial contraction and improve LV ejection fraction62. Pharmacologic therapy for diastolic HF Digoxin In the DIG trial, there was a subgroup of older HF patients with preserved systolic function. The result also showed that relief of symptoms and reduction of rehospitalization could be achieved, but there was no influence on all-cause mortality49. So, digoxin may be an alternative choice in the elderly with diastolic HF. ACE inhibitors Several studies suggest that both ARBs and ACE inhibitors are effective therapy for diastolic HF. First, they are a good choice for systolic HF with reduction in mortality and rehospitalization. In addition, they improve exercise tolerance and clinical symptoms. Second, they block the neurohormonal activation of renin–angiotensin system in diastolic HF31. Finally, they control hypertension, prevent LV hypertrophy or remodeling, and improve LV relaxation and aortic distensibility67–71. In a study of elderly patients (mean age, 80 years) with NYHA Class III HF and diastolic HF (ejection fraction, > 50%), Aronow et al. showed that enalapril can improve functional class, exercise duration, ejection fraction, diastolic filling, and LV mass72. One study (total 1,402 patients) also indicated that ACE inhibitors used in diastolic HF can reduce all-cause mortality and HF death73. However, another study of elderly HF patients with preserved LV function suggested that ACE inhibitors may increase mortality in these patients61,74. The powerful, randomized, controlled PEP-CHF trial reported the morbidity and mortality in elderly HF patients (> 70 years) with LV ejection of ≥ 40%. By 1 year, reductions in the primary outcome (hazard ratio [HR], 0.692; 95% confidence interval [CI], 0.474–1.010; p = 0.055) and hospitalizations for HF International Journal of Gerontology | December 2007 | Vol 1 | No 4 ■ Congestive Heart Failure in the Elderly (HR, 0.628; 95% CI, 0.408–0.966; p = 0.033) were observed, and functional class (p < 0.030) and 6-minute corridor walk distance (p = 0.011) had improved in those assigned to perindopril75,76. References ARBs In a small double-blind, randomized, controlled trial of 20 elderly patients with diastolic dysfunction, the ARB losartan improved exercise capacity and quality of life and reduced exercise systolic and pulse pressure77. The CHARM-Preserved trial assessed the effect of candesartan in HF patients with ejection fraction of ≥ 40% and indicated that candesartan can reduce hospital admission for HF in patients with preserved systolic function78,79. Results of recent key studies, such as Losartan Intervention For Endpoint Reduction in Hypertension (LIFE), Val-HeFT, CHARM and Valsartan in Acute Myocardial Infarction (VALIANT), add to the evidence that angiotensin II receptor blockers are good choice for the treatment of hypertension in older patients80,81. These trials also indicated that they are appropriate therapy for HF patients and for patients who have experienced acute myocardial infarction, particularly those who are unable to tolerate an ACE inhibitor. The I-PRESERVE trial is currently assessing the effect of the ARB irbesartan in patients with diastolic HF, and results will be reported in the near future82,83. 2. Calcium channel antagonists A small (22 elderly patients) randomized, double-blind, placebo-controlled trial of verapamil in HF patients with ejection fraction of > 45% indicated that there was a 33% improvement in exercise duration and significant improvement in HF score and peak filling rate78,79. 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