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REVIEW ARTICLE CONGESTIVE HEART FAILURE IN THE ELDERLY Chiung-Zuan Chiu 1,2, Jun-Jack Cheng 1,2,3 * 1 School of Medicine, Fu Jen Catholic University, 2 Division of Cardiology, Department of Internal Medicine,
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REVIEW ARTICLE CONGESTIVE HEART FAILURE IN THE ELDERLY Chiung-Zuan Chiu 1,2, Jun-Jack Cheng 1,2,3 * 1 School of Medicine, Fu Jen Catholic University, 2 Division of Cardiology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, and 3 School 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): ] 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 period 1. In the Framingham Heart Study, the incidence of HF increased approximately fivefold from the age of 40 to 70 years 2. 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. Accepted: July 15, 2007 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 HF 3,4. 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 Study 5. Additional predictors of HF in this study were prior stroke, atrial fibrillation, renal dysfunction, reduced ankle-brachial index, increased C- reactive protein, left ventricular (LV) hypertrophy, and reduced forced expiratory volume 5. International Journal of Gerontology December 2007 Vol 1 No Elsevier. 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 men 6. 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 HF 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 months 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 rates 14,15. Both of these may result in age-associated increase in arterial stiffness 16. 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 disease 17. 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 aging Several non-cardiovascular aging changes, including reduced ventilatory capacity, reduced glomerular 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 study 21. 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 group 22, 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 elderly 23. 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 VO 2 during exercise, and their exercise intolerance is as severe as that of age-matched systolic HF patients 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 dysfunction 24. 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 symptoms 24. 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 144 International Journal of Gerontology December 2007 Vol 1 No 4 Congestive Heart Failure in the Elderly decreased peak exercise VO 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 dyspnea 27,28. Most diastolic HF patients (88%) have a history of chronic systemic hypertension 29. 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 function 30. 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 exercise 31. 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 disease 32. 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 appears to be responsible for a significant portion of patients presenting with acute pulmonary edema 30. 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 elderly 33. 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 International Journal of Gerontology December 2007 Vol 1 No 4 145 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 life 11, 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 VO 2, cardiac output, and other physiologic parameters in older patients with systolic HF 37,38. 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. Pharmacologic Treatment of Systolic HF Over the past 20 years, a large number of clinical trials reported on the efficacy of angiotensin-converting 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 HF 39. 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 diuretics 40. 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 remodeling 41,42. The effect is especially evident in myocardial infarction patients with severe systolic dysfunction (LV ejection fraction, 35%) 41. ARBs 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 146 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 age 43, the larger ELITE-II study failed to confirm this finding 44. 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 tolerance 45. In the RESOLVD trial, the combination of ARBs and ACE inhibitors was associated with more LV remodeling than either agent alone 46. 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 life 47. 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 inhi
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