Studies have shown that elderly patients with heart failure are undertreated with evidence-based therapy, such as angiotensin-converting enzyme inhibitors and beta-blockers, although these therapeutic options appear to be effective in this age group. The risk of some side effects may be increased in elderly patients, and physicians should be aware of those when prescribing therapy. Cardiac resynchronization therapy is predicted to play a major role in future heart failure treatment, including in the elderly population.
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Approximately 2.4 million individuals in the United States have been diagnosed with heart failure,1 and a similar number is likely to have undiagnosed heart failure. The prevalence of heart failure increases sharply with age, and it exceeds 5% among persons older than 65 years. Comparable data have been reported from Western Europe.2
Among elderly patients with heart failure, the proportion of those with preserved left ventricular systolic function increases (Figure), as does the proportion of women with the disease. The presence of some comorbid conditions, such as atrial fibrillation and renal dysfunction, increases with age in heart failure patients, whereas other diseases, such as diabetes and hypertension, behave in a more complex manner. The prevalence of these conditions increases until approximately 80 years of age, but decreases among the oldest heart failure patients. The presence of comorbidity in elderly heart failure patients not only affects prognosis, but it also may complicate therapy and increase the need for follow-up.
It is well recognized that a diagnosis of heart failure based merely on symptoms and physical examination is not reliable.2 The diagnosis may be even more challenging in elderly patients because their symptoms (eg, fatigue, dyspnea, and edema) may be nonspecific and may be present in a large proportion of elderly primary care patients without heart failure. However, given the high prevalence of heart failure among elderly individuals, further diagnostic evaluation should be performed at a low threshold.
Echocardiography is the cornerstone of heart failure diagnosis. The use of natriuretic peptide tests (brain natriuretic peptide or N-terminal pro-brain natriuretic peptide) to rule out heart failure in symptomatic patients may be a feasible way to avoid unnecessary echocardiograms.3 However, peptide levels increase with age, even in patients without heart failure, which may complicate the use of these tests in elderly patients (ie, they have a low positive predictive value). Age-dependent cut-off values have been proposed and substantiated by data,4 but further studies are needed to establish the diagnostic use of natriuretic peptides in the elderly.
Over the past 20 years, numerous effective treatment options for patients with heart failure have emerged. Extensive clinical research has documented the efficacy of these pharmacologic and nonpharmacologic interventions. However, many trials included few, if any, elderly patients. Furthermore, almost all trials excluded patients with nonsystolic heart failure, which in practice prevented a large proportion of elderly heart failure patients from participating. Apart from a few dedicated trials,5,6 current knowledge about the effectiveness of various interventions in elderly patients with heart failure comes from extrapolation of subgroup analyses of the effect of age in the trials.
The use of diuretics is inevitable in the management of most patients with congestive heart failure. Although proof of their long-term beneficial effect in stable heart failure patients will likely never be available, diuretics are essential to managing fluid retention and for relief of congestion. Because of a greater degree of renal dysfunction, larger doses of diuretics are often needed in elderly patients, but at the same time, these patients appear to be at greatest risk for dehydration and prerenal azotemia during overly aggressive diuretic therapy. Meticulous monitoring of fluid status and electrolytes is essential in elderly patients during high-dose loop diuretic treatment, and although many patients can be safely managed in specialized outpatient clinics (see section on Multidisciplinary intervention), hospitalization may be necessary during intensive natriuresis.
Patients who present with gross or refractory edema may be treated successfully with combination therapy using metolazone (Zaroxolyn) in addition to a loop diuretic. This combination appears to be effective and safe, even in elderly patients, if electrolytes and fluid balance are adequately monitored.7
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
Since the first randomized trial of the angiotensin-converting enzyme (ACE) inhibitor enalapril maleate (Vasotec) in New York Heart Association (NYHA) functional class IV patients in the mid-1980s,8 it has been clear that blocking the renin-angiotensin system is essential in patients with heart failure. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARBs) improve functional capacity, reduce the need for hospitalization, and prolong survival in heart failure patients.9 It has turned out that the majority of heart failure patients tolerate the treatment well. A decrease in renal function during ACE inhibitor treatment in elderly patients may be cause for concern. However, it has been documented that the effect of ACE inhibitor treatment does not decline with increasing age.10
Recently, it was shown in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program that treatment with an ARB in patients intolerant to ACE inhibitors was effective in reducing cardiovascular mortality and symptoms compared with placebo. In this study, 23% of patients were older than 75 years, providing reasonable insight to the effect of treatment with candesartan (Atacand) in elderly patients.11 No interaction with age was reported in this study, and it has been further documented that increasing age did not predict long-term discontinuation of the drug, indicating that tolerance was not poorer in elderly patients. Hence, it discouraging that several studies, including the recently published EuroHeart Survey, indicate that patients older than 70 are less likely to be discharged with an ACE inhibitor after an admission for heart failure.12,13 It must be emphasized that ACE inhibitor or ARB treatment in elderly patients should generally be considered safe if renal function is properly monitored, and blockers of the renin-angiotensin system should be systematically tried in all patients.
The use of beta blockers in patients with heart failure due to left ventricular systolic dysfunction is well founded, based on 3 major randomized clinical trials.14-16 Indeed, beta blockers have been proven highly effective in reducing morbidity and mortality in heart failure. However, the mean age in these trials was 63 years, and 2 studies excluded patients older than 80 years of age. Reassuringly, subgroup analyses of the importance of age on the effect of beta blockers in these trials have not shown that the effect declines with increasing age.16-18
Recently, the results of the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors (SENIORS), which evaluated the effect of the beta blocker nebivolol in heart failure patients aged 70 years or more, have shown that beta blockade is also effective in elderly individuals. Interestingly, the latter trial also included patients with nonsystolic heart failure, making it particularly relevant to the geriatric heart failure population with respect to underlying pathophysiology. In the SENIORS trial, there was no interaction between left ventricular systolic function and effect of nebivolol on outcome.
Over the past several years of implementing beta-blocker therapy in the heart failure patient population, there has been considerable concern about side effects, particularly in elderly patients. Comorbid conditions, such as orthostatic hypotension, preexisting conduction disturbances, chronic obstructive pulmonary disease, and peripheral artery disease, which are particularly common in elderly patients, were expected to limit the use of beta blockers in the oldest patients. However, several studies have shown that the incidence of side effects during beta-blocker uptitration is not greater in elderly patients, and an equal proportion of younger and elderly patients generally tolerate the treatment.18-20 It appears that elderly patients usually tolerate somewhat lower doses of beta blockers than younger patients.19 Because this was also the case in the randomized studies showing the effect of treatment independently of age, it probably signifies that the beta-blocker doses needed to suppress the deleterious effects of the sympathetic nervous system in older patients are smaller. Although this should not remove focus from the importance of uptitration of beta blockers to the maximum tolerated dose in the elderly, it shows that patients can also benefit from smaller doses and, consequently, adherence to therapy should be strongly encouraged.
Spironolactone (Aldactone) has been documented to reduce morbidity and mortality in NYHA functional class III-IV patients with left ventricular systolic dysfunction.21 Recently, eplerenone (Inspra), an aldosterone blocker without the hormonal side effects known to occur with spironolactone, has been proven effective in patients with left ventricular systolic dysfunction and heart failure following an acute myocardial infarction.22 Taken together, there is now strong evidence that blocking the renal, cardiac, and vascular effects of aldosterone is beneficial in heart failure patients. The mean age in these studies was 65 years. In neither trial was any interaction with age shown, indicating that patients older than 65 years of age would be expected to benefit to a similar degree as younger patients.
Some published studies, however, have expressed concern about the safety of aldosterone blockers in clinical practice. In particular, the risk of hyperkalemia and renal dysfunction has been highlighted. Because elderly heart failure patients often have considerable renal dysfunction, which is frequently underestimated by serum creatinine values, it could be speculated that this group of patients would be at particular risk.
Indeed, several studies have shown that the incidence of hyperkalemia is considerably higher in clinical practice than reported in randomized trials,23-25 and, at least in some studies, advanced age has been found to be a predictor of hyperkalemia and increasing serum creatinine.23,25 Hence, particular attention should be paid to potassium levels and renal function in elderly patients treated with aldosterone inhibitors. Patients with an estimated glomerular filtration rate of < 30 mL/min or serum creatinine level > 2.0 mg/dL should not be started on therapy. Potassium supplements should be discontinued or decreased, and serum potassium and creatinine levels should be monitored closely, particularly in patients with evidence of moderate renal dysfunction. As life-threatening hyperkalemia appears to develop particularly during episodes of dehydration or other causes of prerenal azotemia, patients should be advised to interrupt therapy if severe diarrhea or similar conditions develop.
Cardiac resynchronization and implantable defibrillators
Cardiac resynchronization therapy (CRT), alone or in combination with an implantable cardiac defibrillator (ICD), has been shown to be superior to optimal medical therapy in selected patients with left ventricular dyssynchrony. In the Cardiac Resynchronization—Heart Failure study, which showed improved survival using CRT in patients with bundle branch block, 25% of the patients were older than age 72.26 There were no indications that CRT was less effective in the older subjects of the study population. Cardiac resynchronization therapy did not only provide improved survival, but it also improved functional status in approximately 3 of 4 patients with a CRT indication.
Although more studies are needed to improve pre-implant identification of positive responders to CRT and more data on complication risks are awaited, CRT will likely play an important part in the treatment of advanced heart failure in the future, including for elderly patients. For some older patients, implanting an ICD may be an appropriate intervention in case of recurrent hemodynamically destabilizing ventricular arrhythmias not well controlled by antiarrhythmic drugs.
Prophylactic ICD implantation in heart failure patients (ie, in patients without known ventricular arrhythmias) was studied in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) study and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Both studies included mostly younger patients, and in both trials, there was a trend toward a smaller effect in the elderly participants, even though they were highly selected. Hence, there is little evidence to support the prophylactic implantation of ICDs in patients older than 75 years of age.
Indeed, implantation of an ICD, even if it prolongs life, may reduce the quality of life, for example, by increasing the burden (or fear) of inappropriate shocks, which affects a substantial portion of patients. If confronted with the therapeutic options, many elderly patients may place more emphasis on quality of life than on prolonging life per se. This should be kept in mind when managing all aspects of heart failure treatment in elderly patients, but may be particularly relevant in the case of prophylactic ICD therapy, which offers “only” prolonged survival but no improvement of symptoms. It is important to emphasize that the preferences of elderly patients regarding life-prolonging interventions are highly variable, and a thorough discussion of these issues with each patient is mandatory.27
From the previously discussed data, it is clear that a number of effective interventions to treat heart failure have been developed over the last 2 decades. However, several studies have documented that far from all patients receive adequate care.12 Elderly patients appear to be at highest risk for undertreatment.13 Hence, we need strategies to ensure that evidence-based treatment is implemented in all heart failure patients.
To this end, dedicated clinics, often with a specialized nurse as the key resource, have evolved. These heart failure clinics have different designs, but the general aim is to deliver optimal medical care and support to heart failure patients. A heart failure physician should be involved in the care process but does need to see the patients on all visits to the clinic. Ideally, a physiotherapist, a dietician, and perhaps a psychologist should be affiliated with the program. Such programs have proven effective in preventing readmission for heart failure compared with usual care in several randomized trials.28 Many of these trials specifically targeted elderly patients, with a mean age older than 70 years in the majority of the studies. Ongoing trials will evaluate whether home visits by heart failure nurses are more effective than clinic treatment alone, an option that might be particularly attractive for elderly patients with advanced heart failure who may find it difficult to attend the clinic on a regular basis.29
The prognosis of heart failure patients has improved over the past few decades,30 but the improvement has been less pronounced in the elderly population.31 It is not surprising that advancing age has an independent, negative effect on both short- and long-term prognosis in heart failure, and the prognosis of elderly patients with heart failure is grave.
In a recent study, it was reported that patients hospitalized with moderate systolic heart failure faced a median expected survival time of 2.4 years if they were aged 71 to 80 years and 1.4 years if they were aged 80 years or more.13 In patients with more advanced systolic dysfunction, life expectancy was even shorter. It is conceivable that prognosis in elderly heart failure patients will improve if evidence-based treatment is also widely applied in this patient population.
Heart failure is a major medical problem in the elderly population. Given the predicted demographic development in the Western world, the disease will not only be a problem for individual patients, but it will also have a major effect on the health care system and future socioeconomics. It appears that the multiple available treatment options are also effective in elderly heart failure patients, but the use of caution is often required, as the risk of side effects may be increased in this population. Strategies to ensure implementation of evidence-based therapy in elderly patients with heart failure are needed. Specialized heart failure clinics relying on heart failure nurses may represent a possible solution, and the promotion of such programs should be encouraged.