Heart failure (HF) is prevalent in aging populations worldwide. It has become a significant health care burden in developed countries, especially in the elderly (age ≥65) [1–3]. Importantly, HF is a progressive disorder [4–6]. Its prevalence increases steeply with age, from <1% in the 20- to 39-year age group to >20% in individuals aged ≥80 [3]. It is commonly the end-stage in the cardiovascular disease (CVD) continuum (Fig. 1) and the final common pathway of several diseases, particularly coronary heart disease (CHD) and hypertension (Fig. 1). Pathophysiologically, HF can be regarded as a progressive disorder that is superimposed on an ongoing aging process in a disease continuum leading to ultimate disability and death (Fig. 1). The aging process results in a host of physiological and biological changes (Table 1) [7] that contribute to progression of the HF syndrome. In that construct, cardiovascular risk factors and comorbidities such as type 2 diabetes, obesity, hyperlipidemia and oxidative stress (Table 2) contribute to the march toward HF, end-stage heart disease and death (Fig. 1).

Fig. 1
figure 1

Heart failure, aging and the cardiovascular disease continuum. Heart failure can be considered as a progressive disorder in a disease continuum superimposed on the aging process and leading to disability and ultimate death. Progressive changes during aging and the cardiovascular disease continuum contribute to augment the heart failure burden in the elderly. EF = ejection fraction; LV = left ventricular

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Table 1 Cardiovascular risk factors and heart failure
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Table 2 Some aging-related changes pertinent for heart failure
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Definition of elderly

The current definition of elderly is arbitrary and there is no accurate biomarker of aging. In most developed countries, the chronological age of 65 that coincides with the retirement age is the accepted cutoff for defining the elderly and is also regarded as the onset of old age [8]. This definition originated in Britain. The British Friendly Societies Act of 1875 defined old age as any age after 50, and the age of 60 or 65 was used for eligibility in Pension plans [9]. In the absence of a better definition, the age of eligibility for retirement pensions became the accepted definition by default [8].

Since aging is a progressive biological process, old age can be considered to begin when active contribution to society is no longer possible [10]. In developing countries, social role is the predominant means of defining old age [11]. Recent socio-economic studies suggest that a multidimensional definition that combines chronological, functional and social factors would be preferable [8].

In developed countries, however, given the advances in therapy for CVD—including CHD, acute coronary syndromes (ACS), myocardial infarction (MI), hypertension and HF—the future elderly population can be expected to contribute more and more meaningfully to society beyond the arbitrary cutoff of 65 years.

Time may have come for the century-old arbitrary socio-economic cutoff age of 65 used for defining the elderly to be revised upwards to ≥85 to match the modern trends, progress in therapy, longer survival with improved quality of life, and social expectations.

Categories of heart failure

The current management guidelines consider HF as the result of structural and functional cardiac disorders that impair ventricular filling and ejection [4–6] and classify it into 2 broad categories to guide management: (1) diastolic heart failure (DHF), HF with preserved ejection fraction (HF/PEF), HF with preserved systolic function (HF/PSF) or HF with normal EF (HF/NEF); and (2) systolic heart failure (SHF) or HF with low EF (HF/low-EF).

Changing demographics and epidemiology

The elderly population (i.e. age ≥65) has been increasing steadily over the last 30 years [3, 7, 12]. Concurrently, the prevalence of HF in the elderly has increased and with it, the associated high mortality, prolonged morbidity, frequent hospitalizations and utilization of costly resources [3, 12]. The estimated cost associated with HF for 2010 is ~39.2 billion dollars [3].

Three main factors may explain the high prevalence of HF in the elderly: (1) aging-related biological factors; (2) prolonged exposure to cardiovascular risk factors during aging; and (3) comorbid conditions associated with aging [7, 12]. Several studies showed that HF begins to increase after the age of 45 [13]. The two most common causes of HF, MI and hypertension, are also more common in the elderly and the risk of HF increases with antecedent MI and hypertension [3]. The average age for a first MI is 66 in men and 70 in women [3] and post-MI HF increases with age. The reported incidence of HF is 20% at age 80 and increases with the severity of hypertension [3]. Among elderly HF patients, 80% men and 70% women are estimated to die within 8 years [3].

Patients with MI, especially ST-segment elevation MI (STEMI), usually develop dilative left ventricular (LV) remodeling leading to HF/low-EF [7] (Fig. 1). Several clinical trials have shown that both LV remodeling and dysfunction post-STEMI are more severe in elderly than non-elderly (i.e. age <65) patients [7, 14]. In contrast, patients with hypertension usually develop concentric LV remodeling and fibrosis [3, 6, 7] leading to HF with preserved LV ejection fraction (HF/PEF) (Fig. 1).

In population studies of HF/low-EF patients between 1980 and 2000, most were elderly, with many aged >80 [15, 16]. Readmission rates ranged between 27 and 47% within 3 to 6 months after discharge [15] and have not improved [16]. Importantly, HF/PEF accounts for ~50% of all HF patients and its prevalence is higher in the elderly [17, 18]. Of note in a recent study of HF/PEF patients, all were aged >80 with a mean age of 87 [19].

Recent studies suggest that the mode of death may differ in the two categories of HF. Data from clinical trials suggest that ~90% of HF patients die from cardiovascular causes, with 50% from progressive HF and pump failure (non-sudden death) and the rest from sudden death related to arrhythmia and ischemic events [20]. The Seattle Heart Failure Model (SHFM) score was shown to predict relative risk of sudden death (low score) versus pump-failure death (high score) in ambulatory NYHA class II to IV HF patients [21].

STEMI is not only more prevalent in the elderly but survivors develop HF/low-EF [3]. Clinical studies show that elderly STEMI patients represent a high-risk group with higher morbidity and mortality [3–7, 12]. Despite improved post-STEMI therapies with coronary reperfusion by percutaneous coronary intervention (PCI) and pharmacological drugs such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers (ARBs), β-blockers and statins, an excess of cardiovascular deaths still occur in the elderly [7, 12]. Survival has not improved significantly in elderly compared to non-elderly STEMI patients [3]. Elderly survivors continue to do poorly, with more adverse left ventricular (LV) remodeling and heart failure compared to non-elderly survivors [7, 12]. An early mortality gain with improved post-STEMI therapy may be at the cost of prolonged morbidity. Management of elderly patients with ACS and STEMI as suggested in the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines [12, 22] can reduce mortality but survivors may increase the HF burden.

HF therapies and implications for the elderly

The ACC/AHA management guidelines [4, 5] recommend a comprehensive therapeutic approach that addresses the 4 stages in the progression of structural and functional changes associated with HF: (1) stage-A with risk of HF but no structural changes or symptoms; (2) stage-B with structural changes but no signs or symptoms; (3) stage-C with structural changes and prior or current symptoms; and (4) stage-D with severe refractory HF requiring specialized interventions.

Randomized clinical trial (RCT) data on therapy exclusively for elderly patients with HF/low-EF or HF/PEF is lacking. The elderly were undeniably under-represented in RCTs of HF/low-EF therapies. However, the guidelines provide recommendations for the use of pharmacological as well as non-pharmacological therapies in both non-elderly and elderly HF/low-EF patients, with certain caveats for the elderly [4–6]. RCTs of medical therapies over the last 3 decades have shown mortality and morbidity benefits with ACE inhibitors, ARBs, β-blockers and aldosterone antagonists for primarily non-elderly patients with HF/low-EF. In these RCTs, the therapies also showed mortality and morbidity benefits in elderly patient subgroups with HF/low-EF [4–6], hence supporting their use. The guidelines also support the use of hydralazine, nitrates, digoxin and diuretics for HF/low-EF.

Specific medical therapy for HF/PEF is totally lacking but several studies are in progress. Current recommendations for the treatment of HF/PEF include control of hypertension, control of ventricular rate in patients with atrial fibrillation, control of pulmonary congestion and peripheral edema with diuretics, treatment of coronary artery disease and demonstrable myocardial ischemia with coronary revascularization, restoration and maintenance of sinus rhythm in patients with atrial fibrillation, and use of digoxin in selected patients [4–6].

Several non-pharmacological therapies are recommended for HF therapy [Table 3]. Although data specifically on the elderly is lacking, this group can benefit significantly from implantable cardioverter-defibrillator (ICD) devices, cardiac resynchronization therapy (CRT) and other specialized therapies [5]. Barring certain caveats, the eligible elderly HF patient should not be denied these treatments.

Table 3 Non-pharmacological therapies for heart failure
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Over the last 30 years, improvement in therapies for CVD, especially STEMI and hypertension [4–6], have increased the number of non-elderly patients who survive into old age, thereby expanding the elderly population with HF [3–6]. Several studies have suggested that outcome is poor in the elderly [23, 24]. The main reason is that evidence-based HF therapy is not optimally applied in the elderly and very elderly [25]. In addition, trial data on therapy of HF/PEF using those therapies or novel pharmacological drugs have not shown mortality benefit in non-elderly or elderly patients [4–6]. This is of particular concern since HF/PEF accounts for nearly half of all HF patients and its prevalence is even higher in the elderly [17, 18]. Also, current medical therapies were found to be suboptimal for very elderly patients with HF/PEF, with 69% of patients aged >80 dying over 5 years [19].

Problems and caveats with medical therapy of HF in the elderly

As noted, treatment of the elderly with HF is sub-optimal. The reasons include under-diagnosis, under-treatment, under-use and under-dosage of recommended pharmacotherapies in patients with HF/low-EF [25]. Comorbidities are common, aggravate HF, complicate therapy and increase the total HF burden. Other problems can complicate management and need special attention. Polypharmacy can lead to drug interactions, raising issues of efficacy and safety. Frailty and cognitive impairment lead to reduced compliance. Response to diuretics, ACE-inhibitors, β-blockers and/or positive inotropes may be blunted. The elderly show increased susceptibility to renal dysfunction, impairment of sodium and water excretion, and postural hypotension, and aggravation of hypotension with the treatments (e.g. ACE-inhibitors, β-blockers, nitrates, hydralazine). Hypotension may be complicated by impaired balance and proprioception, sick sinus syndrome and bradyarrhythmias that may be further aggravated by drugs that reduce heart rate such as β-blockers and digoxin. However, β-blockers should not be withheld unless contraindicated since they reduce mortality.

Because of physiological and pathophysiological changes associated with aging, several precautions are necessary with HF pharmacotherapy in the elderly. Therapy must be individualized and consider aging-specific changes in physiology, drug metabolism, drug pharmacokinetics and tolerance, comorbidities, polypharmacy and drug-drug interactions [4–6]. However, these considerations should not deter therapy.

Conclusions

HF in the elderly is a growing problem worldwide. This growth is associated with increased morbidity, morbidity, hospitalization and costs due to HF. There is therefore urgent need for increased awareness, more research not just into the biology of aging at the basic level but also at the clinical level, with more clinical trials in elderly patients with HF/low-EF as well as HF/PEF. Only more research will lead to novel strategies and discovery of new therapeutic targets for managing the 2 main classes of HF in the elderly.