Aging and Heart Failure With Preserved Ejection Fraction

Epidemiology of HFpEF in Seniors

As the population ages, the rates of cardiovascular diseases increase, including HTN, coronary artery disease (CAD), and congestive heart failure (CHF). Currently CHF affects over 6.5 million adults with annual health care costs of $24 billion, and half of CHF cases are patients with a preserved EF. HFpEF is particularly prevalent among seniors with a mean age of +70 and affecting 13% of persons +80 years of age. By 2050, the senior population is estimated to exceed 86 million individuals. Clinicians must be prepared to evaluate, diagnose, and treat various causes of dyspnea and differentiate them from expected physiologic changes due to aging.

Elderly patients with HFpEF are a particularly vulnerable population. CHF is the leading cause of hospitalization in patients over age 65 years, and over half of these admissions are HFpEF. An evaluation of elderly hospitalized HF patients found impaired quality of life and depression symptoms to be more prevalent in HFpEF compared to heart failure with reduced ejection fraction (HFrEF), while physical limitation and impaired cognition were similar. In the Cardiovascular Health Study, frailty was found in 6.9% of participants over the age of 65. Frailty has been proposed as a syndrome of unintentional weight loss, exhaustion, weakness, slow walking speed, and low physical activity. In TOPCAT, the presence of frailty was associated with higher risk of HF hospitalization as well as mortality for patients with HFpEF. In HFpEF, patient-centered outcomes are either similar to or worse than HFrEF, and the morbidity of the disease in the elderly is increased when combined with frailty. It is important for clinicians caring for these patients to recognize elderly HFpEF patients as high risk for poor outcomes.

The role HFpEF plays in the death of seniors remains unclear, and there is a higher burden of cardiovascular death in this syndrome than previously thought. Two clinical trials of elderly patients with HFpEF, TIME-CHF and PEP-CHF, reported a cardiovascular cause of death in 60% and 70% of total deaths, though a subanalysis of TIME-CHF demonstrated higher rates of non-CV death in subjects with HFpEF compared to HFrEF. Over 300,000 deaths in the United States per year are attributed to HFpEF, and the mortality rates in HFpEF remain steady, in contrast to HFrEF where mortality has started to decline. The body of literature regarding the mode of death in HFpEF is heterogeneous, and competing risks play a role that needs to be further defined.

The Role of Comorbidities

While chronologic age can be measured easily, biologic aging may be more relevant for development of HFpEF in a senior population. Increasing age is associated with many of the comorbidities associated with HFpEF, including HTN, diabetes, CAD, renal dysfunction, and atrial fibrillation (AFib). Each of these comorbidities is known to negatively impact diastolic function, and each is highly prevalent in HFpEF ( Box 31.1 ; Tables 31.1 and 31.2 ). In clinical practice, it is likely that both chronologic aging and biologic aging contribute to development of HFpEF in the elderly as the cardiovascular system takes multiple hits ( Fig. 31.1 ). This multiple hit hypothesis may be what transitions seniors from changes of diastolic function to pathologic HFpEF. Most of the studies discussed in this chapter attempt to separate the effects of aging from the effects of comorbidities by excluding subjects with known comorbid conditions. While helpful when addressing the cardiovascular changes attributable to solely aging, in practice the presence of cardiovascular comorbidities should increase the index of suspicion for HFpEF in the elderly.

AFib in particular is a defining comorbidity of HFpEF. AFib is highly prevalent in HFpEF and associated with similar risk factors and comorbidities. In a subanalysis of the CHARM-Preserved trial, AFib coexisted with HFpEF in 29% of subjects and was negatively associated with cardiovascular mortality and hospitalization. In AFib trials, HFpEF is present in 8% to 24% of subjects. This relationship is more challenging in clinical practice, since patients without true HFpEF may have dyspnea on exertion or even pulmonary edema when ventricular rates are rapid, but once their rhythm is controlled, their symptoms improve. Yet AFib begets HFpEF, which begets AFib. For example, chronically elevated LA pressures cause LA dilation, remodeling, and then an atrial cardiomyopathy. This pathology in turn creates a favorable substrate for AFib. Furthermore, obesity, HTN, and diabetes are associated with atrial and ventricular remodeling that may lead to both AFib and HFpEF. Finally, AFib impairs late ventricular filling and is thought to impair hemodynamics in HFpEF, though clinical studies are lacking to evaluate this theory. Given their similarities in presentation and risk factors, the presence of either AFib or HFpEF in an elderly patient with other typical comorbidities should raise the clinical suspicion for the other.

Clinical Course of HFpEF in Seniors

The most common clinical presentation of HFpEF in seniors is fatigue and exertional dyspnea. However, there are many conditions that may lead to dyspnea or fatigue, some pathologic, some the result of aging. For example, there is an expected decline in maximal oxygen uptake (VO ₂ max), the body’s ability to utilize oxygen, which is seen with each decade of life. Furthermore, seniors have been shown to have decreased muscle mass, oxygen-carrying capacity of the blood, and lung function. Like VO ₂ max, forced expiratory volume in 1 sec (FEV1) decreases with each decade of life. Several pathologic conditions, such as obstructive CAD, intrinsic lung disease, depression, or systemic illnesses may also present with exertional dyspnea or fatigue and are common among seniors. While a variety of diseases cause dyspnea, HFpEF is a common culprit. HFpEF generally presents later in life, and the incidence of HFpEF overtakes HFrEF in the seventh decade of life. HFpEF makes up 90% of incident CHF diagnoses in elderly women. A prototypical elderly HFpEF patient is female and likely to have HTN, obesity, diabetes, or AFib, but there is great diversity in the disease. Thus a clinician must approach dyspneic patients with a broad perspective to appropriately identify the source.

Diagnosis of HFpEF in Seniors

The American Heart Association/American College of Cardiology (AHA/ACC) definition from 2013 consists of symptoms of HF ( Box 31.2 ) and an EF of 50% and above ( Box 31.3 ). The AHA/ACC guidelines do not specify measures of diastolic function or left venticular (LV) filling pressures. In contrast, the European Society of Cardiology (ESC) guidelines recommend evaluating filling pressures either invasively through pulmonary capillary wedge pressure (PCWP) or LV end-diastolic pressure (EDP) or by estimating volume overload through elevated E/e′ ratio or elevated brain natriuretic protein (BNP). Neither guideline refers to graded diastolic dysfunction as defined by the American Society of Echocardiography (ASE), though this classification is what is reported to many clinicians. The formal diagnostic criteria for HFpEF are no different for seniors than other populations.

For decompensated HFpEF patients with acute congestion and a preserved EF, the diagnosis is straightforward. However, many patients with early stages of HFpEF may present with dyspnea on exertion without clear physical evidence to suggest HF. For these patients, the diagnosis can be challenging. The most reliable method to establish the diagnosis is invasive hemodynamic exercise testing, where a pathologic increase in LV filling pressure is detected with a right heart catheter during exercise. Alternatively, a noninvasive diastolic stress test can be performed to estimate elevated LV filling pressures with exercise, though such markers are imprecise (see Chapter 18 ). Recently, Reddy et al. proposed a diagnostic score, call the H2FPEF, which combines a number of clinical and echocardiographic characteristics to identify those at risk for HFpEF. Age over 60 years is one of the scoring markers and thus corresponds with increased odds of having HFpEF in their cohort. While the widespread applicability of this score for diagnosing HFpEF is unknown, it has strong potential to identify those who warrant further evaluation, particularly among the elderly who are likely to have a higher score.

Currently, the ASE diastolic function guidelines do not have a formal role in detecting or diagnosing HFpEF, even though abnormal diastolic function is a hallmark of the disease. There are many reasons for this omission, but primarily it highlights the complex nature of diastolic function and the transition to a disease state. The 2016 ASE guidelines focus on using echocardiographic markers specifically to detect increased LA pressures in patients with myocardial pathology. Yet decompensated HFpEF patients, where this approach is most apt, are diagnosed clinically with relative ease. With the focus on elevated resting LA pressures, euvolemic HFpEF patients may not be detected by an echo performed at rest. Three analyses of HFpEF clinical trials confirm that when diastolic function is assessed by an echo in clinically adjudicated HFpEF patients, upwards of 30% have normal diastolic function ( Fig. 31.2 ). The progression from normal cardiac function to decompensated HFpEF is likely a gradual decline that involves multiple cardiac and noncardiac mechanisms. The individual components of diastolic function that can ultimately lead to HFpEF are each impacted by aging differently.