Management of Heart Failure in Special Populations : Older Patients, Women, and Racial/Ethnic Minority Groups

Epidemiology (see also Chapter 18 )

HF is predominantly a disorder of older adults with prevalence and incidence rates that increase progressively with age. Of the nearly 6.5 million adults with HF in the United States, 50% are at least 75 years of age, and prevalence among those over the age of 80 years exceeds 13% in both men and women. The disparity between sexes seen in younger adults is abolished at advanced age with a slightly higher prevalence in women than men. The prevalence and incidence of HF are similar in older whites and African Americans.

In addition to age, risk factors for the development of HF in the older population include ischemic heart disease, systolic hypertension, widened pulse pressure, diabetes, chronic lung disease, renal dysfunction, atrial fibrillation, left ventricular hypertrophy, and obesity. Of these risk factors, systolic hypertension has the greatest population attributable risk, especially among women, for the development of HF. HF has a profound impact on the quality of life in older adults, and is an independent risk factor for cessation of driving and loss of functional capacity as evidenced by a decline in activities of daily living (ADLs) and independent ADLs (IADLs).

Incident HF in older adults is predominately characterized by the phenotype of HF with normal or preserved ejection function (HFpEF) ( see also Chapter 39 ). More than 50% of older patients with HF have HFpEF, and the proportion increases with age. There is also a female preponderance in HFpEF. Women with HFpEF are more likely than men to be older and obese, and to have chronic kidney disease and hypertension, but less likely to have an ischemic cause, atrial fibrillation, or chronic obstructive pulmonary disease. Thus, the profile of the typical older person with HF contrasts with that of middle-aged patients enrolled in HF trials ( Table 40.1 ).

Prognosis

Older age is an independent predictor of reduced survival in patients with HF, as it is with any chronic illness. In addition, common age-associated comorbidities, such as anemia, chronic kidney disease, and cognitive impairment, contribute to increased mortality after adjusting for age, sex, and race.

Despite major advances in HF therapy over the past two to three decades, overall mortality rates among patients with HFpEF have not declined ( see also Chapter 39 ). In the Framingham Heart Study, the annual mortality rate for HFpEF was 8.9%, which is approximately two-fold higher than age-matched controls, but only half that reported for HF with reduced ejection fraction (HFrEF) (19.6%). However, among patients hospitalized for HF, mortality is similar in HFpEF and HFrEF. Additionally, hospitalization for HFpEF is increasing relative to HFrEF. Among Medicare beneficiaries, HF is associated with the highest 30-day readmission rate, with approximately one in five individuals being rehospitalized at 30 days. Among older patients discharged with HF, a majority of 30-day readmissions are for conditions other than HF, suggesting that interventional strategies will need to be patient-centered rather than HF-specific.

Data from community-dwelling older subjects with HF suggest that the cause of death differs between patients with HFpEF versus HFrEF. Among patients with HFpEF, noncardiovascular conditions are the leading cause of death (49%), whereas coronary heart disease accounts for the greatest proportion (43%) in patients with HFrEF.

Pathophysiology

The pathophysiology of HF differs in older compared with younger adults due to age-related alterations in left ventricular filling dynamics and declines in cardiovascular reserve. As a result, mild to moderate stressors that would be relatively well tolerated in younger patients can precipitate acute HF in older adults. Age-related changes in other organ systems can also impair the ability of older adults to compensate for HF and can alter the response to pharmacologic therapy. The superimposition of normal aging means that at equivalent levels of impairment in cardiac function the clinical severity of HF is more advanced in older patients (i.e., higher New York Heart Association [NYHA] functional class). In addition, multimorbidity and geriatric syndromes are the rule rather than the exception in older adults with HF, and recent evidence suggests that these coexisting conditions likely contribute to the pathophysiology of HFpEF.

Diagnosis and Clinical Features

Older adults with HF have chronic exercise intolerance, reduced quality of life, frequent hospitalizations, and high health care costs. Importantly, morbidity in older adults with HFrEF or HFpEF is similar, with comparable exercise intolerance and impairments in quality of life.

The diagnosis of HF is challenging in older adults who are more likely to have other conditions that mimic the symptoms and signs of HF. A reliable history may be more difficult to obtain due to cognitive dysfunction or sensory impairment, making corroborating history from a family member or caregiver particularly helpful. Atypical presentations are more common in older adults, in whom HF may manifest as somnolence, confusion, disorientation, weakness, fatigue, gastrointestinal disturbances, or failure to thrive. Older adults may fail to perceive a gradual but progressive decline in exercise tolerance, and physicians often attribute this to advancing age or other conditions, thereby limiting early identification of HF. Care must be taken to exclude other potential causes for the signs and symptoms of HF ( Table 40.2 ). Serial assessments of functional capacity using standard tests (e.g., 6-minute walk distance or gait speed) and evaluation of ADLs and IADLs can be helpful adjuncts in quantifying and monitoring functional capacity. Both chest radiography and echocardiography have lower specificity for diagnosing HF in older patients, thus contributing to diagnostic uncertainty. Natriuretic peptide assays aid in diagnosing HF, assessing disease severity, and evaluating response to treatment. However, natriuretic peptide levels increase mildly with aging, are higher in women than in men, and are affected by renal function, anemia, and obesity; thus, the predictive accuracy of the assays is reduced in older patients. These difficulties notwithstanding, the diagnosis of HFpEF should be based on symptoms and/or signs of HF in combination with a left ventricular ejection fraction (LVEF) ≥50%, exclusion of other primary causes of the symptom complex, and with or without evidence for diastolic dysfunction or elevated natriuretic peptides.

Frailty and Cognitive Dysfunction

Frailty is a systemic syndrome characterized by impaired physiologic reserve, slowness, weakness, and wasting. It is associated with, but distinct from, aging, disability, and comorbid illness. Frailty and cognitive dysfunction are highly prevalent in older patients with HF, ranging from 25% to 80%, which is nearly double the prevalence in age-matched cohorts without HF. Both entities independently predict mortality in patients with HF, and the magnitude of effect is similar to traditional measures such as ejection fraction or systolic blood pressure. The relationship between HF and both frailty and cognitive dysfunction is bidirectional so that patients with HF are at significantly increased risk for frailty and dementia. Due to the variable manifestations of these syndromes in patients with HF, particularly in the early stages, periodic screening for frailty and cognitive dysfunction is recommended.

Since HF is a chronic condition, and successful management is contingent on effective self-care (i.e., adherence to a complex and ever-changing medical regimen, the need to follow dietary restrictions, monitoring of symptoms, engaging in exercise or physical therapy, and keeping follow-up appointments with multiple providers), impaired cognitive function can contribute to unfavorable outcomes, including recurrent hospitalizations and mortality. Yet, despite the negative impact of cognitive dysfunction on outcomes, these deficits often go unrecognized. Accordingly, implementing strategies to improve recognition of cognitive impairment (e.g., through routine screening) and tailoring treatment to individuals with cognitive dysfunction may enhance patient care and outcomes.

Identification of cognitive impairment in older adults with HF should prompt interventions to maximize adherence to self-management programs and to minimize the hazards of complex medical regimens. As the risk for adverse drug effects increases exponentially with the number of drugs prescribed, all unnecessary (and perhaps even some indicated) medications should be discontinued. Basic principles of transitional care dictate that early clinical follow-up is essential in this vulnerable group of patients. Clear written instructions and communication of medication changes to individuals assisting cognitively impaired older adults with HF is mandatory. If mobility limits an older adult’s ability to attend an office visit, then an early postdischarge home health visit by trained allied health professionals should be scheduled to reduce unplanned readmissions or death.

Treatment

Goals of therapy in older HF patients include relief of symptoms, improvement in functional capacity and quality of life, reduction in hospital admissions, and improved survival. In older patients, preservation of independence and maintenance of a satisfactory quality of life may be more important than survival. Optimal management requires a systematic approach comprising: (1) accurate diagnosis, (2) search for reversible or treatable etiologies, (3) judicious use of medications, (4) management of risk factors, (5) patient and caregiver education, (6) enhancement of self-management skills, (7) coordination of care across disciplines, and (8) close follow-up.

A recent meta-analysis demonstrated the efficacy of a multidisciplinary approach to HF care in reducing hospitalizations, improving quality of life, reducing total costs, and increasing survival ( see also Chapter 47 ). Many such studies included older patients who are ideal candidates for multidisciplinary care. One randomized trial involving patients aged 70 and older with either HFpEF or HFrEF demonstrated a 56% reduction in 90-day HF rehospitalizations. Other important strategies in HF disease management include: (1) smoking cessation, (2) moderation in alcohol use, (3) administration of pneumococcal and influenza vaccinations, (4) control of polypharmacy and over-the-counter medications, (5) consideration of cardiac rehabilitation, and (6) palliative care and end-of-life planning. Table 40.3 outlines potential members of a multidisciplinary team and their roles in promoting optimal patient care.

Biomarker Guided Therapy (see also Chapter 33 )

Given the high prevalence of chronic HF in older adults coupled with the fact that HF is associated with the highest rate of 30-day readmissions of all chronic conditions, there has been considerable interest in the use of biomarkers to guide therapy. The TIME-CHF investigators demonstrated that HF therapy guided by N-terminal B-type natriuretic peptide (BNP) did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment in a cohort of older adults. A meta-analysis of 12 randomized studies demonstrated that the use of cardiac peptides to guide pharmacologic therapy significantly reduced mortality and HF hospitalizations in patients with chronic HF. However, there was a strong interaction with age, such that outcomes were significantly improved by natriuretic peptide-guided therapy in younger patients (≤75 years; OR 0.45, 95% CI 0.21–0.97, P = .043), but not in older patients (>75 years; OR 0.80, 95% CI 0.42–1.51, P = .493). More recently, the GUIDE-IT trial failed to demonstrate a beneficial effect of N-terminal pro B-type natriuretic peptide (NT-proBNP)–guided therapy on cardiovascular mortality or time to first HF hospitalization relative to usual care, with similar findings in patients younger or older than age 75.

Pharmacologic Interventions for HFrEF (see also Chapter 37 )

While clinical trials have demonstrated the beneficial effects of ACE inhibitors in patients with HFrEF, older patients have been under-represented and there have been no trials specifically evaluating outcomes in this age group. However, a meta-analysis of published trials with stratification by age (<55 years, 55–64 years, 65–74 years, ≥75 years) demonstrated no heterogeneity in treatment effects by age for the combined outcomes of death, or myocardial infarction (MI) and death, or readmission for HF, suggesting a consistent benefit across age groups, although the magnitude of benefit appeared to be less among those over the age of 75 years. The use of ACE inhibitors in older patients may be complicated by preexisting renal dysfunction, renal artery stenosis, orthostatic hypotension, and increased susceptibility to side effects due to concomitant therapy; for example, drug interactions with nonsteroidal antiinflammatory drugs (NSAIDs) or other medications.

Angiotensin-receptor blockers (ARBs) are a reasonable alternative to ACE inhibitors in chronic HF but combination therapy with an ACE inhibitor and ARB is not recommended due to the increased risk for adverse events without clear benefit.

Several large randomized trials have shown that long-term beta-blockade is beneficial in patients with HFrEF. Patients up to age 80 have been included in these trials, and subgroup analyses indicate that beta-blockers are as effective in older as in younger adults. Older patients often have relative contraindications to beta-blockers, such as bradycardia, heart block, bronchospastic lung disease, or severe peripheral arterial disease. Nonetheless, indications for beta-blockers are similar in older and younger patients with HFrEF, although initiation and dose titration should be more cautious.

In the Randomized Aldactone Evaluation Study (RALES), subgroup analysis showed similar mortality benefits in patients ≥67 years of age (relative risk 0.68) compared to those less than 67 years of age (relative risk 0.74). Since significant hyperkalemia is more common in older adults prescribed spironolactone in usual care settings, close monitoring for side effects, including renal impairment and hyperkalemia, is warranted.

The Digitalis Investigation Group (DIG) study demonstrated similar effects of digoxin in younger and older patients, but toxicity was more common in older adults. The volume of distribution and renal clearance of digoxin decline with age, so that lower doses, e.g., 0.125 mg daily or less, are needed to achieve a therapeutic effect in older adults.

In the PARADIGM-HF trial, valsartan-sacubitril was associated with 20% reduction in the primary outcome of death from cardiovascular causes or hospitalization for HF (HR 0.80, 95% CI 0.73–0.87, P < .001) compared to enalapril among patients with NYHA class II-IV HF and an LVEF ≤40%. All-cause mortality was also reduced by 16% (HR 0.84, 95% CI 0.76–0.93, P < .001). Among patients ≥75 years of age (N = 1563, 18.5% of trial population), results were similar to those in younger patients ( Fig. 40.1 ).

In the SHIFT study, patients with symptomatic HF, an LVEF ≤35%, and a resting heart rate ≥70/minute despite maximally tolerated beta-blockers were randomized to ivabradine or placebo and followed for a median of 22.9 months. Ivabradine reduced the primary composite outcome of cardiovascular death or hospitalization for worsening HF by 18% (HR 0.82, 95% CI 0.75–0.90, P < .0001), with similar findings in patients older versus younger than age 65, although there was a slight trend to lower efficacy in older patients ( P for interaction by age .099) ( Fig. 40.2 ).

Device Therapy for HFrEF

Although implantable cardioverter-defibrillators (ICDs) reduce mortality from sudden cardiac death in patients with HF and an LVEF ≤35% ( see Chapter 38 ), few older patients were enrolled in the ICD trials, and a meta-analysis concluded that the benefit of ICDs in reducing mortality is lower in older compared to younger patients. This age-associated decline in benefit is most likely attributable to the higher risks of death from both nonarrhythmic causes and “nonshockable” rhythms (i.e., asystole and pulseless electrical activity) in older patients. In addition, major complications related to ICD implantation are twice as common in patients ≥80 years than in younger patients. Although current guidelines do not advocate age-based criteria for ICD implantation, it is acknowledged that data are limited in older patients and a shared decision-making process is recommended when considering ICD therapy, especially in patients with competing comorbidities or frailty. Patients should be advised about the potential benefits and risks of ICD implantation, including the possibility of an adverse effect on quality of life. Although many older patients elect to forego ICD implantation after an informed discussion, those who desire an ICD should not be denied a device solely on the basis of age. In these patients, it is appropriate to discuss circumstances under which the patient would want to have the device deactivated, especially at the end of life due to progressive HF or other terminal illness.

Cardiac resynchronization therapy (CRT) improves symptoms, exercise tolerance, quality of life, and survival in selected patients with advanced HFrEF, persistent limiting symptoms despite conventional medical therapy, and dyssynchronous left ventricular contraction. Although few older patients have been enrolled in the CRT trials, observational studies indicate that the benefits of CRT are age-independent. Since a primary objective of CRT is to improve symptoms and quality of life, it is appropriate to offer CRT, with or without an ICD, to older patients who meet criteria for device implantation.

Implantable left ventricular assist devices (LVADs) reduce symptoms, increase exercise tolerance, and improve quality of life and survival in selected patients with advanced HFrEF, including adults in their 70s and 80s ( see also Chapter 45 ). Originally developed as a “bridge” to heart transplantation, LVADs are now often implanted as “destination therapy” in patients who are not transplant candidates. As a result, an increasing number of older adults are receiving LVADs, and this trend is likely to accelerate as the safety and efficacy of these devices continue to improve. Older patients are at increased risk for LVAD-related complications, particularly gastrointestinal bleeding and stroke, and patients with advanced comorbidities or frailty may not be suitable candidates. Notably, however, a recent study demonstrated that frailty decreased in approximately half of older adults (mean age 70 years) after 6 months of LVAD therapy. In addition, small studies of LVADs in highly selected septuagenarians and octogenarians have reported favorable effects on quality of life and survival, so age alone should not be considered an absolute contraindication to LVAD implantation.

Pharmacologic Interventions for HFpEF

Pharmacological therapies for HFpEF have been reviewed in detail in Chapter 39 . Although there have now been multiple trials testing diverse pharmacologic agents in predominantly older patients with HFpEF, none have been shown to reduce mortality, and the effects of these agents on other clinical outcomes, including hospitalizations, exercise tolerance, and quality of life, have been modest. Several additional trials are ongoing, including PARAGON-HF, which compares sacubitril-valsartan to valsartan alone in patients with HFpEF (NCT 01920711), and a series of studies evaluating sodium-glucose co-transporter-2 (SGLT-2) inhibitors in patients with HF, but at the present time there are no proven pharmacologic therapies for the treatment of HFpEF.

Nonpharmacologic Interventions for HFpEF

While pharmacologic interventions for HFpEF in older adults have been disappointing, nonpharmacologic approaches, including diet and exercise, are emerging as promising therapeutic targets. In one study, exercise training improved peak oxygen consumption in patients with HFpEF, an effect mediated primarily by an increase in peak arterial–venous oxygen difference. This suggests that peripheral mechanisms (i.e., improved microvascular and/or skeletal muscle function) contribute to improved exercise capacity after exercise training in HFpEF. Dietary interventions have been understudied in older adults, especially those with HFpEF. In animal models, salt sensitivity is associated with a low renin state accompanied by renal dysfunction, hypertension, and obesity. In a small study in patients with HFpEF, the DASH/sodium restriction diet reduced systolic blood pressure, arterial stiffness, and oxidative stress, and improved diastolic function, ventricular-arterial coupling, and submaximal exercise tolerance. More recently, a 20-week intervention combining calorie restriction and exercise training was found to be more effective than either intervention alone in improving peak oxygen consumption in obese older adults with HFpEF, although there was no significant effect on patient-reported quality of life.