CHAPTER 65: CARDIOVASCULAR DISEASE IN THE ELDERLY: PATHOPHYSIOLOGY AND CLINICAL IMPLICATIONS

Most cardiovascular diseases (CVDs) increase in prevalence and severity with age, and most clinicians provide care for a substantial number of elderly patients with disorders of the heart and vascular system. According to the American Heart Association, nearly 70% of all US adults ≥ 60 years old and more than 85% of those ≥ 80 years old have known CVD (Fig. 65–1).¹ Despite earlier treatment of risk factors and progressive improvements in therapies over the past several decades, heart disease remains the leading cause of death in the Medicare population. Furthermore, more than half of all cardiovascular procedures in the United States are performed in patients aged 65 years and older, and the total cost for CVD in this population exceeded $115 billion in 2011.¹ With the progressive aging of our population,^2,3 these figures will continue to rise. For these reasons, an understanding of the effects of aging on the development of CVD and the utility of cardiovascular therapies in the context of other age-related medical concerns (eg, multimorbidity, polypharmacy, frailty) is critical for reducing risk and improving outcomes in older patients.

Normal aging is associated with diffuse changes in cardiovascular structure and function (Table 65–1).^4,5 These processes have important effects on the cardiovascular system, with direct clinical implications (Table 65–2). Taken together, these changes contribute to the exponential rise in the incidence and prevalence of CVD in the geriatric population, including the marked increase in incidence of coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), and stroke in older adults. In addition, cardiovascular aging promotes the emergence of many age-associated CVD syndromes, including isolated systolic hypertension (the dominant form of hypertension in older adults), HF with preserved ejection fraction (HFpEF), calcific aortic stenosis, and “sick sinus syndrome.” Each of these conditions is discussed in subsequent sections of this chapter.

Aging is also associated with important changes in other organ systems that interact with the cardiovascular system and have implications for the clinical presentation and management of cardiovascular disorders (see Table 65–1). Renal function declines progressively with age, resulting in diminished capacity to maintain fluid and electrolyte homeostasis and predisposing to volume overload, cardiorenal syndrome, and electrolyte abnormalities (eg, in response to diuretics). Commonly used cardiovascular medications such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid antagonists (MRAs), and diuretics may contribute to worsening renal function. Conversely, advanced chronic kidney disease (eg, estimated glomerular filtrate rate < 30 mL/min/1.73 m²) mandates cautious use or avoidance of many drugs that are the foundation of guideline-directed medical therapy.

Age-associated reductions in pulmonary reserve contribute to increased dyspnea, reduced exercise capacity, and impaired quality of life in older patients with CVD, particularly among those with HF. Alterations in the neurohormonal system contribute to increased risk for side effects from cardiovascular medications, especially lightheadedness, falls, and syncope. Age-related impairment in the thirst mechanism predisposes to intravascular volume contraction and prerenal azotemia.

With increasing age, changes in the hemostatic system shift the intrinsic balance between thrombosis and fibrinolysis in the direction of thrombosis. As a result, older adults are at increased risk for both venous thromboembolic disease (ie, deep venous thrombosis and pulmonary embolism), as well as thrombosis in the arterial system, including myocardial infarction (MI), left atrial appendage thrombus in AF, and stroke. Despite these changes, and perhaps paradoxically, older adults are also at increased risk for bleeding complications with all antiplatelet, anticoagulant, and fibrinolytic agents, as exemplified by increased incidence of intracranial hemorrhage in older adults receiving prasugrel or fibrinolytic agents (see later Ischemic Heart Disease section). In addition, age-associated declines in muscular mass (sarcopenia) and bone mass (osteopenia) contribute to reductions in exercise tolerance, adversely affect balance, and predispose to injurious falls. Further, aging is associated with altered pharmacokinetics and/or pharmacodynamics of almost all medications, so that drug dosages tested in clinical trials involving predominantly younger and healthier patients may not be appropriate for the majority of older adults.

Finally, as discussed in more detail in the next section, coexisting illnesses and geriatric syndromes greatly increase the complexity of managing cardiovascular disorders in older adults. Similarly, optimal management of older adults must consider a host of other factors, including life expectancy, functional limitations, lifestyle and quality of life, psychosocial and behavioral issues (eg, depression, social support), and financial concerns.

In sum, older adults with CVD represent an extraordinarily heterogeneous population, often with considerable complexity, for which high-quality evidence from clinical trials is generally inadequate, and for whom standard guideline recommendations (which typically focus on a single cardiovascular disorder) may not be applicable. Hence, the approach to management of elderly patients is fundamentally different from that used in younger patients and must be individualized to ensure that care is well aligned with patient-centered goals.

Geriatric syndromes refer to multifactorial problems of old age that do not fit into classical disease categories.⁶ Key examples include frailty, cognitive impairment, delirium, functional decline, falls, and incontinence. The interrelationships of CVD with multimorbidity, polypharmacy, and geriatric syndromes are complex (Fig. 65–2). First, CVD is a risk factor for geriatric syndromes, and geriatric syndromes may in turn contribute to new onset or progression of CVD. Second, when CVD and noncardiovascular conditions coexist, the risk of geriatric syndromes and adverse health outcomes is higher than the risk associated with either condition alone (ie, disease-disease interaction). Third, a medication used to treat one condition may worsen another condition (drug-disease interaction) or increase the risk of drug-related adverse events (drug-drug interaction). Such interactions are more likely to occur as the number of medications increases. Fourth, the presence of geriatric syndromes is a poor prognostic marker for mortality, functional decline, and lack of treatment benefit in older adults with CVD. In particular, the degree of frailty may affect an individual’s likelihood of positive and negative outcomes after cardiovascular procedures.^7,8 This section outlines how assessing common geriatric conditions can help individualize cardiovascular care in older adults.

Multimorbidity

Multimorbidity, the presence of two or more chronic conditions, affects over two-thirds of older adults^9,10 and is associated with an increased risk of mortality, disability, nursing home admission, and health care utilization.^9,10,11 Multimorbidity frequently involves CVD—coexistence of a cardiometabolic condition and osteoarthritis was the most common multimorbidity pattern in several population-based studies.¹² Among Medicare beneficiaries, the dyad of hypertension and hyperlipidemia was most prevalent (53%), and other common conditions were ischemic heart disease, diabetes, and arthritis.^10,13 In addition, over 50% of Medicare beneficiaries with HF, stroke, or AF have more than five chronic conditions.⁹ Prevalent noncardiovascular conditions include arthritis, anemia, chronic kidney disease, cataracts, chronic obstructive pulmonary disease, dementia, and depression.¹³ Furthermore, noncardiovascular conditions account for almost half of readmissions after HF or MI in older adults.¹⁴ Therefore, identifying common patterns of multimorbidity may guide clinical decisions by helping clinicians prioritize interventions most likely to have a positive impact on overall outcomes.

When prescribing medications, clinicians should be aware that combining multiple evidence-based recommendations according to each disease-based guideline may not be feasible or may even be harmful in older adults with multimorbidity.¹⁵ Because certain multimorbidity patterns may increase the risk of adverse drug-disease and drug-drug interactions,¹⁰ trade-offs between different conditions are inevitable. There are three major domains of the equation required to make individualized treatment decisions: expected benefits, potential risks, and patient-level factors (Fig. 65–3). Personal goals and preferences should be incorporated into decision making by involving the patient to set priorities among competing treatments for different conditions.¹⁶ The likelihood of benefit versus risk of a treatment should be assessed on the basis of relevant evidence and the patient’s prognosis. To maximize adherence, clinicians need to consider the feasibility of a proposed treatment regimen as well as overall treatment burden from pharmacologic and nonpharmacologic therapies for all chronic conditions.

Polypharmacy

Polypharmacy is typically defined as concomitant use of five or more medications.¹⁷ Use of prescription medications and prevalence of polypharmacy have increased markedly over the past decade.¹⁸ The number of chronic conditions and prescribing practices aligned with disease-based guidelines are directly correlated with polypharmacy.^17,19 Approximately 40% of community-dwelling older adults take at least five medications,¹⁷ and 20% take medications that may exacerbate coexisting conditions.²⁰ For example, arthritis is often treated with nonsteroidal anti-inflammatory drugs, which antagonize the effects of many cardiovascular medications (ACEIs, ARBs, diuretics) and also increase risk for MI, HF, and worsening renal function. The number of medications and treatment complexity are associated with nonadherence, drug-related adverse events, financial burden, and caregiver stress.^{15,17,20,21,22,23,24,25} Although evidence-based management of CVD often warrants therapeutic polypharmacy, CVD medications are responsible for 25% of preventable adverse events caused by medications.²⁶ Because the majority of clinical trials of CVD treatment excluded older adults with multimorbidity and polypharmacy, the incremental benefit and harm of a drug when added to an already complex treatment regimen remain unclear.²⁷

Some evidence suggests that the benefit of guideline-recommended CVD treatments may be less in patients with certain multimorbidity patterns.¹⁹ Clinicians should carefully weigh the benefit of prescribing a new medication against the risk of adverse events, reduced adherence to other essential treatments, and financial burden.¹⁶ To justify prescribing, the expected time horizon to benefit needs to be shorter than the patient’s life expectancy (eg, avoid statins for primary prevention if life expectancy is < 2 years). It is essential to periodically review the indications for each agent to decrease the risk of drug-drug and drug-disease interactions.²⁸ When the indication for a medication is unclear, a time-limited withdrawal trial may be useful (eg, discontinuing a proton pump inhibitor that was initiated for stress ulcer prophylaxis in the hospital). A gradual taper and careful monitoring for withdrawal symptoms or worsening chronic conditions may be needed when a CVD or psychoactive medication is reduced.²⁹ In addition, adopting a standard checklist (eg, the American Geriatrics Society Beer’s list³⁰ or Screening Tool of Older People’s Potentially Inappropriate Prescriptions [STOPP]/Screening Tool to Alert Doctors to the Right Treatment [START] criteria³¹) can effectively reduce use of potentially inappropriate medications and drug-related adverse events in older adults.^32,33

Frailty

Frailty is a geriatric syndrome that is characterized by reduced physiologic reserve in multiple organ systems (eg, the brain or endocrine, immune, musculoskeletal, or cardiovascular systems) to maintain homeostasis after a stressful event and increased vulnerability to adverse health outcomes.³⁴ It is the most problematic manifestation of aging and contributes substantially to the heterogeneity in health status of the aging population. Several criteria for diagnosing frailty have been developed, yielding varying prevalence estimates in the general population, from < 5% using a specific physical performance-based definition to > 50% using a more comprehensive definition.³⁵ The frailty phenotype, derived from the Cardiovascular Health Study, is a widely accepted method for classifying older adults into robust, prefrail, or frail categories based on unintentional weight loss, weak handgrip strength, exhaustion, slow gait speed, and low physical activity.³⁶ Persons with three or more of these criteria are considered frail; those with one or two criteria are considered prefrail. Alternatively, frailty can be quantified using a continuous scale, known as the frailty index, based on accumulation of health deficits (eg, symptoms, signs, diseases, diagnostic test results, functional limitations) in multiple physiologic systems³⁷ or by standard comprehensive geriatric assessment.³⁸ The frailty phenotype may offer better clinical translation by allowing targeted interventions for and monitoring of each component, whereas the frailty index offers better prediction of adverse health outcomes.³⁹

The prevalence of frailty in older adults with CVD ranges from 21% in patients with CAD⁴⁰ to 51% in those with decompensated HF⁴¹ and as high as 50% to 70% in those undergoing transcatheter aortic valve replacement (TAVR).^8,42,43 In the Cardiovascular Health Study, clinical and subclinical CVDs were strongly associated with frailty⁴⁴ and prolonged disability.⁴⁵ In particular, patients with HF were 7.5-fold more likely to have frailty than those without HF.⁴⁴ In the Health, Aging, and Body Composition Study, severe frailty was associated with a 1.9-fold increased risk for HF.⁴⁶ In addition, markers of frailty predicted hospitalizations,⁴⁷ disability,⁴⁸ and mortality⁴¹ in older adults with HF. Mobility impairment, a hallmark of frailty,⁴⁹ is a strong predictor of postoperative complications, mortality, functional decline, and lack of improvement after cardiac surgery or TAVR.^{7,50,51,52,53,54}

Although the relationship between CVD and frailty is bidirectional, it remains to be elucidated whether treating an advanced CVD (eg, TAVR for aortic stenosis) can reverse frailty or whether interventions targeting frailty can improve CVD-related outcomes. Nonetheless, frailty assessment is useful to predict prognosis and guide decision making about CVD management and procedures. If feasible, clinicians should consider using a validated screening instrument for frailty in patients of advanced age.^55,56 A brief mobility test, such as Timed Up-and-Go (Fig. 65–4) or gait speed, is a good alternative to more comprehensive tests, with high sensitivity (0.93-0.99) and moderate specificity (0.62-0.64) for identifying frailty.^57,58 A positive screening test for frailty should be followed with a comprehensive geriatric assessment comprising medical, psychosocial, and functional domains, and development of an individualized care plan. Such a patient-centered approach can prevent functional decline and nursing home admissions in frail older adults.^59,60,61

Cognitive Impairment

Dementia affects 14% of adults aged 70 years or older in the United States, and the prevalence increases with age, from 5% in patients aged 71 to 79 years to 37% in those over 90 years of age.⁶² Mild cognitive impairment, a less severe form of cognitive limitation with relative preservation of functional status, is present in 22% of people ≥ 70 years old.⁶³ The annual rate of progression from mild cognitive impairment to dementia is estimated to be about 12%.⁶³ The prevalence of cognitive impairment in older adults with CVD is higher than that in the general population: 35% in patients undergoing coronary artery bypass graft (CABG) surgery⁶⁴ and 47% in hospitalized patients with HF.⁶⁵ The underlying mechanisms include hypoperfusion, oxidative stress, and inflammation, which lead to diverse cerebrovascular pathologies, including large cerebral infarcts, white matter lesions, lacunes, microinfarcts, and microbleeds.⁶⁶

A unique clinical characteristic of cognitive impairment attributable to CVD is executive dysfunction that manifests as difficulty with complex daily activities required for independent living (eg, managing finances, taking medications, using transportation). Cognitive impairment is associated with poor adherence⁶⁷ and increased risk of readmissions and death in HF patients.^65,68 Thus, cognitive impairment presents a serious challenge in outpatient management of older adults with CVD, and it may be difficult to diagnose among higher functioning patients. Moreover, cognitive impairment is a strong risk factor for delirium in hospitalized patients.⁶⁹

Delirium

Delirium, an acute-onset disturbance in attention and awareness, is present in up to 35% of patients aged 65 years or older on general medical wards⁷⁰ and up to 46% of patients aged 60 years or older after cardiac surgery.⁷¹ Evaluation for delirium requires a brief cognitive assessment, such as the Confusion Assessment Method algorithm comprised of the following four key features: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness.⁷² Use of multiple drugs (ie, polypharmacy), psychoactive drugs (especially benzodiazepines), physical restraints, and bladder catheters are common precipitating factors of delirium in hospitalized patients.⁶⁹ Development of delirium is associated with prolonged hospitalization, functional decline, nursing home admission, and death.⁶⁹ Patients who develop delirium after cardiac surgery may have persistent cognitive decline for up to a year after hospital discharge.⁷¹ Because there is no effective pharmacologic treatment for delirium, nonpharmacologic preventive interventions are the key to avoiding adverse consequences of delirium.⁷³ However, recognition and documentation of cognitive impairment and delirium by clinicians are poor.^65,68,74 Regular use of a validated screening instrument to assess cognitive function is recommended, particularly as a part of preoperative assessment before cardiac surgery or other major procedures.

Functional Decline

The risk of functional decline is greatest in hospitalized older adults. In addition to the debilitating effects of acute illness, hospitalization itself is associated with restricted mobility, enforced dependence, little encouragement of independence, limited access to food and liquids, disturbance of circadian rhythm, and polypharmacy.⁷⁵ These perturbations may predispose patients to delayed recovery, functional decline, cognitive impairment, and falls after hospital discharge. The term post-hospital syndrome refers to an acquired, transient condition of increased vulnerability following hospital discharge.⁷⁶ To mitigate the risk of complications occurring in the early post-hospitalization period, clinicians treating hospitalized older patients with CVD should assess functional status, mobility, and cognition on admission to identify high-risk individuals and then assess these patients daily thereafter to detect functional decline. At discharge, adequate support systems and interventions that promote functional recovery and safety beyond CVD management should be instituted. Multidisciplinary care provided in a dedicated inpatient geriatric unit has been shown to increase home discharge and reduce functional decline in heterogeneous populations of hospitalized older adults with acute medical illness, although dedicated trials in older adults with CVD and multimorbidity are lacking.^77,78

Falls

One-third of community-dwelling adults ≥ 65 years of age fall at least every year, and 5% to 10% of them sustain a fracture, laceration, or head trauma. Risk factors for falls include gait and balance problems, decreased muscle strength, vision impairment, medications, orthostatic hypotension, functional limitations, cognitive impairment, and urinary incontinence.⁷⁹ Symptomatic CVD can contribute to slow gait, decreased muscle strength, functional limitations, and cognitive impairment. Use of psychoactive drugs,^80,81 antihypertensive drugs,^81,82 and loop diuretics⁸³ is common in those with CVD, and these agents have been linked to falls in older adults. In a population-based study, symptomatic HF was associated with a 1.9-fold higher risk of falls.⁸⁴ Falls and fear of falling are also barriers to participating in physical activity.⁸⁵ As such, falls may negatively influence adherence to evidence-based CVD treatments and lifestyle interventions. Fall screening can be done by asking about history of falls and self-reported difficulty with walking or balance or by performing the Timed Up-and-Go test (see Fig. 65–4).⁸⁶ High-risk patients should receive multidisciplinary evaluation and targeted interventions, including gait and balance training.⁸⁷

Urinary Incontinence

Urinary incontinence is an underdiagnosed and undertreated geriatric syndrome that causes significant psychological and physical challenges, including increased risk of falls.⁸⁸ In the community, 11% of men and 16% of women over the age of 60 years experience urinary incontinence at least weekly, and the proportion increases considerably with age.⁸⁹ Like other geriatric syndromes, incontinence has multiple contributing causes, such as atrophic vaginal tissue, infection, delirium, increased urine volume, medications, and mobility impairment,⁹⁰ many of which are affected by CVD and common CVD treatments. Cough from ACEI medications may cause or exacerbate stress incontinence, whereas increased urine volume from diuretics may precipitate urge incontinence. Calcium channel blockers may worsen urinary retention, voiding difficulty, and constipation, leading to urge incontinence. Given the negative impact of urinary incontinence on quality of life and risk of falling, clinicians should ask about urinary incontinence and consider the patient’s preferences and mobility before prescribing medications that may contribute to incontinence. Nonpharmacologic treatment (eg, lifestyle interventions, Kegel exercises, bladder training) should be offered to all incontinent patients.⁹¹

Implications for Cardiovascular Disease Management

The ultimate goal of treating CVD in older adults is to reduce symptoms and prevent future CVD events, thereby improving quality of life, functional status, and survival. Because of the complex interactions among multimorbidity, polypharmacy, and geriatric syndromes (see Fig. 65–2), treatments to improve CVD-related outcomes may not necessarily lead to proportional improvements in quality of life and functional status in older adults comparable to those seen in clinical trials. To maximize the benefits in CVD-related outcomes as well as global outcomes, cardiologists should assess the burden of coexisting noncardiovascular conditions, polypharmacy, and geriatric syndromes, and recognize their significance when considering options for CVD management (Table 65–3). Given the short clinic visit time and fragmented care provided to many patients with multiple medical problems, involvement of a multidisciplinary team that consists of experts in geriatrics, pharmacology, rehabilitation, and social work is encouraged whenever possible to facilitate comprehensive assessment and optimal selection of interventions.

Epidemiology and Risk Factors

The American Heart Association reports that 20% of men and 10% of women between 60 and 79 years of age have ischemic heart disease (IHD), and approximately half of these patients have experienced a previous MI.¹ These proportions increase markedly with age, such that one of every four individuals aged 80 years and older has clinically evident CAD. In autopsy studies, the prevalence of obstructive coronary atherosclerosis increased from 10% to 20% for patients in their 40s to 50% to 70% among patients in their 80s.⁹² In patients referred for CABG in a large clinical trial, older age was associated with more diffuse coronary atherosclerosis, substantially higher rates of left main and triple-vessel disease, and greater degrees of left ventricular wall motion abnormalities and systolic dysfunction.⁹³ In the United States, the average age of first MI is 65 years for men and 72 years for women, with approximately 80% of all coronary-related deaths occurring in the Medicare-aged population.¹ Furthermore, nearly half of the 7 million deaths attributed to IHD across the globe each year occur in the small subgroup of patients ≥ 80 years old.³ For these reasons, a thorough understanding of the nuances in patient presentation, prognosis, and management of IHD among elderly patients is imperative for treating acute and chronic CAD in daily clinical practice.

Risk assessment is the cornerstone of CVD management, and multiple studies have demonstrated the prominent role of age in predicting adverse outcomes in patients with IHD. For example, increasing age is the strongest predictor of IHD events in the Framingham Risk Score,⁹⁴ and the impact of age on IHD risk is substantially greater than for other traditional risk factors, such as hypertension, smoking, or lipid profiles. Similarly, in updated algorithms such as the Reynolds Risk Score, age provides nearly threefold more statistical weight to the final risk estimate than any other risk factor.^95,96 Older age also consistently identifies patients at higher risk for short-term clinical events after acute coronary syndrome (ACS), as noted in the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk models espoused by national guidelines.^97,98 For example, age ≥ 80 years has nearly twice the prognostic significance in the GRACE ACS algorithm (91-100 points) than any other risk factor (46-59 points for the most severe clinical presentations, including profound hypotension or tachycardia, pulmonary edema, cardiac arrest, or renal failure).⁹⁹

Taken together, the structural and functional changes that occur with increasing age, along with the increasing prevalence of most atherosclerotic risk factors and a progressively sedentary lifestyle, all contribute to higher likelihood of developing IHD with increasing age. Furthermore, subclinical cardiovascular and other medical diseases are highly prevalent among older patients.¹⁰⁰ As a result, older patients with IHD often present later and with more severe disease, resulting in substantially higher risks of adverse outcomes.

Clinical Presentation

Typical angina has been described most often in cohorts of middle-aged patients, the majority of whom are male and white. However, older patients with acute MI are more likely to be female and to present with dyspnea, nausea, diaphoresis, altered mental status, or other nonspecific symptoms such as malaise and fatigue (Fig. 65–5).^{5,101,102,103} As a result, the proportion of patients presenting with typical angina decreases with age, which makes the diagnosis of ACS more challenging and often more delayed than in younger individuals. Reduced functional capacity, competing diagnoses with similar symptoms (eg, chronic lung disease or indigestion), and cognitive impairment may further obscure the diagnosis.

Although physical examination has limited utility for the diagnosis of IHD at all ages, the delayed recognition of ACS in elderly patients likely contributes to the higher proportion of patients with more advanced disease and complications at presentation, including signs of pulmonary edema or cardiogenic shock.^5,101 Other findings of more advanced IHD in elderly ACS patients may include altered mental status or confusion, rales, tachycardia, hypoxia, jugulovenous distension, or peripheral edema. Electrocardiographic diagnosis of ACS may be confounded by pre-existing electrical abnormalities, including left bundle branch block, left ventricular hypertrophy, prior MI, repolarization changes from antiarrhythmic drugs, or the presence of ventricular paced rhythm^5,104—again contributing to later recognition of MI in older patients.

Complications of Acute Myocardial Infarction

In conjunction with age-related differences in clinical presentation, increasing age is associated with higher complication rates after MI, including striking increases in short-term mortality after age 65 years (Fig. 65–6).^{101,102,105,106} This increase in risk with age has been demonstrated for both ST-segment elevation MI (STEMI)^107,108,109 and for non–ST-segment elevation ACS (NSTE-ACS).^99,110,111 Of note, quantifiable indices of MI size, such as peak biomarkers or severity of electrocardiographic changes at presentation, are not substantially different between younger and older patients.^102,107,109 Nonetheless, older patients experience markedly higher rates of HF, AF, and cardiogenic shock, which in part reflects age-related cardiovascular changes and diminished cardiovascular reserve.^107,111

With improvements in short-term survival following acute MI during the coronary reperfusion era, postinfarction HF affects a large proportion of elderly ACS patients and is associated with poor outcomes¹¹² (see Chaps. 39 and 42). Right ventricular ischemia or infarction in patients with inferior STEMI is associated with particularly high mortality in elderly patients.¹¹³ Mechanical complications of acute MI (eg, left ventricular free wall rupture, papillary muscle dysfunction with acute mitral regurgitation, ventricular septal rupture, left ventricular aneurysm or pseudoaneurysm formation) have declined in frequency during the reperfusion era, but older age continues to be a risk factor for developing each of these potentially life-threatening complications.¹¹⁴ Electrical events also occur more commonly in older populations, particularly AF and heart block, perhaps as a result of having more extensive CAD and left ventricular dysfunction at the time of ACS presentation.

Overall, the mechanisms underlying worse outcomes among older ACS patients are likely independent of the acute coronary occlusion itself, but instead are related to pathophysiologic changes with age, greater severity of CAD and left ventricular dysfunction at the time of diagnosis, and concomitant medical comorbidities and frailty. Additional aging processes, such as diminished collateral circulation to occluded coronary arteries and lower number and lesser function of endothelial progenitor cells to facilitate myocardial recovery after MI, also contribute to adverse outcomes in older patients.^115,116,117

Pharmacologic Considerations in Older Patients

Older patients, women, and racial/ethnic minorities have been under-represented in randomized clinical trials of ACS therapies,¹¹⁸ despite the high incidence of ACS in the elderly¹¹⁹ and substantially worse outcomes among older patients.¹⁰¹ In general, elderly patients have more advanced atherosclerotic risk factors, more prolonged exposure to these risk factors, and multiple other medical problems that may impact the benefits and risks of all interventions, both pharmacologic and nonpharmacologic. Older patients are also more likely to present with NSTE-ACS than STEMI, which may significantly impact initial therapy.^101,102,106 A large proportion of ACS presentations in older adults is caused by supply-demand mismatch in the setting of fixed coronary obstruction (ie, type II MI according to the World Health Organization classification).¹²⁰ In these cases, there may be less benefit from anticoagulation therapies as a result of lack of intracoronary thrombus. Thus, treatment of older patients with NSTE-ACS often requires greater focus on the underlying factors precipitating the event, such as infection, uncontrolled hypertension, anemia, tachycardia, or other systemic insults (eg, noncardiac surgery, thyroid disease, cancer).⁵ Conversely, the value of aggressive pharmacologic and invasive management in this population is less well established.

Antiplatelet Therapy

Oral Agents

In the largest randomized comparison of aspirin versus placebo in patients with suspected acute STEMI, the benefit of aspirin increased with increasing age, from 1% absolute reduction in 5-week vascular mortality for patients younger than 60 years of age, to 4.7% absolute reduction among patients ≥ 70 years old.¹²¹ More than a decade later, clopidogrel was shown to reduce the composite end point of MI, stroke, or cardiovascular death by 20% when added to aspirin for 1 year after ACS, with similar benefits among patients older or younger than 65 years of age.¹²² Subsequently, prasugrel and ticagrelor were each compared with clopidogrel and demonstrated additional benefits for ACS patients. However, these more potent antiplatelet therapies had disparate effects on elderly patients. Specifically, prasugrel reduced recurrent MI more effectively than clopidogrel in patients younger than 75 years of age,¹²³ but there was loss of benefit for patients aged ≥ 75 years and a significant increase in major bleeding complications (including intracranial hemorrhage) in this age group. In contrast, ticagrelor reduced recurrent MI and cardiovascular death when compared with clopidogrel during the first year after ACS, and ticagrelor was not associated with higher bleeding rates in the elderly. However, there was a somewhat attenuated benefit among the 15% of the 18,000 trial participants older than 75 years.^124,125 In a follow-up trial evaluating ticagrelor versus placebo in patients with prior MI, the 12% of the trial patients ≥ 75 years old had similar benefits and bleeding risks as the overall trial population.¹²⁶

An additional medication, vorapaxar, was recently approved in the United States for patients with prior MI (> 2 weeks previously) or peripheral arterial disease at high risk of ischemic events. In a large trial, vorapaxar added to aspirin and clopidogrel reduced thrombotic events but was associated with higher bleeding rates.¹²⁷ Because most patients with recent MI are already treated with aspirin and another oral antiplatelet medication, the principal role for vorapaxar in the geriatric population may be in select patients with peripheral arterial disease at low risk of bleeding.

Intravenous Agents

The role of intravenous antiplatelet therapy in ACS is more difficult to define, both for younger and older patients. Glycoprotein IIb/IIIa inhibitors appear to reduce reinfarction and overall infarct size at the time of NSTE-ACS, with patients at higher risk deriving the most benefit, but few studies have enrolled patients aged > 75 years, and the risk of bleeding complications increases with age.^5,128 One study of ACS patients demonstrated higher event rates in octogenarians randomized to glycoprotein IIb/IIIa inhibitor therapy,¹²⁹ and current guidelines recommend avoiding these medications entirely in the setting of fibrinolytic therapy for STEMI in patients ≥ 75 years of age.⁹⁸ Because these drugs are associated with greater bleeding risks in the elderly, use of glycoprotein IIb/IIIa inhibitors should probably be limited to select older individuals with high thrombosis risk and low bleeding risk. The intravenous platelet inhibitor cangrelor has a different mechanism of action than the glycoprotein IIb/IIIa inhibitors, and clinical trials evaluating cangrelor demonstrated similar benefits among patients older and younger than age 75 years.¹³⁰ However, the magnitude of bleeding risk associated with cangrelor remains unclear¹³¹; thus, the safety of this drug in elderly patients requires further study.

Duration of Oral Antiplatelet Therapy

In recent years, multiple studies have demonstrated benefit from continuing dual antiplatelet therapy beyond the first year after acute MI.^126,132 However, the risk of bleeding during long-term therapy must be carefully weighed against the diminishing anti-ischemic benefit beyond the first year. For example, in the largest randomized trial to date evaluating prolonged dual antiplatelet therapy after drug-eluting stent placement, approximately 10% of the 10,000 study patients were ≥ 75 years old.¹³³ These individuals appeared to have somewhat less benefit, but also lower bleeding rates, than the overall study population during the 18 additional months of clopidogrel therapy (perhaps representing a selection bias for enrolling “healthier” elderly patients eligible for prolonged antiplatelet therapy). Although the optimal duration of dual antiplatelet therapy requires further study, at present, it seems reasonable to limit extended use beyond 1 year to elderly patients with prior MI at lower risk of bleeding.

Antithrombotic Therapy

Intravenous unfractionated heparin has been a standard ACS therapy for decades, but recent guidelines have espoused the use of enoxaparin, bivalirudin, and related compounds as alternatives to heparin.^97,98 Although these newer agents appear to provide more predictable or better targeted antithrombotic activity than heparin, nearly all of them are cleared through renal mechanisms. This is problematic in elderly ACS patients, given the age-related decline in renal function, thus contributing to the substantially higher risks of bleeding with age.^134,135 Despite these risks, older and younger subjects in clinical trials derived similar benefits from the newer antithrombotic therapies.^136,137 Thus, these agents appear to be reasonable choices as long as dosing is carefully adjusted to account for renal function, weight, and other factors (eg, frailty) in the elderly.

Long-term oral antithrombotic medication (eg, warfarin, apixaban, rivaroxaban, dabigatran, edoxaban) in combination with dual antiplatelet therapy further increases bleeding risks, especially in older patients. Because the prevalence of AF, heart valve replacement, venous thromboembolism, and other indications for anticoagulation increases with age, the dilemma of “triple therapy” becomes more common when treating older patients with IHD. In an observational study, nearly 5000 older patients with AF undergoing percutaneous coronary intervention (PCI) for acute MI had substantially higher rates of major bleeding with triple therapy (vs those receiving dual antiplatelet therapy alone), with no difference in ischemic events.¹³⁸ The concept of temporarily withholding aspirin is controversial and requires further study, but it appears to be a reasonable option for elderly patients at higher risk of bleeding. Alternatively, bare metal stents may be considered for these higher risk individuals,^139,140 particularly when performing PCI for stable coronary disease, to provide shorter exposure to triple therapy (acknowledging that the risk of restenosis is higher with bare metal stents).

β-Blockers

As noted previously, older patients with acute MI often present later, with a greater burden of medical comorbidities, and with more extensive complications from the infarct. Increasing age is also associated with higher risk of complications from β-blocker therapy, including hypotension, bradycardia, HF, and cardiogenic shock.¹⁴¹ Nonetheless, when administered judiciously, β-blockers reduce mortality, recurrent ischemia, and arrhythmias in acute MI, and the 23% reduction in mortality among elderly patients (in a pooled analysis of multiple β-blocker trials) was significantly greater than the effect in younger patients.⁵ The same analysis demonstrated 6 lives saved per 100 older patients treated, whereas younger patients had only 2 lives saved per 100 treated. Furthermore, subgroup analyses from β-blocker trials suggest that the majority of the long-term survival benefit after MI occurs in patients aged ≥ 65 years.^142,143 However, all of these studies were conducted prior to the reperfusion era, and the value of early β-blocker therapy in contemporary practice is less clear. To minimize side effects and complications associated with β-blocker therapy in the elderly, these drugs should be started at low doses and titrated slowly,^5,98 and immediate intravenous β-blocker injection should be avoided in most elderly MI patients.¹⁴¹

Angiotensin and Aldosterone Inhibitors

A large meta-analysis of ACEI therapy for acute MI confirmed a significant reduction in mortality for older patients, particularly for those aged 65 to 74 years.¹⁴⁴ The absolute benefit of ACEI was nearly three times greater for older patients than for younger patients, with most trials demonstrating 17% to 34% relative risk reductions in the geriatric subgroups.^145,146,147 ARBs are reasonable alternatives to ACEIs in HF, but ACEIs are the preferred agents after acute MI in both younger and older populations.¹⁴⁸ Because most of the benefits occur in MI patients with HF or left ventricular systolic dysfunction,¹⁴⁴ more judicious use of these medications may be warranted in elderly patients with preserved systolic function. Both ACEIs and ARBs must be titrated carefully in older individuals, as the risk of medication-induced hypotension, renal failure, and hyperkalemia increases with age and comorbidity burden.

The MRAs spironolactone and eplerenone reduce fibrosis and adverse remodeling after myocardial injury.^149,150 In patients with acute MI and left ventricular dysfunction or HF treated with MRAs, those older or younger than 65 years of age experience similar reductions in morbidity and mortality.¹⁵¹ However, an analysis from Canada demonstrated much higher rates of hospitalization for hyperkalemia and renal failure after the widespread adoption of spironolactone for treating HF.¹⁵² Thus, given the increased prevalence of renal dysfunction in the geriatric population, the use of MRAs in elderly individuals requires meticulous monitoring of serum creatinine and potassium levels.

Statins

In the absence of major contraindications, statins are indicated for all patients with established vascular disease, and particularly those with IHD or prior ACS.^{97,98,104,153} Numerous studies have confirmed the benefits of statins in older patients,^{154,155,156,157} although few patients over 80 years of age have been enrolled in clinical trials.^158,159 Because elderly individuals are at increased risk for myalgias, fatigue, and both functional and cognitive impairment related to statin therapy,^{160,161,162,163} older patients should be monitored for these adverse drug effects. In addition, the use of statins in patients of advanced age should consider life expectancy, overall cardiovascular risk, and patient preferences. Nonetheless, the greatest benefits from statins occur in high-risk patients following vascular events,¹⁶⁴ so statins are indicated in almost all older patients with established IHD and life expectancy of at least 1 to 2 years (although lower doses may be considered).

Other Anti-Ischemic Medications

Nitrates, calcium channel blockers, morphine, and other anti-ischemic medications have not reduced mortality in ACS clinical trials; thus, the primary indication for these agents is to alleviate symptoms, with similar recommendations for older and younger patients.^{97,98,104,153} As always, careful titration is important in elderly patients, given the potential for increased side effects (eg, hypotension, bradycardia, mental status changes). Ranolazine is indicated for management of chronic stable angina, with patients older or younger than 65 years of age deriving similar benefits in exercise duration, frequency of angina attacks, and number of nitroglycerin tablets needed per week.^165,166,167 However, side effects such as dizziness, constipation, nausea, headache, and abdominal discomfort were more common in patients aged > 65 years. In patients with NSTE-ACS, ranolazine is safe, but does not improve clinical outcomes, and effects were similar in patients older or younger than 75 years of age.¹⁶⁸

Reperfusion and Revascularization

Acute Reperfusion for ST-Segment Elevation Myocardial Infarction

Although the absolute benefit of fibrinolytic therapy is greatest in older patients at high risk for complications from STEMI, the risk of catastrophic bleeding also increases markedly after 75 years of age (see Fig. 65–6).^105,169 In clinical trials of fibrinolysis for STEMI, intracranial hemorrhage occurred in approximately 1% to 2% of patients aged > 75 years versus 0.5% to 1% of younger patients.^170,171 Thus, although older age is not a contraindication to fibrinolytic therapy, the risk-benefit ratio must be carefully evaluated in patients with frailty or advanced age, particularly because few patients aged > 85 years were enrolled in the fibrinolytic trials for acute MI.^172,173,174

Recent guidelines have moved toward recommending primary PCI over fibrinolysis in most patients with STEMI as a result of clinical trials showing greater efficacy and fewer serious bleeding events with contemporary PCI techniques.⁹⁸ In particular, elderly patients enrolled in these studies had improved survival with primary PCI for STEMI,^175,176 and a small trial limited to patients ≥ 75 years of age also demonstrated superiority of PCI over fibrinolysis.¹⁷¹ To minimize bleeding risks in patients of advanced age, an additional 30-minute delay beyond the standard 90-minute “door-to-balloon time” is permitted when the delay allows for primary PCI instead of thrombolysis in the geriatric population.¹⁰⁴

Reperfusion in Non–ST-Segment Elevation Acute Coronary Syndrome

Older age is a major risk factor for adverse ACS outcomes, as well as for procedural complications, both from cardiovascular issues (eg, access site problems, complex vascular anatomy, coronary calcification precluding adequate stent delivery) and from other medical comorbidities (eg, renal dysfunction, cognitive impairment or agitation with sedation, bleeding risks in frail patients). Despite these concerns, in most studies, older patients treated with an early invasive approach to NSTE-ACS experienced reductions in death or recurrent MI.^177,178 In a recent unblinded trial of 457 patients ≥ 80 years of age with NSTE-ACS, early coronary angiography and revascularization were associated with a significant reduction in urgent revascularization or recurrent MI over a median follow-up time of 1.5 years when compared with initial medical therapy alone.¹⁷⁹ Of note, the benefit of invasive management declined with age and was no longer evident among patients ≥ 90 years of age. With these competing concerns in mind, the decision to pursue an invasive approach among patients with advanced age must be individualized, with consideration of anticipated benefits, potential risks, and patient preferences. Among elderly patients with lower risk ACS characteristics, intensification of medical management alone is often a reasonable option.

Revascularization in Cardiogenic Shock

In a clinical trial evaluating revascularization therapy for patients with ACS complicated by cardiogenic shock, patients younger than 75 years of age had lower mortality with early PCI or CABG, whereas patients aged > 75 years did not.^180,181 However, patients enrolled in the trial registry (and thus removed from the randomization process) had improved outcomes with early revascularization, including elderly individuals.¹⁸² Newer data suggest higher rates of cardiogenic shock after STEMI during the past decade, with greater utilization of early PCI and circulatory support devices, along with lower in-hospital mortality over time.¹⁸³ Of note, patients over 75 years of age continued to have lower utilization of early revascularization and support devices, and despite gradual reductions in mortality that mirrored the improvements seen in younger patients, overall mortality remained nearly twice as high in older patients. Larger support devices such as Impella (Abiomed, Danvers, MA) may help stabilize some of these patients while awaiting myocardial recovery after revascularization, but the impact of these interventions on clinical outcomes is uncertain, and optimal patient selection remains challenging (see Chap. 42).^184,185 Nonetheless, with continued technological advancements and greater clinical experience, these devices may play an important role in managing select elderly patients with shock physiology complicating ACS.

Stable Ischemic Heart Disease

As with ACS, chronic angina may manifest differently or at a later stage in older patients. Prolonged exposure to risk factors, concomitant medical diseases, and aging processes likely contribute to the more advanced atherosclerosis discovered in older patients at the time of IHD diagnosis. For example, chronic lung disease, diabetic neuropathy, cognitive impairment, and sedentary lifestyle may contribute to delayed recognition of IHD in older patients.⁵ Medical therapies for chronic IHD are similar in older and younger patients, with emphasis on relief of symptoms and prevention of disease progression using statins, aspirin, and appropriate blood pressure and diabetes management (see Chap. 43). Dual antiplatelet therapy beyond the first year after ACS or coronary stent implantation appears to primarily benefit patients with prior MI—at a cost of higher bleeding rates—and should be considered for select elderly patients at higher risk of recurrent ischemic events and lower risk of bleeding.^186,187

Coronary revascularization should be considered for elderly patients with chronic IHD and either high-risk coronary anatomy or persistent ischemic symptoms despite optimal medical therapy.¹⁸⁸ Complications of PCI and CABG are more common among patients ≥ 80 years old,^189,190 but hospital mortality has continued to decline over the past two decades in both younger and older patients despite substantial increases in comorbidity.¹ Increasing age is a potent risk factor for arrhythmias after CABG (especially AF; see Chap. 44), as well as for postoperative delirium and cognitive impairment.¹⁹¹

Despite these concerns, revascularization is associated with excellent clinical outcomes among appropriately selected patients of advanced age (ie, octogenarians and nonagenarians), including fewer symptoms and improved quality of life compared with medical therapy alone.^{188,192,193,194} Thus, advanced age alone should not be considered a contraindication to either PCI or CABG. In the past decade, several studies have compared PCI and CABG in patients with left main or multivessel CAD, demonstrating higher rates of repeat revascularization after PCI, but similar rates of other clinical outcomes (MI, stroke, and death) between the two approaches.^195,196 As a result, many elderly patients with severe IHD choose multivessel PCI over CABG, thus trading the higher perioperative risk and longer recovery time for the greater likelihood of needing repeat PCI during short-term follow-up. Coupled with additional improvements in PCI (ie, radial artery access, newer stents with lower restenosis and thrombosis rates, smaller catheters, and lower contrast volumes), these trends likely explain why CABG rates in the United States have continued to decline since 1997, whereas PCI rates in the geriatric population have remained relatively constant.¹

Nonpharmacologic Therapy

Medication adherence and polypharmacy may challenge efforts to reduce the risk of recurrent cardiovascular events in older patients with established IHD. Cognitive impairment may lead to missed doses of medications, inability to recall instructions, or confusion about the multiple therapies prescribed. Substantial effort has been devoted to discussing these issues in contemporary guidelines¹⁸⁸; instructions must be discussed clearly, caregivers should also receive these instructions, and close surveillance for drug-drug interactions or medication side effects should be implemented. These concerns are particularly relevant for antiplatelet therapies after ACS or stent placement, as premature discontinuation of these medications is the primary cause of short-term stent thrombosis, reinfarction, and cardiovascular death.¹⁹⁷

Other supportive measures during and after IHD events are important as well. For example, hospitalized patients with STEMI commonly receive narcotics and are relatively bedbound while recovering in the intensive care unit, so implementation of a bowel regimen is important for these individuals, many of whom already have impaired bowel function.¹⁸⁸ Cardiac rehabilitation is markedly underused in the geriatric population, despite proven reductions in mortality and improvements in quality of life,¹⁹⁸ although referral rates have increased in recent years.¹⁹⁹ Older patients unable to attend formal cardiac rehabilitation for logistical or transportation reasons should be referred for a home-based rehabilitation program if available.

Epidemiology and Pathophysiology

Approximately 10% of all individuals aged ≥ 80 years have an established diagnosis of HF, and half of the HF hospitalizations each year in the United States occur in patients aged 75 years and older.¹ At 40 years of age, the lifetime risk of developing HF is nearly 20%, and this remains true at 80 years of age despite a much shorter life expectancy in octogenarians. In addition, mortality from HF increases with age, and HF is the most common and costly reason for acute hospitalization in the Medicare program.

Although the high prevalence of HF in elderly patients is partly related to improved survival from acute MI and other CVDs, other age-related factors contribute to the development of HF including long-standing hypertension (present in 75% of patients with HF), vascular stiffness, left ventricular diastolic dysfunction, sinus node dysfunction, progressive valvular heart disease, coronary ischemia, and reduced responsiveness to β-adrenergic stimulation.⁵ As a result, a gradual erosion in cardiovascular reserve with age results in an exponential rise in HF among older individuals. Studies in healthy older adults have confirmed that the effects of normal aging lead to altered preload, afterload, heart rate, and contractility—the four major determinants of cardiac output—thus resulting in a progressive decline in peak cardiopulmonary performance, even in the absence of clinically evident CVD (Fig. 65–7).²⁰⁰ Stated another way, an otherwise healthy 90-year-old individual is likely to have exercise capacity and cardiovascular reserve equivalent to a younger person with New York Heart Association functional class III HF.

Heart Failure Prevention

In populations with stage A or stage B HF, clinical guidelines recommend preventative measures, such as lowering blood pressure,²⁰¹ particularly in elderly patients.²⁰² Generalized deconditioning is pervasive in elderly patients with HF, and exercise physiology studies have demonstrated that nearly half of dyspnea in HF patients is related to skeletal, diaphragmatic, and intercostal muscle weakness, beyond cardiopulmonary dysfunction alone.²⁰¹ This suggests that breathing exercises and interventions designed to strengthen respiratory muscles may be beneficial in reducing symptoms, but studies testing this hypothesis in older patients with HF are lacking. As with IHD, older patients with HF also need extensive support and counseling to avoid medication and dietary nonadherence, which are leading causes of rehospitalization in this population.

Clinical Presentation and Evaluation in Older Patients

Although dyspnea and exercise intolerance are the cardinal symptoms of HF, exertional symptoms may be less prominent in sedentary older patients, and atypical symptoms such as anorexia and mental status changes become more prevalent with increasing age.⁵ In addition, concomitant noncardiac conditions such as anemia, renal dysfunction, or lung disease often contribute to exercise intolerance in older adults, and it may be difficult to determine the primary etiology of patients’ symptoms. Similarly, physical examination findings associated with HF may be lacking or nonspecific in older adults. For example, pulmonary crackles may be a result of chronic lung disease or atelectasis, and dependent edema may be secondary to malnutrition (hypoalbuminemia), venous insufficiency, or medications (especially calcium channel blockers).

As in younger patients, older individuals with suspected HF should have an echocardiogram to evaluate systolic and diastolic function, chamber size and wall thickness, valve function, the pericardium, and pulmonary arterial pressure. B-type natriuretic peptide (BNP) and N-terminal pro-BNP may be helpful in distinguishing HF from noncardiac sources of dyspnea among patients presenting to the emergency department,²⁰³ but these levels tend to increase with age and other comorbidities (eg, renal dysfunction, pulmonary hypertension, cardiac arrhythmias).²⁰⁴ As a result, the predictive accuracy of natriuretic peptides decreases with increasing age, especially in women.²⁰⁵ Careful assessment for changes in medications (eg, initiation of a nonsteroidal anti-inflammatory drug) or recent procedures or surgeries (in which intravenous fluid may have been administered) may help elucidate the cause of an HF exacerbation.

Pharmacotherapy of Heart Failure

Because the majority of HF trials have enrolled few elderly patients, there is uncertainty about the benefits of medical and procedural therapies in older patients.²⁰⁶ Nonetheless, guidelines generally extrapolate from effects demonstrated in younger patient populations.²⁰¹ As a result, most guideline recommendations for HF therapy are similar across age groups, including hemodynamic stabilization after hospital admission, correction of volume overload, careful surveillance of renal function and electrolytes while titrating medications, and implementing therapeutic interventions based on results of large-scale clinical trials (see Chaps. 70 and 71).

Diuretics

Although the long-term risks and benefits of loop diuretics remain controversial,^207,208,209 these medications are essential for reducing pulmonary congestion and peripheral edema during HF exacerbations, and they also play a key role in maintaining normal volume status during long-term HF management.²⁰¹ Older patients are generally more prone to develop renal dysfunction and electrolyte abnormalities during diuretic therapy, so close monitoring is imperative.⁵

Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Neprilysin Inhibitors

In clinical trials of ACEIs for HF with reduced ejection fraction (HFrEF), similar improvements in mortality, quality of life, and HF hospitalizations were noted in older and younger patients,²¹⁰ although the benefit may be attenuated above 75 years of age.²¹¹ Older patients experience higher rates of hypotension and renal dysfunction (likely related to pre-existing renal impairment), but other adverse effects, such as ACEI-associated cough and angioedema, are unrelated to age. In general, in the absence of contraindications, elderly patients with HFrEF should undergo ACEI titration to dosage levels achieved in clinical trials, with close monitoring for side effects or complications of therapy.^201,212,213

In HF patients intolerant to ACEIs, ARBs are an effective alternative, with comparable benefits across the age spectrum.^214,215 In three large HF trials of candesartan that included 1736 subjects aged ≥ 75 years, candesartan was associated with a 14% reduction in death or HF hospitalization, which was similar to findings in younger patients.²¹⁶ As with ACEIs, older age confers higher risk for adverse hemodynamic and renal complications. In addition, combined ACEI and ARB therapy is not recommended as a result of increased risk for adverse events without incremental benefit.^201,217

Recently, the combination of valsartan with the neprilysin inhibitor sacubitril was compared to enalapril in patients with HFrEF.²¹⁸ In this study, valsartan-sacubitril reduced the composite end point of HF hospitalization or death, with similar reductions in each component end point. Furthermore, benefits were similar among the 49% of trial subjects aged > 65 years, as well as the 19% of subjects aged > 75 years. Side effects were generally mild, although there was a higher rate of symptomatic hypotension with the combination drug. Additional studies are needed to evaluate the effects of neprilysin inhibition in older patients with multimorbidity or frailty.

β-Blockers and Ivabradine

β-Blockers improve left ventricular function and reduce mortality in patients with cardiomyopathy and HF,^219,220 including older patients with HFrEF.^221,222 However, elderly patients are more prone to developing symptomatic bradycardia, hypotension, fatigue, or fluid retention during titration of therapy. Therefore, starting at a low dose and titrating gradually is imperative in these individuals.

Recently, ivabradine was approved in the United States for patients with symptomatic HFrEF and continued heart rates above 70 bpm despite maximally tolerated β-blocker therapy.²²³ Although the primary clinical trial of ivabradine demonstrated reductions in mortality and HF hospitalizations beyond conventional medical therapy, the effect was somewhat blunted in patients aged > 65 years (borderline statistical significance for the interaction with age). In addition, clinically important bradycardia was more common in the ivabradine group. Nonetheless, ivabradine may provide an additional therapeutic option for older adults with HFrEF who are unable to tolerate β-blockers or who have higher heart rates on maximally tolerated doses of β-blockers.

Aldosterone Antagonists

Although the indications for MRA therapy in patients with symptomatic HFrEF are similar in younger and older patients,^201,224 older patients are more susceptible to worsening renal function and hyperkalemia, as noted previously.¹⁵² In addition, the overall benefits of MRAs may be reduced in elderly patients, with one registry study suggesting no mortality benefit and higher rates of 30-day readmission for hyperkalemia in Medicare patients (mean age 78 years).²²⁵ Thus, judicious patient selection and close monitoring of renal function and electrolytes are essential for older patients receiving MRA therapy.

Hydralazine and Nitrates

The combination of hydralazine and nitrates provided additional benefit in a clinical trial of African American HF patients with functional class III or IV symptoms treated with concomitant ACEIs and β-blockers.²²⁶ However, patients in this trial were relatively young (mean age 57 years), so it is unclear whether the findings can be extrapolated to older patients. In addition, dosing of hydralazine/nitrates is three times daily, which can be problematic in older patients, with polypharmacy or cognitive dysfunction affecting medication adherence.

Digoxin

Although post hoc subgroup analysis of the Digitalis Investigation Group suggested that digoxin may have favorable effects on mortality when serum levels are maintained < 1.0 ng/mL,²²⁷ use of digoxin is generally limited to patients with persistent symptoms despite optimal therapy, as described earlier.^201,228 The risks and benefits of digoxin are similar in older and younger patients, including those ≥ 80 years of age.²²⁹ Nonetheless, elderly patients have higher rates of symptoms attributed to digoxin, and other factors associated with digoxin toxicity (renal dysfunction, electrolyte disturbances, drug-drug interactions, bradycardia, cardiac amyloid) are more prevalent in older patients. Thus, treatment must be individualized, and low doses should be used to maintain trough serum digoxin concentrations < 1.0 ng/mL.⁵

Heart Failure With Preserved Left Ventricular Ejection Fraction

Nearly half of the geriatric HF population has preserved or only mildly reduced left ventricular systolic function (ie, HFpEF),^230,231 and HF in these patients is generally related to long-standing hypertension, diabetes, renal dysfunction, and vascular and ventricular stiffening. Current guidelines recommend similar approaches to younger and older patients with HFpEF, including management of volume status, and minimizing factors known to promote HF exacerbations, such as uncontrolled hypertension, arrhythmias (especially AF), myocardial ischemia, worsening renal function, dietary indiscretion, or medication nonadherence.²⁰¹ Of note, no studies to date have demonstrated mortality benefit for any pharmacological treatments for HFpEF, and effects on other outcomes have been modest (Table 65–4; see Chap. 70 for further details).

Nonpharmacologic Therapies

Lifestyle Modifications

HF is a chronic illness that requires substantial self-care by patients in order to optimize outcomes, especially with regard to reducing HF exacerbations and recurrent hospitalizations—irrespective of whether the phenotype is HFrEF or HFpEF.^5,201 Although adherence to medications and dietary restrictions is essential for HF patients of all ages, older patients are often additionally challenged by limited access to HF-healthy meals, social isolation with limited travel options (eg, to shop for food and obtain medications), complex medication regimens, and financial constraints. Older patients with HF at increased risk for adverse outcomes should be referred to a multidisciplinary HF management program, if available.^201,232 Similarly, exercise training and structured cardiac rehabilitation are associated with improved health status and reductions in HF hospitalizations,²³³ so cardiac rehabilitation should be prescribed when possible for older patients who fulfill criteria for participation.

Implantable Device Therapies

The role of device therapy in the contemporary management of HF is discussed elsewhere (see Chap. 70). Only a small fraction of patients enrolled in trials evaluating cardiac resynchronization therapy (CRT) were aged > 80 years, but patients above and below the median age in the trials (approximately 65 years) derived equivalent benefits.^234,235,236 In addition, observational data have demonstrated improvements in quality of life among octogenarians,²³⁷ suggesting that CRT is a reasonable option in elderly HF patients who meet criteria for device implantation.

In contrast to CRT, the use of implantable cardioverter-defibrillators (ICDs) in elderly patients with HFrEF often poses a difficult quandary. Whereas CRT improves quality of life, ICDs may prolong life without improving quality of life^236,238,239—an effect not always considered desirable in elderly patients with symptomatic HF or poor quality of life as a result of other medical comorbidities. Again, few patients aged > 80 years were enrolled in clinical trials evaluating ICDs in HF, and the mortality benefit of ICD placement declines with age as a result of competing causes of death.²⁴⁰ Thus, selection of elderly patients for ICD placement must include a realistic appraisal of the potential benefits and risks, with inclusion of the patient and family in the decision-making process. There should also be a discussion of clinical scenarios in which the patient might want to consider disabling the ICD function (eg, terminal illness or unacceptably poor quality of life).²⁴¹ Similar discussions should occur prior to “routine” generator changes caused by battery end-of-life.

Heart transplantation is a therapeutic option for small numbers of patients with advanced HF up to 75 years of age, with similar outcomes in younger and older individuals.²⁴² However, a substantially larger number of patients with refractory HFrEF may be considered for ventricular assist devices (VADs). Newer generation devices have led to less invasive surgical implantation procedures, acceptable complication rates, and favorable effects on cardiovascular health status in elderly subjects.²⁴³ Although experience in patients ≥80 years old remains limited, VAD implantation in this population is likely to increase as a result of technological advances, lower complication rates, and more refined criteria for patient selection. Nonetheless, consideration of a VAD as destination therapy requires a detailed discussion of all available options through a process of shared clinical decision making.

Prognosis and End-of-Life Care

Nearly half of all patients discharged with a primary diagnosis of HF are readmitted to the hospital within 6 months, and 20% to 25% are readmitted within 30 days. Multidisciplinary programs reduce readmissions by 20% to 25%,²⁴⁴ but repeat admissions remain problematic, and well over 50% of readmissions occur for diagnoses other than HF. In addition, repetitive admissions are a marker for declining prognosis and contribute to deterioration in functional status and quality of life, especially in elderly patients with multimorbidity and frailty.

The overall prognosis for elderly HF patients is poor, with 1-year mortality close to 25% and 5-year survival rates of only 20% to 25% (ie, worse than for most forms of cancer). Older age and dementia are potent predictors of adverse outcomes; other prognostic factors include renal dysfunction, hyponatremia, and worse functional status.²⁴⁵ End-of-life discussions, including patient-centered goals of care and preferences regarding resuscitation status, should be undertaken early after diagnosis, particularly among patients with advanced age or other high-risk characteristics for early mortality.²⁴⁶ Because the course of HF is unpredictable, patients should be encouraged to develop a living will and designate durable power of attorney for health care. Consultation with palliative or hospice care specialists is recommended in patients with short estimated life span (eg, < 6 months) as a result of refractory functional class IV symptoms, advanced age, frailty, or poor overall health.^5,247

The prevalence of most acquired cardiac valve disorders increases with age. Furthermore, because medical therapies for valvular heart disease are limited, procedural and surgical treatments play a prominent role in management. In this context, the ability of an elderly patient to recover from such procedures must be weighed against the severity of symptoms and prognosis related to the underlying disease process. With refinements in surgical and anesthetic techniques, plus the shift toward less invasive or percutaneous valve procedures in recent years, more geriatric patients are becoming eligible for repair or replacement.

Aortic Stenosis

The prevalence of symptomatic aortic stenosis (AS) increases from 0.2% in patients aged > 60 years to nearly 10% in those ≥ 80 years of age.^5,248 As a result, over 70% of all aortic valve procedures are performed in the geriatric population, and AS is the most common valvular abnormality requiring surgical or percutaneous intervention. Symptoms may not be as prominent in elderly patients with sedentary lifestyle, resulting in delayed presentation or incidental diagnosis of severe AS at the time of presentation for other medical problems.⁵ In addition, although physical findings are generally similar in younger and older patients, older individuals with severe AS are less likely to exhibit delayed upstroke of the carotid pulse wave (pulsus tardus et parvus) as a result of increased arterial stiffness.

Because older patients are more likely to have left ventricular systolic dysfunction, the prevalence of low-flow, low-gradient AS increases with age. Paradoxical low-flow, low-gradient AS with normal systolic function is more common in older individuals as well. Assessing the response to dobutamine infusion may be helpful in distinguishing severe AS from “pseudo” severe AS (ie, low calculated aortic valve area in the absence of severe obstruction to flow), but in some cases, cardiac catheterization with hemodynamic studies is needed to clarify AS severity. In addition, almost all older patients with AS who are being considered for a valve procedure require coronary angiography to evaluate for IHD, which has shared pathophysiology with AS and is present in at least 50% of geriatric patients with significant AS.²⁴⁹

Until recently, surgical aortic valve replacement (SAVR) has been the only effective treatment for severe AS, with limited roles for medical therapy or balloon valvuloplasty (see Chap. 47). Elderly patients deemed to be reasonable surgical candidates have excellent outcomes in observational SAVR registries, with average survival similar to actuarial tables of the general population (ie, nearly 7 years for patients aged 80-84 years and more than 6 years among patients ≥ 85 years old).²⁵⁰ Predictors of adverse outcomes after SAVR are similar to those in younger patients, including severe left ventricular dysfunction, AF, more complex surgery (eg, requiring concomitant CABG or multivalve surgery), cerebrovascular disease, and the need for emergency surgery. Age is not usually considered a major risk factor for perioperative death, but multimorbidity and frailty portend less favorable outcomes.

The development of TAVR has revolutionized the treatment of elderly and frail AS patients who are not considered suitable candidates for SAVR. Clinical trials and observational studies have demonstrated the feasibility and equivalence (and sometimes superiority) of TAVR when compared with medical or surgical therapy for intermediate-risk, high-risk, or “inoperable” patients with severe AS.^{251,252,253,254} Importantly, TAVR has been evaluated in patients with extensive medical comorbidities or other high-risk features for SAVR and, thus, the clinical trials included substantial numbers of patients aged > 80 years and a large number over 90 years of age (mean age 83-84 years). Because patients in this age range with complex morbidity and frailty have been systematically excluded from most clinical trials, the development and testing of TAVR represent a significant advancement both in the management of patients with AS and, more broadly, for the general population of elderly patients with CVD. However, despite the manifest benefits of TAVR for many elderly patients with severe AS, up to 25% of patients who undergo the procedure do not survive 1 year, and another 20% to 30% do not experience clinically meaningful improvements in quality of life.²⁵⁵ Thus, careful patient selection is imperative, partly to minimize procedural complications, but also to ensure that these procedures are not overused in patients with low likelihood of deriving meaningful benefit.²⁵⁶

Mitral Regurgitation

The prevalence of significant mitral regurgitation (MR) increases with age, partly as a result of progression of chronic mitral valve disorders such as rheumatic or myxomatous valve disease, but also as a consequence of myocardial ischemia or mitral annular dilation from dilated cardiomyopathy.^5,249 As a result, most mitral valve surgeries are performed in the Medicare age group. Observational data suggest that mitral valve surgery is associated with better outcomes when performed prior to left ventricular dilation,²⁵⁷ but as with other cardiac conditions, older patients may present with more advanced disease as a result of sedentary lifestyles or confounding medical comorbidities.

When surgery for MR is performed prior to ventricular dilation and dysfunction, outcomes are favorable, with survival rates in the elderly similar to those predicted for the general population.²⁵⁸ However, recovery following mitral valve surgery in elderly patients tends to be slower when compared with aortic valve surgery.^5,249 As noted for SAVR, many older individuals are considered too high risk for mitral valve surgery as a result of severe ventricular dysfunction or other medical problems. In recent years, the development of transcatheter mitral repair has allowed select older individuals to undergo nonsurgical mitral valve therapy with favorable clinical outcomes.^259,260

Other Valve Disorders

In geriatric patients, the etiology of aortic insufficiency is likely to be related to chronic diseases such as hypertension, myxomatous degeneration of the aortic valve leaflets, or aneurysmal dilation of the ascending aorta. Some older patients may also develop complications from aortic dissection, endocarditis, long-standing rheumatic valve deformities, or autoimmune processes. Management is similar to that for younger patients,²⁴⁹ and operative mortality is generally favorable in older patients with preserved left ventricular systolic function (see Chap. 47).

Some elderly patients (particularly those with advanced chronic kidney disease) may experience progressive valvular and mitral annular calcification leading to mitral stenosis. This process rarely leads to stenosis severe enough to warrant surgical intervention, but pulmonary venous congestion and pulmonary hypertension may develop over time.

Tricuspid regurgitation in the geriatric population usually occurs as a consequence of right ventricular dilation, commonly attributable to pulmonary hypertension, chronic lung disease, or left HF.²⁴⁹ Surgical intervention is generally reserved for patients with severe tricuspid regurgitation who are undergoing simultaneous CABG or other valvular surgery. As with aortic and mitral valve disease, percutaneous techniques for treating severe tricuspid regurgitation are under development. Stenotic lesions of the tricuspid or pulmonic valves are rare in older patients, although carcinoid heart disease may occasionally present in the geriatric age group.

Infective endocarditis, once a condition predominantly affecting younger patients, is now primarily a disorder of older adults. Progressive valvular calcification and degeneration in older patients contribute to a higher risk of structurally abnormal heart valves and thus higher rates of potential infections. Older individuals are also at higher risk for developing bacteremia as a result of increased prevalence of immune deficiencies (ie, cancer, malnutrition, autoimmune diseases, and their associated medical therapies), periodontal disease, other infections such as pneumonia, or iatrogenic complications (eg, indwelling catheters, hemodialysis, noncardiac surgeries or procedures).⁵ Elderly patients with endocarditis may not manifest typical symptoms of infection or heart valve dysfunction, leading to delayed diagnosis at a more advanced stage of disease. As a result, major complications such as valve destruction and HF, or perivalvular abscess with progressive heart block, may be present at the time of endocarditis diagnosis, thus necessitating operative intervention.²⁴⁹ Management of endocarditis is similar in older and younger patients, but outcomes are worse in older patients with both medical and surgical treatments, largely because of higher complication rates and the impact of medical comorbidities.

Progressive fibrosis and calcification along with degeneration of the cardiac electrical system contribute to high rates of arrhythmias and conduction disturbances in older adults. At a cellular level, electrical impulse generation is slower, and there are more competing impulses from non-nodal atrial and ventricular tissues. At the clinical level, these changes explain why > 75% of pacemakers and > 50% of ICDs are placed in the Medicare population.¹ Because these processes increase the incidence of both bradyarrhythmias and supraventricular tachyarrhythmias, many elderly patients develop “sick sinus syndrome” or “tachy-brady syndrome,” in which symptoms such as fatigue, dyspnea, palpitations, dizziness, or falls may occur as a result of either slow or rapid ventricular heart rates.⁵ Short-term ambulatory monitoring (24-48 hours) or event monitoring is commonly used to identify these syndromes and verify the association of symptoms with arrhythmia. Exercise treadmill tests may be used to evaluate for stress-induced arrhythmias or chronotropic incompetence, and implantable loop recorders may be considered for patients with infrequent symptoms or falls.

Bradycardia, Heart Block, and Pacemakers

The progressive degeneration of sinus node pacemaker cells results in only 10% continuing to function normally by 75 years of age.⁵ Similar processes occur in the tissues surrounding the sinus node and within the conduction pathways, contributing to the development of sinoatrial exit block or atrioventricular nodal block. Simultaneously, autonomic input to the heart may change with advancing age, resulting in carotid sinus hypersensitivity, vagally mediated bradycardia, and lack of compensatory sympathetic upregulation. As a result, elderly patients experience high rates of symptomatic bradyarrhythmias, with symptoms ranging from lightheadedness, exertional intolerance, or syncope to more subtle presentations, such as confusion, fatigue, or falls.

In older patients with symptoms that may be attributable to a bradyarrhythmia, evaluation for potentially reversible causes is essential (see Chap. 86). Reduction in dosage or withholding of cardiac medications such as β-blockers, diltiazem, verapamil, digoxin, clonidine, or antiarrhythmic drugs may be necessary to improve symptoms. Other medications and medical conditions may contribute to bradycardia as well, such as anticholinergic effects of donepezil and related drugs, drug-drug interactions, or worsening of hepatic or renal clearance of medications. In addition, hypothyroidism, hypoglycemia, electrolyte disorders, and coronary ischemia may cause bradycardia (or mimic symptoms of bradycardia) and should be considered in the differential diagnosis. Indications for pacemaker placement in the geriatric population are similar to those recommended for younger patients.²³⁶

Supraventricular Tachyarrhythmias

The prevalence of supraventricular arrhythmias increases with age, and initial evaluation should include assessments for electrolyte disturbances, thyroid dysfunction, anemia, infection, pulmonary embolus, or structural cardiac disease, according to the patient’s clinical presentation. In the Baltimore Longitudinal Study of Aging, short runs of supraventricular arrhythmias were common in healthy older subjects rigorously screened to exclude those with overt CVD. These arrhythmias were not associated with coronary events, but 15% of these individuals developed AF during follow-up, as compared with < 1% of those without atrial runs.²⁶¹ Similar findings were noted among patients with nonsustained supraventricular arrhythmias during exercise, with 10% developing sustained tachyarrhythmias versus 2% of those without atrial runs on exercise testing.²⁶² In addition, the incidence of exercise-induced tachycardia increased from near zero among the youngest patient subgroup to approximately 10% in patients ≥ 90 years of age. In elderly patients, sinus node dysfunction may result in prolonged sinus pauses and associated symptoms after termination of a supraventricular tachyarrhythmia. When the tachy-brady syndrome occurs (as noted earlier), treatment of bradycardia may require a pacemaker to facilitate more intensive suppression of tachycardia.

Atrial Fibrillation and Flutter

AF is the most common sustained and clinically important supraventricular arrhythmia in the geriatric population. Nearly one in four adults will develop AF during their lifetime, with a marked increase with age from < 1% prevalence before 40 years of age to approximately 10% after 80 years of age (Fig. 65–8).²⁶³ In another study, the incidence of AF in men increased more than 50-fold with increasing age, from 21 per 100,000 people annually among individuals aged < 45 years to 1077 per 100,000 people annually among those aged 85 years and older.¹ In women, the increase was more than 150-fold, from 7 to 1204 per 100,000 people annually among those aged < 45 years versus ≥ 85 years. The increase in AF incidence and prevalence is in part attributable to age-related atrial fibrosis, atrial remodeling, and electrical signaling abnormalities. In addition, the increasing prevalence of hypertension, IHD, valve disease, lung disease, chemotherapy, cardiac or noncardiac surgery, diabetes, and other common medical comorbidities associated with the onset of AF contributes to the higher rates of AF with increasing age.

Presentation and Evaluation

As with other CVDs, elderly patients with AF may not experience typical symptoms such as palpitations or dizziness. These individuals frequently describe exertional intolerance, fatigue and malaise, altered cognition, or no symptoms at all.⁵ Some patients present with acute pulmonary edema as a result of the sudden loss of the atrial contribution to end-diastolic volume and cardiac output at the onset of AF, whereas others may experience syncope or falls. Unfortunately, AF is occasionally first recognized when a patient presents with a stroke, transient ischemic attack, or other systemic embolic event, or during monitoring following such an event.

The evaluation of new or recurrent AF is similar in geriatric patients as for younger populations, and includes thyroid and electrolyte assessments plus echocardiography to identify valvular heart disease, cardiomyopathy, pulmonary hypertension, or pericardial disease.²⁶⁴ Pulmonary embolism should be considered in sedentary older patients, as well as those recovering from recent surgery, especially in those with obesity or other risk factors for venous thromboembolic disease. In addition, obstructive sleep apnea is a common and often unrecognized cause or contributing factor to the development of AF in older patients.

Rate and Rhythm Management

Several randomized trials comparing rate-control and rhythm-control strategies have failed to show a significant difference between the two approaches with respect to major clinical outcomes, including stroke, other thromboembolic events, or death.^264,265 In one large trial involving older patients, the rhythm-control strategy was associated with more-frequent hospitalization for management of recurrent AF, although the use of ablation therapy in this study was uncommon.²⁶⁵ Despite these findings, maintenance of sinus rhythm (regardless of the strategy chosen) appears to be associated with better quality of life when compared with persistent or permanent AF,^266,267 and there is preliminary evidence to suggest that chronic AF is a risk factor for cognitive impairment in older adults.²⁶⁸ For these reasons, many clinicians recommend at least one attempt to restore sinus rhythm in patients with recent-onset AF, even in those who are minimally symptomatic.²⁶⁴ In addition, patients with persistent moderate or severe symptoms despite efforts to control the heart rate with medical therapy should be considered for rhythm control or, alternatively, ablation of the atrioventricular node with pacemaker implantation. Amiodarone is the most effective agent currently available for maintaining sinus rhythm in patients with AF, but it has an adverse side effect profile, particularly during long-term use, and interacts with a wide range of other medications commonly used by older adults^5,264 (see Chap. 87 for further discussion).

The use of catheter ablation procedures for management of AF in older patients is evolving. Few older patients were enrolled in the clinical trials evaluating catheter ablation, and older patients tend to have more adverse prognostic factors for ablation when compared to younger patients, including persistent or permanent rather than paroxysmal AF, large left atrial size, and more atrial fibrosis and scarring. Nonetheless, catheter ablation of AF appears to have similar efficacy and safety in carefully selected older patients.^269,270 Surgical ablation of AF using a modification of the Maze procedure is associated with long-term maintenance of sinus rhythm in up to 90% of patients, including older adults.²⁷¹ Although surgical ablation can be performed as a stand-alone procedure, it is usually performed in conjunction with CABG and/or valve surgery in patients with indications for those interventions.

Regardless of the approach taken to treat AF symptoms, prevention of thromboembolism is a critical component of AF management. Indeed, as noted in one survey of patients with CVD, older individuals wish to avoid stroke more than any other common adverse event, even death.²⁷² Not only does older age increase the risk of developing AF, but increasing age is also a potent risk factor for stroke among AF patients. In the Framingham Heart Study, approximately 1.5% of strokes in patients younger than 50 years of age were attributed to AF, whereas 23.5% of strokes were related to AF among patients aged ≥ 80 years.²⁷³ Accordingly, age > 75 years is incorporated as a major risk factor for stroke in the CHADS₂ score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke),²⁷⁴ and the more recent CHA₂DS₂-VASc algorithm (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) assigns 1 point for age 65 to 74 years and 2 points for age 75 years and older.²⁷⁵ Systemic anticoagulation therapy is recommended for all patients with CHA₂DS₂-VASc scores of 2 or greater,²⁶⁴ and because female sex adds an additional point to the overall score, all men ≥ 75 years old and all women ≥ 65 years old should be considered for anticoagulation.

Anticoagulation

One of the most common reasons for withholding anticoagulation in elderly patients with AF is concern about falls and fall-related bleeding. Several studies have demonstrated that the reduction in stroke risk is substantially greater than the risk of serious fall-related bleeding complications in patients with AF.^276,277 Furthermore, a meta-analysis of patients ≥ 75 years of age enrolled in 10 randomized trials of the new oral anticoagulant agents demonstrated no significant difference in bleeding risk with the new drugs when compared with warfarin, and similar efficacy for reduction of thromboembolic events as in younger patients.²⁷⁸ Although clinical trial patients are generally “healthier” than the broader population of older adults seen in clinical practice, the preponderance of evidence suggests that most elderly patients are candidates for anticoagulation therapy for AF, including those with frailty or perceived fall risk. Reduction in medication dosage should be strongly considered in elderly patients with increased bleeding risk (eg, apixaban 2.5 mg twice daily, rivaroxaban 15 mg daily, or dabigatran 75-110 mg twice daily).²⁷⁹

In patients at high risk for stroke, but with prohibitively high bleeding risk (eg, prior life-threatening bleeding or intracranial hemorrhage), several devices have been developed for reducing thromboembolism originating from the left atrial appendage (see Chap. 83). The Watchman device appears to be noninferior to warfarin therapy in selected patients younger and older than 75 years of age.²⁸⁰ The Lariat device cinches closed the mouth of the left atrial appendage using a transpericardial approach. Surgical amputation of the appendage is also an option for patients undergoing cardiac surgery for other indications. Although studies are needed in elderly patients, these procedural approaches provide an alternative to anticoagulation therapy in selected individuals with AF.

Atrial Flutter

Management of atrial flutter is similar in older and younger patients (see Chap. 83). The general approach is analogous to that discussed earlier for AF, except that catheter-based ablation of the flutter pathway has greater efficacy than for AF, and it is also more effective than antiarrhythmic drugs.^5,264,281 Thus, elderly individuals with isolated atrial flutter should be considered for catheter ablation, although periprocedural complication rates may be somewhat higher in older patients.

Ventricular Arrhythmias

Aging is associated with progressive fibrosis and degeneration of the infranodal electrical conduction pathways.⁵ As a result, isolated premature ventricular depolarizations, nonsustained runs of ventricular tachycardia, and sustained ventricular arrhythmias increase in frequency with age. In addition, chronic cardiac conditions such as IHD, cardiomyopathy, and left ventricular hypertrophy contribute to the higher incidence of these arrhythmias. In the Baltimore Longitudinal Study of Aging, in which individuals with ischemic ST-segment changes with exercise were excluded, isolated premature ventricular complexes were found in 0.5% of men aged 20 to 40 years versus 8.6% of men aged ≥ 60 years.²⁸² The age-related increase in ventricular ectopy was not associated with subsequent coronary events and was not observed in women.²⁶¹ Findings were comparable for exercise-induced ventricular arrhythmias.²⁸³ Management of ventricular arrhythmias is similar in older and young patients, including treatment of underlying HF, ischemia, valve disease, and electrolyte disorders (see Chap. 85).

The pervasive theme regarding CVD in the geriatric population is quite simple: elderly patients undergo structural and functional changes over time, which—in conjunction with long-standing exposure to cardiovascular risk factors and noncardiovascular comorbidities—result in higher prevalence, more advanced clinical presentations, and worse prognosis of nearly all forms of CVD. On the other hand, management becomes more complex with age, as most CVDs occur in the context of multiple other competing medical conditions, and medical and procedural therapies are associated with higher risks of complications. As a result, choosing the appropriate treatment often requires shared decision making, beginning at the onset of therapy and continuing throughout the disease course. Because most clinical trials have failed to enroll the oldest and frailest subjects, benefits and risks are uncertain in these patients, and treatment must be individualized according to patient and family preferences, particularly when quality of life is deemed to be more important than long-term survival.²⁸⁴ As our population continues to age, substantial additional research into CVD prevention and management in older adults is imperative.