The Heterogeneity of Old Age: Healthy Aging in Older Adults Undergoing TAVR

“From the classics one learned that old age began at fifty-five to sixty. This conventional wisdom, derived from the age ladder of Hippocrates, was endlessly repeated. According to Hippocrates, a springtime of old age might be defined up to 70; a green old age from 70 to 75; “real” old age, 75 to 80; an ultimate, 80-90; and caducity, 90 onward, by which death was both certain and welcome”, Peter N. Stearns; Old Age in European Society: The Case of France.

Healthy aging, prolongation of life, and immortality have been addressed by writers and scholars from the ancient to the contemporary times. Predating Homer’s writings by 1,500 years, the ancient Mesopotamian poems, the Epic of Gilgamesh, sought to explore ways to increase longevity and attain an eternal life. Later, the ancient Greeks put more emphasis on chronologic age and divided the lifespan into four age categories with old age beginning at sixty.(1) In modern times, chronologic age became more prominent in society with the introduction of the retirement age and the inclusion in the Medicare Programs. When Medicare was initiated in 1965, the life expectancy in the U.S. was 70.2 years. Between 1965 and 1984, the life expectancy increased by 15% and in 2019, Medicare covered more than 63 million Americans above 65 years of age. This massive growth of the older adult population introduced several clinical conditions that are more prevalent at very old age.

Cardiovascular disease is closely associated with aging. Several clinical cardiovascular conditions are more prevalent at older age including severe symptomatic aortic stenosis. The introduction of transcatheter heart valves for the management of valvular heart disease presented many geriatric concepts to cardiovascular studies that influenced outcomes and were considered important for success of structural interventions. These include frailty syndrome, physical disability, cognitive decline, dementia, loneliness, and others. In clinical context, these conditions do not fit into one disease category, and thus they are collectively termed by gerontologists as “geriatric syndromes”. These conditions modify our ability to treat older patients successfully with invasive cardiovascular therapeutics. Patients with the highest burden of these age-associated conditions are at increased risk of complications during interventions including thrombotic and bleeding complications, extended hospital stays, readmission, and mortality.(2,3) Cardiovascular complications in turn lead to bed rest, immobility, delirium, and muscle wasting, all of which lead to worsening of these geriatric conditions. For these reasons, attention to these conditions at the extremes of age remains critical as we attempt more complex structural interventions among older adults.(4,5)

In this issue of JACC: Cardiovascular Interventions, Strange et al(6) used the Danish nationwide administrate registry to identify older patients >60 years of age who underwent first-time TAVR in Denmark from 2014 to 2021 and who were alive at discharge. The primary outcome of the study was first time admission to a nursing home and a secondary outcome was the cumulative incidence of competing risk of death. The main findings of this study are: (1) the rate of admission to nursing homes for TAVR was 6.3% (95% CI 5.5% to 7.1%) and that rate is similar to age and gender matched controls from the general population; (2) the incidence of nursing home admission increases by three-fold at the extreme of advanced age at 11.6% (95%CI: 8.5 to 13.8%); and most importantly (3) factors that were associated with nursing home admissions were older age, frailty, living alone, and the presence of atrial fibrillation (Figure 1).

Figure 1.

The Heterogeneity of Old Age: Healthy Aging in Older Adults Undergoing TAVR. Two thirds of older adults more than 85 years of age are discharged alive to their homes after TAVR, but the burden of geriatric syndromes determine the rate of admission to nursing home facilities.

This study has several strengths. The authors have shown that TAVR procedures are effective in treating severe symptomatic aortic stenosis even at extremes of age. Two out of three patients above 85 years of age were discharged home alive after their index TAVR admission. These estimates come counter to earlier arguments that TAVR procedures should not be performed in older adults at extreme age because of futility and limited life expectancy.(7) Second, the study makes it clear that when considering TAVR procedures, distinctions between “young-old” versus “old-old” patients are necessary because the older group have 3-fold increased risk for nursing home admissions and much higher burden of geriatric syndromes. This highlights the fact older adults above 85 years often have distinct underlying biologic changes including unique hemodynamic profiles, poor renal function, lower muscle mass, and metabolic dysregulation that affect their response to therapy and predispose them to higher risk of hospital complications. Refinement in the assessment of risk profile for these older patients must be nuanced to include evaluation of the burden of frailty, cognitive impairment, functional assessment, and social support. These factors may ultimately influence the long-term success of transcatheter heart procedures at extremes of age. An apparent weakness of the study lies in its external validity to countries outside Denmark. In the Danish registry, a granular description of the age-associated risks is not clearly described making direct comparisons to U.S. population challenging. Finally, many clinicians tend to refer older adults ≥85 years of age to nursing home after their index TAVR admission resulting in selection bias in the incidence rate ratio towards the “old-old” group.

Studying geriatric syndromes in the context of cardiovascular interventions could be helpful not only in predicting procedural success, but also in efforts for defining futility. Futility has been defined as “an advanced curative and life-prolonging treatments that would almost certainly result in a quality of life the patient has previously stated that he or she would not want” or “when there is no reasonable expectation that the patient will improve sufficiently to survive outside the acute care setting”.(8) This highlights the importance of establishing the goals of care for the “old-old” patients from the outset as part of the work-up for structural heart disease intervention.(9) What matters most to patients in the face of increasingly complex decisions should be evaluated in a structured fashion to focus on patient priorities, core domains, and transition planning. The involvement of a specialist in geriatric cardiology for older adults above 85 years is critical for assessing these needs that extend beyond an assessment of chronologic age alone.

Advancement in cardiovascular interventions have resulted in improving the lifespan of cardiac patients, but a larger impact of the field should also focus on limiting disability and enhancing quality of life after structural interventions. The World Health Organization defines healthy aging as “the process of developing and maintain the functional ability that enables wellbeing in older age”.(10) One intervention to foster healthy aging is cardiac rehabilitation, a comprehensive secondary prevention cardiovascular disease management program that utilizes exercise training, behavioral modification, education, and psychosocial counseling to improve both clinical and functional outcomes following cardiovascular interventions. The beneficial effects of cardiac rehabilitation programs extend to improvement in mortality, and rehospitalization, as well as improved cardiorespiratory fitness, physical function, self-efficacy, and quality of life. Recent studies are now using the platform of cardiac rehabilitation as an opportunity to develop personalized approaches to cardiovascular therapeutics within the context each patient’s aggregate healthcare challenges.(11)

While clinical differences across chronologic ages are an important consideration, heterogeneity of aging within the same chronologic age groups is also crucial to contemplate. In fact, in modern times, measures of chronologic aging are increasingly being deemphasized in favor of measures of biological or physiologic aging, such as geriatric syndromes, when evaluating patients for invasive cardiovascular therapeutics.(11) Biological age becomes even more important in later stages of life, with stronger associations with patient’s functional abilities and health trajectory following invasive cardiovascular procedures and more influence on outcomes.(12) Several pragmatic trials focused on enrolling more representative populations of older adults are underway. Efforts to standardize the data collected from older adults are needed for functional abilities, burden of frailty, cognitive impairment, muscle mass, social support, and other issues of cardiovascular aging. The pragmatic device trials will also ensure the capture of more patient-centered outcomes sensitive to change beyond mortality and major adverse cardiovascular events.

The age ladder of Hippocrates was helpful in recognizing that there are clear distinctions between “young-old” and “old-old”. As the population ages further, refinement in our approach to aging continues particularly for interventional cardiologists who are on the quest to improve procedural success, limiting risk, and extending quality of life for conditions that are most prevalent at extremes of age. The next step for our field is to fine-tune how we distinguish healthy aging from pathologic aging in our oldest patients, while developing tools to capture the nuanced heterogeneity of aging for our most vulnerable patients undergoing invasive cardiovascular procedures.