Commentary based on Jaiswal A, Gadela NV, Baran D, et al. Clinical outcomes of older adults listed for heart transplantation in the United States. J Am Geriatr Soc 2021;69:2507-17.¹

Top 5 Take-Home Points (A Geriatric Cardiology Perspective):

• Chronological age in isolation should not preclude candidacy for heart transplantation (HT) and/or mechanical support.
• The routine assessment of clinical frailty in older patients with advanced heart failure is necessary to risk stratify patients for advanced therapies but has yet to widely penetrate clinical practice.
• In addition to survival, function and quality of life should be a routine outcomes measure in older patients with advanced heart failure to evaluate the efficacy of heart failure therapeutics and interventions.
• A careful multi-disciplinary assessment including a focus on geriatric syndromes (falls, incontinence, cognitive dysfunction and mood disorders, etc.) is essential in evaluating older adults for advanced heart failure therapies including HT and ventricular assist devices (VAD).
• Future studies of advanced heart failure therapies would ideally include geriatric focused outcome measures including days alive out of hospital or home days, gait speed and function, especially mobility, to better inform patients and their caregivers in order to facilitate shared decision making.

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Rationale for Study:
The overall goal was to determine if age ≥70 should be a relative contraindication to transplant. To accomplish this goal, researchers compared waitlist and post-transplant outcomes between patients >70 years and those younger than 70 years.

Funding: N/A

Methods

Study Design: Retrospective cohort

Cohort: Patients >18 listed for HT from January 2000-August 2018 in the United States (US) as reported in the Scientific Registry of Transplant Recipients (SRTR)

Exposure: Age ≥70 at time of listing for HT

Outcome(s):

• Temporal and geographic trends for HT listings by age group
• Waitlist mortality and incidence of HT by age group (>70 vs. <70)
• 5-year mortality post-transplant mortality by age group (≥70 vs. <70)
• Additional outcomes: 1-year mortality, episodes of graft failure, and stroke

Statistical Analysis:

• Evaluated temporal and geographic trends for HT by age group using Cochran-Mantel-Haenszel test
• Differences in waitlist mortality and incidence of HT by age group were evaluated using an adjusted Fine and Gray competing risk regression model
• Kaplan-Meier method and log-rank test to detect differences in post-transplant mortality by age group (≥70 vs. <70)
• Cox proportional hazards regression models to estimate the association between age group and mortality controlling for serum creatinine, body mass index (BMI), ischemic time, total Mortality Prediction After Cardiac Transplantation (IMPACT) score, donor-recipient predict heart mass (PHM) ratio, and time on waitlist
• Evaluated incidence of stroke and graft failure between age groups using multiple logistic regression models adjusted for relevant risk factors

Results:
The analysis included 57,285 adults ≥18 years of age listed for HT, of which 1,203 (2.1%) were ≥70 years of age. Notably, the proportion of those patients listed as septuagenarians increased from 25% (n=30) in 2000 to 11% (n=132) in 2017. Geographic areas with the highest proportions of septuagenarian listings were California, Texas and New York. Compared with patients <70, those listed at ≥70 were more likely to be White (87.4% vs. 75.7%), have a history of ischemic cardiomyopathy (52.8% vs. 34.3%) with more medical comorbidities. Septuagenarians had lower rates of previous extracorporeal membrane oxygenation (ECMO) use (0.3 vs. 1.2%) but higher left ventricular assist device (LVAD) use (18.8% vs. 18.0%) and a shorter time on the waitlist compared to their younger counterparts (median 46 vs. 103 days).

Waitlist outcomes showed a similar cumulative incidence of death between age groups (sub-hazard ratio [SHR] 0.96, 95% confidence interval [CI] 0.79-1.16), however older patients listed for HT were more likely to be transplanted than their younger counterparts (SHR 0.1.49, 95% CI 1.37-1.62). Compared with those ≤70, septuagenarians were more likely to be transplanted from the waitlist (SHR 1.49, 95% CI 1.37-1.62). For those who received HT, 1-year and 5-year mortality in the ≥70 and ≤70 groups were 11.5% versus 10.4% and 20.4% versus 19.2%. While unadjusted Kaplan-Meier analyses showed lower survival in those ≥70 (log-rank p=0.03), Cox proportional hazards model adjusted for recipient creatinine, BMI, ischemic time, Index for the IMPACT score, PHM ratio, and time on the waitlist, revealed no significant difference in 5-year mortality by age group (HR 1.06, 95% CI 0.91-1.25). Stroke incidence was higher in those ≥70 compared to those <70 (3.5% vs. 2.5%, OR 1.71, 95% CI 1.03-2.84), the majority of which occurred ≥3 years post-transplant. Additionally, the incidence of graft failure was similar in both age groups (1.5 vs. 1.8%, OR 0.92, 95% CI 0.52-1.65).

Limitations of study:
Limitations include the retrospective, observational nature of the study, and the lack of assessment of clinical frailty, which may confound the relationship between age and transplant outcomes.

Expert Article Review: Until recently, little was known regarding trends and outcomes for cardiac transplantations in septuagenarian patients in the contemporary era. To answer this question, Jaiswal et al. published an article in the Journal of the American Geriatric Society examining outcomes among 57,285 patients listed for HT from January 2000-August 2018 using the Scientific Registry of Transplant Recipients (SRTR).¹ The main findings from the study were that the number of septuagenarians being listed for HT is increasing over time. Further, patients ≥70 had similar waitlist mortality compared to those patients ≤70 with similar post-transplant survival. The authors report a higher rate of stroke and similar rate of graft failure in septuagenarians compared to younger recipients.

When interpreting the results of this interesting analysis, it is important to remember that septuagenarians who are listed for HT represent a highly selected group with lower rates of frailty, comorbidity and higher functional status compared to their unlisted counterparts. When taking this into account, it is however reasonable to conclude that chronologic age alone should not preclude one from HT. As was outlined by the Frailty Heart Workgroup during a 2020 consensus conference on frailty in HT, there is a need for objective frailty assessment tools for risk stratification in patients with advanced heart failure, especially as the proportion of patients being referred for HT are of higher chronological age.² Overall, a careful multi-disciplinary assessment including a focus on geriatric syndromes such as falls, incontinence, cognitive dysfunction, mood disorders, etc. will be essential in evaluating older adults for advanced heart failure therapies including HT and VAD. Future analyses may focus on routine, systemic assessment of frailty, resilience, comorbidity, and functional status as part of the HT evaluation in septuagenarians to optimize outcomes with HT in this population.

References

1. Jaiswal A, Gadela NV, Baran D, et al. Clinical outcomes of older adults listed for heart transplantation in the United States. J Am Geriatr Soc 2021;69:2507-17.
2. Kobashigawa J, Shah P, Joseph S et al. Frailty in heart transplantation: report from the heart workgroup of a consensus conference on frailty. Am J Transplant 2021;21:636-44.

Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support, Geriatric Cardiology

Keywords: Creatinine, Heart-Assist Devices, Extracorporeal Membrane Oxygenation, Quality of Life, Body Mass Index, Proportional Hazards Models, Retrospective Studies, Transplant Recipients, Frailty, Logistic Models, Caregivers, Confidence Intervals, Accidental Falls, Mood Disorders, Decision Making, Shared, Functional Status, Heart Transplantation, Heart Failure, Risk Factors, Registries, Stroke, Comorbidity, Outcome Assessment, Health Care, Contraindications, Cardiomyopathies, Risk Assessment, Hospitals

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