Frailty in Advanced Heart Failure: A Consequence of Aging or a Separate Entity?

Abstract

There are over 5 million Americans with heart failure (HF), the majority of whom are over age 65. Frailty is a systemic syndrome associated with aging that produces subclinical dysfunction across multiple organ systems and leads to an increased risk for morbidity and mortality. The prevalence of frailty is about 10% in community-dwelling elderly and 20% in those with advanced HF, and increases in both cohorts with age. Yet the relationship between the primary frailty of aging and frailty secondary to HF remains poorly defined. Whether the frailty of these two populations share similar etiologies or exist as separate entities is unknown. Teasing apart potential molecular, cellular, and functional differences between the frailty of aging and that of advanced HF has implications for risk stratification, quality of life, and pharmacological and therapeutic interventions for advanced HF patients.

Keywords: frailty; geriatric cardiology; heart failure; sarcopenia.

Figure 1

Progression to frailty in aging and heart failure. The primary frailty of aging and HF-related frailty have significant similarities. Older age and multiple medical problems are risk factors for the development of both types of frailty. The pathophysiological mechanisms of both include elevated inflammatory markers (ie, TNFα and IL-6), as well as dysregulated neurohormonal systems (ie, cortisol and insulin signaling). With respect to skeletal muscle, both groups have evidence of mitochondrial dysfunction and a shift in the cellular architecture of the muscle fibers. These molecular and structural changes result in decreased aerobic capacity, impaired functional status, and ultimately increased morbidity and mortality.