Accelerated Cardiac Aging in Patients With Congenital Heart Disease

Abstract

An increasing number of patients with congenital heart disease (CHD) survive into adulthood but develop long-term complications including heart failure (HF). Cellular senescence, classically defined as stable cell cycle arrest, is implicated in biological processes such as embryogenesis, wound healing, and aging. Senescent cells have a complex senescence-associated secretory phenotype (SASP), involving a range of pro-inflammatory factors with important paracrine and autocrine effects on cell and tissue biology. While senescence has been mainly considered as a cause of diseases in the adulthood, it may be also implicated in some of the poor outcomes seen in patients with complex CHD. We propose that patients with CHD suffer from multiple repeated stress from an early stage of the life, which wear out homeostatic mechanisms and cause premature cardiac aging, with this term referring to the time-related irreversible deterioration of the organ physiological functions and integrity. In this review article, we gathered evidence from the literature indicating that growing up with CHD leads to abnormal inflammatory response, loss of proteostasis, and precocious age in cardiac cells. Novel research on this topic may inspire new therapies preventing HF in adult CHD patients.

Biological Age in Congenital Heart Disease—Exploring the Ticking Clock

“…The observation of more age-related complications at a younger age, as described above, raised the hypothesis of an elevated biological age in patients with CHD [9,39]. A higher biological age than chronological age is also known as accelerated aging.…”

“…The newly aging group of patients with CHD has come into the spotlight. Namely, the impact of imperfect hemodynamics as well as early life traumas resulting from often repeated early life surgeries and hospitalizations on the lifespan of these patients needs to be assessed [9,11,39]. Data indeed suggest a higher pace of aging in patients with CHD [9,39].…”

“…Namely, the impact of imperfect hemodynamics as well as early life traumas resulting from often repeated early life surgeries and hospitalizations on the lifespan of these patients needs to be assessed [9,11,39]. Data indeed suggest a higher pace of aging in patients with CHD [9,39]. This is illustrated in Figure 1, showing that surgery and residual lesions impact the aging dynamics thus accelerating the development of age-related comorbidities.…”

“…When assessing the unique health challenges faced by individuals with CHD, it is clear that factors such as the congenital heart defect itself, the (multiple) surgeries and interventions, the early life exposure to radiation, and the often incomplete correction of congenital heart lesions could collectively subject the patient to a considerable degree of physical, metabolic, and psychological stress [39]. All these stressors, mainly encountered in early life, have the potential to induce premature aging.…”

Coagulation Profile in Neonates with Congenital Heart Disease: A Pilot Study

“…Congenital heart disease (CHD) is the most common congenital anomaly, with an estimated prevalence of moderate to severe CHD, about 6 cases per 1000 births [1]. They are typically classified into cyanotic and acyanotic.…”