Frailty in Wild-Type Transthyretin Cardiac Amyloidosis: The Tip of the Iceberg

Abstract

ATTRwt-CA occurs in elderly patients and leads to severe heart failure. The disease mechanism involves cardiac and extracardiac infiltration by amyloid fibrils. The objectives of this study are to describe the frailty phenotype in patients with ATTRwt-CA and to assess the associations between frailty parameters, the severity of cardiac involvement, and the course of amyloid disease. We used multidimensional geriatric tools to prospectively assess frailty in patients with ATTRwt-CA consulting (in 2018–2019) in the French National Reference Center for Cardiac Amyloidosis. We included 36 patients (35 males; median age: 82 years (76–86). A third of the patients were categorized as NYHA class III or IV, and 39% had an LVEF below 45%. The median serum NTproBNP was 3188 (1341–8883) pg/mL. The median duration of amyloidosis was 146 months (73–216). The frequency of frailty was 50% and 33% according to the physical frailty phenotype and the Short Emergency Geriatric Assessment questionnaire, respectively. Frailty affected a large number of domains, namely autonomy (69%), balance (58%), muscle weakness (74%), malnutrition (39%), dysexecutive syndrome (72%), and depression (49%). The severity of CA was significantly associated with many frailty parameters independently of age. Balance disorders and poor mobility were also significantly associated with a longer course of amyloid disease. Frailty is frequent in patients with ATTRwt-CA. Some frailty parameters were significantly associated with a longer course of amyloid disease and CA severity. Taking into account frailty in the assessment and management of ATTRwt should improve patients’ quality of life.

Implications of Extra-cardiac Disease in Patient Selection for Heart Transplantation: Considerations in Cardiac Amyloidosis

“…34,35 Frailty is estimated to occur in 33-50% of patients with wild-type ATTR cardiac amyloidosis, in domains including (among others) autonomy, balance and muscle weakness. 36 Such estimates are generally comparable to the prevalence of moderateto-severe malnutrition and frailty among all patients evaluated for heart transplantation, but their prevalence after heart transplantation in cardiac amyloidosis has been reported only occasionally. 23,32,31 Their effect on survival in heart transplant recipients with amyloidosis has not been ascertained.…”

Assessment and Management of Older Patients With Transthyretin Amyloidosis Cardiomyopathy: Geriatric Cardiology, Frailty Assessment and Beyond

“…Vitreous opacities causing blurred vision occur mostly with certain ATTRh genotypes ( 4 , 32 ). Lastly, hearing loss is common in ATTRwt ( 37 ), which may promote social isolation and depression and contribute to frailty in older patients ( 38 , 39 ).…”

“…Frailty was also associated with all-cause mortality independent of ATTR-CM disease stage ( 62 ). Another report examining frailty phenotype in ATTRwt patients found a prevalence of frailty of 50% and 33% using the physical frailty phenotype and Short Emergency Geriatric Assessment questionnaire, respectively ( 38 ). Balance disorders and poor mobility were associated with duration of amyloid disease ( 38 ).…”

“…Another report examining frailty phenotype in ATTRwt patients found a prevalence of frailty of 50% and 33% using the physical frailty phenotype and Short Emergency Geriatric Assessment questionnaire, respectively ( 38 ). Balance disorders and poor mobility were associated with duration of amyloid disease ( 38 ). The severity of cardiac amyloidosis was also associated with multiple frailty domains independent of age ( 38 ).…”

“…Balance disorders and poor mobility were associated with duration of amyloid disease ( 38 ). The severity of cardiac amyloidosis was also associated with multiple frailty domains independent of age ( 38 ). Frailty evaluation has become an important component of evaluation and risk prediction prior to cardiovascular therapeutic interventions such as TAVR and CABG, and it has been speculated that assessing frailty may be similarly predictive of response to novel disease modifying therapy for ATTR-CM patients ( 62 , 63 ).…”