Transthyretin cardiac amyloidosis (ATTR-CA) predominantly affects older adults with multiple chronic conditions, leading to significant physical, cognitive, and emotional challenges. New disease-modifying drugs are effective in early stages, prompting a shift toward comprehensive assessments, including functional capacity and quality of life. However, these assessments may not fully capture the complexity of older ATTR-CA patients, especially regarding frailty and mood disorders, which can influence symptom reporting. Thus, integrating comprehensive geriatric assessment tools into routine clinical practice may be crucial to detect early signs of frailty or functional impairment that could impact outcomes and mitigate futility and ageism in the decision-making process. This review highlights the importance of evaluating multimorbidity, disability, and frailty in older patients with ATTR-CA to optimize management strategies.
Key words
cardiac amyloidosis; comprehensive geriatric assessment; frailty; prognosis; risk stratification
Abbreviations and Acronyms
6MWT6-minute walking testAFatrial fibrillationATTR-CATransthyretin cardiac amyloidosisCAcardiac amyloidosisCFSClinical Frailty ScaleCGAcomprehensive geriatric assessmentHFheart failureSPPBShort Physical Performance Batte
Transthyretin cardiac amyloidosis: the need for an integrated approach
Transthyretin cardiac amyloidosis (ATTR-CA) derives by the deposition of misfolded transthyretin (TTR) as amyloid fibrils in the heart interstitium. While wild-type ATTR is sporadic, aging-associated, and observed mostly in older men1, 2, 3, 4 and accounts for up to 15% of all cases of heart failure (HF) after the age of 80 years, hereditary ATTR is heterogeneous in presentation (from exclusively cardiac to neurologic or to a mixed phenotype).2 Whenever red flags are present in a HF patient, the diagnosis must be promptly suspected to facilitate early diagnosis and improve outcomes.5
ATTR-CA is the quintessential form of HF with preserved ejection fraction in older individuals with upward and leftward shifts in the end-diastolic pressure volume relation leading to small ventricular chambers with high filling pressures: these patients present with multiple geriatric competing risks3 such as ischemic heart disease, atrial fibrillation (AF), hypertension, diabetes, and stroke, which contribute to a higher risk of disability or functional impairment.6,7 Multimorbidity and related polypharmacy increase the risk of drug-drug interactions with adverse events. Furthermore, advanced disease stage may be associated with worse neuro-autonomic dysfunction (particularly in hereditary ATTR) and need for diuretics, which are predictors of adverse outcomes8,9 and are linked to increased risk of syncope and falls. Means of assessing the degree of this complexity and its long-term outcome is currently an unmet need. As such, patients with ATTR-CA may benefit from a tailored management strategy based on the comprehensive geriatric assessment (CGA), which takes into consideration a broad spectrum of clinical and functional domains