Phenotypes of vulnerability and prognosis in older adults with cardiovascular disease

In older adults with cardiovascular disease (CVD), functional status, rather than comorbidities, is often more relevant to prognosis.1 Yet, most routine monitoring and prognostic algorithms were developed in younger or trial-selected populations and overlook functional and nutritional domains, which increase the likelihood of long-term disability.2–5 As octogenarians and nonagenarians are increasingly evaluated for complex clinical conditions like transthyretin cardiac amyloidosis (ATTR-CA)6 or therapeutic procedures like transcatheter aortic valve implantation (TAVI), the need for individualized risk assessment beyond traditional metrics has become pressing. In the present study, we assessed whether a simple, hierarchical model based on physical performance, malnutrition, and disability identifies reproducible vulnerability phenotypes associated with all-cause mortality, irrespective of CVD and optimal medical treatment. We prospectively evaluated 1086 consecutive TAVI, ATTR-CA, or chronic heart failure (HF) patients aged ≥ 75 years who underwent standardized comprehensive geriatric assessment (CGA) across seven Italian tertiary centres from 2019 to 2023 (Florence, Bologna, Turin, Rome, Naples, Ferrara, Padua; Careggi University Hospital Ethics Committee: 22586_oss, P/903/253). After excluding 130 individuals with incomplete CGA, 956 patients were included. Functional status, nutrition, and physical performance were assessed using the Basic Activities of Daily Living (BADL, disability: preserved BADL ≤ 3), the Mini Nutritional Assessment-Short Form (MNA-SF, malnutrition ≤11), and the Short Physical Performance Battery (SPPB, available only for 796 individuals, impaired mobility: SPPB ≤ 6).7,8 Short Physical Performance Battery was not assessed in participants with disability (BADL ≤ 3), as they were unable to perform the test and was used to re-stratify those with BADL > 3.