https://doi.org/10.1007/s00392-025-02625-4
1Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland
Background: Frailty is defined by increased vulnerability to stressors, and is associated with higher mortality, longer hospital stays and functional decline in patients with cardiovascular disease. However, evidence on frailty in transthyretin cardiac amyloidosis (ATTR) is lacking. We evaluated the Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment to assess frailty in these patients.
Methods: We conducted a prospective, single-centre, observational study of consecutive patients presenting to our specialised cardiac amyloidosis outpatient clinic between 02/2023 and 06/2024. Baseline data and disease-related quality of life were collected. The MPI score (range 0 to 1, with 1 indicating higher degree of frailty) was calculated from 63 separate items divided into eight domains including activities of daily living, instrumental activities of daily living, cognition, nutrition, pressure ulcer risk, comorbidity, polypharmacy and social support.
Results: Data of 173 patients were analysed. Median age was 81 (76-85), 160 (93%) were male. The mean MPI score was 0.25±0.12. 128 patients (80%) belonged to the MPI-1 group (low risk, 0-0.33), 35 (20%) to the MPI-2 group (intermediate risk, 0.34-0.66) and 0 patients to the MPI-3 group (high risk, >0.66). Patients in the MPI-2 group had significantly worse renal function, higher NT-proBNP, larger left atria, and more often a history of stroke (Table). In terms of functional parameters, patients in the MPI-2 group had a significantly lower 6-minute walk distance, a worse quality of life according to the Minnesota Living with Heart Failure Questionnaire, more limitations due to polyneuropathy and a worse NYHA class. There was a trend towards fewer patients receiving tafamidis in the MPI-2 group (p=0.055).
Conclusion: This is the first study to show that frailty according to a comprehensive geriatric assessment is common in ATTR cardiac amyloidosis and that it is associated with cardiac and non-cardiac morbidity and worse functional parameters. Understanding the role of frailty in this disease could improve risk assessment, inform treatment decisions and improve patient outcomes, particularly in light of new therapies such as tafamidis.
Table: Baseline patient characteristics in the total population and by frailty status according to MPI score
| Overall (n=173) | MPI 1 (n=138) |
MPI 2 (n=35) | p-value | |
| Age (years) | 81 (76-85) | 81 (76-84) | 81 (76-86) | 0,502 |
| Female | 13 (7,5) | 10 (7,2) | 3 (8,6) | 0,728 |
| NYHA class ≥ 3 | 29 (16,8) | 18 (13) | 11 (31,4) | 0,009 |
| 6-minute walk distance (m) | 376 ± 111 | 393 ± 112 | 306 ± 74 | <0,001 |
| Minnesota Living with Heart Failure Questionnaire | 23 (12-42) | 22 (11-38) | 41 (22-51) | 0,004 |
| R-ODS-Score (PNP) | 40 (32-43) | 41 (34-44) | 30 (24-38) | <0,001 |
| Decompensation with hospitalisation | 23 (13,3) | 15 (10,9) | 8 (22,9) | 0,091 |
| Tafamidis therapy | 161 (93,1) | 131 (94,9) | 30 (85,7) | 0,055 |
| NT-proBNP (pg/ml) | 1981 (987-3429) | 1845 (984-3002) | 2987 (1515-5593) | 0,005 |
| Troponin T (ug/L) | 0,042 (0,029-0,060) | 0,041 (0,028-0,058) | 0,050 (0,034-0,069) | 0,057 |
| GFR <60 ml/min | 107 (62) | 80 (58) | 27 (77) | 0,037 |
| Anemia (Hb < 13.0 g/dl ♂, < 12.0 g/dl ♀) | 48 (28) | 34 (25) | 14 (40) | 0,074 |
| History of stroke | 17 (9,9) | 9 (6,6) | 8 (23,5) | 0,007 |
| EF (%) | 60 (52-60) | 60 (52-60) | 60 (55-60) | 0,547 |
| GLS (%) | -13,38 ± 4,39 | -13,72 ± 4,4 | -11,88 ± 4,12 | 0,053 |
| IVSd (mm) | 16 (14-19) | 16 (14-19) | 16 (15-19) | 0,492 |
| LA volume index (ml/ m2) | 46,1 (37,5-56,3) | 45,2 (36,9 -54,9) | 53,6 (41,2-64,2) | 0,017 |