Weak grip, slow rise - associations with cardiac enzymes and NYHA functional class: handgrip strength and chair rise test performance as potential prognostic markers in cardiac ATTR and AL amyloidosis

Background and Purpose

Cardiac Amyloidosis (CA) is a progressive infiltratory cardiomyopathy which is associated with skeletal muscle weakness and reduced physical performance and frequently affects the elderly. New York Heart Association (NYHA) functional class, NT-proBNP and high-sensitive Troponin T (hsTNT) are well-established markers of disease severity and prognosis in CA. Validated measures of muscle strength are hand grip testing (HG) and 5 times chair rise test performance (5CRT), but their clinical utility in CA is currently not known.

We aimed to investigate whether HG and 5CRT performance associate with NYHA functional class, NT-proBNP and hsTNT in patients with CA.

Methods

This is a cross-sectional analysis of ambulatory patients with transthyretin (ATTR) and light chain (AL) CA presenting at the Amyloidosis Centre of our University Hospital in Germany. Diagnosis of CA was ascertained by tissue biopsy or non-invasive diagnostic algorithms. Patients underwent standardized assessments. NYHA stage was determined by the treating physician. HG was measured with a hydraulic dynamometer, the 5CRT was performed on a chair without armrests with arms crossed.

Low HG performance was defined as <27 kg for men and <16 kg for women. Low 5CRT performance was defined as >15 sec to complete 5 rises. NT-proBNP and hsTNT levels between low and normal muscle performance groups were analysed by the Kruskal-Wallis test, NYHA class distributions between performance groups was analysed by the chi-square test.

Results

146 patients were included in this study. 78.1% had ATTR- and 21.9% had AL- CA. Mean (SD) age was 76 (8) years, 79.5% were men. Median (quartiles) NT-proBNP was 1803 (790, 3815) pg/ml and hsTNT was 39 (26, 58) pg/ml. 13.7% had NYHA I, 46.6% had NYHA II, 39.7% had NYHA III. Low HG was found in 53 (36%) and low 5CRT in 91 (62%).

Low HG was associated with higher NT-proBNP (median 2438 pg/ml in low HG vs 1509 pg/ml in normal HG, p= 0.015) and hsTNT (median 46.4 pg/ml in low HG vs 35.3 pg/ml in normal HG, p= 0.005). Low 5CRT was significantly associated with higher hsTNT (median 42.8 pg/ml in low 5CRT vs 33.6 pg/ml in normal 5CRT, p= 0.037), but not with higher NT-proBNP (p= 0.156).

Patients with low HG exhibited higher NYHA stages than patients with normal HG (NYHA I 6 (11.3%) vs 14 (15.1%), NYHA II 19 (35.8%) vs 49 (52.7%), NYHA III 28 (52.8%) vs 30 (32.3%), p= 0,049). Patients with low 5CRT also exhibited higher NYHA stages than patients with normal 5CRT (NYHA I 6 (6.6%) vs 14 (25.5%), NYHA II 36 (39.6%) vs 32 (58.2%), NYHA III 49 (53.8%) vs 9 (16.4%), p <0,001).

Conclusion

In patients with ATTR- and AL-CA simple measures of skeletal muscle strength - HG strength and 5CRT - associate with established prognostic factors – NT-proBNP, hsTNT and NYHA functional class. Therefore HG and 5CRT may also serve as pragmatic predictors of adverse outcome in CA patients. Prospective cohort studies should elucidate their prognostic impact.median NT-proBNP and hsTNT by subgroupsFor image description, please refer to the figure legend and surrounding text.NYHA Stages by performance groupsFor image description, please refer to the figure legend and surrounding text.