Angiotensin-converting enzyme inhibitors attenuate circulating CAF22 and physical decline in congestive heart failure: Diagnostic implications of CAF22.

Aims: Age-associated muscle loss, termed sarcopenia is the major cause of physical disability in patients with congestive heart failure (CHF). Angiotensin-converting enzyme inhibitors (ACEi) are commonly used to treat CHF patients; however, their impacts on the neuromuscular junction (NMJ) and sarcopenia in CHF patients remain poorly understood. We aim to investigate the potential impact of ACEi on NMJ and CHF-induced sarcopenia.

Methods: The cardiac function, short physical performance battery, handgrip strength (HGS), appendicular skeletal mass index, gait speed (GS) and plasma c-terminal agrin fragment-22 (CAF22), a marker of NMJ degradation, were assessed in controls (n = 81) and CHF patients treated with (n = 134) or without (n = 145) ACEi.

Results: Irrespective of treatment, HGS and GS, indicators of sarcopenia, were profoundly declined in the patients with CHF vs. controls. However, patients on ACEi demonstrated significantly better HGS and GS compared to non-ACEi patients (P < .001). The level of CAF22 was significantly lower (P < .0001) in the ACEi-treated compared to non-ACEi CHF patients. Further, the level of CAF22 was inversely correlated (R² = .33, P < .0001) with HGS in both ACEi and non-ACEi CHF patients, while CAF22 was inversely correlated with GS and short physical performance battery only in ACEi-treated but not in patients on other therapies without ACEi. The receiver operating characteristic curve analysis revealed CAF22 as a potential diagnostic marker (95% confidence interval: 0.785-0.883; P < .0001) for CHF.

Conclusion: Collectively, these findings strongly suggest that ACEi limits CHF-induced neuromuscular disjunction and physical disability in CHF. CAF22 has shown diagnostic implications for CHF.