Cardiac myosin-binding protein C is a novel marker of myocardial injury and fibrosis in aortic stenosis.

OBJECTIVE: Cardiac myosin-binding protein C (cMyC) is an abundant sarcomeric protein and novel highly specific marker of myocardial injury. Myocyte death characterises the transition from hypertrophy to replacement myocardial fibrosis in advanced aortic stenosis. We hypothesised that serum cMyC concentrations would be associated with cardiac structure and outcomes in patients with aortic stenosis. METHODS: cMyC was measured in two cohorts in which serum had previously been prospectively collected: a mechanism cohort of patients with aortic stenosis (n=161) and healthy controls (n=46) who underwent cardiac MRI, and an outcome cohort with aortic stenosis (n=104) followed for a median of 11.3 years. RESULTS: In the mechanism cohort, cMyC concentration correlated with left ventricular mass (adjusted β=11.0 g/m2 per log unit increase in cMyC, P<0.001), fibrosis volume (adjusted β=8.0 g, P<0.001) and extracellular volume (adjusted β=1.3%, P=0.01) in patients with aortic stenosis but not in controls. In those with late gadolinium enhancement (LGE) indicative of myocardial fibrosis, cMyC concentrations were higher (32 (21-56) ng/L vs 17 (12-24) ng/L without LGE, P<0.001). cMyC was unrelated to coronary calcium scores. Unadjusted Cox proportional hazards analysis in the outcome cohort showed greater all-cause mortality (HR 1.49 per unit increase in log cMyC, 95% CI 1.11 to 2.01, P=0.009). CONCLUSIONS: Serum cMyC concentration is associated with myocardial hypertrophy, fibrosis and an increased risk of mortality in aortic stenosis. The quantification of serum sarcomeric protein concentrations provides objective measures of disease severity and their clinical utility to monitor the progression of aortic stenosis merits further study. CLINICAL TRIAL REGISTRATION: NCT1755936; Post-results.

The relationship between preoperative frailty and outcomes following transcatheter aortic valve implantation: a systematic review and meta-analysis.

Aims: Transcatheter aortic valve implantation (TAVI) is an increasingly common intervention for patients with aortic stenosis deemed high risk for major cardiac surgery, but identifying those who will benefit can be challenging. Frailty reflects physiological reserve and may be a useful prognostic marker in this population. We performed a systematic review and meta-analysis of the association between frailty and outcomes after TAVI. Methods and Results: Five databases were searched between January 2000 and May 2015. From 2623 articles screened, 54 were assessed for eligibility. Ten cohort studies (n = 4592) met the inclusion criteria of reporting a measure of frailty with early (≤30 days) or late (>30 days) mortality and procedural complications following TAVI as defined by the Valve Academic Research Consortium (VARC). Frailty was associated with increased early mortality in four studies (n = 1900) (HR 2.35, 95% CI 1.78-3.09, P < 0.001) and increased late mortality in seven studies (n = 3159) (HR 1.63, 95% CI 1.34-1.97, P < 0.001). Objective frailty tools identified an even higher risk group for late mortality (HR 2.63, 95% CI 1.87-3.70, P < 0.001). Frail individuals undergoing TAVI have a mortality rate of 34 deaths per 100 patient years, compared with 19 deaths per 100 patient years in non-frail patients. There was limited reporting of VARC procedural outcomes in relation to frailty, preventing meta-analysis. Conclusion: Frailty assessment in an already vulnerable TAVI population identifies individuals at even greater risk of poor outcomes. Use of objective frailty tools may inform patient selection, but this requires further assessment in large prospective registries.