Significant efforts are currently undertaken to reduce functional mitral regurgitation (FMR) in patients with chronic heart failure in the hope to improve prognosis. We aimed to assess the prognostic impact of FMR in heart failure with reduced ejection fraction (HFrEF) under optimal medical therapy (OMT) and various conditions of HFrEF. We further intended to identify a heart failure phenotype, where FMR is most likely a driving force and not a mere bystander of the disease. We prospectively included 576 consecutive HFrEF patients into our long-term observational study. Functional [i.e. New York Heart Association (NYHA) class], echocardiographic, invasive haemodynamic, and biochemical (i.e. NT-proBNP, MR-proANP, MR-proADM, CT-proET-1, copeptin) measurements were performed at baseline. During a median follow-up of 62 months (interquartile range 52-76), 47% of patients died. Severe FMR was a significant predictor of mortality [hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.34-2.30; P < 0.001], independent of clinical (adjusted HR 1.61, 95% CI 1.22-2.12; P = 0.001), and echocardiographic (adjusted HR 1.46, 95% CI 1.09-1.94; P = 0.01) confounders, OMT (adjusted HR 1.81, 95% CI 1.25-2.63; P = 0.002), and neurohumoral activation (adjusted HR 1.38, 95% CI 1.03-1.84; P = 0.03). Subanalysis revealed that severe FMR was associated with poor outcome in an intermediate-failure phenotype of HFrEF i.e. patients with NYHA class II (adjusted HR 2.17, 95% CI 1.07-4.44; P = 0.03) and III (adjusted HR 1.80, 95% CI 1.17-2.77; P = 0.008), moderately reduced left ventricular function (adjusted HR 2.37, 95% CI 1.36-4.12; P = 0.002), and within the second quartile (871-2360 pg/mL) of NT-proBNP (adjusted HR 2.16, 95% CI 1.22-3.86; P = 0.009). In a patient cohort under OMT, the adverse prognostic impact of FMR is given predominantly in a sub-cohort of a specific intermediate-failure phenotype-well-defined functionally, haemodynamically, biochemically, and morphologically.

Objective Patients with cancer may display elevated levels of B-type natriuretic peptide (BNP) and high-sensitive troponin T (hsTnT) without clinical manifestation of cardiac disease. This study aimed to evaluate circulating cardiovascular hormones and hsTnT and their association with mortality in cancer. Methods We prospectively enrolled 555 consecutive patients with a primary diagnosis of cancer and without prior cardiotoxic anticancer therapy. N-terminal pro BNP (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), copeptin, hsTnT, proinflammatory markers interleukin 6 (IL-6) and C reactive protein (CRP), and cytokines serum amyloid A (SAA), haptoglobin and fibronectin were measured. All-cause mortality was defined as primary endpoint. Results During a median follow-up of 25 (IQR 16–31) months, 186 (34%) patients died. All cardiovascular hormones and hsTnT levels rose with tumour stage progression. All markers were significant predictors of mortality with HRs per IQR of 1.54 (95% CI 1.24 to 1.90, p<0.001) for NT-proBNP, 1.40 (95% CI 1.10 to 1.79, p<0.01) for MR-proANP, 1.31 (95% CI 1.19 to 1.44, p<0.001) for MR-proADM, 1.21 (95% CI 1.14 to 1.30, p<0.001) for CT-proET-1, 1.22 (95% CI 1.04 to 1.42, p=0.014) for copeptin and 1.21 (95% CI 1.13 to 1.32, p<0.001) for hsTnT, independent of age, gender, tumour entity and stage, and presence of cardiac comorbidities. NT-proBNP, MR-proANP, MR-proADM and hsTnT displayed a significant correlation with IL-6 and CRP. Conclusions Circulating levels of cardiovascular peptides like NT-proBNP, MR-proANP, MR-proADM, CT-pro-ET-1 and hsTnT were elevated in an unselected population of patients with cancer prior to induction of any cardiotoxic anticancer therapy. The aforementioned markers and copeptin were strongly related to all-cause mortality, suggesting the presence of subclinical functional and morphological myocardial damage directly linked to disease progression.