The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. A total of 847 stable patients with advanced HFrEF (57.4 ± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6 ± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited more stable HF marked by lower BNP level (400 vs. 642 ng/l), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p < 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73 m2) and better QoL (MLHFQ: 36 vs. 48 points, p = 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p = 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p = 0.01). MET treatment in patients with advanced HFrEF and DM is associated with improved outcome by mechanisms beyond the improvement of blood glucose control.
Background: The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. Methods: A total of 847 stable patients with advanced HFrEF (57.4± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. Results: A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited lower BNP, higher eGFR, better LV and RV function, less mitral and tricuspid regurgitation, were using smaller doses of diuretics (all p< 0.05) and had better QoL (MLHFQ: 36 vs. 48 points, p= 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p= 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p= 0.01).Conclusion: MET treatment in patients with advanced HFrEF and DM is associated with better quality of life and improved outcome, by mechanisms beyond the improvement of blood glucose control. MET should stay among frontline drugs for treatment of DM in patients with HFrEF.
BackgroundRight ventricular (RV) function is currently being evaluated solely according to the properties of RV myocardium. We have tested a concept that in patients with heart failure with reduced ejection fraction (HFrEF), RV assessment should integrate the information about both RV function as well as size.MethodsA total of 836 stable patients with HFrEF (LVEF 23.6 ± 5.8%, 82.8% males, 68% NYHA III/IV) underwent echocardiographic evaluation and were prospectively followed for a median of 3.07 (IQRs 1.11; 4.89) years for the occurrence of death, urgent heart transplantation or implantation of mechanical circulatory support.ResultsRV size (measured as RV-basal diameter, RVD1) was significantly associated with an adverse outcome independent of RV dysfunction grade (p = 0.0002). The prognostic power of RVD1 was further improved by indexing to body surface area (RVD1i, p < 0.05 compared to non-indexed value). A novel parameter named RV global dysfunction score (RVGDs) was calculated as a product of RVD1i and the degree of RV dysfunction (1–4 for preserved RV function, mild, moderate and severe dysfunction, respectively). RVGDs showed a superior prognostic role compared to RV dysfunction grade alone (ΔAUC >0.03, p < 0.0001). In every subgroup of RVGDs (<20, 20–40, 40–60, >60), patients with milder degree of RV dysfunction but more dilated RV had similar outcome as those with more severe degree of RV dysfunction but smaller RV size (all p > 0.50), independent of tricuspid regurgitation severity and degree of pulmonary hypertension.ConclusionRV dilatation is a manifestation of RV dysfunction. The evaluation of RV performance should integrate the information about both RV size and function.
Aims: There is no biomarker reflecting right ventricular dysfunction in HFrEF patients used in clinical practice. We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy. Methods and Results: The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than 2.5-fold) in blood plasma of HF patients with severe RV dysfunction (n=30) compared to those with preserved RV function (n= 31). A subsequent ELISA-based confirmatory analysis of circulating FGF-23 in a large cohort of patients (n= 344, 72.7% NYHA III/IV, LVEF 22.5%, 54.1% with moderate/severe RV dysfunction), followed by multivariable regression analysis, revealed that the plasma FGF-23 level was most significantly associated with RV dysfunction grade (p= 0.0004) and congestion in the systemic circulation (p= 0.03), but not with LV-ejection fraction (p= 0.69) or estimated glomerular filtration rate (eGFR, p= 0.08). FGF-23 was associated with the degree of RV dysfunction in both sub-cohorts (i.e. in patients with and without congestion, p<0.0001). The association between FGF-23 and RV-dysfunction remained significant after the adjustment for BNP (p= 0.01). In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p=0.59). The Cox proportional hazard model revealed that circulating FGF-23 was significantly associated with adverse outcomes even after adjusting for BNP, LVEF, RV dysfunction grade and eGFR. Conclusion: Circulating FGF-23 is a biomarker of right ventricular dysfunction in HFrEF patients regardless of congestion status.
Background: The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. Methods: A total of 847 stable patients with advanced HFrEF (57.4± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. Results: A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited more stable HF marked by lower BNP level (400 vs. 642 ng/L), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p< 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73m2) and better QoL (MLHFQ: 36 vs. 48 points, p= 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p= 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p= 0.01).Conclusion: MET treatment in patients with advanced HFrEF and DM is associated with better quality of life and improved outcome, by mechanisms beyond the improvement of blood glucose control.
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