Cardiac remodeling in patients with heart failure with mildly reduced ejection fraction and metabolic disorders: association with biomarkers and autonomic nervous system parameters

Aim. The high prevalence of obesity in a cohort of patients with heart failure and mildly reduced ejection fraction (HFmrEF) determines the relevance of clarifying the role of biomarkers and autonomic imbalance in myocardial remodeling, taking into account metabolic risk factors.

Material and methods. We examined 19 men with postinfarction cardiosclerosis and class II HFmrEF (median age 62 years), overweight/class I-II obesity, type 2 diabetes in 53/47%, 48% of cases, respectively, who received therapy. The biomarker panel included N-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, pro-collagen I C-terminal propeptide (PICP), N-terminal propeptide of procollagen type III (PIIINP), C-terminal telopeptide of type I collagen, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix proteinase-1 (TIMP-1), leptin and adiponectin. Heart rate variability (HRV) and turbulence were obtained using 24-hour Holter monitoring. We assessed the time and frequency domains of HRV (24 h) and 5 min recordings of wakefulness at rest, calculated TO (turbulence onset) and TS (turbulence slope).

Results. Significant positive associations of leptin and TIMP-1 levels with left ventricular hypertrophy markers were confirmed. Positive correlations of peak e' with following HRV indicators were revealed: SDNN (r=0,68; p=0,02) and RMSSD (r=0,69; p=0,003). Lower TS values were associated with higher index parameters of left ventricular mass (p<0,05 for all). Associations of biomarkers with autonomic nervous system (ANS) were observed: MMP-9 with RMSSD (r=0,54) and pNN50 (r=0,51); TIMP-1 with TO (r=0,46); PICP/PIIINP ratio with HFn (5 min) (r=-0,49); NT-proBNP/adiponectin ratio with SDNN (r=-0,49); leptin level with TS (r=-0,54) (p<0,05 for all).

Conclusion. In patients with HFmrEF of ischemic origin and additional metabolic risks, serum biomarkers of fibrosis, adipokines, and ANS parameters are associated mainly with markers of increased left ventricular filling pressure. The study results predetermine the further search for potential risk-stratification markers of unfavorable myocardial remodeling and prognosis in large samples of patients with metabolic deviations and HF with EF >40% against the background of modern drug therapy.

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