Potential role of peripheral blood mononuclear cell ' s mitochondrial respiratory dysfunction in heart failure severity prediction in patients with cardioverter-defibrillator implantation indications

Background  It has been reported that the mitochondrial respiratory dysfunction (MRD) is important mechanisms affecting the heart failure (HF) pathogenesis. We sought to evaluate the potential role of MRD of peripheral blood mononuclear cells (PBMC) in HF severity prediction in patients with cardioverter-defibrillator implantation indications.

Methods  In this single-center study patients with HF of New York Heart Association (NYHA) I-III functional class (FC) and cardioverter-defibrillator implantation indications underwent transthoracic echocardiography (TTE) and MRD assessment using PBMC. Mitochondrial respiration rate (MRR) indicators (pyruvate + malate + adenosine diphosphate; succinate + adenosine diphosphate; pyruvate + malate – adenosine diphosphate V_4.1; succinate – adenosine diphosphate) were calculated. Correlations between HF NYHA FC, TTE and MRR indicators were evaluated. Based on our data, we developed a risk model regarding HF severity.

Results  Of 53 (100.0%) HF patients, 33 (62.3%) had mild exercise intolerance (1^st group) and 20 (37.7%) had moderate-to-severe exercise intolerance (2^nd group). Patients with mild exercise intolerance were likely to have a higher V_4.1 (P < 0.001) values. V_4.1 was independently associated with moderate-to-severe exercise intolerance in univariate and multivariate logistic regression (OR = 0.932, 95% CI: 0.891–0.975, P < 0.001).

Conclusions  The severity of HF is associated with PBMC mitochondrial respiratory dysfunction in patients with cardioverter-defibrillator implantation indications. Our HF severity risk model including V_4.1 parameters is able to distinguish patients with mild and moderate-to-severe exercise intolerance. Further investigations of their predictive significance are warranted.