Abstract Introduction Heart failure (HF) is a clinical syndrome associated with high morbidity. Mitochondria are critical for normal cardiomyocyte function, and the metabolic stress associated with HF leads to mitochondrial damage that is normally cleared by the autophagy/lysosome system and cardiomyocytes. Decreased peripheral mitochondrial DNA copy number, a biomarker of mitochondrial dysfunction, has been shown to be inversely associated with HF risk and long-term outcomes. However, the potential relationship between circulating mitochondrial DNA (cell-free (cf)-mtDNA) and the pathogenesis of HF in the general population is controversial. Purpose To analyse the levels of cf-mtDNA in the plasma of patients with HF with different phenotypes and compare them with those of individuals from a control population. Methodology A retrospective study was performed on plasma samples from a cohort of HF patients (n=296, median age 66.5, 74.0% male). Plasma from non-pathological donors was used as a control group (n=85, median age 47.3, 41.2% male). The cf-mtDNA was isolated using a specific kit and the number of copies was quantified by PCR based on the quantification of the gene encoding the mitochondrial 12S rRNA and the SYBR-Green method. Statistical analyses were performed using GraphPad Prism v8. Results Plasma cf-mtDNA levels were significantly lower in patients with HF than in controls (4710.4±7596.3 vs 5384.8±6217.7, p0.01). The inverse association between cf-mtDNA and incident HF was statistically significant only in HF with reduced ejection fraction (HFrEF) patients (4606.5±7567.2 vs 5384.8±6217.7, p 0.05) but not in HF with preserved EF patients (HFpEF). A sub-cohort including patients with reduced and mildly reduced left ventricle EF (50%) was grouped according to the New York Heart Association (NYHA) functional class. The results showed that patients in NYHA functional class I-II had higher levels of cf-mtDNA than patients in NYHA functional class III-IV, but we found no statistically significant differences. When the same cohort was grouped according to the presence of ischaemic pathology, we found that patients with non-ischaemic pathology had lower values than those with ischaemic pathology, but we found no statistically significant differences between groups. Conclusions The data obtained suggest the potential utility of cf-mtDNA as an easily quantifiable molecular biomarker in processes associated with the pathogenesis of HF.
Vazquez et al. (Sat,) studied this question.