Mitochondrial Structural Abnormalities and Cardiac Reverse Remodeling in Patients With Systolic Dysfunction.
Level 3 - non-randomized controlled study
Observational cohort study evaluating prognostic structural factors.
PubMed 39370292 · doi:10.1253/circj.CJ-24-0451
What was done
Ninety-one patients with left ventricular (LV) systolic dysfunction who underwent right ventricular endomyocardial biopsy (EMB) were followed for 1 year. Biopsy specimens were evaluated by electron microscopy for mitochondrial size, outer membrane disruption, and cristae disorganization. Patients were categorized by presence or absence of LV reverse remodeling (LVRR), and tracked for a composite primary endpoint of cardiovascular death and unplanned heart failure (HF) hospitalization.
What was found
LVRR occurred in 52 patients (57.1%) and was absent in 39 (42.9%). Cristae disorganization was present in 21 patients (23.1%), appearing in 6 of 52 (11.5%) LVRR-positive patients versus 15 of 39 (38.5%) LVRR-negative patients (P=0.005). Over 1 year, 16 patients (17.6%) reached the primary endpoint (2 cardiovascular deaths [2.2%] and 14 HF hospitalizations [15.4%]). Cristae disorganization was significantly associated with the endpoint (P=0.002), independent of age, systolic blood pressure, B-type natriuretic peptide, and mitral regurgitation.
Why it matters
These findings link specific ultrastructural mitochondrial defects directly to clinical outcomes and reverse remodeling capacity in systolic heart failure, highlighting cristae integrity as a potential prognostic biomarker in biopsied patients.
Limits
The sample size was small (n=91) with a brief 1-year follow-up and very few hard mortality events (2 deaths). Biopsies were taken from the right ventricular septum rather than the LV itself, and selection bias is likely given the requirement for invasive biopsy. Specific effect estimates (such as hazard ratios and confidence intervals) were not reported in the abstract.
Cited by
- supports Cardiac biopsies from patients who have heart failure or died of cardiac degeneration show poor mitochondrial health as a hallmark signature.