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Updated: Jun 15, 2025
In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography
Published on: February 16, 2016
Myocardial ultrastructure of human heart failure with preserved ejection fraction
Mariam Meddeb1, Navid Koleini1, Aleksandra Binek2
1Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Insights
Obesity worsens heart failure with preserved ejection fraction (HFpEF). Severe obesity damages heart muscle structure, impairing energy production and fat processing, regardless of diabetes status.
Area of Science:
- Cardiology
- Pathology
- Metabolic Diseases
Background:
- Heart failure with preserved ejection fraction (HFpEF) affects over half of heart failure patients, characterized by high morbidity and mortality.
- Obesity is a primary comorbidity in HFpEF, significantly worsening disease progression and patient prognosis.
- Previous studies indicate myocardial abnormalities in morbidly obese HFpEF patients, including impaired calcium-stimulated tension and disrupted mitochondrial and lipid metabolism gene expression.
Purpose of the Study:
- To investigate the impact of severe obesity on the myocardial ultrastructure in patients with HFpEF.
- To correlate observed ultrastructural changes with myocardial proteomics data.
Main Methods:
- Septal myocardial biopsies were obtained from patients with HFpEF.
- Transmission electron microscopy was used to assess myocardial ultrastructure.
- Myocardial proteomics was performed to analyze protein expression related to metabolic pathways.
Main Results:
- Significant sarcomere disruption and sarcolysis were observed in HFpEF patients.
- Mitochondrial abnormalities, including swelling and cristae dissolution, and increased lipid droplet accumulation were prominent, especially in severely obese patients.
- These changes were independent of comorbid diabetes.
- Proteomic analysis revealed reduced expression of proteins involved in fatty acid uptake, processing, oxidation, and mitochondrial respiration, particularly in the most obese HFpEF patients.
Conclusions:
- Severe obesity induces significant myocardial ultrastructural damage in HFpEF, including sarcomere and mitochondrial pathology.
- Obesity-related myocardial dysfunction in HFpEF is linked to impaired fatty acid metabolism and mitochondrial function.
- These findings highlight the detrimental role of obesity in HFpEF pathophysiology and suggest potential therapeutic targets.
Abstract:
Over half of patients with heart failure have a preserved ejection fraction (>50%, called HFpEF), a syndrome with substantial morbidity/mortality and few effective therapies1. Its dominant comorbidity is now obesity, which worsens disease and prognosis1-3. Myocardial data from patients with morbid obesity and HFpEF show depressed myocyte calcium-stimulated tension4 and disrupted gene expression of mitochondrial and lipid metabolic pathways5,6, abnormalities shared by human HF with a reduced EF but less so in HFpEF without severe obesity. The impact of severe obesity on human HFpEF myocardial ultrastructure remains unexplored. Here we assessed the myocardial ultrastructure in septal biopsies from patients with HFpEF using transmission electron microscopy. We observed sarcomere disruption and sarcolysis, mitochondrial swelling with cristae separation and dissolution and lipid droplet accumulation that was more prominent in the most obese patients with HFpEF and not dependent on comorbid diabetes. Myocardial proteomics revealed associated reduction in fatty acid uptake, processing and oxidation and mitochondrial respiration proteins, particularly in very obese patients with HFpEF.
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