ArticleCardiovascular research2018
Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening.
Article in Cardiovascular research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 2 of them syntheses that pooled it.
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Who cites it
126 citing papers in PubMed, 2 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Heart Failure with Preserved Ejection Fraction and Diastolic Dysfunction in Patients with Chronic Obstructive Pulmonary Disease: a Systematic Review.Current heart failure reports · 2026Pooled it
- Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2020Pooled it
- Early Cardiac Dysfunction in Adolescents With Low Vigorous Physical Activity.Journal of the American Heart Association · 2025Trial
- Intracoronary physiological indices for coronary microvascular dysfunction: from concept to clinical application.Cardiovascular intervention and therapeutics · 2026Review
- Coronary Microvascular Dysfunction in Hemodialysis-Dependent End-Stage Renal Disease: Prevalence, Characteristics, and Prognostic Implications.Circulation reports · 2026Article
- Peak filling rate assessed by myocardial perfusion imaging predicts adverse outcomes in women with chronic coronary syndromes.Quantitative imaging in medicine and surgery · 2026Article
- Pitfalls of Therapies Targeting the Nitric Oxide Signaling Pathway in Heart Failure With Preserved Ejection Fraction.Journal of cardiovascular pharmacology · 2026Review
- Association of the triglyceride-glucose index with subclinical left ventricular dysfunction in type 2 diabetes mellitus: mediation by myocardial energetic efficiency and resting perfusion.Cardiovascular diabetology · 2026Article
- The association between adiposity and cardiac function in patients with early breast cancer receiving cardiotoxic therapies.Breast cancer research : BCR · 2026Article
- Left ventricular non-compaction in heart failure: contemporary perspective on diagnostic challenges and treatment opportunities.Heart failure reviews · 2026Review
- Compliance modulation of a soft robotic atrioventricular model of heart failure with preserved ejection fraction.Nature communications · 2026Article
- The Impact of L Arginine's Anti-Apoptotic, Anti-Inflammatory, and Anti-Fibrotic Effects in Modulating Diabetic Cardiomyopathy: The Role of microRNA-155b in the Diagnosis of Diabetic Cardiomyopathy.International journal of molecular sciences · 2026Article
- Prognostic Stratification Based on Left Ventricular Diastolic Dysfunction and Coronary Microvascular Dysfunction in Patients Without Functional Coronary Artery Stenosis.Circulation reports · 2026Article
- From kidney injury to cardiac dysfunction: the central role of oxidative stress in diabetes and CKD.Basic research in cardiology · 2026Article
- Pathogenesis and Therapeutic Advances in Heart Failure with Preserved Ejection Fraction.Reviews in cardiovascular medicine · 2026Review
- Sublingual microcirculation-derived glycocalyx barrier impairment independently predicts progression of asymptomatic left ventricular diastolic dysfunction in elderly Chinese adults.Frontiers in cardiovascular medicine · 2026Article
- Prognostic significance of stress hyperglycemia ratio in coronary microvascular dysfunction among chronic coronary syndrome patients.Frontiers in cardiovascular medicine · 2026Article
- Pathophysiology of HFpEF: Insights from a Metabolic-Mitochondrial Perspective.International journal of molecular sciences · 2025Review
- When in doubt, pig it out: a versatile translational platform to study CKD, HFpEF, and CKM syndrome.American journal of physiology. Heart and circulatory physiology · 2025Review
- Neutrophil expression of CD41/CD61 complex contributes to their adhesiveness in both healthy individuals and heart failure patients.BMC immunology · 2025Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aims: More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities. Methods and results: DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6 months. Eight female healthy swine on normal pig-chow served as controls. The DM + HC + HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained. Conclusions: The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.