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Published on: June 14, 2016
Myocardial structure and function differ in systolic and diastolic heart failure
Loek van Heerebeek1, Attila Borbély, Hans W M Niessen
1Department of Physiology, Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
Insights
Systolic heart failure (SHF) and diastolic heart failure (DHF) exhibit distinct left ventricular (LV) myocardial structural and functional differences. These cardiomyocyte abnormalities support the clinical separation of SHF and DHF phenotypes.
Area of Science:
- Cardiology
- Cardiovascular Research
- Heart Failure Pathophysiology
Background:
- Distinguishing between systolic heart failure (SHF) and diastolic heart failure (DHF) is clinically important.
- Left ventricular (LV) myocardial structure and function were investigated in patients with SHF and DHF.
Purpose of the Study:
- To compare LV myocardial structure and function in patients with SHF versus DHF.
- To identify distinct cardiomyocyte abnormalities contributing to different heart failure phenotypes.
Main Methods:
- LV endomyocardial biopsy samples from SHF (n=22) and DHF (n=22) patients were analyzed.
- Histomorphometry, electron microscopy, and isolated cardiomyocyte mechanical assessments were performed.
- Passive and total force generation in cardiomyocytes were measured after stretching and calcium activation.
Main Results:
- DHF patients had larger cardiomyocyte diameter but similar collagen fraction compared to SHF patients.
- Myofibrillar density was lower in SHF cardiomyocytes.
- DHF cardiomyocytes showed higher passive force but comparable total force, with a greater reduction after protein kinase A stimulation.
Conclusions:
- Significant differences in LV myocardial structure and cardiomyocyte function exist between SHF and DHF.
- These distinct abnormalities underpin the different phenotypes of systolic and diastolic heart failure.
- Findings support the clinical separation of heart failure into SHF and DHF categories based on underlying myocardial characteristics.
Background:
To support the clinical distinction between systolic heart failure (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial structure and function were compared in LV endomyocardial biopsy samples of patients with systolic and diastolic heart failure.
Methods And Results:
Patients hospitalized for worsening heart failure were classified as having SHF (n=22; LV ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had coronary artery disease or biopsy evidence of infiltrative or inflammatory myocardial disease. More DHF patients had a history of arterial hypertension and were obese. Biopsy samples were analyzed with histomorphometry and electron microscopy. Single cardiomyocytes were isolated from the samples, stretched to a sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated with calcium-containing solutions to measure total force. Cardiomyocyte diameter was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/-2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable. After administration of protein kinase A to the cardiomyocytes, the drop in Fpassive was larger (P<0.01) in DHF than in SHF.
Conclusions:
LV myocardial structure and function differ in SHF and DHF because of distinct cardiomyocyte abnormalities. These findings support the clinical separation of heart failure patients into SHF and DHF phenotypes.
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