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Published on: July 26, 2018
Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction
Ramón Martos1, John Baugh, Mark Ledwidge
1Heart Failure Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Insights
Diastolic heart failure (DHF) involves active fibrosis, increasing ventricular stiffness. This study found elevated collagen and matrix metalloproteinase markers in hypertensive patients with DHF, indicating a fibrotic process contributing to the condition.
Area of Science:
- Cardiology
- Biochemistry
- Pathophysiology
Background:
- Diastolic heart failure (DHF) pathophysiology is unclear, potentially involving active fibrosis and increased ventricular stiffness.
- Hypertension is a key risk factor, impacting diastolic function and heart filling.
Purpose of the Study:
- Investigate collagen metabolism in hypertensive patients across different diastolic function phases.
- Determine the role of fibrotic markers in patients with and without DHF.
Main Methods:
- Studied 86 hypertensive patients categorized by DHF presence and diastolic function severity.
- Assayed serum levels of procollagen peptides (type I, III), matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs.
- Utilized Doppler-echocardiography to assess diastolic filling parameters (E/A ratio, deceleration time, isovolumic relaxation time).
Main Results:
- Patients with DHF showed significantly higher levels of serum carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 compared to those without DHF.
- More severe diastolic dysfunction phases correlated with increased levels of collagen peptides, MMP-2, and tissue inhibitor of MMP-1.
- Within each diastolic dysfunction phase, DHF patients consistently exhibited elevated fibrotic markers.
Conclusions:
- Serological evidence supports an active fibrotic process in DHF.
- Fibrotic markers are more pronounced in advanced stages of diastolic dysfunction.
- Findings may elucidate DHF pathophysiology and suggest novel diagnostic and therapeutic targets.
Background:
The pathophysiology of diastolic heart failure (DHF) is poorly understood. One potential explanation is an active fibrotic process that produces increased ventricular stiffness, which compromises filling. The present study investigates collagen metabolism in hypertensive patients in different phases of diastolic function with and without proven DHF.
Methods And Results:
We studied 86 hypertensive patients divided into groups according to the presence of DHF (32 with, 54 without) and phase of diastolic function (20 with normal function, 38 with impaired relaxation, 10 with pseudonormalization, and 16 with restrictive-like filling). Serum carboxy-terminal, amino-terminal, and carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, matrix metalloproteinases (MMPs; total MMP-1, active MMP-2, and MMP-9), and tissue inhibitor of MMPs levels were assayed by radioimmunoassay and ELISA. Doppler-echocardiographic assessment of diastolic filling was made with measurements of E/A ratio, E-wave deceleration time, and isovolumic relaxation time. Serum carboxy-terminal telopeptide of procollagen type I, carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 levels (P<0.001 for all, controlled for age and gender) were greater in patients with DHF than in those without. When we controlled for age and gender, levels of serum carboxy-terminal telopeptide of procollagen type I, tissue inhibitor of MMP-1, amino-terminal propeptide of procollagen type III (all P<0.001), carboxy-terminal telopeptide of procollagen type I (P=0.008), and MMP-2 (P=0.03) were greater in more severe phases of diastolic dysfunction. Within phases of diastolic dysfunction, serum carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 were elevated in those with DHF compared with those without DHF (all P<0.001).
Conclusions:
These data demonstrate serological evidence of an active fibrotic process in DHF, which is more marked in more severe diastolic dysfunction. This observation may help explain the pathophysiology of DHF and may suggest new avenues for diagnostic and therapeutic intervention.
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