Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension.
Level 4 - case-series / case-control
Cross-sectional comparative study using human myocardial tissue biopsies
PubMed 18071071 · doi:10.1161/CIRCULATIONAHA.107.728550
What was done
Left ventricular endomyocardial biopsy specimens were examined from 64 heart failure patients without coronary artery disease, categorized into two groups: 28 patients with normal left ventricular ejection fraction (LVEF; 16 with diabetes mellitus) and 36 patients with reduced LVEF (10 with diabetes mellitus). Biopsy samples were analyzed to quantify myocardial collagen volume fraction, advanced glycation end products (AGEs) deposition, and isolated cardiomyocyte resting tension.
What was found
Diabetic heart failure patients had higher diastolic left ventricular stiffness regardless of LVEF, with distinct underlying mechanisms: - In reduced LVEF: Diabetes significantly increased myocardial collagen volume fraction (from 14.6±1.0% to 22.4±2.2%, P<0.001) and AGE deposition (from 8.8±2.5 to 24.1±3.8 score/mm2, P=0.005). - In normal LVEF: Diabetes significantly increased cardiomyocyte resting tension (from 5.1±0.7 to 8.5±0.9 kN/m2, P=0.006), while collagen volume fraction did not increase and the increase in AGE deposition was not statistically significant (8.2±2.5 to 15.7±2.7 score/mm2, P=NS).
Why it matters
This study demonstrates that the mechanism of left ventricular diastolic stiffening in diabetic cardiomyopathy depends on ejection fraction phenotype: extracellular fibrosis and AGE cross-linking dominate in heart failure with reduced LVEF, whereas intrinsic cardiomyocyte resting tension predominates in heart failure with normal LVEF.
Limits
The total sample size was small (n=64, with subgroup sizes of 10 and 16 diabetic patients). The cross-sectional biopsy design cannot establish longitudinal progression or causality. Patients with coronary artery disease were excluded, limiting generalizability to typical multi-comorbid diabetic heart failure populations. Abstract does not report diabetes duration, glycemic control, or pharmacological treatments.
Cited by
- supports Chronically elevated blood glucose levels react with collagen in cardiac tissue, causing stiffening of the myocardium and pericardium and lowering cardiac compliance.