J Cardiovasc Ultrasound.  2014 Jun;22(2):72-79. 10.4250/jcu.2014.22.2.72.

Association of Myocardial Angiogenesis with Structural and Functional Ventricular Remodeling in Aortic Stenosis Patients with Normal Ejection Fraction

• Lee SP
• Kim HK
• Kim YJ
• Oh S
• Sohn DW

• KMID: 2177462
• DOI: http://doi.org/10.4250/jcu.2014.22.2.72

Abstract

BACKGROUND
Although rarefaction of myocardial angiogenesis has been shown to be associated with left ventricular (LV) systolic dysfunction in animal models of ventricular hypertrophy, this relationship has not been investigated in depth nor validated in humans. We aimed to analyze the relationship of myocardial angiogenesis with various functional and structural ventricular remodeling parameters in moderate to severe aortic stenosis (AS) patients with normal LV ejection fraction (LVEF).
METHODS
A total of 38 moderate or severe AS patients with LVEF > 50% were enrolled for the current study and all patients underwent LV endomyocardial biopsy at the septum during aortic valve replacement. The biopsy specimens were stained for platelet endothelial cell adhesion molecule-1 (CD31) to analyze the density of blood vessels in the myocardium.
RESULTS
The degree of myocardial angiogenesis tended to increase with worse myocardial systolic function, LV filling pressure and progressed ventricular hypertrophy (Spearman's rho = -0.388, p = 0.016 for LVEF; Spearman's rho = 0.442, p = 0.007 for E/e'; Spearman's rho = 0.424, p = 0.008 for LV mass index). The degree of myocardial angiogenesis was also significantly associated with the degree of aortic valve stenosis (Spearman's rho = -0.368, p = 0.023). There was significant difference in the degree of myocardial angiogenesis according to the LV geometry (p = 0.016 for mean difference between different LV geometry groups by analysis of variance). Significant predictors of myocardial blood vessel density were LV mass index (beta = 0.398, p = 0.010) and LVEF (beta = -0.313, p = 0.028).
CONCLUSION
There is a close relationship between myocardial angiogenesis and LV remodeling in moderate to severe AS patients with normal LVEF, with angiogenesis increasing with LV hypertrophy. Further studies to demonstrate the mechanism underlying this phenomenon is warranted.

Keyword

Angiogenesis; Aortic stenosis; Echocardiography; Ventricular remodeling

MeSH Terms

Antigens, CD31
Aortic Valve
Aortic Valve Stenosis*
Biopsy
Blood Vessels
Echocardiography
Humans
Hypertrophy
Models, Animal
Myocardium
Ventricular Remodeling*
Antigens, CD31

Figure

• 

  Fig. 1 Correlation between ventricular function and myocardial blood vessel density. Significant negative correlation between left ventricular (LV) ejection fraction and myocardial blood vessel density (A), in contrast to significant positive correlation between E/e' and myocardial blood vessel density (B) and also, LV global longitudinal strain (C).

• 

  Fig. 2 Correlation between structural parameters of aortic stenosis and myocardial blood vessel density. Significant positive correlation between left ventricular mass index and myocardial blood vessel density (A), in contrast to significant positive correlation between aortic valve area and myocardial blood vessel density (B).

• 

  Fig. 3 Examples of myocardial blood vessel density according to left ventricular (LV) geometric remodeling. A: An example of a myocardial sample from a male patient with normal LV geometry [LV mass index 112.9 g/m2 and relative wall thickness (RWT) 0.45]. The LV ejection fraction (LVEF) was 64% and E/e' 7.5. The myocardial blood vessel density was 1.59% of the total myocardium analyzed. B: An example of a myocardial sample from a male patient with eccentric hypertrophy (LV mass index 134.3 g/m2 and RWT 0.38). The LVEF was 58% and E/e' 16.1. The myocardial blood vessel density was 2.17% of the total myocardium analyzed. C: An example of a myocardial sample from a female patient with concentric hypertrophy (LV mass index 161.9 g/m2 and RWT 0.49). The LVEF was 55% and E/e' 25.4. The myocardial blood vessel density was 2.62% of the total myocardium analyzed. All specimens were stained for platelet endothelial cell adhesion molecule-1 immunostaining and visualized under 100 × field.

• 

  Fig. 4 Difference of the myocardial blood vessel density according to left ventricular (LV) remodeling pattern. There was significant difference of blood vessel density according to the LV geometry (p = 0.016 for mean difference between groups with ANOVA). ANOVA: analysis of variance.

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