Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis

Abstract

Objectives: The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis.

Background: Effort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD).

Methods: Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product.

Results: Compared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p < 0.0001), and CFR (1.19 ± 0.38 vs. 2.23 ± 0.88; p < 0.0001) and higher minimal coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (<1.3 ml/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased left ventricular mass, and age were the only independent predictors of impaired coronary vasodilator function.

Conclusions: Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.

Keywords: PET; amyloidosis; coronary microvascular function; myocardial blood flow; strain.

Figure 1. A. Mildly abnormal N-13 ammonia myocardial perfusion imaging in a subject with transthyretin amyloidosis. B. CT coronary angiogram and histopathology images

Rest and vasodilator stress N-13 ammonia PET images in a familial transthyretin amyloid subject are shown in short axis, horizontal long axis and vertical long axis projections. The images show a reversible perfusion defect in the mid and basal septum, despite normal epicardial coronary arteries on CT coronary angiography. His coronary flow reserve was 1.3 (significantly impaired). This subjects’ myocardial biopsy low power photomicrograph (H&E stain) demonstrates near complete loss of myocytes with extensive amyloid deposition. The second and third high power photomicrographs (H&E and SAB stains, respectively) show a small vessel whose lumen has been obliterated by vascular amyloid deposition.

Figure 2. Mean rest and stress myocardial blood flow, coronary flow reserve per unit left ventricular mass in the LVH and the amyloid groups

The rest myocardial blood flow (MBF) was higher in the left ventricular hypertrophy (LVH) group. Peak stress MBF, coronary flow reserve (CFR-unadjusted)* and CFR were significantly lower in the amyloid compared to the LVH groups.

Figure 3. Longitudinal strain at the base, mid ventricle and apex

Mean longitudinal strain at the base, mid ventricle and the apex in the left ventricular hypertrophy (LVH) compared to the amyloid groups. Mean longitudinal strain was significantly reduced in the amyloid compared to the LVH group only in the base and mid ventricular regions.

Figure 4. Relation between left ventricular mass and rest, stress myocardial blood flow, coronary flow reserve and minimal coronary vascular resistance in the study groups

The relation between left ventricular (LV) mass and rest, stress myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary vascular resistance in left ventricular hypertrophy (LVH, blue) and amyloid subjects (red). LV mass was lower in the LVH subjects compared to the amyloid subjects. But, at similar degrees of LV mass, amyloid subjects demonstrate lower rest, stress MBF and lower CFR and higher minimal coronary vascular resistance.

Figure 5

Relation between mean longitudinal left ventricular (LV) strain and rest and stress myocardial blood flow (MBF), coronary flow reserve (CFR), minimal coronary vascular resistance and LV mass in the LVH (blue) and amyloid (red) subjects.

Figure 5

Relation between mean longitudinal left ventricular (LV) strain and rest and stress myocardial blood flow (MBF), coronary flow reserve (CFR), minimal coronary vascular resistance and LV mass in the LVH (blue) and amyloid (red) subjects.