Diastolic dysfunction in women with signs and symptoms of ischemia in the absence of obstructive coronary artery disease: a hypothesis-generating study

Abstract

Background: Angina, in the absence of obstructive coronary artery disease, is more common in women, is associated with adverse cardiovascular morbidity and mortality, and is a major burden to the healthcare system. Although advancements have been made to understand the mechanistic underpinning of this disease, the functional consequence remains unclear.

Methods and results: Cardiac magnetic resonance imaging was performed to assess left ventricular function in 20 women with signs and symptoms of ischemia, but no obstructive coronary artery disease (cases), and 15 age- and body mass index-matched reference controls. Functional imaging included standard cinematic imaging to assess left ventricular morphology and global function, along with tissue tagging to assess left ventricular tissue deformation. Systolic function was preserved in both cases and controls, with no differences in ejection fraction (mean±SE: 63.1±8% versus 65±2%), circumferential strain (-20.7±0.6% versus -21.9±0.5%), or systolic circumferential strain rate (-105.9±6.1% versus -109.0±3.8% per second). In contrast, we observed significant differences between cases and controls in diastolic function, as demonstrated by reductions in both diastolic circumferential strain rate (153.8±8.9% versus 191.4±8.9% per second; P<0.05) and peak rate of left ventricular untwisting (-99.4±8.0° versus -129.4±12.8° per second; P<0.05).

Conclusions: Diastolic function is impaired in women with signs and symptoms of ischemia in the absence of coronary artery disease, as assessed by cardiac magnetic resonance tissue tagging. These results are hypothesis-generating. Larger studies are needed to define the exact mechanism(s) responsible and to establish viable treatment strategies.

Keywords: diastole; magnetic resonance imaging; myocardial ischemia; women.

Figure 1

(A, top) Representative cardiac magnetic resonance image, obtained at the level of the papillary muscles, with a tissue tagging sequence. (A, bottom) Analysis was performed using commercially available software (HARP, Diagnosoft), with user input limited to tracing the epicardium and endocardium of a single cardiac phase (end-systolic). The software then constructs a “mesh” which tracks tissue deformation over a single cardiac cycle, using the harmonic phase. (B) Representative tracing of circumferential strain (solid black line) and circumferential strain rate(dashed line), over a single cardiac cycle. (C) Representative data tracing of apical (red line) and basal (blue line) rotation, net torsion (solid black line), and the rate of ventricular twisting (dashed line), over a single cardiac cycle.

Figure 2

Magnetic resonance tissue tagging reveals differences in diastolic function in women with angina who were free from obstructive coronary artery disease (cases) and a group of age-and BMI-matched reference controls (controls). (A) Circumferential strain from a representative case (solid line) and a representative control (dashed line) subject. Time 0 represents end-systole. Red-dashed line illustrates differences in the rate of relaxation. (B) Summary data showing significant reductions in circumferential diastolic strain rate in cases compared to controls. (C) Left ventricular torsion in a representative case (solid line) and a representative control (dashed line) subject. Time 0 represents end-systole. Red-dashed line illustrates differences in the rate of ventricular untwisting. (D) Summary data showing significant reductions in the rate of left ventricular untwisting in cases compared to controls. Data reported as a mean ± SE.