Left ventricular diastolic dysfunction in women with nonobstructive ischemic heart disease: insights from magnetic resonance imaging and spectroscopy

Abstract

Ischemic heart disease, in the absence of obstructive coronary artery disease, is prevalent in women and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology carries much risk and is a significant burden to the health care system. This review summarizes the current state of knowledge on nonobstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD.

Keywords: coronary microvascular disease; diastolic function; ischemic heart disease.

Fig. 1.

A: circumferential strain rate profile from a representative women with nonobstructive coronary artery disease (case) and a representative age-, sex- and body mass index (BMI)-matched control. B: summary data showing significant reductions in circumferential diastolic strain rate in cases compared with controls. C: left ventricular untwisting in a representative case and control. D: summary data showing significant reductions in peak untwisting rate in cases compared with controls. Note that in both A and C, time starts at end systole and advances to end diastole. Data are means + SE. Figure republished from Nelson et al. (42).

Fig. 2.

A: myocardial tissue tracking in a representative midventricular short-axis cine image. Left: contours are drawn on the endo- and epicardial boarders at a single phase of the cardiac cycle. Middle: tissue tracking software propagates the contours automatically and follows the motion of the contour throughout the cardiac cycle; displayed as motion vectors across the ventricular wall. Right: strain (circumferential or radial) can then be displayed in the form of color maps throughout the cardiac cycle. In this case, circumferential strain is displayed. With this data derived, diastolic strain rate is simply calculated as the time derivative of either circumferential or radial strain. B and C: group differences in radial diastolic strain rate and circumferential diastolic strain rate, respectively. C and D: group differences in peak radial and circumferential strain, respectively. *P < 0.05. Figure republished from Nelson et al. (41).

Fig. 3.

A: ¹H magnetic resonance spectroscopy (MRS) measurement of myocardial fat accumulation. A single voxel was positioned in the intraventricular septum, and ¹H MRS was acquired at end systole and in end expiration. Myocardial water (4.8 ppm), myocardial metabolites [e.g., carnitine, creatinine, trimethylamine, 3–3.5 ppm (ppm)], and methylenes of fatty acids in myocardial triglyceride (1.4 ppm) are shown. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. B: summary data showing elevated myocardial triglyceride content in cases with nonobstructive coronary artery disease compared with reference controls. C: summary data showing reduced diastolic circumferential strain rate in cases compared with controls. D: myocardial triglyceride content correlated inversely with diastolic circumferential strain rate (r = 0.779; P = 0.002). Figure republished from Wei et al. (74).

Fig. 4.

Three part mechanistic hypothesis: 1) risk factor conditions (hypertension, dyslipidemia, dysglycemia, loss of estrogen) promote a pro-inflammatory and pro-oxidative state, rendering the coronary microvasculature vulnerable; 2) disruption of vasoregulatory properties of the coronary vasculature result in repeated episodes of transient myocardial ischemia; and 3) repeat ischemic episodes lead to ectopic fat deposition in the myocardium (i.e., cardiac steatosis), progressive impairment of cardiomyocyte relaxation, and diffuse myocardial fibrosis. Together, this negative cascade of events leads to diastolic dysfunction and heart failure.