Maladaptive Remodeling in Women with Signs and Symptoms of Ischemia and Elevated Left Ventricular End-diastolic Pressure

Background: Women with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD) often have elevated left ventricular end-diastolic pressure (LVEDP). We have previously demonstrated that this is linked with coronary microvascular dysfunction (CMD). However, elevated LVEDP in the absence of CMD has not been well examined. Methods: 182 women with signs and symptoms of ischemia and no obstructive CAD underwent invasive coronary reactivity testing (CRT), LVEDP measurement at rest, and rest cardiac magnetic resonance imaging (CMRI, 1.5 T). CMD was assessed using a Doppler wire in the left anterior descending artery and intracoronary injections of adenosine and acetylcholine. Overall, 35/182 (19%) women had no evidence of CMD, with coronary flow reserve ≥ 2.5, coronary blood flow response ≥ 50%, and acetylcholine diameter response > 0%. CMRI measured LV size, mass and function. Two-sample T test and Fisher Exact Test were used for statistical analysis. Results: Of the 35 women without CMD, 20 (57%) had elevated LVEDP (≥15 mmHg) (mean 18 ± 3 mmHg) compared to 15 with normal LVEDP (11 ± 3 mmHg). The elevated LVEDP group had significantly lower end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) and a higher mass-to-volume ratio compared to the normal LVEDP group (Table). Resting systolic and diastolic blood pressures were also higher in the elevated LVEDP group. All other functional parameters were not significantly different. Conclusion: The presence of elevated LVEDP is associated with a significantly higher mass-to-volume ratio and lower EDVI and ESVI in women without CMD. Prior studies have shown that increased mass-to-volume ratio is independently associated with increased cardiovascular events, especially heart failure. These results suggest that these women may have a maladaptive remodeling process and that this phenotype should not be ignored despite having no evidence of CMD on CRT.