Association between coronary microvascular dysfunction and exercise capacity in dilated cardiomyopathy

Abstract

Background: Aerobic exercise capacity is an independent predictor of mortality in dilated cardiomyopathy (DCM), but the central mechanisms contributing to exercise intolerance in DCM are unknown. The aim of this study was to characterize coronary microvascular function in DCM and determine if cardiovascular magnetic resonance (CMR) measures are associated with aerobic exercise capacity.

Methods: Prospective case-control comparison of adults with DCM and matched controls. Adenosine-stress perfusion CMR to assess cardiac structure, function and automated inline myocardial blood flow quantification, and cardiopulmonary exercise testing to determine peak VO₂ was performed. Pre-specified multivariable linear regression, including key clinical and cardiac variables, was undertaken to identify independent associations with peak VO₂.

Results: Sixty-six patients with DCM (mean age 61 years, 47 male) were propensity-matched to 66 controls (mean age 59 years, 47 male) based on age, sex, body mass index, and diabetes. DCM patients had markedly lower peak VO₂ (19.8 ± 5.5 versus 25.2 ± 7.3 mL/kg/min; P < 0.001). The DCM group had greater left ventricular (LV) volumes, lower systolic function, and more fibrosis compared to controls. In the DCM group, there was similar rest but lower stress myocardial blood flow (1.53 ± 0.49 versus 2.01 ± 0.60 mL/g/min; P < 0.001) and lower myocardial perfusion reserve (MPR) (2.69 ± 0.84 versus 3.15 ± 0.84; P = 0.002). Multivariable linear regression demonstrated that LV ejection fraction, extracellular volume fraction, and MPR, were independently associated with percentage-predicted peak VO₂ in DCM (R² = 0.531, P < 0.001).

Conclusion: In comparison to controls, DCM patients have lower stress myocardial blood flow and MPR. In DCM, MPR, LV ejection fraction, and fibrosis are independently associated with aerobic exercise capacity.

Keywords: Cardiovascular magnetic resonance; Dilated cardiomyopathy; Exercise capacity; Myocardial perfusion reserve.

Association between coronary microvascular dysfunction and exercise capacity in dilated cardiomyopathy. In this prospective study using cardiovascular magnetic resonance and cardiopulmonary exercise testing, patients with dilated cardiomyopathy had similar rest but lower stress myocardial blood flow and lower myocardial perfusion reserve compared to controls. In multivariable linear regression incorporating key clinical and imaging parameters, left ventricular ejection fraction, extracellular volume fraction, and myocardial perfusion reserve were independently associated with peak VO₂ in dilated cardiomyopathy. DCM dilated cardiomyopathy, ECV extracellular volume fraction

Fig. 1

Study flow diagram. Summary of study enrollment and exclusions. BMI body mass index, CMR cardiovascular magnetic resonance, CPET cardiopulmonary exercise testing, DCM dilated cardiomyopathy

Fig. 2

Comparison of quantitative perfusion between the DCM and control groups. Patients with DCM had similar rest (left) but lower stress (middle) MBF and lower myocardial perfusion reserve (right) compared to the control group. P values were adjusted for ethnicity and systolic blood pressure. Boxplots were generated using the Tukey method. DCM dilated cardiomyopathy, MBF myocardial blood flow

Fig. 3

Rest and stress myocardial blood flow and myocardial perfusion reserve in patients with DCM. There was no difference in rest MBF, stress MBF, or MPR in the DCM patients when stratified as LBBB (n = 21) or non-LBBB (n = 45), presence (n = 39) or absence of LGE (n = 27), with an LV EF ≤35% (n = 21) or >35% (n = 45), and genotype positive (n = 14) or negative (n = 39). EF ejection fraction, LBBB left bundle branch block, LGE late gadolinium enhancement, LV left ventricular, MBF myocardial blood flows, MPR myocardial perfusion reserve