Coronary Flow Reserve Predicts Major Adverse Cardiac Events and All-Cause Mortality in Heart Transplant Recipients

Abstract

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) after heart transplantation (HTx) affects the epicardial arteries and veins and also the coronary microcirculation. In the absence of proximal epicardial artery stenosis, coronary flow velocity reserve (CFVR) reflects the function of the myocardial microcirculation. We aimed to determine the prognostic value of 1) CFVR and 2) a combination of CFVR and left ventricular global longitudinal strain (LVGLS) in HTx patients. <h3>Methods</h3> CFVR was evaluated using pulsed wave Doppler echocardiography in 98 HTx patients (median 6.9 years from HTx) examined with coronary angiography. Patients were enrolled from 2013 to 2018 and prospectively followed until June 1^st 2020. All-cause mortality and major adverse cardiac events (MACE) including heart failure, significant CAV progression, coronary intervention or cardiovascular death, were recorded. <h3>Results</h3> Median follow-up was 3.2 [interquartile range 1.9-5.1] years. Patients with low CFVR (<2.0, n=20) had a significantly reduced event-free survival rate compared with patients with high CFVR (≥2.0, n=78) (35% vs. 82%, hazard ratio (HR) 4.6, 95% CI 2.3-9.1, <i>p</i><0.0001) and had a higher rate of mortality than patients with high CFVR with an absolute difference of 43.3% (65.3% vs. 22.0%; HR 5.0, 95% CI 2.1-11.9, <i>p</i><0.0001). By combining low CFVR and low LVGLS magnitude (>-15.5%), we obtained a strong predictive model for MACE (HR 10.5, 95% CI 4.5-24.5, <i>p</i><0.0001) and all-cause mortality (HR 10.3, 95% CI 3.5-30.6, <i>p</i><0.001), which remained strong after adjustment for angiographic CAV. <h3>Conclusion</h3> CFVR strongly predicts MACE and all-cause mortality in HTx-patients. A model combining low CFVR and low LVGLS magnitude was a strong model for MACE and all-cause mortality prediction and could be considered as a non-invasive method for routine CAV surveillance.