Coronary Flow Evaluation in Heart Transplant Patients Compared to Healthy Controls Documents the Superiority of Coronary Flow Velocity Reserve Companion as Diagnostic and Prognostic Tool

Abstract

BackgroundDistinct contributions by functional or structural alterations of coronary microcirculation in heart transplantation (HT) and their prognostic role have not been fully elucidated. We aimed to identify the mechanisms of coronary microvascular dysfunction (CMD) in HT and their prognostic implications.Methods134 patients, surviving at least 5 years after HT, without evidence of angiographic vasculopathy or symptoms/signs of rejection were included. 50 healthy volunteers served as controls. All underwent the assessment of rest and hyperemic coronary diastolic peak flow velocity (DPVr and DPVh) and coronary flow velocity reserve (CFVR) and its inherent companion that is based on the adjusted quadratic mean: CCFVR = √{(DPVr)2 + (DPVh)2}. Additionally, basal and hyperemic coronary microvascular resistance (BMR and HMR) were estimated.ResultsBased on CFVR and DPVh, HT patients can be assigned to four endotypes: endotype 1, discordant with preserved CFVR (3.1 ± 0.4); endotype 2, concordant with preserved CFVR (3.4 ± 0.5); endotype 3, concordant with impaired CFVR (1.8 ± 0.3) and endotype 4, discordant with impaired CFVR (2.0 ± 0.2). Intriguingly, endotype 1 showed lower DPVr (p < 0.0001) and lower DPVh (p < 0.0001) than controls with lower CFVR (p < 0.0001) and lower CCFVR (p < 0.0001) than controls. Moreover, both BMR and HMR were higher in endotype 1 than in controls (p = 0.001 and p < 0.0001, respectively), suggesting structural microvascular remodeling. Conversely, endotype 2 was comparable to controls. A 13/32 (41%) patients in endotype 1 died in a follow up of 28 years and mortality rate was comparable to endotype 3 (14/31, 45%). However, CCFVR was < 80 cm/s in all 13 deaths of endotype 1 (characterized by preserved CFVR). At multivariable analysis, CMD, DPVh < 75 cm/s and CCFVR < 80 cm/s were independent predictors of mortality. The inclusion of CCFVR < 80 cm/s to models with clinical indicators of mortality better predicted survival, compared to only adding CMD or DPVh < 75 cm/s (p < 0.0001 and p = 0.03, respectively).ConclusionA normal CFVR could hide detection of microvasculopathy with high flow resistance and low flow velocities at rest. This microvasculopathy seems to be secondary to factors unrelated to HT (less rejections and more often diabetes). The combined use of CFVR and CCFVR provides more complete clinical and prognostic information on coronary microvasculopathy in HT.

TMAD enters the toolbox for evaluating selected heart transplant patients

“…Prognosis after heart transplant (HTX) depends on occurrence of specific complications such as acute cellular rejection episodes, cardiac allograft vasculopathy (CAV), 1 and restrictive left ventricular (LV) function, best characterized by the LV filling pattern, which is affected by factors such as heart rate (HR), blood pressure, and surgical technique. 2 Evaluation of HTX patients is not only complicated by the (initial) denervated state and possible sex-mismatch issues, but also by the fact that the heart excels in the capability to adapt, thereby potentially masking minor deterioration.…”

“…If analyzed in a comprehensive manner, the method allows identification of four endotypes of coronary microvascular impairment. 1…”

“…Prognosis after heart transplant (HTX) depends on occurrence of specific complications such as acute cellular rejection episodes, cardiac allograft vasculopathy (CAV), 1 and restrictive left ventricular (LV) function, best characterized by the LV filling pattern, which is affected by factors such as heart rate (HR), blood pressure, and surgical technique 2 …”

In search for the optimal ventricular systolic dysfunction metric that associates with reduced exercise capacity

“…A major shortcoming of the isolated use of any dimensionless ratio is the neglect of the associated companion (C) metric, which may be relevant 6 . For example, the companion associated with coronary flow reserve was documented to offer superiority as a diagnostic and prognostic tool (while also featuring physical dimensions) for evaluating coronary microvasculopathy after heart transplantation 7 …”

“…6 For example, the companion associated with coronary flow reserve was documented to offer superiority as a diagnostic and prognostic tool (while also featuring physical dimensions) for evaluating coronary microvasculopathy after heart transplantation. 7…”