Quantitative myocardial contrast echocardiography: a new method for the non-invasive detection of chronic heart transplant rejection

Abstract

Chronic heart transplant rejection, i.e. cardiac allograft vasculopathy (CAV) is a major adverse prognostic factor after heart transplantation (HTx). This study tested the hypothesis that the relative myocardial blood volume (rBV) as quantified by myocardial contrast echocardiography accurately detects severe CAV as defined by coronary intravascular ultrasound (IVUS). Forty-five HTx patients underwent a total of 50 quantitative IVUS measurements for intima thickness assessment (>1 mm = severe CAV; the reference method). Simultaneously, the two factors constituting myocardial perfusion (mL/min/g) were obtained by transthoracic contrast echocardiography at rest: rBV (the test method), a measure of microvascular density (mL/mL), and its exchange rate β (1/s; a measure of coronary conductance) after mechanical contrast bubble disruption.Sixty-nine per cent (31 of 45) of the HTx patients showed severe CAV. rBV at rest was equal to 0.17 ± 0.05 in the group without severe CAV, and it was equal to 0.12 ± 0.07 in the group with severe CAV (P = 0.0157). Conversely, β amounted to 6.4 ± 4.5 in the former and to 10.3 ± 6.2 in the latter group (P = 0.0410), thus, maintaining normal resting myocardial perfusion at 1 mL/min/g. IVUS determined intima thickness correlated significantly and inversely with rBV at rest. An rBV value at rest <0.14 accurately detected severe CAV (intima thickness >1 mm): area under the receiver operating characteristics curve = 0.844, P = 0.004, sensitivity = 0.90, specificity = 0.75. Severe CAV can be detected using the non-invasive method of quantitative myocardial contrast echocardiography. rBV at rest amounting to <14% of the surrounding tissue accurately detects coronary intima thickness >1 mm as determined invasively by IVUS. NCT00414895.