Differently from general population of patients with coronary artery disease, there are only few studies comparing the accuracy of DSE, MSCT and coronary angiography for detecting CAV in cardiac transplant recipients . The uniqueness of our study is that all our patients underwent the three techniques, and introduced in the DSE protocol the valuation of the ESPVR for diagnosing CAV. At our knowledge, indeed, this is the first study in which ESPVR is used to assess LV contractility, coronary anatomy and quality of life in a population of asymptomatic heart transplant recipients. The results of the present study are broadly consistent with the previous evidences suggesting that the challenge of inotropic reserve with catecholamine infusion is useful to unmask depressed contractile reserve in a left ventricle with latent dysfunction. Even more clinically relevant and original, this technique significantly improves the prediction of CAV in comparison with MSTC, reducing the risk of useless invasive interventions.
Difficulty in detecting and treating CAV remains the major limiting factor for survival after heart transplantation. The disease is silent in most of cases mainly because of cardiac denervation.
First modality and diagnostic test for detecting CAV is the anatomic one: coronary angiography CA is still the reference standard for diagnosing CAV, in spite of its invasive nature not free from complications and the exposure to ionizing radiation and to iodinated contrast media given to patients taking immunosuppressive medications. Up today, many centers perform annual evaluations to establish the presence and severity of CAV after heart transplantation .
Another relevant anatomic modality to detecting CAV, although non-invasive, is MSCT. In 2000, Knollmann and co-workers  compared, in 112 heart transplant recipients, the electron-beam CT features of coronary arteries with those of biplane coronary angiography and intracoronary ultrasound. They found that electron-beam CT had a sensitivity of 94%, a specificity of 79%, a positive predictive value of 43%, and a negative predictive value of 99% for detecting coronary stenosis. Similar results, comparing cardiac multi-detector computed tomography angiography and coronary angiography, were found by von Ziegler and co-workers . From these data appear a high negative predictive value and an unsatisfactory positive predictive value of this diagnostic tool. Our results are in line with those previously reported that lead to overestimate the coronary disease with the clinical implication of an inappropriate request for coronary angiography, which implies the use of nephrotoxic agents. As expected, many heart transplant recipients have chronic kidney disease due to cyclosporine or other immunosuppressive therapy: in our population 88% of the patients were treated with cyclosporine. It is a very important problem that the cardiologists have to think about when prescribe a MSCT.
Moreover, we analyzed the presence of any possible relationship between ESPVR and quality of life. Theoretically a loss of contractile reserve could carry to a worse physical activity: it can be caused by a classic ischemic mechanism, due to a reduced blood supply in situations of increased cardiac output (i.e. catecholamine infusion), or by an inflammatory response as in the heart transplant rejection. Both mechanisms cannot be identified either by CA or by MSCT, and a functional test is requested to reveal whether a reduced functional capacity may be associated with a latent ventricle dysfunction.
Our results seem confirm this hypothesis: patients with flat-biphasic ESPVR, indeed, have lower scores in all the 8 subscales of the SF-36 questionnaire, and this is statistically significant for general health, mental health and vitality. Also in that single patient with flat-biphasic ESPVR and negative coronary angiography, the results of the SF-36 were coherent with the inotropic reserve found.
Our study has several limitations.
Calculation of the ESPVR requires measurement of the LV pressure at the end-systole. Because only non-invasive measurements were available, cuff systolic pressure was substituted for end-systolic pressure.
The overall patient population was small, thus limiting the generalizability of our findings. Studies with a larger sample size and longer follow-up are warranted.
Finally, in all patients on β-blocking agents, therapy was kept unchanged and may have influenced, at least in part the results. However, the optimal dose of dobutamine to assess contractility and recognize CAV is not defined and it did not appear ethical to withdraw a life-saving therapy.