New Non‐Invasive Technologies in Cardiac Transplant Follow‐Up: Acquired Evidence and Future Options
Valeria PergolaGiulia MattesiElena CozzaNicola PradeganChiara TessariCarlo Maria DellinoMaria Teresa SavoFilippo AmatoAnnagrazia CecereMartina Perazzolo MarraFrancesco TonaAndrea Igoren GuaricciGiorgio ContiGino GerosaSabino IlicetoRaffaella Motta
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Abstract:
Heart transplantation (HT) represents the mainstream therapy of end-stage heart failure for selected patients with a median survival of more than 10 years after surgery and substantial improvement in quality of life. Current guidelines suggest a variety of examinations including invasive (coronary angiography and endomyocardial biopsy (EBM) and non-invasive methods (echocardiography, stress echocardiography, computed tomography, PET and MRI) to monitor HT patients. Guidelines do not specify the timing of echocardiographic evaluations and do not recommend echocardiography as an alternative to serial EMB in rejection monitoring [2]. They still recommend as gold standard coronary angiography to be done 1 year after surgery and every 2 years after. In this review we will discuss the advantages of non-invasive techniques over the invasive ones for an adequate follow-up of HT patients.Keywords:
Endomyocardial Biopsy
Gold standard (test)
Cardiac transplantation is a valid therapeutic option for advanced chronic heart failure, with a one year survival of 60-80%. Although the introduction of cyclosporine has markedly improved survival in heart transplant recipients, early detection of cardiac allograft rejection remains the major problem to be solved. At present, the diagnosis of cardiac rejection has been based on the results of endomyocardial biopsy, which remains actually as the gold standard for rejection surveillance. However, ideally the detection of cardiac rejection should be noninvasive to allow frequent follow-up of the patients. Several attempts have been made to find a noninvasive alternative to replace endomyocardial biopsy, doppler-echocardiography being the most promising technique. A review of current noninvasive methods for graft rejection detection will be discussed emphasising the importance of doppler-echocardiography.
Endomyocardial Biopsy
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Graft rejection
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The endomyocardial biopsy has defined the diagnosis of rejection in cardiac transplantation and has historically been a vital tool when rejection rates following transplantation were high. Surveillance biopsies have been the cornerstone of post-transplant management, as signs or symptoms of rejection are non-specific. With significant improvements in immunosuppressive therapy, however, the incidence of clinically significant rejection has declined, bringing into question the need for routine surveillance biopsy. This article reviews the current role of the endomyocardial biopsy in the management of patients following cardiac transplantation.The endomyocardial biopsy is also limited by sub-optimal interobserver reproducibility, a lack of consensus with regard to treating certain grades of rejection, and often a lack of histological findings in patients with hemodynamic compromise, which frequently responds to anti-rejection therapy. Recent refinements, however, have allowed improved diagnosis of antibody mediated rejection, a relatively recently recognized entity. Moreover, a number of non-invasive modalities have been investigated recently as potential substitutes for the endomyocardial biopsy in detecting rejection.Despite the development of a variety of non-invasive methods for the detection of rejection, the endomyocardial biopsy will remain important in the management of patients following cardiac transplantation, as non-invasive techniques are associated with low specificity for the diagnosis of rejection. A new standardized classification will likely improve the utility of the biopsy by simplifying interpretation of cellular rejection and importantly allowing recognition of antibody-mediated rejection.
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Endomyocardial biopsy remains the gold standard of diagnosis of acute cellular rejection after heart transplantation. However, routine biopsies are of major inconvenience to patients and are also risky and costly. In the present research we considered possibility of non-invasive diagnosis of acute cellular rejection in patients after orthotopic heart transplantation. Results of research are based on studying 34 endomyocardial biopsys in combination with Holter monitoring and ECHO findings in 21 heart recipients. It is demonstrated that case follow-up with Holter monitoring and ECHO is mandatory for diagnosis of acute cellular rejection and optimal treatment tactics.
Endomyocardial Biopsy
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Graft rejection
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Congestive heart failure is associated with the increase risk of death or cardiac transplantation. The ability of current techniques to predict outcome in heart failure is rather limited. Identification of the patients at risk of cardiac death or requiring heart transplantation is clinically important. The changing rate of left ventricular pressure during the cardiac cycle is an important parameter in the assessment of myocardial systolic function. Non-invasive echocardiographic method--dP/dt has been proposed to determine the isovolumic phase of cardiac function. The aim of this study was to evaluate the ability of Doppler-derived dP/dt to predict survival in patients with congestive heart failure.Thirty one patients (22M, 9W), mean age 55 +/- 11.2 years, with CHF (LVEF < 45%, NYHA II-IV class) and chronic mitral regurgitation were analyzed. The echocardiography, cardiopulmonary exercise test and clinical follow-up were performed in all of them. The ejection fraction was calculated using the Simpson's method from apical 4-chamber view. The dP/dt index was derived from the continuous-wave Doppler spectrum. The mean follow-up period was 28.5 +/- 12 months. According to the clinical status the patients were divided into two groups: group I--21 event-free patients and group II--10 patients who experienced primary events (5 died and 5 underwent heart transplantation).In the group of primary events patients there was noted a significant decrease of the dP/dt index in comparison to the event-free patients: 463 mmHg/s vs 839 mmHg/s (p=0.0001). The correlation between dP/dt and ejection fraction, left ventricular end-diastolic diameter as well as between the parameters of cardiopulmonary exercise test VO2peak, VO2AT, VE/VCO2peak was found.Doppler echocardiographic index of dP/dt can predict the outcome in patients with congestive heart failure. Dp/dt can be useful as a prognostic factor in patients with CHF. A significant correlation was observed between dP/dt and VO2peak as well as VE/VCO2peak which are independent prognostic predictors.
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The optimal duration and frequency of routine surveillance endomyocardial biopsy (EMB) have been questioned in the current era of heart transplantation (HT), where the advances in immunosuppression and donor selection strategies have led to a decline in acute allograft rejection. We investigated the utility of routine EMB beyond 6 months post-HT. A single-center retrospective review was performed on 2963 EMBs from 220 HT recipients over 10 years. Each EMB was categorized into protocol or symptom-triggered biopsy and reviewed for rejection. Heart transplant recipients with ≥2 known risk factors for rejection were designated as an elevated risk group. The majority of rejections occurred within 3 months following HT. The yield of routine protocol EMBs was significantly lower than symptom-triggered EMBs, not only during the first 6 months post-HT (1.6% vs. 33.3%, P < .0001), but more so during the 6-12 months (0.1% vs 83.0%, P < .0001). A similar pattern was observed in heart transplant recipients at both elevated and standard risk for rejection. In conclusion, EMB was found to be a low-yield screening modality for rejection beyond 6 months post-HT.
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