What Ejection Fraction Qualifies For Heart Transplant – The combination of editors and reviewers is the most recent provided in the Loop research profile and may not reflect their status at the time of review.
Acute Cellular Rejection in Heart Transplant Patients: Insights into Global Longitudinal Strain, Myocardial Exercise and Chagas Disease Exclusive Groups
What Ejection Fraction Qualifies For Heart Transplant
Background: Echocardiographic markers associated with asymptomatic acute cellular rejection (ACR) in orthotopic heart transplant (HT) patients are under investigation. The aim of our study was to determine clinical and myocardial strain imaging (MSI) variables assessed by echocardiography associated with ACR during the first year of HT. A separate analysis was performed to compare variables during the first 6 months of HT, when ACR had a prevalence in 60% of patients. Another analysis evaluated the exclusive population with Chagas disease as the cause of HT.
Circulation: Heart Failure
Methods: We prospectively studied 67 patients with less than 1 year of HT, 36 patients without ACR (41% male, age 49 ± 12 years, 52% Chagas disease as the cause of heart failure), and 31 patients with ACR (59%). male, age 55 ± 8 years, 74% Chagas disease as a cause of heart failure). Conventional echocardiographic and MSI measurements of global longitudinal strain (GLS) of the left ventricle (LV) and right ventricular free wall (RV-FWLS) and myocardial work (MW) of the left ventricle were obtained by an experienced echocardiologist. Clinical variables, such as the presence of diabetes, hypertension, and immunosuppressant medications, were compared between groups.
Results: HT patients with ACR were older and used more cyclosporine for immunosuppression. The ACR positive group had increased relative wall thickness and LV mass index and LVGLS similar to RV-FWLS compared to the ACR negative group. However, the MW analysis found a positive increase in global work efficiency (GWE) in ACR. Multivariate analysis identified older age, cyclosporine use, LV mass index, and GWE as independent predictors of detecting rejection. A separate analysis was performed for patients with less than 6 months of HT. Similar MSI was observed in both groups, with a trend for increased GWE in ACR patients and a significantly increased LV mass index in the ACR group. An exclusive group of Chagas patients as the primary cause of HT was analyzed, and similar MSI results for LVGLS, RV-FWLS, and MW were observed for both ACR and non-rejection groups. Additionally, survival rates at 2 years were similar between the Chagas disease groups.
Conclusion: LVGLS and RV-FWLS were similar between patients with or without ACR in the first year after HT. Conversely, GWE, LVGLS derivative and LV mass index are elevated in positive ACR and may be markers for rejection. An increase in LV mass index was also found in the subgroup analysis of patients less than 6 months after HT; however, MSI was similar regardless of ACR. For chagasic patients, rejection in the first year did not increase mortality in the 2-year follow-up, and MSI parameters were similar between patients with or without ACR. In the multivariate analysis to predict ACR, the independent parameters in this study were old age, cyclosporine use, LV mass index, and GWE.
Heart transplantation (HT) is the gold standard treatment for end-stage heart failure. Significant improvements in patient selection and perioperative management have reduced postoperative complications, and early survival has improved dramatically. However, acute cellular rejection (ACR) is the main problem in the early period after HT, and about 25-32% of patients experience multiple graft rejection in the first year (60% in the first 6 months) (1, 2). It is the main cause of death among patients with HT, especially chagasic recipients in developing countries, occurring in 10-14% of all patients with ACR, despite efforts to develop new immunosuppressive protocols (1).
Heart Failure With Preserved Ejection Fraction
Most patients with ACR are asymptomatic or have nonspecific symptoms, some degree of neurohormonal activation occurs (3), and endomyocardial biopsy (EMB) continues to be the best method for diagnosis (4). However, EMB is an invasive method with significant complications, including perforation, pneumothorax, cardiac tamponade, arrhythmia, and damage to the tricuspid valve (1). The pursuit of non-invasive alternatives to ACR has been a goal in the early years of HT (1, 5).
Asymptomatic ACR is not usually associated with reduced left ventricular ejection fraction (LVEF). However, new technologies in echocardiography by Doppler tissue analysis and global longitudinal strain (GLS) with speckle detection are important to detect early myocardial injury despite normal LVEF (5).
A recent study by Mingo-Santos et al. (6) suggested that LV free wall longitudinal strain and RV free wall strain (FWLS) may help to significantly push back ACR in the first year after HT. Other studies have found similar results for GLS (7-9). Combined with biomarkers, Cruz et al. (7) reported that patients with ACR had significantly lower LVGLS, RV-FWLS, and LV-Twist values and higher troponin I levels than patients without significant ACR.
On the other hand, Ambardekar et al. (10) found changes in myocardial strain and strain rate as assessed by 2D-STE in a serial study from asymptomatic biopsy-proven rejection patients in the first year after HT, agreeing with the findings of Tseng et al. (9).
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Therefore, as a result of these conflicting findings about GLS in HT, echocardiographic markers for ACR are still under investigation. Furthermore, myocardial work (MW), an index derived from strain/stress curves, has not been reported in HT (11).
Interestingly, despite HT, patients with Chagas disease still have other aspects of the disease, such as the deterioration of the autonomic nervous system (12), which can alter the neurohormonal response produced by the reactivation of ACR and Chagas as a differential diagnosis for ACR (1) . .
The aim of our study was to determine clinical and myocardial strain imaging (MSI) as assessed by echocardiography associated with ACR in the first year of HT. We present an important methodological framework for echocardiographic analysis in the first 6 months in a population with exclusive Chagas disease as the cause of HT.
From January 2017 to December 2019, we prospectively included adult patients with less than 1 year of orthotopic HT at the Institute of Cardiology and Heart Transplantation, Brasília, Federal District, Brazil, in our study. EMB surveillance was performed followed by a transthoracic echocardiogram on the same day, less than 4 hours apart.
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Patients were divided into two groups according to the results of EMB according to the grading system of the International Society for Heart and Lung Transplantation (ISHLT) 2004 (4): (1) without ACR (grade 0 and 1) and with ACR (grade). 2 and 3). The HT rejection group was compared with HT without rejection in terms of clinical and echocardiographic parameters.
This study was approved by the Ethics Committee of Cardiology and Heart Transplantation of the Federal District Institute, Brasília, Brazil, and the inscription number in Plataforma Brazil as a Certificate of Ethical Award Presentation is 65910517.0.0000.0026. All patients provided written informed consent to participate in this study.
We included patients with less than 1 year of orthotopic HT who came to our institution to undergo EMB surveillance and who were asymptomatic and hemodynamically stable. EMB and echocardiogram were performed on the same day. The protocol at our institution is to perform an echocardiogram less than 4 hours after EMB to diagnose procedure-related complications (13) and before leaving outpatients who only come for biopsy and follow-up.
Patients with ejection fraction below 53%, reactivation of Chagas disease, humoral rejection (4), irregular heart rhythm, unconvincing EMB (1), and limited echocardiographic acoustic window were excluded.
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Patients enrolled in EMB follow-up periodically, only once in the first year of orthotopic HT. In total, 71 patients were included, but 4 were included according to exclusion criteria: 1 for poor acoustic window, 1 for inconclusive EMB (insufficient material), 1 for Chagas reactivation, and 1 for ejection fraction <53%; 67 patients remained available for study (Figure 1).
Figure 1. Flow chart of HT patients with or without acute cellular rejection. This study involved 67 patients who underwent HT. Patients with poor acoustic windows, with inconclusive EMB (insufficient material), with Chagas reactivation, and with ejection fraction <53% were not included. Finally, 67 patients with HT were included in this study. Among them, 36 patients were in the NACR group and 31 patients were in the PACR group. Statistical analysis for sample size was performed with power analysis based on the mean and standard deviation of the same study (7). HT, heart transplant; EMB, endomyocardial biopsy; NACR, negative acute cellular rejection; PACR, positive acute cellular rejection.
Endomyocardial biopsy is performed invasively through the femoral vein under fluoroscopy. Usually, at least 3-5 segments are collected, aiming for the area of the interventricular septum, accessed by the right ventricle. Samples were analyzed with an optical microscope after hematoxylin and eosin (H&E) staining (1, 4). A pathologist blinded to the echocardiogram results analyzed all biopsies and cellular rejection was classified according to the ISHLT grading system (4). Class 0 and 1 are considered to represent no significant cellular rejection (1). Grades 2 and 3 represent significant cellular rejection, and a change in immunosuppressant medication is usually required (1). EMB was performed according to our institutional protocol once a week in the first month of HT, every 15 days in the second month, and monthly from