ABC | Volume 114, Nº4, April 2020

Original Article Carrion et al. Right ventricular dysfunction and heart transplant Arq Bras Cardiol. 2020; 114(4):638-644 monitoring per hospital protocol, and their data were analyzed during the first 18 months of follow-up after HTx. Of the 20 patients who received transplants (all via the bicaval technique), 19 were included in this analysis, and one patient who died before the first endomyocardial biopsy due to hyperacute graft rejection was excluded. The standard institutional follow-up protocol, which served as a guide for this study, consisted of weekly biopsies in the first month post-HTx; biopsies every other week during the second and third months post-HTx; monthly biopsies from the fourth to the sixth month post-HTx; and subsequent biopsies every three to four months until 18 months of follow-up had been completed. Each biopsy was followed by echocardiography, seeking to detect post-biopsy complications. Of the 257 biopsies performed up to July 2017, 170 had corresponding echocardiograms with images suitable for strain analysis by the speckle-tracking method and were thus included in this study (Figure 1). Comparisons were made among biopsy/echocardiogram pairs with no (0R) or mild (1R) evidence of rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n = 15). This study was conducted in accordance with the standards set out in the Declaration of Helsinki, and its protocol was approved by the institutional Research Ethics Committee. Echocardiographic Analysis All echocardiograms were recorded and analyzed offline on a TOMTEC workstation (TomTec Imaging Systems, Unterschleißheim, Germany) by an experienced echocardiographer (LJBMC) blinded to clinical data and to the corresponding biopsies. Measurements were obtained according to American Society of Echocardiography (ASE) standards, including septal and posterior wall thicknesses; diameters of the LV, RV, aorta, and left atrium; transmitral flow; mitral and tricuspid annular relaxation velocities; and tricuspid annular excursion. Echocardiographic measures of RV function were performed using the apical 4-chamber view. Tricuspid annular plane systolic excursion (TAPSE) was measured as the vertical displacement of the tricuspid annulus from end-diastole to end-systole using M-mode. The tissue Doppler-derived tricuspid lateral annular systolic velocity wave (S wave) was obtained aligning the basal segment and the tricuspid annulus with the Doppler cursor. RV fractional area change (FAC) was evaluated by manual tracing of RV areas as follows: (RV end-diastolic area − RV end-systolic area) / RV end-diastolic area × 100. Analysis of myocardial deformation (GLS) was performed using specific B-mode speckle-tracking software for the LV and the RV (2D CPA TTA2.20.01, TomTec). This software circumvents angle dependency and identifies cardiac motion by tracking multiple reference points over time. At end-systole, as defined by ECG, three landmarks were established at the endocardial edge (two basal and one apical), with automatic detection of speckles along the endocardial edge of the specified cavity (LV or RV). Manual adjustments were made when necessary. In the LV, peak-systolic strain for each 2D apical view (two-, three-, and four-chamber) was automatically obtained from the mean of the 6 traced segments, while LV GLS was obtained by averaging the peak‑systolic strain of apical views. In the RV, RV GLS was defined as the peak‑systolic strain that combined the free wall and the septum (Figure 2). All patients were in sinus rhythm, and a single cardiac cycle was analyzed. Images in which poor quality precluded speckle analysis in two or more consecutive segments, images covering less than one complete cardiac cycle, or excessively tangential views were excluded. LV and RV end-systolic and end-diastolic volumes were used to derive other measures of myocardial function, such as LVEF (by the modified Simpson method) and RV FAC. Intraobserver variability for LV GLS and RV GLS was assessed in a sample of 20 randomly selected echocardiograms. The coefficient of variation was 3.8% and 6.7% for LV GLS and RV GLS, respectively. Intraclass correlation coefficients were 0.96 for LV GLS (95% confidence interval: 0.91 – 1.0) and 0.80 for RV GLS (95% confidence interval: 0.59 – 1.0). Endomyocardial Biopsy Endomyocardial biopsies were scheduled as required by the standard institutional protocol. All were performed through an internal jugular vein access, at the catheterization laboratory. During the procedure, a sheath was advanced to the interventricular septum through the tricuspid valve, and 3 – 6 small fragments were retrieved with a cardiac bioptome for histological analysis. Tissue samples were evaluated by a single experienced pathologist who was blinded to the results of the echocardiographic studies. Biopsies were examined for ACR, graded on a scale from 0R to 3R, according to the International Society for Heart and Lung Transplantation (ISHLT) classification. 13 All patients with biopsies classified as ≥ 2R were treated with a standard regimen for rejection, while those with biopsies classified as 1R were monitored closely and remained on maintenance immunosuppression therapy, following institutional protocols. Statistical Analysis Normally distributed continuous data were expressed as means and standard deviations, and categorical data were shown as absolute and relative frequencies. Echocardiography variables were compared using ANOVA adjusted for each HTx patient accounting for repeated measurements. All statistical analyses were performed in the SPSS software package. All tests were two-sided, and p-values < 0.05 were considered statistically significant. Results Most HTx recipients (n = 19) followed in this study were women (n = 11; 58%), with a mean age of 48 ± 12.4 years. In general, few had other comorbidities, and the main etiology of heart failure was of non-ischemic origin. Donors were mostly young men, with a mean age of 29 years (Table 1). Of the 257 biopsies performed in this period, the results of 66% (n = 170) correlated with echocardiography. Of the biopsies excluded from analysis (87 without corresponding echocardiograms), 24 showed 1R rejection; two showed 2R rejection; and one showed 3R rejection. Of the 170 biopsies 639