Long-Term Prognostic Value of Coronary CTA in Orthotopic Heart Transplant Recipients.

OBJECTIVE. This study aimed to evaluate the long-term prognostic value of coronary CTA (CCTA) in heart transplant recipients. MATERIALS AND METHODS. The records of 114 patients who had undergone a heart transplant (mean age, 61.7 ± 11.1 [SD] years; 83.3% men) and who underwent CCTA for the surveillance of coronary allograft vasculopathy (CAV) from June 2007 to December 2017 were retrospectively evaluated for the occurrence of major adverse cardiovascular events (MACEs) (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, coronary revascularization, cardiac arrhythmias, stroke, and retransplant). Patients were classified according to the presence of nonobstructive CAV (lumen reduction < 50%) or obstructive disease (lumen reduction ≥ 50%) and using a coronary segment involvement score (SIS). Differences in MACE rate between groups were compared. RESULTS. Obstructive CAV was observed in 12 heart transplant recipients (10.5%). During a mean follow-up of 67.5 ± 41.4 months the overall rates of MACE were 50% and 14.7% in patients with obstructive and nonobstructive CAV, respectively (p < .05), resulting in an odds ratio for MACE of 6 (95% CI, 1.7-21.2). Comparison of event-free survival showed a hazard ratio (HR) of 5 (95% CI, 1.95-13; p =. 004) for patients with obstructive disease. The presence of four or more stenotic coronary segments (SIS ≥ 4) was associated with a higher rate of events (HR, 3.46; 95% CI, 1.46-8.23). CONCLUSION. In patients who have undergone a heart transplant, CCTA offers a significant long-term prognostic impact on the prediction of MACEs.

Gender differences in heart transplantation: Twenty-five year trends in the nationwide Spanish heart transplant registry.

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993-2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25-year study period. HT rate was higher in men, although this decreased over the 25-year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre-HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality-related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001).

Systolic High-Pitch Coronary CT Angiography for Evaluation of the Coronary Arteries in Heart Transplant Recipients.

OBJECTIVE. The purpose of this study was to evaluate the feasibility, image quality, and radiation dose of high-pitch coronary CT angiography (CCTA) in orthotopic heart transplant (OHT) recipients. SUBJECTS AND METHODS. Twenty-two consecutive OHT recipients (16 men, six women; median age, 66.5 years [interquartile range, 51.3-70.3 years]; median heart rate, 91 beats/min [interquartile range, 79.3-97.3 beats/min]) underwent CCTA with a third-generation dual-source CT scanner in high-pitch mode to rule out coronary allograft vasculopathy. Data acquisition was triggered at 30% of the R-R interval. Two independent observers blindly assessed image quality on a per-segment, per-vessel, and per-patient basis using a 4-point scale (4, excellent; 1, not evaluative). Scores 2-4 indicated diagnostic quality. Studies were compared with previously performed retrospective ECG-gated examinations, when available. Interobserver agreement on the image quality was assessed with kappa statistics. Radiation dose was recorded. RESULTS. A total of 322 coronary segments were evaluated. Diagnostic image quality was observed in 97.5% of the segments. Interobserver agreement for image quality assessment was very good on a per-patient (κ = 0.82), per-vessel (κ = 0.83), and per-segment basis (κ = 0.89). The median per-patient image quality score was 4.0 (3.0-4.0) for the entire coronary tree. A comparison of image quality scores between high-pitch and retrospective ECG-gated CCTA examinations showed no significant differences, but the estimated mean radiation dose was significantly lower for the high-pitch mode (median dose-length product, 31.6 mGy × cm [interquartile range, 23.1-38.8 mGy × cm] vs 736.5 mGy × cm [interquartile range, 655.5-845.7 mGy × cm], p < 0.001). CONCLUSION. Performing single-heartbeat high-pitch CCTA during the systolic phase of the cardiac cycle in OHT recipients results in diagnostic image quality in coronary angiograms at very low radiation dose.

Quantitative assessment of left ventricular size and function in cardiac transplant recipients: Side-by-side comparison of real time two-dimensional echocardiography, contrast-enhanced two-dimensional echocardiography, three-dimensional echocardiography, and contrast-enhanced three-dimensional echocardiography as compared to magnetic resonance imaging.

INTRODUCTION: We evaluate the ability of 2D non-contrast-enhanced echocardiography (CE-echo), 2DCE-echo, 3D-echo, 3D non-CE-echo, and 3DCE-echo to evaluate allograft function and dimensions in orthotropic heart transplantation (OHT). Cardiac resonance (CMR) was used as reference. METHODS: Twenty six consecutive OHT-recipients were prospectively recruited. Bland-Altman, Spearman rank, and concordance-correlation coefficients (CCC) were determined. RESULTS: Good CCCs were found between the four modalities and CMR for ejection fraction (r ≥ 0.72/P < 0.001; r ≥ 0.77/ P < 0.001; r ≥ 0.51/ P < 0.23; r ≥ 0.75/ P < 0.001, respectively). Highest intraclass correlation coefficient (ICC) was for 2D CE-echo(CCC = 0.77). End-diastolic volume(EDV) measurements statistically differed when 2D non-CE-echo, 2DCE-echo, and 3D non-CE-echo were compared with the cross-sectional imaging modalities, but they did not differ significantly from 3DCE-echo. End-systolic volume (ESV) and stroke volume (SV) differed statistically between the four modalities; however, SV measured by CMR and 3DCE-echo were comparable. Overall, 2D non-CE-echo, 2DCE-echo, and 3D non-CE-echo showed lower mean EDV, ESV, and SV than CMR. ICC was that of the ESV variable in the 4 techniques, with the values of the ICC of the 3DCE-echo technique superior to the rest. Overall, the best CCC were found for 3DCE(r = 0.88, 0.92 and 0.76 for EDV, ESV and SV, respectively). CONCLUSION: Routine use of 3DCE-echo may allow more comprehensive cardiac assessment in cardiac transplant recipients.

First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study.

This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.

Generation of Self-Induced Myocardial Ischemia in Large-Sized Cardiac Spheroids without Alteration of Environmental Conditions Recreates Fibrotic Remodeling and Tissue Stiffening Revealed by Constriction Assays.

A combination of human-induced pluripotent stem cells (hiPSCs) and 3D microtissue culture techniques allows the generation of models that recapitulate the cardiac microenvironment for preclinical research of new treatments. In particular, spheroids represent the simplest approach to culture cells in 3D and generate gradients of cellular access to the media, mimicking the effects of an ischemic event. However, previous models required incubation under low oxygen conditions or deprived nutrient media to recreate ischemia. Here, we describe the generation of large spheroids (i.e., larger than 500 µm diameter) that self-induce an ischemic core. Spheroids were generated by coculture of cardiomyocytes derived from hiPSCs (hiPSC-CMs) and primary human cardiac fibroblast (hCF). In the proper medium, cells formed aggregates that generated an ischemic core 2 days after seeding. Spheroids also showed spontaneous cellular reorganization after 10 days, with hiPSC-CMs located at the center and surrounded by hCFs. This led to an increase in microtissue stiffness, characterized by the implementation of a constriction assay. All in all, these phenomena are hints of the fibrotic tissue remodeling secondary to a cardiac ischemic event, thus demonstrating the suitability of these spheroids for the modeling of human cardiac ischemia and its potential application for new treatments and drug research.

Prognosis after heart transplant in patients with hypertrophic and restrictive cardiomyopathy. A nationwide registry analysis.

INTRODUCTION AND OBJECTIVES: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. METHODS: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). RESULTS: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). CONCLUSIONS: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality.

Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

[Standard versus extended primary cytomegalovirus prophylaxis in solid organ transplantation]. / Profilaxis primaria estándar versus prolongada de la infección por citomegalovirus en el trasplante de órgano sólido.

BACKGROUND AND OBJECTIVE: We compared the efficacy and safety of standard vs. extended primary cytomegalovirus (CMV) prophylaxis in solid organ transplantation. MATERIALS AND METHODS: Retrospective cohort study of CMV seronegative recipients who received CMV prophylaxis after solid organ transplantation from seropositive donor (D+/R-) (2007-2017). CMV infection in the first two years after transplantation in recipients with prophylaxis longer or shorter than 100 days were compared. RESULTS: CMV infection occurred in 29 of 66 patients (43.9%) with prophylaxis. Forty-five patients (68.2%) received extended prophylaxis. CMV infection and disease rates were not different between patients with extended and standard prophylaxis. However, extended prophylaxis was associated with a higher rate of myelotoxicity (68.9% vs. 42.9%, p<0.05). CONCLUSIONS: Extending primary CMV prophylaxis over 100 days did not prevent late-onset infection but it was associated with hematological toxicity.