Objectives
Indication for Reduction of Ascending Aortoplasty (RAA) and long-term outcomes remain unclear. This study analyzed the outcomes after nonreinforced RAA in two Austrian centers.
Methods
...Patients with RAA at two Austrian centers between 6/2,009 and 6/2,017 were retrospectively analyzed. Aortic diameters were measured by CT pre- and post-operatively. Patients were assigned according to valve morphology and imaging modality.
Results
Overall, 253 patients underwent RAA women: 30.8%; median age 74 (63–79) years with a mean preoperative ascending diameter of 44.7 (±3.5) mm. RAA-related postoperative adverse events occurred in 1.2% (
n
= 3) over a follow-up of a median of 3.8 (2.4–5.5) years: One type A aortic dissection, one lethal aortic rupture at the suture line, and one suture line bleeding with cardiac tamponade and need of surgical revision. The overall survival rate was 89.7%. Aortic valve morphology itself was no risk factor for mortality (Log-Rank: 0.942). One hundred and forty patients had a tricuspid TAV: (55.3%) aortic valve and 113 patients had a bicuspid aortic valve BAV: (44.7%). Redilatation to a diameter >50 mm according to CT follow-up occurred in 5.7% (
n
= 5 of 87). One patient needed reoperation with RAA and aortic valve replacement due to a prosthesis-patient mismatch after aortic valve replacement and aortic redilatation.
Conclusion
Non-reinforced RAA is a safe, feasible, and reproducible procedure with low rates of perioperative complications in selected patients primarily undergoing aortic valve repair with a dilated ascending aorta. Aortic valve morphology has no impact on mortality after RAA.
The proportion of older donors and recipients is constantly rising in heart transplantation (HTX). The impact of age on different outcomes after HTX has been studied; however, effects of interaction ...between donor and recipient age remain elusive.
This retrospective cohort study comprised 1,190 patients who underwent HTX between 1984 and 2011 at the Medical University Vienna. Multivariable models consisted of a basic set that included donor age, recipient age, and transplant eras and were adjusted for 2 sets of 6 possible confounders and 3 mediator variables. Cox models were used to estimate the risk of death. To search for age-related effects on the development of cardiac allograft vasculopathy (CAV), we applied cause-specific Cox models and proportional sub-distribution hazard models for competing risk data.
Survival was 80%, 77%, 69%, and 56% after 1, 2, 5, and 10 years, respectively. Donor age (hazard ratio HR, 1.1; 95% confidence interval CI, 1.0-1.2), recipient age (HR, 1.1; 95% CI, 1.0-1.2), admission from intensive care unit to HTX (HR, 1.5; 95% CI, 1.2-1.9), and diabetes (HR, 1.4; 95% CI, 1.1-1.7) were identified as significant independent risk factors for death. Significant risk factors for CAV were donor age (HR, 1.4; 95% CI, 1.3-1.5) and male recipient sex (HR, 1.5; 95% CI, 1.0-2.2). Recipient age was inversely associated with initiation of CAV (HR, 0.8; 95% CI, 0.8-1.0). Analysis of the interaction between donor and recipient age was not significant for death (p = 0.8) or CAV (p = 0.6).
We found no interaction between donor and recipient age negatively affecting mortality and CAV. The identified independent risk factors may have implications for allocation strategies in elderly recipients.
Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an ...option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports.
We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate.
Data were available from 19 centers in North America (
= 7), South America (
= 1), and Europe (
= 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (
= 62), coronary artery disease (CAD) (
= 16), constrictive pericarditis (
= 17), aortic pathology (
= 13), and myxoma (
= 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (
= 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively.
Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.
Aim of this study was to describe the real-world use of extracorporeal photopheresis (ECP) and assess its impact on clinical outcomes in the modern era of heart transplantation.
Seven transplant ...centers from 5 European countries participated in this retrospective, observational, single-arm chart review study. All patients received ECP after heart transplantation in 2015 or later. Data were extracted from medical records between November 2020 and December 2021.
Overall, 105 patients were enrolled and followed for an average of 2 years after initiation of ECP. Reasons to start ECP were acute cellular rejection (35.2%), rejection prevention (32.4%), mixed rejection (18.1%), and antibody-mediated rejection (14.3%). Rejection ISHLT grades improved from start to end of ECP treatment in 92% of patients treated with ECP for rejection. Of patients who started ECP to prevent rejection, 88% remained free from any rejection despite a reduction of calcineurin inhibitors. Overall survival was 95%, and no deaths were related to ECP. Safety events occurred in 18 patients, of which 13 experienced complications with venous access.
This study, the largest European ECP study in heart transplantation, demonstrates that ECP can effectively be used to treat different rejection types and to prevent rejection in the modern era of immunosuppression. Patients with rejections who have received ECP have shown high response as measured by histological improvements in ISHLT classification. A high percentage of patients in the prevention group remained free from rejection despite reduction in immunosuppression, in particular calcineurin inhibitors.
The Molecular Microscope (MMDx) system classifies heart transplant endomyocardial biopsies as No-rejection (NR), Early-injury, T cell-mediated (TCMR), antibody-mediated (ABMR), mixed, and possible ...rejection (possible TCMR, possible ABMR). Rejection-like gene expression patterns in NR biopsies have not been described. We extended the MMDx methodology, using a larger data set, to define a new "Minor" category characterized by low-level inflammation in non-rejecting biopsies.
Using MMDx criteria from a previous study, molecular rejection was assessed in 1,320 biopsies (645 patients) using microarray expression of rejection-associated transcripts (RATs). Of these biopsies, 819 were NR. A new archetypal analysis model in the 1,320 data set split the NRs into NR-Normal (N = 462) and NR-Minor (N = 359).
Compared to NR-Normal, NR-Minor were more often histologic TCMR1R, with a higher prevalence of donor-specific antibody (DSA). DSA positivity increased in a gradient: NR-Normal 24%; NR-Minor 34%; possible ABMR 42%; ABMR 66%. The top 20 transcripts distinguishing NR-Minor from NR-Normal were all ABMR-related and/or IFNG-inducible, and also exhibited a gradient of increasing expression from NR-Normal through ABMR. In random forest analysis, TCMR and Early-injury were associated with reduced LVEF and increased graft loss, but NR-Minor and ABMR scores were not. Surprisingly, hearts with MMDx ABMR showed comparatively little graft loss.
Many heart transplants currently diagnosed as NR by histologic or molecular assessment have minor increases in ABMR-related and IFNG-inducible transcripts, associated with DSA positivity and mild histologic inflammation. These results suggest that low-level ABMR-related molecular stress may be operating in many more hearts than previously estimated. (ClinicalTrials.gov #NCT02670408).
We explored the changes in gene expression correlating with dysfunction and graft failure in endomyocardial biopsies.
Genome-wide microarrays (19,462 genes) were used to define mRNA changes ...correlating with dysfunction (left ventricular ejection fraction LVEF ≤ 55) and risk of graft loss within 3 years postbiopsy. LVEF data was available for 1,013 biopsies and survival data for 779 patients (74 losses). Molecular classifiers were built for predicting dysfunction (LVEF ≤ 55) and postbiopsy 3-year survival.
Dysfunction is correlated with dedifferentiation—decreased expression of normal heart transcripts, for example, solute carriers, along with increased expression of inflammation genes. Many genes with reduced expression in dysfunction were matrix genes such as fibulin 1 and decorin. Gene ontology (GO) categories suggested matrix remodeling and inflammation, not rejection.
Genes associated with the risk of failure postbiopsy overlapped dysfunction genes but also included genes affecting microcirculation, for example, arginase 2, which reduces NO production, and endothelin 1. GO terms also reflected increased glycolysis and response to hypoxia, but decreased VEGF and angiogenesis pathways. T cell-mediated rejection was associated with reduced survival and antibody-mediated rejection with relatively good survival, but the main determinants of survival were features of parenchymal injury.
Both dysfunction and graft loss were correlated with increased biopsy expression of BNP (gene NPPB).
Survival probability classifiers divided hearts into risk quintiles, with actuarial 3-year postbiopsy survival >95% for the highest versus 50% for the lowest.
Dysfunction in transplanted hearts reflects dedifferentiation, decreased matrix genes, injury, and inflammation. The risk of short-term loss includes these changes but is also associated with microcirculation abnormalities, glycolysis, and response to hypoxia.
Abstract
OBJECTIVES
Tricuspid regurgitation (TR) in patients who had heart transplants is associated with poor outcome. The increased risk for surgical and postoperative complications might be ...reduced in these vulnerable patients by transcatheter therapies.
METHODS
All patients with a prior heart transplant (HTX) undergoing transcatheter edge-to-edge repair in the tricuspid position (T-TEER) were prospectively enrolled in an institutional registry.
RESULTS
Seven patients who had heart transplants (5/7 female) at a mean age of 53 48; 64 and median TRI-SCORE of 14 7; 22 underwent T-TEER to treat symptomatic TR ≥ IV in an elective (n = 6) and urgent (n = 1) setting, respectively. The median time from HTX to T-TEER was 13 years. A total of 2 (n = 4) and 3 (n = 3) clips were implanted with a technical success in 6/7 (one single- device detachment). TR reduction was effective and durable within a median echocardiographic follow-up time of 10 months (TR baseline vs last follow-up: P = 0.03). Further, significant right ventricular remodelling (right ventricular end-diastolic diameter: 50 mm–36 mm, P = 0.02), decrease in the inferior vena cava diameter (24 mm–18 mm, P = 0.04) and in the gamma-glutamyl-transferase (255 U/l–159 U/l, P = 0.04) was found. Four of 7 patients were free of cardiovascular death (n = 1, 267 days after T-TEER), cardiac redo surgery (n = 1) and heart failure hospitalization (n = 2) and had no further clinical signs of right heart failure.
CONCLUSIONS
T-TEER after HTX is feasible and effective regarding TR reduction in a short-term follow-up. The initial results may pave the way for a novel approach in TR management in patients having HTX.
Significant tricuspid regurgitation (TR) is reported in up to 7% of patients after a heart transplant (HTX) 1, 2 and is associated with an increased risk for lethal right heart failure 3, 4.
In severely ill patients undergoing urgent heart transplant (HTX), immunosuppression carries high risks of infection, malignancy, and death. Low-dose immunosuppressive protocols have higher rejection ...rates. We combined extracorporeal photopheresis (ECP), an established therapy for acute rejection, with reduced-intensity immunosuppression. Twenty-eight high-risk patients (13 with high risk of infection due to infection at the time of transplant, 7 bridging to transplant via extracorporeal membrane oxygenation, 8 with high risk of malignancy) were treated, without induction therapy. Prophylactic ECP for 6 months (24 procedures) was initiated immediately postoperatively. Immunosuppression consisted of low-dose tacrolimus (8-10 ng/ml, months 1-6; 5-8 ng/ml, >6 months) with delayed start; mycophenolate mofetil (MMF); and low maintenance steroid with delayed start (POD 7) and tapering in the first year. One-year survival was 88.5%. Three patients died from infection (POD 12, 51, 351), and one from recurrence of cancer (POD 400). Incidence of severe infection was 17.9% (
= 5, respiratory tract). Within the first year, antibody-mediated rejection was detected in one patient (3.6%) and acute cellular rejection in four (14.3%). ECP with reduced-intensity immunosuppression is safe and effective in avoiding allograft rejection in HTX recipients with risk of severe infection or cancer recurrence.
