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While studies have shown an association between microRNAs and cardiac rejection, the clinical relevance of a preidentified miRNA signature as a noninvasive biomarker has never been assessed in prospective multicentric unselected cohorts. To address this unmet need, we designed a prospective study (NCT02672683) including recipients from 11 centers between August 2016 to March 2018. The objective was to validate the association between 3 previously identified circulating microRNA (10a, 92a, 155) and the histopathological diagnosis of rejection. Both relative and absolute (sensitivity analysis) quantifications of microRNAs were performed. Overall, 461 patients were included (831 biopsies, 79 rejections). A per-protocol interim analysis (258 biopsies, 49 rejections) did not find any association between microRNA and rejection (microRNA 10a: odds ratio (OR) = 1.05, 95% confidence intervals (CI) = 0.87-1.27, p = 0.61; 92a: OR = 0.98, 95%CI = 0.87-1.10, p = 0.68; 155: OR = 0.91, 95%CI = 0.76-1.10, p = 0.33). These results were confirmed in the sensitivity analysis. The analysis of the remaining sera was stopped for futility. This study shows no clinical utility of circulating microRNAs 10a, 92a, and 155 monitoring in heart allograft recipients., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated the ability of T1 and T2 mapping cardiovascular magnetic resonance to assess myocardial involvement in Takotsubo syndrome (TTS). We hypothesized that non-contrast mapping techniques can be accurate and sufficient., Methods: We prospectively analysed 30 patients with TTS and 34 controls. CMR was performed a mean 5 days after the onset of symptoms and after a mean 3 month follow-up., Results: On admission, compared to controls, TTS patients had significantly higher global T2 values (59 ± 8 ms vs 51 ± 4 ms, p < 0.001), native T1 (1053 ± 75 ms vs 960 ± 61 ms, p < 0.001) and extracellular volume (ECV) fraction (29% ± 5 vs 23% ±3, p < 0.001). The sensitivity and specificity for T2 (cut off: 56 ms) were 62% and 97% respectively; for native T1: (cut off 1011 ms) were 72% and 91% respectively; and for ECV (cut off: 27%) were 72% and 97% respectively. Combining T2 and native T1 provided the best sensitivity (91.7%) with a good specificity (88.2%). No patients had late gadolinium enhancement. Segmental analysis showed that T2, native T1 and ECV values were significantly higher in regions with wall motion abnormalities (WMA) compared to normokinetic segments (62 ± 9 ms vs 55 ± 5 ms, p < 0.001; 1060 ± 65 ms vs 1025 ± 56 ms, p = 0.02; and 34% ± 5 vs 29% ± 1, p = 0.02). At follow up, native T1 and ECV values did not normalized., Conclusion: In TTS patients, a non-contrast mapping technique provides a high diagnostic accuracy allowing identification of acute and persistent myocardial injury. Segmental analysis showed that myocardial injury is preferably detected in segments with WMA., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Cardiac sarcoidosis (CS) is a challenging diagnosis. Patients may progress to end-stage congestive heart failure and require cardiac transplantation without ever having been diagnosed. Characteristics and outcomes of patients with granulomas in the explanted hearts are unknown., Methods: All French heart transplantation centers were contacted to participate in the study. Each center searched through local databases for the cases of non-caseating granuloma in the explanted hearts between 2000 and 2017. Data before and after transplantation were recorded from medical charts. Survival of CS and all- cause heart transplantation patients were compared., Results: Fifteen patients (10 men, 5 women) received a diagnosis of CS based on pathologic data of the explanted heart and were recruited for the study. All patients were diagnosed as non-ischemic dilated or hypertrophic cardiomyopathy and presented congestive heart failure. Eight patients (53%) had ventricular rhythm disturbances, and 3 (20%) a complete heart block. Ten out of 13 patients (77%) had extracardiac radiological signs compatible with sarcoidosis on chest computed tomography (CT) scans. One patient died 3 months after transplantation from infectious complications. The 14 remaining patients were still alive at the end of the study (median follow-up of 28.8 months). One patient had a second heart transplantation 5 years later because of chronic allograft vasculopathy. One patient presented a relapse of CS confirmed by myocardial biopsies 9 years after transplantation, requiring an escalation of immunosuppressive therapy., Conclusion: CS may be undiagnosed before heart transplantation. In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: The purpose of our study was to assess the impact of revised versus original criteria on the prevalence of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) criteria in cardiac magnetic resonance (CMR) studies., Background: Recently, the ARVC/D task force criteria have been revised, aiming for a better diagnostic sensitivity. The implications of this revision on clinical decision making are unknown., Methods: We retrospectively evaluated the CMR scans of 294 patients referred for ARVC/D between 2005 and 2010, and determined the presence or absence of major and minor CMR criteria using the original and the revised task force criteria. Previously, major and minor abnormalities were identified by the presence of right ventricle dilation (global or segmental), right ventricle microaneurysm, or regional hypokinesis. The revised criteria require the combination of severe regional wall motion abnormalities (akinesis or dyskinesis or dyssynchrony) with global right ventricle dilation or dysfunction (quantitative assessment)., Results: Applying the original criteria, 69 patients (23.5%) had major original criteria, versus 19 patients (6.5%) with the revised criteria. Forty-three patients (62.3%) with major original criteria did not meet any of the revised criteria. Using the original criteria, 172 patients (58.5%) had at least 1 minor criterion versus 12 patients (4%) with the revised task force criteria; 167 patients (97%) with minor original criteria did not meet any of the revised criteria. In the subgroup of 134 patients with complete diagnostic work-up of ARVC, 10 patients met the diagnosis of proven ARVC/D without counting imaging criteria. Only 4 of 10 met major criteria according to the revised CMR criteria; none met minor criteria. However, 112 of 124 patients without ARVC/D were correctly classified as negative by major and minor criteria (specificity 94% and 96%, respectively)., Conclusions: In our experience, the revision of the ARVC/D task force imaging criteria significantly reduced the overall prevalence of major and minor criteria. The revision, although maintaining a high specificity, may not have improved the sensitivity for identifying patients with ARVC/D. Larger studies including follow-up are required., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Outcomes in recipients who have undergone combined heart and kidney transplantation have mainly been addressed in small, single-center studies. We studied long-term results of combined heart and kidney transplantation in a large multicenter cohort., Methods: Between 1984 and 2007, 67 consecutive patients (61 men and 6 women) from 3 French centers underwent combined heart and kidney transplantation. At transplantation, 38 (57%) were receiving dialysis. All patients received immediate triple immunosuppression therapy (anti-calcineurin, steroids, azathioprine, or mycophenolate)., Results: Overall actuarial survival rates were 62.0%, 60.3%, 53.3%, and 46.5% at 1, 3, 5, and 10 years, respectively. These rates were similar to those observed in 2981 isolated heart recipients at the 3 participating centers during the same period (respectively, 71.0%, 65.2%, 60.1%, and 47.2%, p = 0.6). Survival tended to improve during the last decade (1996 to 2007) and reached 71.1%, 67.5%, and 60% at 1, 3, and 5 years. Cardiac allograft rejection requiring treatment occurred in 12 (17.9%). Coronary artery vasculopathy developed in 3 (9.3%). Kidney allograft rejection occurred in 9 (13.4%). Kidney graft survival was 95.9% at 1, 3, 5, and 10 years., Conclusions: Long-term survival rates in a large cohort of combined heart and kidney recipients are similar to those of isolated heart recipients in France. The rates of acute heart and kidney rejection and angiographic coronary artery vasculopathy were low in this patient population.

Owing to the actual increase of mechanical circulatory support durations, total or partial replacement of ventricular assist devices (VADs) will most certainly have to be performed with increasing frequency. Herein we report the case of a patient in whom an INCOR (Berlin Heart AG, Berlin) implantable axial-flow pump was replaced without the use of cardiopulmonary bypass (CPB), underscoring some of the unique features provided by this system.

Background: Conventional antibody induction therapy is currently used in heart transplantation despite safety concerns. This 6-month, prospective, randomized, multicenter, open-label study examined whether basiliximab offers a tolerability benefit compared with anti-thymocyte globulin (ATG) while maintaining similar efficacy in de novo heart transplant recipients., Methods: Adult heart transplant recipients were randomized to receive basiliximab (20 mg on Day 0 and Day 4) or ATG (2.5 mg/kg/day for 3 to 5 days) with cyclosporine, mycophenolate mofetil and steroids. The primary safety end-point was a composite of serum sickness, fever, cutaneous rash, anaphylaxis, infection, thrombocytopenia, leukopenia and post-transplant proliferative disease. Efficacy was assessed by a composite end-point of death, graft loss, acute rejection Grade > 1B, acute rejection associated with hemodynamic compromise or treated with antibody therapy, or loss to follow-up, whichever occurred first., Results: Eighty patients were randomized and analyzed. By Month 6, the incidence of the composite safety end-point was significantly lower with basiliximab than with ATG (50.0% vs 78.6%, p = 0.01), and infectious death was less frequent in the basiliximab group (0 of 38 vs 6 of 42, p = 0.027). The composite efficacy end-point occurred in 24 patients (63.2%) in the basiliximab arm vs 28 patients (66.7%, p = not significant [NS]) receiving ATG. Acute rejection episodes of Grade > or = 1B were reported with similar frequency (50% with basiliximab vs 45.2% with ATG, p = NS); 7 patients (18.4%) in the basiliximab group and 3 (7.1%) in the ATG group had rejection Grade > or = 3A., Conclusions: These results suggest that basiliximab offers improved tolerability with similar efficacy compared with current polyclonal antibody induction therapy in de novo heart transplant patients.

Background: Coronary vasomotor responses to sympathetic stimulation vary with endothelial-layer integrity or presence of atherosclerosis. Our study objective was to assess the effects of phenylephrine-induced alpha-adrenergic stimulation on coronary vasomotion in heart transplant recipients with and without graft atherosclerosis., Methods: Intracoronary phenylephrine (alpha(1)-selective agonist) was injected in 6 control subjects, 9 recipients with angiographically normal coronary arteries and 8 recipients with mild or moderate atherosclerosis. Coronary flow velocity was measured using a Doppler guide-wire. The diameters of 3 epicardial segments of the left coronary artery and coronary blood flow and resistance were assessed at baseline, after infusion of increasing acetylcholine doses (10(-7) and 10(-6) mol/liter) and after phenylephrine (150- to 200-microg bolus). Systemic and coronary hemodynamic parameters were measured immediately after acetylcholine and 1, 3, 5, 7, 10 and 15 minutes after phenylephrine., Results: Phenylephrine induced similar significant increases in rate pressure product in the 3 groups. Acetylcholine induced epicardial vasodilation in controls and vasoconstriction in transplant recipients. Phenylephrine induced epicardial vasodilation in controls and in angiographically normal recipients; subsequent vasoconstriction occurred in this last group. In the recipients with angiographic abnormalities, sustained vasoconstriction occurred. At peak phenylephrine effect, coronary blood flow (CBF) increased significantly (p < 0.001 vs baseline) in all 3 groups. Coronary resistance decreased in the 3 groups but the decrease was smaller in the recipients with angiographic abnormalities (p < 0.05 vs controls)., Conclusions: In heart transplant patients, graft atherosclerosis unmasks the direct coronary vasoconstricting effects of pharmacologic alpha-adrenergic stimulation.

Little is known about the management of dual-organ transplantation for sickle-cell disease (SCD)-related complications. In this case study, we report the successful outcome of combined heart and kidney transplantation in a patient with SCD. The recipient was a 33-year-old man with homozygous SCD, who developed end-stage heart and renal failure requiring combined heart and kidney transplantation. The patient was managed with pre-operative blood transfusion and moderate hypothermic cardiopulmonary bypass, with limited peri-operative complications. During the first 6 months there was one episode of acute heart rejection without concomitant renal rejection. Eighteen months after surgery, the patient is at home without vaso-occlusive crises or septic complications. Heart and renal allograft function is preserved, without coronary artery vasculopathy, but with asymptomatic moderate transplant renal artery stenosis. SCD is managed by periodic transfusion. This case study demonstrates that combined heart and kidney transplantation is feasible in patients with SCD. Careful attention to peri- and post-operative management is required.

Objectives: The aim of the present study was to assess the effects of selective B1-receptor stimulation with des-Arg9-bradykinin on coronary vasomotion in transplanted and non-transplanted patients., Background: Bradykinin B1-receptors have been identified on endothelial and smooth muscle cells in human coronary arteries in vitro; however, their physiologic role in the coronary circulation is unknown., Methods: Twelve heart transplant patients were compared with 10 control subjects at 3.2 +/- 2.2 months after surgery. Coronary flow velocity was measured using guide-wire Doppler. The diameter of 3 epicardial segments of the left coronary artery and coronary blood flow were assessed at baseline, immediately after infusions of increasing doses of des-arginine(Arg9)-bradykinin at estimated coronary blood concentrations of 5.4 x 10(-9), 5.4 x 10(-8), 5.4 x 10(-7) and 1.6 x 10(-6) mol/liter, and of acetylcholine at 10(-8), 10(-7) and 10(-6) mol/liter)., Results: Des-Arg9-bradykinin induced a similar decrease in all measured epicardial diameters in both groups and no change in coronary blood flow. Vasoconstriction was significant only at the 2 highest concentrations: -6 +/- 9% (p < 0.01) and -7 +/- 11% (p < 0.01) in control subjects, and -8 +/- 8% (p < 0.001) and -9 +/- 11% (p < 0.001) in heart transplant patients. Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in transplant patients. The presence of allograft rejection did not modify the responses to des-Arg9-bradykinin with regard to both conductance and resistance vessels., Conclusions: Kinin B1-receptors exist and can be stimulated in humans. The vasoconstrictive action on epicardial coronary arteries of des-Arg(9)-bradykinin in humans argues for a predominant action of B1-receptor stimulation at the level of smooth muscle cells.

Background: Patients with diabetes constitute a high-risk population for myocardial revascularization due to extensive coronary disease., Objective: To compare the early postoperative outcomes of patients with diabetes undergoing off-pump or on-pump coronary artery bypass surgery., Methods and Results: Over a four-year period (1995 to 1998), 885 diabetics were operated for primary isolated coronary bypass; 156 patients had off-pump and 729 had on-pump coronary artery bypass surgery. Patients in the off-pump group were significantly older, had a higher incidence of hypertension and renal failure, and received fewer distal anastomoses (2.7 versus 2.9, P=0.004). Postoperative myocardial infarction, reintubation and postoperative use of intra-aortic balloon pump occurred significantly more frequently in the off-pump group (10.3% versus 5.5%, P=0.04; 8.3% versus 3.6%, P=0.03; 7.7% versus 1.5%, P=0.0001, respectively). Multivariate analysis revealed that type of surgery was an independent predictor of these complications, which occurred 1.9, 2.7 and 7.9 times more often, respectively, in the off-pump group. The 30-day mortality rate was not significantly different between the groups., Conclusions: Off-pump coronary artery bypass surgery is associated with an increased early postoperative morbidity in patients with diabetes and, thus, should be used with caution.