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Aims: The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). Methods and results: All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40–250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N‐terminal pro‐B‐type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six‐fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05). Conclusions: A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre‐HT patients. [ABSTRACT FROM AUTHOR]

Antibody-mediated rejection (AMR) diagnosis, has continually evolved, from a simple description in 19901 to a standardized definition in 2013 with histopathologic and immunopathologic features irrespective of graft dysfunction or donor-specific antibodies (DSA).2 Due to diagnostic criteria evolution and routine screening absence, the reported prevalence of AMR is variable.3 Moreover, due to the lack of standardized treatment, its management is far from unanimous and represents a continued challenge. After the second-line treatment, 6 patients (40%) had persistent AMR (Figure 1) and 6 patients (50%) had persistent DSA with MFI > 5000 (Table 1). [Extracted from the article]

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. [Copyright &y& Elsevier]

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. 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. 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. CS may be undiagnosed before heart transplantation. In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques. • Cardiac sarcoidosis may be undiagnosed before heart transplantation. • In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques. • Long term outcomes of sarcoidosis after cardiac transplantation are similar to those of all-cause transplantations recipients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Heart transplantation in patients supported with ventricular assist devices (VADs) entails a high risk of injury at resternotomy. Prior femorofemoral bypass is the preferred approach in these patients, but poor venous drainage may restrict arterial flow rate. Patients and methods: We compared bypass parameters, transfusion requirements and postoperative outcome in 33 consecutive patients (40.4±12.2 years old, 28 men) assisted with the Thoratec® paracorporeal VAD (mean duration, 3.0±2.96 months) undergoing transplantation using either gravity siphon drainage (GSD, n =16) or kinetic assisted venous drainage (KAVD, n =17). Results: Cannulation technique, perfusion pressure, temperature and duration were similar between groups. There were no significant differences in arterial re-infusion flow rates (GSD, 3.6±0.7 vs KAVD, 3.8±0.6l/min, p =0.5). KAVD patients had a lower mean SvO2 and a higher desaturation index than GSD patients (69.5±4.6 vs 76.1±5.4mmHg, p =0.004; and 0.63±0.23 vs 0.25±0.63, p =0.0001, respectively). Perioperative requirements in fresh frozen plasma and platelet transfusions were significantly higher in KAVD patients. However, there were no differences in postoperative patient outcome. Conclusion: Perceived benefits on venous return associated with KAVD do not necessarily translate into improved arterial re-infusion flow rates and should be weighed against the hazards of increased venous air aspiration and blood product requirements. [Copyright &y& Elsevier]

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 ≥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 ≥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. [Copyright &y& Elsevier]

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 α-adrenergic stimulation on coronary vasomotion in heart transplant recipients with and without graft atherosclerosis. Methods: Intracoronary phenylephrine (α1-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-μg 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 α-adrenergic stimulation. [Copyright &y& Elsevier]