R. Moayedifar

Increased Thromboembolic Events With Dabigatran Compared With Vitamin K Antagonism in Left Ventricular Assist Device PatientsCLINICAL PERSPECTIVE

Background— Left ventricular assist device–supported patients are usually anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term vitamin K antagonist therapy can be complicated by unstable international normalized ratio values and patient-related compliance problems. Therefore, direct thrombin inhibitors may represent an alternative to vitamin K antagonists. Methods and Results— Thirty HeartWare ventricular assist device patients with stable renal function were planned for this prospective, randomized, open-label, single-center study. Patients were randomized to receive either phenprocoumon or dabigatran in addition to aspirin for long-term anticoagulation. Treatment duration was scheduled for 1 year and stopped after observation of a primary end point. Dabigatran dose was 110 and 75 mg BID in patients with normal or impaired renal function (glomerular filtration rate >80 mL/min or between 80 and 30 mL/min, respectively). The study was stopped prematurely for safety reasons after 16 patients (61±8 years, 1 female) were randomized. Thromboembolic events occurred in 4 subjects receiving dabigatran (50%) and in 1 receiving phenprocoumon (13%; P=0.28). No major bleeding was recorded, and no patient died during the study. Median time to treatment termination was significantly shorter in dabigatran patients (8.5 versus 12.0 months; P=0.015). Conclusions— Thromboembolic events on dabigatran led to early termination of a randomized controlled trial of dabigatran versus phenprocoumon in left ventricular assist device patients. Clinical Trial Registration— https://www.clinicaltrials.gov. Unique identifier: NCT02872649.

Diminished impact of cytomegalovirus infection on graft vasculopathy development in the antiviral prophylaxis era - a retrospective study

Evidence concerning an association between cytomegalovirus (CMV) infection and accelerated cardiac allograft vasculopathy (CAV) is inconclusive. Data were analyzed retrospectively from 297 consecutive heart transplants between 1.1.2002 and 31.12.2012. Patients ≤18 years of age, survival, and follow‐up ≤1‐year post‐transplant and patients with early CAV were excluded. CMV‐infection was diagnosed and monitored closely in the first year. CAV was diagnosed by coronary angiography via left heart catheterization, and results were categorized according to the International Society of Heart and Lung Transplantation (ISHLT) scoring system. Risk factors for CAV were tested in a multivariable model. Median follow‐up was 7.5 years (IQR: 5.6–10.3). CMV infection in the first year after transplantation occurred in 26% of patients (n = 78), CMV disease in 5% (n = 15). CAV ≥1 ISHLT was detected in 36% (n = 108). Incidence of CAV >1 ISHLT and severity of CAV increased over time. No statistically significant association between CMV infection and disease within the first year and risk of CAV after 1‐year post‐HTx was detected in the univariate (P = 0.16) and multivariable [hazard ratio (HR), 1.36; confidence interval (CI), 0.89–2.07; P = 0.16] Cox regression. In the multivariable Cox regression, donor age (HR, 1.04; 95% CI, 1.02–1.06; P < 0.01) and acute cellular rejection (ACR) ≥2R in the first year after HTx (HR, 1.77; 95% CI, 1.06–2.95; P = 0.03) were independent risk factors for CAV development. In our cohort, CMV infection and disease in the first year after transplantation did not significantly influence the risk of CAV in the long‐term follow‐up.

Donor heart selection and outcomes: An analysis of over 2,000 cases

BACKGROUND Decision-making when offered a donor heart for transplantation is complex, and supportive data describing outcomes according to acceptance or non-acceptance choices are sparse. Our aim was to analyze donor heart acceptance decisions and associated outcomes at a single center, and after subsequent acceptance elsewhere. METHODS This investigation was a retrospective analysis of data obtained from the University of Vienna Medical Center and Eurotransplant centers for the period 2001 to 2015. RESULTS Our center accepted 31.8% (699 of 2,199) of donor hearts offered. Unlike other centers, the acceptance rate, with or without transplantation, did not increase over time. Of the donor hearts rejected by our center, 38.1% (572 of 1,500) were later accepted elsewhere. Acceptance rates were twice as high for donor hearts initially rejected for non-quality reasons (339 of 601, 56.4%) compared with initial rejection for quality reasons (233 of 899, 25.9%). Three-year patient survival rate was 79% at Vienna; for donor hearts initially rejected by Vienna for non-quality reasons or quality reasons, it was 73% and 63%, respectively (p < 0.001). Outcomes at other centers after transplantation of grafts rejected by Vienna varied according to the reason for rejection, with good 3-year survival rates for rejection due to positive virology (77%), high catecholamines (68%), long ischemic time (71%), or low ejection fraction (68%), but poor survival was observed for hearts rejected for hypernatremia (46%), cardiac arrest (21%), or valve pathology (50%). CONCLUSIONS A less restrictive policy for accepting donor hearts at our center, particularly regarding rejection for non-quality reasons or for positive virology, high catecholamine levels, longer ischemic time, or low ejection fraction, could expand our donor pool while maintaining good outcomes.

Extracorporeal membrane oxygenation support for right ventricular failure after left ventricular assist device implantation

OBJECTIVES Right ventricular (RV) failure complicating left ventricular assist device implantation is associated with increased mortality. Despite a lack of supporting evidence, venoarterial extracorporeal membrane oxygenation (ECMO) support is increasingly being used as an alternative to traditional temporary RV support. We report our institutional experience with ECMO-facilitated RV support after left ventricular assist device implantation. METHODS We retrospectively reviewed the concept of temporary ECMO support for perioperative RV failure in 32 consecutive left ventricular assist device (mean age 52 ± 14 years; male 84.4%; ischaemic cardiomyopathy 40.6%; INTERMACS Level I 71.8%; INTERMACS Level II 6.3%; INTERMACS Level III 12.5%; INTERMACS Level IV-VII 9.4%; HeartWare ventricular assist device 75%; HeartMate II: 25%) from May 2009 to April 2014. The study end points were RV recovery during ECMO support, mortality and causes of death. RESULTS Twenty-nine (90.6%) patients were successfully weaned from ECMO support after RV recovery. Three (9.4%) patients expired during ECMO support. ECMO support improved RV function and haemodynamic parameters (central venous pressure 13 mmHg vs 10 mmHg, P < 0.01; mean pulmonary artery pressure 28 mmHg vs 21 mmHg, P < 0.01; cardiac output 5.1 l/min vs 5.9 l/min, P = 0.09) over a median period of 3 (range 1-15) days. Thirty-day and in-hospital mortality were 18.8% and 25%, respectively. One-year survival was 75%, causes of death were multiorgan dysfunction syndrome (50%), sepsis (25%), haemorrhagic stroke (12.5%) and ischaemic stroke (12.5%). Causes of death during ECMO support were ischaemic stroke, sepsis and multiorgan dysfunction syndrome. CONCLUSIONS Temporary ECMO-facilitated RV support is associated with good long-term outcomes and high rates of RV recovery.

Long-term heart transplant outcomes after lowering fixed pulmonary hypertension using left ventricular assist devices†

OBJECTIVES Fixed pulmonary hypertension (fPH) is a contraindication for heart transplantation (HTX). Left ventricular assist device (LVAD) implantation as a bridge to candidacy can reverse fPH in patients with terminal heart failure by chronic left ventricular unloading. We report our institutional experience with terminal heart failure patients and fPH that were successfully bridged to candidacy and underwent subsequent HTX. METHODS We retrospectively reviewed the data of 79 patients with terminal heart failure and fPH who were successfully bridged to candidacy for HTX with 6 different LVAD devices at our centre from October 1998 to September 2016 (Novacor n = 4, MicroMed DeBakey n = 29, DuraHeart n = 2, HeartMate II n = 14, HVAD n = 29 and MVAD n = 1). Median duration of LVAD support was 288 days (range 45-2279 days). Within the same timeframe, a control group of 48 patients underwent HTX after bridge-to-transplant LVAD therapy for reasons other than PH. Study end points were (i) development of fPH after LVAD implantation, (ii) post-transplant outcomes and (iii) incidence of severe adverse events. RESULTS Pulmonary vascular resistance, assessed by vasodynamic catheterization, was 4.3 ± 1.8 WU before LVAD implantation. After a median support period of 89 days (interquartile range 4-156 days), pulmonary vascular resistance decreased to 2.0 ± 0.9 WU (P ≤ 0.001), and patients were listed for HTX. Median duration of LVAD support in the study group was 288 days (45-2279 days). We observed 2 patients (2.5%) with acute right heart failure who required extracorporeal mechanical support after HTX in the study group. Long-term post-transplant survival between the study group (3 years: 83.5%, 5 years: 81.0%) and the control group (3 years: 87.5%, 5 years: 85.4%) was comparable (log-rank: P = 0.585). CONCLUSIONS LVAD implantation as a bridge to candidacy reverses fPH in patients with terminal heart failure. Post-HTX survival is excellent and comparable to results obtained in patients without fPH at the time of HTX listing.

High dose catecholamine donor support and outcomes following heart transplantation

BACKGROUND Higher dose norepinephrine donor support is a frequent reason for donor heart decline, but its associations with outcomes after heart transplantation are unclear. METHODS We retrospectively analyzed 965 patients transplanted between 1992 and 2015 in the Heart Transplant Program Vienna. Stratification was performed according to donor norepinephrine dose administered before organ procurement (Group 0: 0 µg/kg/min; Group 1: 0.01 to 0.1 µg/kg/min; Group 2: >0.1 µg/kg/min). Sub-stratification of Group 2 was performed for comparison of high-dose subgroups (Group HD 1: 0.11 to 0.4 µg/kg/min; Group HD 2: >0.4 µg/kg/min). Associations between groups and outcome variables were investigated using a multivariable Cox proportional hazards model and logistic regression analyses. RESULTS Donor norepinephrine dose groups were not associated with overall mortality (Group 1 vs 0: hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.87 to 1.43; Group 2 vs 0: HR 1.07, 95% CI 0.82 to 1.39; p = 0.669). No significant group differences were found for rates of 30-day mortality (p = 0.35), 1-year mortality (p = 0.897), primary graft dysfunction (p = 0.898), prolonged ventilation (p = 0.133) and renal replacement therapy (p = 0.324). Groups 1 and 2 showed higher rates of prolonged intensive care unit stay (18.9% vs 28.5% vs 27.5%, p = 0.005). High-dose subgroups did not differ significantly in 1-year mortality (Group HD 1: 14.3%; Group HD 2: 17.8%; p = 0.549). CONCLUSIONS Acceptance of selected donor hearts supported by higher doses of norepinephrine may be a safe option to increase the donor organ pool.

Response by Andreas et al to Letter Regarding Article, “Increased Thromboembolic Events With Dabigatran Compared With Vitamin K Antagonism in Left Ventricular Assist Device Patients: A Randomized Controlled Pilot Trial”

We thank Heinrich-Nols and Kreuzer for their valuable and very detailed response regarding the indication of dabigatran, its dosing regimen, and relevant considerations regarding monitoring of anticoagulation. We had to shorten our initial article significantly and were not able to address all points regarding dabigatran dosing and management.1 The dose was chosen in 2010 according to the approved indication at that time, which was the primary prevention of …