Philipp Angleitner

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.

Minimally invasive approaches for implantation of left ventricular assist devices

The era of intracorporal continuous flow pumps has initiated significant success of left ventricular assist device (LVAD) surgery. However, median sternotomy has been the only surgical approach for implantation over many years. During the last decade, less-invasive access ways gained popularity. Within this review, we describe our own clinical experience in minimally invasive ventricular assist device (VAD) surgery and summarize the current scientific literature on this topic.

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

OBJECTIVESnRight 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.nnnMETHODSnWe retrospectively reviewed the concept of temporary ECMO support for perioperative RV failure in 32 consecutive left ventricular assist device (mean age 52u2009±u200914u2009years; 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.nnnRESULTSnTwenty-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 13u2009mmHg vs 10u2009mmHg, Pu2009<u20090.01; mean pulmonary artery pressure 28u2009mmHg vs 21u2009mmHg, Pu2009<u20090.01; cardiac output 5.1u2009l/min vs 5.9u2009l/min, Pu2009=u20090.09) over a median period of 3 (range 1-15)u2009days. 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.nnnCONCLUSIONSnTemporary 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†

OBJECTIVESnFixed 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.nnnMETHODSnWe 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 nu2009=u20094, MicroMed DeBakey nu2009=u200929, DuraHeart nu2009=u20092, HeartMate II nu2009=u200914, HVAD nu2009=u200929 and MVAD nu2009=u20091). Median duration of LVAD support was 288u2009days (range 45-2279u2009days). 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.nnnRESULTSnPulmonary vascular resistance, assessed by vasodynamic catheterization, was 4.3u2009±u20091.8 WU before LVAD implantation. After a median support period of 89u2009days (interquartile range 4-156u2009days), pulmonary vascular resistance decreased to 2.0u2009±u20090.9 WU (Pu2009≤u20090.001), and patients were listed for HTX. Median duration of LVAD support in the study group was 288u2009days (45-2279u2009days). 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 (3u2009years: 83.5%, 5u2009years: 81.0%) and the control group (3u2009years: 87.5%, 5u2009years: 85.4%) was comparable (log-rank: Pu2009=u20090.585).nnnCONCLUSIONSnLVAD 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.

A Standardized Telephone Intervention Algorithm Improves the Survival of Ventricular Assist Device Outpatients: VAD TELEPHONE INTERVENTION ALGORITHM

Abstract Ventricular assist devices (VADs) are an established therapeutic option for patients with chronic heart failure. Continuous monitoring of VAD parameters and their adherence to guidelines are crucial to detect problems in an early stage to optimize outcomes. A telephone intervention algorithm for VAD outpatients was developed, clinically implemented and evaluated. During the phone calls, a structured inquiry of pump parameters, alarms, blood pressure, INR, body weight and temperature, exit‐site status and heart failure symptoms was performed and electronically categorized by an algorithm into 5 levels of severity. VAD outpatient outcomes without (nu2009=u200971) and with bi‐weekly telephone interviews in their usual care (nu2009=u200925) were conducted using proportional hazard Cox regression, with risk adjustment based on a propensity score model computed from demographics and risk factors. From February 2015 through October 2017, 25 patients (nu2009=u20093 HeartMate II, nu2009=u20094 HeartMate 3 and nu2009=u200918 HeartWare HVAD) underwent 637 telephone interventions. In 57.5% of the calls no problems were identified, 3.9% were recalled on the next day because of alarms. In 26.5% (nu2009=u2009169), the VAD Coordinator had to refer to the physician due to elevated blood pressure (nu2009=u2009125, >85 mm Hg), INRu2009<u20092.0 oru2009>u20094.0 (nu2009=u200924) or edema (nu2009=u200910), 11.9% of the calls led to a follow‐up because of equipment or exit‐site problems. Propensity‐adjusted 2‐year survival (89% vs. 57%, Pu2009=u20090.027) was significantly higher for the telephone intervention group. Continuous, standardized communication with VAD outpatients is important for early detection of upcoming problems and leads to significantly improved survival.

High dose catecholamine donor support and outcomes following heart transplantation

BACKGROUNDnHigher dose norepinephrine donor support is a frequent reason for donor heart decline, but its associations with outcomes after heart transplantation are unclear.nnnMETHODSnWe 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.nnnRESULTSnDonor 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).nnnCONCLUSIONSnAcceptance 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.1nnThe dose was chosen in 2010 according to the approved indication at that time, which was the primary prevention of …