Peter Ivak

Evaluation of von Willebrand factor with a fully magnetically levitated centrifugal continuous-flow left ventricular assist device in advanced heart failure

BACKGROUND Contemporary continuous-flow left ventricular assist devices (CF-LVADs) are associated with degradation of von Willebrand factor (vWF) high-molecular-weight multimers (HMWMs), a critical factor supporting platelet function. We hypothesized that the HeartMate 3 fully magnetically levitated LVAD, designed to reduce circulatory shear stress, favorably influences these hemostatic parameters. METHODS Fifteen consecutive HeartMate 3 LVAD patients were compared with 11 consecutive HeartMate II controls. Serial plasma samples were collected pre-implant and on Days 2, 7, 30 and 45 post-operatively. Changes in vWF HMWMs were evaluated by 2 independent, study-blind hematologists and confirmed using densitometry-based computerized software. Ristocetin cofactor (RiCO) and vWF antigen (vWF Ag) were measured using standard protocols with enzyme-linked immunosorbent assay. RESULTS HeartMate 3 patients and HeartMate II controls had a mean age of 67.3 ± 1.4 and 52.8 ± 2.5 years, respectively (INTERMACS Profiles 2 to 4 in 93.3% and 91%, respectively). HeartMate 3 group demonstrated a significantly greater preservation of HMWMs compared with the HeartMate II group, with the most prominent decrease occurring by Day 2 post-operatively and sustained through 45 days (71.94% vs 31.16%, p = 0.001). Laboratory values (normalized to baseline) for RiCO activity, vWF Ag and RiCO:vWF Ag ratio remained in the functional range with no statistically significant differences observed between groups. CONCLUSION The HeartMate 3 LVAD is associated with enhanced hemocompatibility compared with the HeartMate II LVAD, as demonstrated by the improved preservation of vWF HMWMs, In contrast, effects on HMWM degradation appeared to be dissociated from functional attributes. Further confirmation of these findings in randomized clinical trials is warranted.

The impact of angiotensin II type 1 receptor antibodies on post-heart transplantation outcome in Heart Mate II bridged recipients

OBJECTIVES Antibodies targeting angiotensin II type 1 receptor (AT1R) have been associated with malignant hypertension, autoimmune diseases and acute rejection and graft loss in solid organ transplantation. The aim of our study was to assess the impact of anti-AT1R antibodies on survival and incidence of acute cellular rejection (ACR) and pathology antibody-mediated rejection (pAMR) in a population of heart transplant recipients who were bridged to transplantation with a durable mechanical assist device Heart Mate II. METHODS Sera of 69 consecutive heart transplant recipients transplanted between October 2008 and August 2014 were tested for the presence of angiotensin II type 1 receptor antibodies before Heart Mate II device implantation and at the time of transplantation. Overall survival and post-transplant rejection-free survival were compared between antibody-negative and antibody-positive recipients using Kaplan-Meier and log-rank tests. RESULTS Anti-AT1R antibodies were present in 8 patients (11.6%) before Heart Mate II implantation. During the left ventricular assist device (LVAD) bridging, 44 patients (63.8%) who were initially anti-AT1R antibody-negative became positive, leaving 17 (24.6%) anti-AT1R antibody-negative patients at the time of transplantation for all comparisons. One- and 5-year survival was 88 ± 8 and 76 ± 10% for anti-AT1R antibody-negative and 87 ± 5 and 81 ± 7% for anti-AT1R antibody-positive patients, respectively (P = 0.582). Freedom from ACR at 1 year was 68 ± 12% for anti-AT1R-negative and 75 ± 6% for anti-AT1R-positive recipients (P = 0.218). None of the anti-AT1R-negative patients developed AMR 1 year post-transplantation, whereas freedom from pAMR in anti-AT1R-positive recipients was 98 ± 2% (P = 0.198). CONCLUSIONS Our data showed no difference in the overall post-heart transplant survival and freedom from acute cellular and antibody-mediated rejection between anti-AT1R-negative and anti-AT1R-positive recipients. Further research is needed to assess the role of anti-AT1R antibodies in the risk stratification of LVAD-bridged recipients on the post-heart transplantation outcomes.

Evaluation of low-intensity anti-coagulation with a fully magnetically levitated centrifugal-flow circulatory pump—the MAGENTUM 1 study

BACKGROUND The HeartMate 3 left ventricular assist system is engineered to avoid pump thrombosis, yet bleeding complications persist. We investigated the safety of low-intensity anti-coagulation in patients with the HeartMate 3. METHODS The Minimal AnticoaGulation EvaluatioNTo aUgment heMocompatibility (MAGENTUM 1) pilot study is a prospective, single-arm study of low-intensity warfarin anti-coagulation in patients implanted with the HeartMate 3 pump. After standard warfarin anti-coagulation (international normalized ratio [INR] 2.0 to 3.0) and aspirin for 6 weeks post-implant, patients were transitioned to a lower INR target range of 1.5 to 1.9. The primary end-point was a composite of survival free of pump thrombosis, disabling stroke (modified Rankin score [MRS] >3), or major bleeding (excluding peri-operative bleeding) with at least 6-month post-implant follow-up. Time in therapeutic range (TTR) was measured to assess anti-coagulation target efficacy using the Rosendaal method. A safety algorithm to monitor for signs of pump thrombosis was developed and implemented. RESULTS We enrolled 15 patients (mean age 57.3 ± 13.3 years), 13 men with advanced heart failure (67% with INTERMACS Profiles 2 or 3), irrespective of therapeutic goal of bridge-to-transplant or destination therapy. The primary end-point was met in 14 of 15 (93 ± 6%) patients; 1 patient developed recurrent gastrointestinal bleeding. The TTR during the reduced anti-coagulation phase (6 weeks to 6 months) was 75.3 ± 8.6%. No thrombotic events occurred. CONCLUSIONS This pilot study suggests low-intensity anti-coagulation targeting an INR between 1.5 and 1.9 is achievable and safe with the HeartMate 3 cardiac pump in the short-term phase, 6-months post-implant. A large-scale trial is now warranted.

Mechanical cerebral thrombectomy in a BiVAD patient awaiting cardiac transplantation

1Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic 2 First Faculty of Medicine, Charles University, Prague, Czech Republic 3 Second Faculty of Medicine, Charles University, Prague, Czech Republic 4 Third Faculty of Medicine, Charles University, Prague, Czech Republic 5Department, of Radiology, Military University Hospital, Prague, Czech Republic

Friedreich’s ataxia and advanced heart failure: An ethical conundrum in decision-making

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Biphasic response in number of stem cells and endothelial progenitor cells after left ventricular assist device implantation: A 6 month follow-up ☆

BACKGROUND Continuous blood flow could have deleterious effects on endothelium and vascular health. This could have serious consequences in patients with heart failure treated with continuous flow left ventricular assist devices (LVAD). Therefore, we studied effect of LVAD on three circulating vascular biomarkers: stem cells (SC), endothelial progenitor cells (EPC) and microparticles (MP). METHODS In 23 patients (5 women) with end-stage heart failure, SC, EPC and MP were measured before, and 3 and 6months after implantation of LVAD (HeartMate II). SC were defined using determination of surface antigen expression as mononuclear CD34+/CD45low+ cells and EPC as mononuclear CD34+/CD45low+/KDR+ cells. MP concentrations were determined by ELISA method. RESULTS Three months after LVAD implantation numbers of SC and EPC significantly decreased (p=0.01 and p=0.001, respectively). On the contrary, between 3rd and 6th month after implantation they significantly increased (p=0.006 and p=0.003, respectively).MP did not change significantly during the study despite exerting similar trend as SC and EPC. CONCLUSIONS Observed biphasic changes of SC and EPC might reflect two processes. First, shortly after LVAD implantation, improved tissue perfusion could lead to decrease in ischemic stimuli and ensuing decrease of SC and EPC. Second, continuous flow between 3rd and 6th month produced by LVAD could lead to increase of SC and EPC through activation of endothelium. This explanation could be supported also by similar trend in the changes of concentrations of MP.

Minimally invasive removal of a temporary RVAD.

We describe a minimally invasive technique for the removal of a temporary right ventricular assist device (RVAD) that provided support concomitant with durable left ventricular assist device support. The RVAD cannulas are mobilized through a small subxiphoid incision at the cannula exit site. Both cannulas are transected subcutaneously, then occluded with plugs made of rolled bovine pericardium, and the skin is closed. The cannula remnants are left in place until heart transplantation is accomplished. To minimize risk of thrombus formation at the cannula tips and subsequent embolization into the right atrium or pulmonary artery, anticoagulation is increased to achieve an international normalized ratio (INR) in the range of 2.5–3.0.

The impact of Angiotensin II Type 1 Receptor antibodies on morbidity and mortality in Heart Mate II supported recipients.

AIMS One of the proposed limitations of left ventricular assist device (LVAD) therapy is high degree of sensitization. Apart from human leukocyte antigen (HLA), antibodies against Angiotensin II Type 1 Receptor (AT1R) have been associated with adverse outcomes. The purpose of this study was to compare complications and survival of anti - AT1R positive versus negative Heart Mate II (HMII) recipients. METHODS Altogether 96 patients received HMII at our institution between 2008 and 2012. These were stratified into three groups: antibody positive before implantation (AT1R+), antibody conversion during support (AT1R-/+) and patients who remained antibody negative (AT1R-). Survival, major on-device adverse events and post-transplant rejections were assessed with Kaplan-Meier and log-rank tests. RESULTS Two year on-device and overall survival was 78 ± 12% and 75 ± 10% in AT1R-, 60 ± 23% and 60 ± 15% in AT1R+ and 92 ± 6% and 87 ± 5% in AT1R-/+ group (P = 0.409, P = 0.185). Freedom from major adverse event at two years for AT1R-, AT1R+ and AT1R-/+ was 49 ± 14%, 53 ± 16% and 41 ± 11% (P = 0.875). Freedom from rejection was 63 ± 17% in patients who were both anti-AT1R and HLA negative and 65 ± 13% in those who were antibody positive (P = 0.788). CONCLUSION Patients who were anti-AT1R antibody positive had similar on-device survival and rate of complications in comparison to those who were antibody negative. In transplanted patients, there were no differences in the overall survival and rejection between the groups.