Maria Mountis

Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis

BACKGROUND We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Major Bleeding During HeartMate II Support

OBJECTIVES The aim of this study was to characterize a single-center experience of major bleeding complications during HeartMate II (HMII) (Thoratec Corp., Pleasanton, California) left ventricular assist device support, with focus on the subtypes and temporal patterns of post-operative bleeding. BACKGROUND Bleeding complications are the most common post-operative adverse events after HMII implantation. The timing of bleeding events, relationship to coagulation status, and effect on post-operative survival are incompletely understood. METHODS From October 2004 to June 2010, 139 HMII recipients at the Cleveland Clinic received 145 devices as a bridge to transplant or destination therapy for advanced heart failure. Major bleeding was defined using Interagency Registry for Mechanically Assisted Circulatory Support criteria, with an additional category created to maximize sensitivity for events. Pre-operative variables, coagulation status, and bleeding recurrence were assessed for correlation to primary events using modulated renewal within a multivariable analysis. RESULTS The cumulative occurrence of major bleeding was 58% during 171 patient-years of follow-up. There were 1.14 major bleeds per patient-year, with 44% occurring as repeat bleeding events. A first bleed did not predict subsequent bleeding. The greatest risk of bleeding was noted within 2 weeks post-implantation. The international normalized ratio profile correlated poorly with the risk of bleeding. Bleeding early after surgery was associated with reduced survival while on HMII support. CONCLUSIONS The risk of bleeding peaks early after HMII implantation. Bleeding of thoracic and gastrointestinal sources dominates these events, although many patients undergo transfusions for anemia without an apparent source of hemolysis or bleeding.

Mechanical circulatory support after heart transplantation

OBJECTIVE Mechanical circulatory support (MCS) may be used for severe graft failure after heart transplantation, but the degree to which it is lifesaving is uncertain. METHODS Between June 1990 and December 2009, 53 patients after 1417 heart transplants (3.7%) required post-transplant MCS for acute rejection (n=17), biventricular failure (n=16), right ventricular failure (n=16), left ventricular failure (n=1), or respiratory failure (n=3). Although support was occasionally instituted remotely post-transplant (5>1 year), in 39 (73%) instances it was required within 1 week. Initial mode of support was extracorporeal membrane oxygenation in 43 patients (81%), biventricular assist device in 4 (7.5%), and right ventricular assist device in 6 (11%). RESULTS Risk of requiring respiratory support was highest in those with restrictive cardiomyopathy as indication for transplant, women, and those with elevated pulmonary pressure or renal failure. Complications of support, which increased progressively with its duration, included stroke in two patients (3.8%), infection in two (3.8%), and reoperation for bleeding (seven instances) in four (7.0%). Nineteen patients (36%) recovered and were removed from support, five (9.4%) underwent retransplantation (four after biventricular failure and one after acute rejection), and 29 died while on support (55%). Overall survival after initiating support was 94%, 83%, 66%, and 43% at 1, 3, 7, and 30 days, respectively. Patients requiring support for biventricular failure had better survival than those having acute rejection or other indications (P=0.03). Survival after retransplantation or removal from support following recovery was 88% at 1 year and 61% at 10 years. CONCLUSION Severe refractory heart failure after transplantation is a rare catastrophic event for which MCS offers the possibility of recovery or bridge to retransplantation, particularly for patients with biventricular failure in the absence of rejection. Early retransplantation should be considered in patients who show no evidence of graft recovery on MCS.

Risk factors, mortality, and timing of ischemic and hemorrhagic stroke with left ventricular assist devices

BACKGROUND Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement. METHODS Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed. RESULTS Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p < 0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not. CONCLUSIONS Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry

BACKGROUND The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. METHODS Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. RESULTS The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). CONCLUSIONS Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies.

INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) Profiling Identifies Ambulatory Patients at High Risk on Medical Therapy after Hospitalizations for Heart Failure

Background—INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles provide important prognostic information for patients with advanced heart failure (HF) receiving mechanical support. The value of INTERMACS profiling has not been shown for patients followed on medical therapy for advanced HF at centers that also offer mechanical circulatory support. Methods and Results—This prospective, observational study enrolled 166 patients with chronic New York Heart Association class III–IV HF, ejection fraction ⩽30%, and ≥1 HF hospitalization in the previous year, excluding patients listed for transplant or receiving chronic intravenous inotropic therapy. Subjects were followed for at least 12 months or until death, mechanical support, or transplant. Baseline features, quality of life, and outcomes were compared according to INTERMACS profile. Mean age was 57 years, ejection fraction 18%, and 57% had HF >5 years, whereas 23% of subjects were INTERMACS profile 4, 32% profile 5, and 45% profile 6/7. At 1 year, only 47% of this ambulatory advanced HF cohort remained alive on medical therapy. Patients in INTERMACS profile 4 were more likely to die or require mechanical support, with only 52% of these patients alive without support after the first 6 months. Profile 6/7 patients had 1-year survival of 84%, similar to outcomes for contemporary destination left ventricular assist device recipients. Quality of life using the indexed EuroQol score was poor across profiles 4 to 7, although severe limitation was less common than for ambulatory patients enrolled in INTERMACS before ventricular assist device implantation. Conclusions—Ambulatory patients with systolic HF, a heavy symptom burden, and at least 1 recent HF hospitalization are at high risk for death or left ventricular assist device rescue. INTERMACS profiles help identify ambulatory patients with advanced HF who may benefit from current mechanical support devices under existing indications.

Who wants a left ventricular assist device for ambulatory heart failure? Early insights from the MEDAMACS screening pilot

Who wants a left ventricular assist device for ambulatory heart failure? Early insights from the MEDAMACS screening pilot Garrick C. Stewart, MD, MPH, Michelle M. Kittleson, MD, PhD, Jennifer A. Cowger, MD, Frances L. Johnson, MD, Chetan B. Patel, MD, Maria M. Mountis, DO, Parag C. Patel, MD, J. Eduardo Rame, MD, Jeffrey Testani, MD, Maya E. Guglin, MD, Jeffrey J. Teuteberg, MD, and Lynne W. Stevenson, MD From the Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California; Cardiovascular Center, University of Michigan, Ann Arbor, Michigan; Division of Cardiology, University of Iowa, Iowa City, Iowa; Division of Cardiology, Duke University, Durham, North Carolina; Division of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio; Division of Cardiology, University of Texas Southwestern, Dallas, Texas; Heart and Vascular Center, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Cardiology, University of South Florida, Tampa, Florida; and the Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania

Management of left ventricular assist devices after surgery: bridge, destination, and recovery.

Purpose of review As the use and understanding of mechanical circulatory support (MCS) increases, the management of these devices has become more conventional. The purpose of this review is to discuss the perioperative and long-term management of MCS patients. Recent findings With the advent of axial flow pumps, both perioperative and long-term management are more standardized. The issues of nutrition, physical therapy, drive line care, and readiness to transition to home are becoming more mainstream and are readily accepted into the community. However, many factors remain that are not well defined in dealing with anticoagulation, weaning of MCS, achieving optimal device settings, and end-of-life care. Summary Care for the MCS patient provided in a multidisciplinary team approach is imperative to allow for a seamless transition from the hospital and into the community and successful long-term outcomes.

Outcomes for Patients With Diabetes After Continuous-Flow Left Ventricular Assist Device Implantation

BACKGROUND Diabetes mellitus (DM) is a risk factor for mortality among patients with heart failure as well as for patients who undergo cardiothoracic surgery. However it is unknown whether DM is associated with increased mortality or major complications during continuous-flow left ventricular assist device (CF-LVAD) support. METHODS AND RESULTS We retrospectively reviewed 300 consecutive adults who received CF-LVADs at a single center in the years 2006-2013; 129 patients had DM before LVAD, as defined by American Diabetes Association criteria (HbA1c ≥6.5% and/or taking DM medications). Compared with the non-DM group, DM patients were older, with a higher pre-LVAD body mass index, more ischemic heart failure etiology, and higher pre-LVAD creatinine. Ninety-three patients died on LVAD support, 43 with DM and 50 without DM (P = .4526). After control for 9 covariates in a Cox proportional hazards model, DM was unassociated with all-cause mortality (hazard ratio 0.883, 95% confidence interval 0.571-1.366; P = .5768). Diabetes was also unassociated with the adverse event end points of stroke/transient ischemic attack, intracerebral hemorrhage, pump thrombosis, and device-related infections. CONCLUSIONS Diabetes is common in LVAD recipients (43% of the present cohort) but does not increase mortality or rates of major adverse events during CF-LVAD support.

Case series using the rotaflow system as a temporary right ventricular assist device after heartmate II implantation

The purpose of this study was to investigate the outcomes of using the ROTAFLOW as a temporary right ventricular assist device (RVAD) support in patients who develop right ventricular dysfunction (RVD) at the time of left ventricular assist device (LVAD) implantation with the HeartMate (HM) II. We conducted a retrospective chart review of patients in whom the ROTAFLOW system was used for RV support during HM II implantation from October 2009 to September 2011. Twelve patients received a ROTAFLOW as an RVAD at the time of HM II implantation; 83% had preoperative echocardiography evidence of either moderate or severe RVD. The most common complications in the postoperative period were the need for tracheostomy because of respiratory failure (45%) and mediastinal bleeding requiring exploration (36%). Ninety-one percent of patients survived to discharge, and all were alive at 1 year follow-up. Our results show that temporary RVAD support with the ROTAFLOW system in the setting of RVD at the time of HM II implantation is feasible and effective.