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With the current generation of continuous-flow (CF) left ventricular assist devices (LVADs), patients are able to be supported for longer periods of time. As a result, there has been increasing focus on long-term complications from prolonged mechanical circulatory support, such as acquired aortic insufficiency (AI). In the presence of an LVAD, AI leads to a blind circulatory loop, with a portion of LVAD output regurgitating through the aortic valve (AV) into the left ventricle and back again through the device, limiting effective forward flow and ultimately leading to organ malperfusion and increased left ventricular diastolic pressures. The AV also experiences abnormal biomechanics as a result of limited valve opening in the presence of a CF LVAD. Increased shear stress, elevated transvalvular pressure gradients, and decreased valve open time all contribute to acquired AI. The prognosis of moderate to severe AI in LVAD patients is generally poor and leads to a higher rate of AV replacement and potentially reduced survival. However, there are no evidence-based guidelines for management of this challenging population. In severe AI, experts generally advocate AV replacement or repair, while lesser degrees of AI can be managed medically and/or with adjustments in pump parameters.

Individual ventricular assist device (VAD) design may affect leukocytes and impact immunity. Few studies have presented leukocyte and infection profiles in VAD patients over the course of the implant period. CD11b (MAC-1) expression on granulocytes is an indicator of activation during inflammation, mediating extravasation and the release of reactive oxygen species in tissue. No reported studies have presented MAC-1 expression on circulating granulocytes in VAD patients. Fifty-six patients implanted at a single center with a HeartMate II (HMII; n = 32), HeartWare (HW; n = 12), or Thoratec pneumatic VAD (PVAD; n = 12) between 1999 and 2011 were followed for 120 days of support. The leukocyte profiles and infectious events of all patients were evaluated; additionally, a subset had MAC-1 expression on circulating granulocytes was measured (HMII n = 9; HW n = 7; PVAD n = 4). All groups exhibited a significant peak in leukocyte numbers at postoperative day (POD) 14 while simultaneously experiencing a significant decrease in hematocrit. HMII patients exhibited a 3.2-fold increase in granulocyte MAC-1 expression at POD 14, and the temporal trend over the implant period differed from that experienced by HW patients. Further, HW patients experienced significantly fewer infection events. Alterations in leukocyte profiles and granulocyte activation experienced by VAD patients appear to be device-specific. Elevations in leukocyte activation may be related to an increased risk for infection, although the specific relationship between these phenomena in this patient group is not known.

Objectives This study investigated how the initial intended strategy at left ventricular assist device (LVAD) implantation influenced patient outcomes. Background Left ventricular assist device implantation strategy impacts candidate selection, reimbursement, and clinical trial design; however, concepts of device strategy are continuing to evolve. Methods For patients entered in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) receiving a primary continuous flow LVAD between March 2006 and March 2011, initial strategies were bridge to transplant (BTT), bridge to candidacy (BTC) for transplant, and destination therapy (DT). Primary analyses compared BTT, BTC, and DT outcomes at 6, 12, and 24 months. Results Among 2,816 primary LVAD recipients, implant strategy was 1,060 (38%) BTT, 1,162 (42%) BTC (likely to be listed 796, moderately likely 282, unlikely 84), and 553 (20%) DT. Compared with BTC/DT, those listed at implant (BTT) had similar degrees of ventricular dysfunction and hemodynamic derangement but generally less comorbidity. Survival (alive with LVAD or transplanted) was superior at 24 months for BTT versus BTC versus DT (77.7% vs.70.1% vs. 60.7%, respectively, p Conclusions The currently accepted indications only account for 58% of LVAD implants. Across indications, patients differ by the number and types of comorbidities rather than the need for hemodynamic support. Regardless of initial implant strategy, patients often have long durations of support, and strategies often change over time, challenging the regulatory categorization of LVAD recipients as either BTT or DT.

Background The left atrium (LA) in the transplanted heart (TH) is a surgically created chamber from variable portions of donor and recipient LA. The American Society of Echocardiography (ASE) recommends measuring LA size in native hearts using biplane LA volume index (LAVI) as a more accurate measurement than LA anterior-posterior diameter (LA-APD). We hypothesized that LA-APD underestimates LA size when compared with LAVI in the TH. Methods Patients with a TH from 1/05 to 1/10 who had a transthoracic echocardiogram within 24 months of transplant were studied. Patients were excluded if they had an ejection fraction mild aortic or mitral regurgitation, or poor image quality. Echocardiograms were analyzed for LA-APD and LAVI. LA size was classified as normal, mild, moderate, or severely enlarged based on age and sex specific cutoffs per the ASE. Results Of 297 patients evaluated, 160 met inclusion criteria. Mean age was 57 ± 13 years and 79% were males. Mean LA-APD and LAVI were 4.3 ± 0.6 cm and 36 ± 14 mL/m2, respectively. LAVI correlated with LA-APD (r = 0.43, R2 = 0.18, P

Background Optical coherence tomography (OCT) is a novel intravascular imaging modality with excellent spatial resolution. This study explored the utility of OCT in cardiac transplantation for the detection and characterization of early changes associated with coronary allograft vasculopathy (CAV). Methods Fifteen consecutive patients, 1 to 4 years after transplant with no angiographic evidence of CAV, underwent successful OCT imaging using the Fourier-domain OCT system (C7-XR, St. Jude Medical, St. Paul, MN) in the left anterior descending artery. Analysis included measurements of the lumen, intima, and media layers, and characterization of atherosclerotic plaques. Patients were stratified by intima-to-media (I/M) ratio and classified as normal (≤1) or abnormal (>1). Results Patients were a mean of 2.8 years after transplant, 58 years old, and 92% were men. OCT imaging revealed 8 of 15 patients had intimal hyperplasia with an I/M ratio >1. Comparing those with I/M ratio of ≤1 and >1, the median (interquartile range) intimal thickness was greater (75 [70–101] vs 206 [97–269]μm, p = 0.03), whereas the media thickness was no different (72 [70–103] vs 94 [73–113]μm, p = 0.53). In addition, 7 of 15 patients had lipid-rich or calcified atherosclerotic plaques. Conclusions OCT provides high-resolution quantitative imaging of the coronary arteries and its use allows for detailed assessment of the coronary artery wall and early morphologic changes that occur after cardiac transplantation. The clinical predictive value of these OCT-derived measurements remains to be determined.

Heart transplantation in adults with congenital heart disease (CHD) has historically been associated with sub-optimal survival compared with other indications for transplantation. The purpose of this study was to evaluate survival outcomes after heart transplantation in a contemporary cohort of adults with CHD and to identify risk factors for mortality that may help guide recipient and donor selection.We performed a retrospective analysis of our adult heart transplant database, from January 2001 to February 2011, identifying 19 patients who underwent transplantation for CHD. These patients were compared with a control group of 428 patients who underwent transplantation for indications other than CHD. Kaplan-Meier survival analysis and Cox regression modeling were performed.The mean age for the CHD group was 39.4 ± 13 years vs 54.7 ± 12 years (p0.001). There was no significant difference in survival (CHD vs control) at 30 days (89% vs 92%, p = 0.5567), 1 year (84% vs 86%, p = 0.6976) or 5 years (70% vs 72%, p = 0.8478). The only significant predictor of death in the CHD group was donor organ ischemic time4 hours (HR 13.26, 95% CI 1.3 to 132.2, p = 0.028). There was no significant correlation with recipient age, history of failed Fontan surgery, pre-operative ventilator use, donor:recipient weight ratio0.8, donor:recipient CMV mismatch, model for end-stage liver disease (MELD) score or percent reactive antibody10%.In the modern era, with careful donor and recipient selection, adults with CHD have excellent early and mid-term survival after heart transplantation, rivaling that of recipients with other indications for transplantation.

A patient with a HeartMate II left ventricular assist device who had a body mass index of 52 needed gastric bypass surgery in order to qualify for a heart transplant. Unlike previous experience in which the surgery was performed at the implant hospital, the gastric bypass surgery in this case was performed at a bariatric center of excellence that was a separate facility from the implant hospital. The artificial heart program of the University of Pittsburgh Medical Center worked with the bariatric center of excellence in scheduling the gastric bypass surgery using a multidisciplinary team approach at 2 hospitals to coordinate safe, high-quality patient care in a unique situation.

Ventricular assist devices provide therapeutic options for patients with severe heart failure who have exhausted available medical therapies. With restoration of organ perfusion with ventricular assist devices, the heart failure resolves and quality of life and functional status improve. The current generation of continuous-flow devices present novel challenges to the clinical assessment of patients by substantially reducing or nearly eliminating any palpable pulse. Patients therefore generally have inadequate arterial pulsatility for most noninvasive monitoring devices such as pulse oximeters or automated blood pressure cuffs to work accurately. This article describes the function of continuous-flow devices and how this function affects common monitoring options, as well as how to clinically assess recipients of continuous-flow devices to promptly identify those whose condition may be deteriorating or who may be receiving inadequate perfusion.

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients who have advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and Interagency Registry of Mechanically Assisted Circulatory Support.

The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients with advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and the Interagency Registry of Mechanically Assisted Circulatory Support.

Context: Anticoagulation therapy is common in thoracic transplant recipients. Direct oral anticoagulants (DOACs) are alternatives to warfarin therapy, but characterization of their use in solid organ transplant is absent. Objective: The primary objective of this study was to describe a thoracic transplant patient population initiated on DOAC therapy. Secondary objectives were to assess adverse reactions, venous thromboembolism (VTE) recurrence, and drug–drug interactions during DOAC therapy. Study Design: Single-center retrospective cohort study. Setting: A tertiary care medical center including inpatient hospitalization and outpatient transplant clinic visits. Patients: Thoracic transplant recipients who were initiated on DOACs between May 1, 2011, and March 1, 2015, at the University of Pittsburgh Medical Center were included. Results: A total of 37 patients were included in the analysis. A majority of the patients were lung transplant recipients (86.4%) with a median age of 60.7 years. Twenty-eight patients had a history of VTE. The primary indication for DOAC initiation was VTE (86.5%). Rivaroxaban (78.4%) was the most commonly utilized agent. Dose reductions for major drug interactions (37.8%), renal insufficiency (10.8%), or both (8.1%) occurred within the study. Two patients had breakthrough VTE during DOAC therapy. Eight bleeding events were reported in the cohort, one of which was considered a major bleed. There was no difference in the incidence of bleeding in patients with drug–drug interactions and without drug–drug interactions during DOAC therapy (26.0% vs 7.1%, P = .154). Conclusion: Direct oral anticoagulant therapy was well tolerated by thoracic transplant recipients. Drug interactions and renal dose adjustments were common.

Objectives This study investigates the use of a Bayesian statistical model to address the limited predictive capacity of existing risk scores derived from multivariate analyses. This is based on the hypothesis that it is necessary to consider the interrelationships and conditional probabilities among independent variables to achieve sufficient statistical accuracy. Background Right ventricular failure (RVF) continues to be a major adverse event following left ventricular assist device (LVAD) implantation. Methods Data used for this study were derived from 10,909 adult patients from the Inter-Agency Registry for Mechanically Assisted Circulatory Support (INTERMACS) who had a primary LVAD implanted between December 2006 and March 2014. An initial set of 176 pre-implantation variables were considered. RVF post-implant was categorized as acute ( 14 days) in onset. For each of these endpoints, a separate tree-augmented naive Bayes model was constructed using the most predictive variables employing an open source Bayesian inference engine. Results The acute RVF model consisted of 33 variables including systolic pulmonary artery pressure (PAP), white blood cell count, left ventricular ejection fraction, cardiac index, sodium levels, and lymphocyte percentage. The early RVF model consisted of 34 variables, including systolic PAP, pre-albumin, lactate dehydrogenase level, INTERMACS profile, right ventricular ejection fraction, pro-B-type natriuretic peptide, age, heart rate, tricuspid regurgitation, and body mass index. The late RVF model included 33 variables and was predicted mostly by peripheral vascular resistance, model for end-stage liver disease score, albumin level, lymphocyte percentage, and mean and diastolic PAP. The accuracy of all Bayesian models was between 91% and 97%, with an area under the receiver operator characteristics curve between 0.83 and 0.90, sensitivity of 90%, and specificity between 98% and 99%, significantly outperforming previously published risk scores. Conclusions A Bayesian prognostic model of RVF based on the large, multicenter INTERMACS registry provided highly accurate predictions of acute, early, and late RVF on the basis of pre-operative variables. These models may facilitate clinical decision making while screening candidates for LVAD therapy.

Cardiogenic shock complicating acute myocardial infarctions (CS-AMIs) carries high mortality rates. Early use of durable continuous flow left ventricular assist devices (CF-LVAD) in these patients has traditionally been discouraged. Therefore we sought to assess the efficacy and complications of CF-LVAD use in CS-AMI after stabilization with temporary mechanical support. From January 2006 to November 2014, nine patients underwent CF-LVAD implant after CS-AMI (Heartmate II, six; HVAD, three). All patients required temporary mechanical circulatory support (MCS) before CF-LVAD implant and were interagency registry for mechanically assisted circulatory support profile 1; average time from MI to CF-LVAD implant was 20 days. Overall seven of nine patients (78%) survived to discharge. Survival at 1, 3, 12, and 48 months was 100%, 89%, 67%, and 67%, respectively. Two patients were successfully bridged to transplant and four patients remain alive on device support. The most common post-LVAD complication was stroke, occurring in 55% of patients. Embolic strokes were mild in severity and all patients survived with only mild deficits; hemorrhagic strokes conferred the highest mortality. This study suggests CF-LVADs are potential but high-risk treatment options for CS-AMI patients who stabilize with temporary support. Further studies will help more clearly delineate the benefits and risks of CF-LVAD implant in this population.

Continuous-flow left ventricular assist devices (LVADs) have revolutionized advanced heart failure care. These compact, fully implantable heart pumps are capable of providing meaningful increases in survival, functional capacity, and quality of life. Implantation volumes continue to grow, but several challenges remain to be overcome before LVADs will be considered as the therapy of choice for all patients with advanced heart failure. They must be able to consistently extend survival for the long term (7 to 10 years), rather than the midterm (3 to 5 years) more typical of contemporary devices; they must incorporate design elements that reduce shear stress and avoid stasis to reduce the frequent adverse events of bleeding, stroke, and pump thrombosis; and they must become more cost-effective. The advancements in engineering, implantation technique, and medical management detailed in this review will highlight the progress made toward achieving lifelong LVAD support and the challenges that remain.

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.

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 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.

From the Division of Cardiac Surgery, Northwestern University, Chicago, Illinois; Cardiovascular Division, Brigham & Women’s Hospital, Boston, Massachusetts; Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan; Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, Alabama; Division of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky; Division of Cardiology, Harvard Medical School, Boston, Massachusetts; and the Department of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama.

Objectives This study sought to assess the utility of the Destination Therapy Risk Score (DTRS) in patients with continuous flow left ventricular assist devices (LVAD). Background The DTRS was developed to predict the risk of 90-day in-hospital mortality with pulsatile flow LVAD as destination therapy (DT). Despite ongoing use in patients with continuous flow devices, its utility has not been studied in such populations. Methods The DTRS was determined in 1,124 patients with the continuous flow HeartMate II (Thoratec Corporation, Pleasanton, California) LVAD as a bridge to transplant (BTT, n = 486) and DT (n = 638) and 114 DT patients with the pulsatile flow HeartMate XVE (Thoratec Corporation). Patients were divided into risk groups based on DTRS: low (0–8), medium (9–16), and high (>16). Results The 90-day in-hospital mortality for low-, medium-, and high-risk groups was 8%, 7%, and 16%, respectively, for BTT patients; 9%, 12%, and 19%, respectively, for DT patients; and 11%, 18%, and 25%, respectively, for XVE DT patients. The high-risk groups had more than a 2-fold increased risk of mortality compared with the low-risk groups. However, the area under the receiver-operating characteristic curve for 90-day in-hospital mortality yielded modest values ranging from 0.54 to 0.58 for the HeartMate II BTT and DT groups, respectively. Survival rates over 2 years were statistically significantly different as stratified by the 3 DTRS groups for patients implanted for DT but not for BTT. Conclusions DTRS provides poor discrimination of mortality for BTT patients and only modest discrimination for DT patients receiving continuous flow LVAD.

Right ventricular failure is a significant complication following implantation of a left ventricular assist device (LVAD), which increases morbidity and mortality. Consequently, researchers have sought predictors that may identify patients at risk. However, they have lacked sensitivity and/or specificity. This study investigated the use of a decision tree technology to explore the preoperative data space for combinatorial relationships that may be more accurate and precise. We retrospectively analyzed the records of 183 patients with initial LVAD implantation at the Artificial Heart Program, University of Pittsburgh Medical Center, between May 1996 and October 2009. Among those patients, 27 later required a right ventricular assist device (RVAD+) and 156 remained on LVAD (RVAD-) until the time of transplantation or death. A synthetic minority oversampling technique (SMOTE) was applied to the RVAD+ group to compensate for the disparity of sample size. Twenty-one resampling levels were evaluated, with decision tree model built for each. Among these models, the top six predictors of the need for an RVAD were transpulmonary gradient (TPG), age, international normalized ratio (INR), heart rate (HR), aspartate aminotransferase (AST), prothrombin time, and right ventricular systolic pressure. TPG was identified to be the most predictive variable in 15 out of 21 models, and constituted the first splitting node with 7 mmHg as the breakpoint. Oversampling was shown to improve the senstivity of the models monotonically, although asymptotically, while the specificity was diminished to a lesser degree. The model built upon 5X synthetic RVAD+ oversampling was found to provide the best compromise between sensitivity and specificity, included TPG (layer 1), age (layer 2), right atrial pressure (layer 3), HR (layer 4,7), INR (layer 4, 9), alanine aminotransferase (layer 5), white blood cell count (layer 5,6, &7), the number of inotrope agents (layer 6), creatinine (layer 8), AST (layer 9, 10), and cardiac output (layer 9). It exhibited 85% sensitivity, 83% specificity, and 0.87 area under the receiver operating characteristic curve (RoC), which was found to be greatly improved compared to previously published studies.

Background Implantable cardioverter-defibrillators (ICDs) reduce mortality in heart failure (HF). In patients requiring a ventricular assist device (VAD), the benefit from ICD therapy is not well established. The aim of this study was to define the impact of ICD on outcomes in VAD-supported patients. Methods and Results We reviewed data for consecutive adult HF patients receiving VAD as a bridge to transplantation from 1996 to 2003. The primary outcome was survival to transplantation. A total of 144 VADs were implanted [85 left ventricular (LVAD), 59 biventricular (BIVAD), mean age 50 ± 12 years, 77% male, left ventricular ejection fraction 18 ± 9%, 54% ischemic]. Mean length of support was 119 days (range 1–670); 103 patients (72%) survived to transplantation. Forty-five patients had an ICD (33 LVAD, 12 BIVAD). More LVAD patients had an appropriate ICD shock before implantation than after (16 vs 7; P = .02). There was a trend toward higher shock frequency before LVAD implant than after (3.3 ± 5.2 vs 1.1 ± 3.8 shocks/y; P = .06). Mean time to first shock after VAD implant was 129 ± 109 days. LVAD-supported patients with an ICD were significantly more likely to survive to transplantation [1-y actuarial survival to transplantation: LVAD: 91% with ICD vs 57% without ICD (log-rank P = .01); BIVAD: 54% vs 47% (log-rank P = NS)]. An ICD was associated with significantly increased survival in a multivariate model controlling for confounding variables (odds ratio 2.54, 95% confidence interval 1.04–6.21; P = .04). Conclusions Shock frequency decreases after VAD implantation, likely owing to ventricular unloading, but appropriate ICD shocks still occur in 21% of patients. An ICD is associated with improved survival in LVAD-supported HF patients.

Obesity and heart failure are increasingly common, but the outcomes, weight changes, and adverse events of patients with advanced heart failure and obesity on mechanical support is not well described.We retrospectively reviewed all non-underweight patients with durable mechanical support at a single institution from January 2000 until December 2008 and compared outcomes, weight change, and Interagency Registry for Mechanically Assisted Circulatory Support-defined adverse events between obese and nonobese patients.A total of 169 patients were included; 113 (67%) nonobese and 56 (33%) obese. Baseline characteristics, pump types, and implant duration were similar for both populations with the exception of more diabetes (61% vs 26%, p0.0001) and hypertension (61% vs 42%, p = 0.019) in the obese. Outcomes on mechanical support at 6 months were not different between groups. There was no significant difference between the nonobese and obese groups in the change in body mass index (-0.3 vs -1.0 mg/m(2), p = 0.29) over the duration of support. Obese patients, as compared with the nonobese, had higher incidence rates of sepsis (64.5% vs 34.7%, respectively, p = 0.006) and reoperation for infectious complications (34.2% vs 13.3%, respectively, p = 0.014). Obese patients also had a higher cumulative incidence of sepsis and reoperation for infection. Two-year posttransplant outcomes were not different in the obese and nonobese.Obese patients have similar outcomes on mechanical support, but at the cost of a higher cumulative incidence of sepsis and reoperations for infection; however, obese patients lose little weight while on mechanical support.

Cardiac disease is the leading cause of death in US prevalent hemodialysis (HD) patients. There is a lack of data about the impact of the severity of heart failure (HF) on outcomes and health-related quality of life (HRQoL) in HD patients. We aimed to determine the prognostic importance of the Index of Disease Severity (IDS) of the Index of Coexistent Disease (ICED) scoring system as an HF severity measure.Subanalysis of the Hemodialysis (HEMO) Study, a randomized controlled trial. Relationships between HF severity and mortality and cardiac hospitalizations were determined using Cox proportional hazards models. The relationship between HF severity and HRQoL scores was modeled using linear regression and generalized estimating equations.1,846 long-term HD patients at 15 clinical centers including 72 dialysis units.HF severity classified using the IDS of the ICED scoring system.Mortality (all cause and cause specific), cardiac hospitalizations, and HRQoL.All-cause, cardiac, and infectious deaths; cardiac hospitalizations; and HRQoL scores from the Kidney Disease Quality of Life-Long Form.HF was present in 40% of HD patients. Increasing severity of HF was associated with older age, greater likelihood of diabetes, and lower serum albumin level (all P0.001). Adjusted HRs for all-cause mortality were 1.31 (95% CI, 1.12-1.53), 1.48 (95% CI, 1.19-1.85), and 2.11 (95% CI, 1.43-3.11) for mild, moderate, and severe HF, respectively (P0.001). All-cause, cardiac, and infectious mortality and cardiac hospitalizations increased with increasing severity of HF. Increasing HF severity was associated with decreases in HRQoL, particularly in physical functioning and sleep quality.This study is limited by the small sample size in the most severe HF group.Increasing severity of HF is associated with increased mortality and cardiac hospitalizations and worse HRQoL, especially in perceived physical limitations. These findings emphasize the utility of the IDS of the ICED score as a valid prognostic tool for medical and HRQoL outcomes in the HD population with HF.

Background Renal dysfunction is common before mechanical circulatory support (MCS). Mechanical circulatory support frequently improves renal function, but the impact of pre-MCS renal dysfunction on renal function after cardiac transplantation (CTX) is unknown. Methods Patients with MCS from January 1995 until April 2008 at a single center were included if their MCS duration was at least 60 days and they underwent successful CTX. Patients were followed for 1 year after CTX. Results A total of 116 patients were included in the study. Mechanical circulatory support was biventricular assist device in 28% and left ventricular assist device in 72% (continuous flow left ventricular assist device, 14%). Mean duration of MCS was 124 days. Patients were grouped according to tertiles of pre-MCS creatinine clearance (CrCl): group 1, CrCl less than 45 mL/min; group 2, CrCl between 45 and 65 mL/min inclusive; and group 3, CrCl more than 65 mL/min. Group 3 had the best renal outcomes both after MCS and 1 year after CTX. Regardless of group, patients who had a CrCl of at least 60 mL/min before CTX had similar 1-year posttransplant CrCl (55 versus 53 versus 56 mL/min for groups 1 through 3, respectively; not significantly different). However, the ability to achieve this level of renal function after MCS was less likely in those with the worst renal function before the initiation of MCS (53% versus 74% versus 90% for groups 1 through 3, respectively; p = 0.001). Conclusions The use of MCS leads to improvements in renal function in patients after MCS. However, the renal outcomes after CTX seem to be more dependent on the level of renal function achieved during MCS than on the level of renal function before MCS.

Khandhar SJ, Shah HV, Shullo MA, Zomak R, Navoney M, McNamara DM, Kormos RL, Toyoda Y, Teuteberg JJ. Long-term effects on renal function of dose-reduced calcineurin inhibitor and sirolimus in cardiac transplant patients. Clin Transplant 2012: 26: 42–49. © 2011 John Wiley & Sons A/S. Abstract: Calcineurin inhibitor (CNI)-associated renal insufficiency is common after cardiac transplantation (CTX); however, the addition of sirolimus allows for CNI dose reduction and this strategy may limit CNI renal toxicity. This study examines the long-term effects of such a strategy. Methods: Patients from a single center who had CTX from 1990 to 2007 and who were converted to sirolimus and a dose-reduced CNI were compared to group-matched controls maintained on CNI and an antiproliferative agent. Results: One hundred and fifty-five patients (79 sirolimus and 76 controls) were included and had similar baseline characteristics. Sirolimus was started a mean of 1429 d post-CTX and maintained for a mean of 823 d. Reason for conversion to sirolimus was renal insufficiency (34%), vasculopathy (29%), recurrent rejection (19%), and other (18%). The eGFR was not different between groups at baseline (44.7 mL/min/1.73 m2 vs. 46.0, p = 0.64) or at any point during follow-up: 90 d, 180 d, 1 yr, 2 yr, and 3 yr. Conclusion: Patients converted to a regimen of sirolimus and a dosed-reduced CNI have stable renal function over the following three yr, but do not have an improvement in renal outcomes compared to patients maintained on full dose CNI.

Background Ventricular assist devices (VADs) provide effective treatment for end-stage heart failure; however, most patients experience ≥1 major adverse events (AEs) while on VAD support. Although early, non-fatal AEs may increase the risk of later death during VAD support, this relationship has not been established. Therefore, we sought to determine the impact on 1-year mortality of AEs occurring during the first 60 days of VAD support. Methods A retrospective analysis was performed using prospectively collected data from a single-site database for patients aged ≥18 years receiving left ventricular or biventricular support during 1996 to 2008 and who survived >60 days on VAD support. Fourteen major classes of AEs occurring during this 60-day period were examined. One-year survival rates of patients with and without each major AE were compared. Results The study included 163 patients (80% men; mean age, 49.5 years), of whom 87% were European American, 72% had left ventricular support, and 83% were bridge to transplant. The occurrence of renal failure, respiratory failure, bleeding events, and reoperations during the first 60 days after implantation significantly increased the risk of 1-year mortality. After controlling for gender, age, VAD type, and intention to treat, renal failure was the only major AE significantly associated with later mortality (hazard ratio, 2.96; p = .023). Conclusions Specific AEs, including renal failure, respiratory and bleeding events, and reoperations, significantly decrease longer-term survival. Renal failure conferred a 3-fold increased risk of 1-year mortality. Peri-operative management should focus on strategies to mitigate risk for renal failure in order to maximize later outcomes.

Background Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. Methods We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of geneexpression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. Results During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P = 0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P

This study compares the prognostic value of right ventricular load-adaptability indices to predict right heart failure (RHF) post-left ventricular assist device (LVAD) implantation. From 2009 to 2016, 194 patients who underwent continuous-flow LVAD were included. RHF was defined as unplanned need

Mechanical circulatory support (MCS) is life sustaining for patients with end-stage heart failure. Most devices require abdominal wall transgression, creating a potential for abdominal complications. The incidence and impact of these relatively underreported complications are unknown.A retrospective review was performed on 179 patients who received MCS therapy from 1999 to 2008. Abdominal complications were grouped as abdominal wall, gastrointestinal tract, and solid organ.Ninety-eight patients (55%) experienced 157 abdominal complications. These involved the abdominal wall in 69 (44%), the gastrointestinal tract in 52 (33%), and the solid organs in 36 (23%). Surgical intervention was required in 36% of patients with abdominal wall complications, 19% of patients with gastrointestinal tract complications, and 14% of patients with solid organ complications. Multivariate analysis identified diabetes mellitus (p0.001), emergent device placement (p = 0.019), and preimplant mechanical ventilation (p = 0.045) as independent risk factors for developing an abdominal complication. Kaplan-Meier survival while receiving MCS was significantly reduced for patients with abdominal complications versus those without (p = 0.0142). Multivariate analysis identified only solid organ abdominal complications (p = 0.001) as an independent risk factor for death while receiving device support.Abdominal complications are common in patients supported with MCS devices and significantly reduce survival. Surgical intervention is more frequently required for complications related to the abdominal wall compared with other complications. Patients with significant comorbidities (diabetes mellitus, respiratory failure) requiring urgent or emergent device placement are at higher risk for the development of abdominal complications with an attendant reduction in device-related survival.

The HeartMate II (Thoratec, Pleasanton, CA) is an effective bridge to transplantation (BTT) but requires anti-coagulation with warfarin and aspirin. We evaluated the risk of thromboembolism and hemorrhage related to the degree of anti-coagulation as reflected by the international normalized ratio (INR).INRs were measured monthly for 6 months in all discharged HeartMate II BTT patients and at an event. Each INR was assigned to ranges of INRs. Adverse events analyzed were ischemic and hemorrhagic stroke, pump thrombosis, and bleeding requiring surgery or transfusion. Events were correlated to the INR during the event and at the start of the month.In 331 patients discharged on support, 10 had thrombotic events (9 ischemic strokes, 3 pump thromboses), and 58 had hemorrhagic events (7 strokes, 4 hemorrhages requiring surgery, and 102 requiring transfusions). The median INR was 2.1 at discharge and 1.90 at 6 months. Although the incidence of stroke was low, 40% of ischemic strokes occurred in patients with INRs1.5 and 33% of hemorrhagic strokes were in patients with INRs3.0. The highest incidence of bleeding was at INRs2.5.The rate of thromboembolism during long-term outpatient support with the HeartMate II is low. The low number of thrombotic events appears to be offset by a greater number of hemorrhagic events. An appropriate target INR is 1.5 to 2.5 in addition to aspirin therapy. In patients having recurrent episodes of bleeding, the risk of lowering the target INR appears to be small.

Background: Chronic steroid use after cardiac transplantation (CTX) is accompanied by co-morbidities that are dependent on length of exposure. Methods: A retrospective review of all CTX without induction therapy from 1999–2004. After 2001, an aggressive strategy of steroid weaning was introduced. Results: A total of 165 patients underwent CTX, 82 from 1999–2001 (group 1) and 83 from 2002–2004 (group 2). There were no significant differences in recipient or donor characteristics between group 1 and group 2. The baseline calcineurin was cyclosporine in 41% and 5% (p

ObjectiveA cerebrovascular accident is a devastating adverse event in a patient with a ventricular assist device. The goal was to clarify the risk factors for cerebrovascular accident.MethodsProspectively collected data, including medical history, ventricular assist device type, white blood cell count, thrombelastogram, and infection, were reviewed retrospectively in 124 patients.ResultsThirty-one patients (25%) had 48 cerebrovascular accidents. The mean ventricular assist device support period was 228 and 89 days in patients with and without cerebrovascular accidents, respectively (P < .0001). Sixty-six percent of cerebrovascular accidents occurred within 4 months after implantation. Actuarial freedom from cerebrovascular accident at 6 months was 75%, 64%, 63%, and 33% with the HeartMate device (Thoratec Corp, Pleasanton, Calif), Thoratec biventricular ventricular assist device (Thoratec Corp), Thoratec left ventricular assist device (Thoratec), and Novacor device (WorldHeart, Oakland, Calif), respectively. Twenty cerebrovascular accidents (42%) occurred in patients with infections. The mean white blood cell count at the cerebrovascular accident was greater than the normal range in patients with infection (12,900/mm3) and without infection (9500/mm3). The mean maximum amplitude of the thrombelastogram in the presence of infection (63.6 mm) was higher than that in the absence of infection (60.7 mm) (P = .0309).ConclusionsThe risk of cerebrovascular accident increases with a longer ventricular assist device support period. Infection may activate platelet function and predispose the patient to a cerebrovascular accident. An elevation of the white blood cell count may also exacerbate the risk of cerebrovascular accident even in patients without infection. Selection of device type, prevention of infection, and meticulous control of anticoagulation are key to preventing cerebrovascular accident.

Background: Pre-LVAD analysis of RV function is critical for surgical planning and determines operative outcome. Current imaging techniques have yielded limited success at predicting RV failure (RVF). GBPS is count based without geometric assumption, and allows global and regional RV function

The purpose of this study was to determine the risk factors for ischemic in hemorrhage cerebrovascular events in patients supported by the HeartWare ventricular assist device (HVAD).Patients supported with left ventricular assist devices are at risk for both ischemic and hemorrhagic cerebrovascular events.Patients undergoing implantation with a HVAD as part of the bridge-to-transplant trial and subsequent continued access protocol were included. Neurological events (ischemic cerebrovascular accidents [ICVAs] and hemorrhagic cerebrovascular accidents [HCVAs]) were assessed, and the risk factors for these events were evaluated in a multivariable model.A total of 382 patients were included: 140 bridge-to-transplant patients from the ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) clinical trial and 242 patients from the continued access protocol. Patients had a mean age of 53.2 years; 71.2% were male, and 68.1% were white. Thirty-eight percent had ischemic heart disease, and the mean duration of support was 422.7 days. The overall prevalence of ICVA was 6.8% (26 of 382); for HCVA, it was 8.4% (32 of 382). Pump design modifications and a protocol-driven change in the antiplatelet therapy reduced the prevalence of ICVA from 6.3% (17 of 272) to 2.7% (3 of 110; p = 0.21) but had a negligible effect on the prevalence of HVCA (8.8% [24 of 272] vs. 6.4% [7 of 110]; p = 0.69). Multivariable predictors of ICVA were aspirin ≤81 mg and atrial fibrillation; predictors of HCVA were mean arterial pressure90 mm Hg, aspirin ≤81 mg, and an international normalized ratio3.0. Eight of the 30 participating sites had established improved blood pressure management (IBPM) protocols. Although the prevalence of ICVA for those with and without IBPM protocols was similar (5.3% [6 of 114] vs. 5.2% [14 of 268]; p = 0.99), those with IBPM protocols had a significantly lower prevalence of HCVA (1.8% [2 of 114] vs. 10.8% [29 of 268]; p = 0.0078).Anticoagulation, antiplatelet therapy, and blood pressure management affected the prevalence of cerebrovascular events after implantation of the HVAD. Attention to these clinical parameters can have a substantial impact on the occurrence of serious neurological events. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972).

Cardiac allograft vasculopathy (CAV) is common after cardiac transplantation and remains a leading cause of death. The etiology of CAV is multifactorial and includes traditional risk factors for coronary artery disease, such as hypertension, hyperlipidemia and the metabolic syndrome; however, donor factors, such as age and ischemic time, as well as cytomegalovirus infections, are also risk factors. Furthermore, the immune system contributes to the development of CAV with persistent immune activation and subsequent injury to the vascular endothelium during the life of the graft. 1 Unlike coronary artery disease, CAV tends to develop quickly, sometimes as soon as months after transplant, is typically diffuse, and is the result of fibroproliferative changes rather than lipid deposition. Given the denervation of the allograft, patients with CAV have few, if any, symptoms and thus periodic surveillance of the coronary vasculature is required, but even mild persistent lesions by angiography are predictors for worse long-term survival. 2 The cardiac transplant community defines CAV mostly through its angiographic appearance, although the diffuse, concentric nature of CAV can limit the utility of angiography. 3 Other limitations of angiography include vascular complications, exposure to radiation, cost, resource utilization and the need for nephrotoxic contrast. Many of the non-invasive techniques for the development of CAV pursue a strategy of “going big,” which involves using findings on non-invasive testing that are correlated with the angiographic presence of CAV. The most widespread non-invasive technique has been dobutamine stress echocardiography (DSE). When compared with coronary angiography, DSE has a sensitivity of 80% and specificity of 88%. 1 Single-photon emission computed tomography (SPECT) has also been studied in the transplant population and has a sensitivity of 21% to 92% and specificity of 55% to 100% for the detection of CAV. 4 Coronary computed tomography angiography (CCTA) was initially limited to the assessment of stenosis of large proximal vessels, but can now detect angiographic stenosis of Z50% with a sensitivity of 94% and specificity of 92%, but these examinations still require exposure to

Background— Despite low risk of late rejection after heart transplant (HT), surveillance endomyocardial biopsies (EMBs) are often continued for years. We assessed the cost-effectiveness of routine EMB after 12 months post-HT. Methods and Results— Markov model compared the following surveillance EMB strategies to baseline strategy of stopping EMB 12 months post-HT: (1) every 4 months during year 2 post-HT, (2) every 6 months during year 2, (3) every 4 months for years 2 to 3, and (4) every 6 months for years 2 to 3. Patients entered the model 12 months post-HT and were followed until 36 months. In all strategies, patients had EMB with symptoms; in biopsy strategies after 12 months, EMB was also performed as scheduled regardless of symptoms. One-way and Monte Carlo sensitivity analyses were performed. Stopping EMB at 12 months was dominant (more effective, less costly), saving $2884 per patient compared with the next best strategy (every 6 months for year 2) and gaining 0.0011 quality-adjusted life-years. Increasing the annual risk of asymptomatic rejection in years 2 to 3 from previously reported 2.5% to 8.5% resulted in the biopsy every 6 months for year 2 strategy gaining 0.0006 quality-adjusted life-years, but cost $4 913 599 per quality-adjusted life-year gained. EMB for 12 months was also no longer dominant when mortality risk from untreated asymptomatic rejection approached 11%; competing strategies still cost >$200 000 per quality-adjusted life-year as that risk approached 99%. Conclusions— Surveillance EMB for 12 months post-HT is more effective and less costly than EMB performed after 12 months, unless risks of asymptomatic cellular rejection and its mortality are strikingly higher than previously observed.

OBJECTIVES: Preoperative liver dysfunction may influence haemostasis following ventricular assist device (VAD) implantation. The Model for End-stage Liver Disease (MELD) score was assessed as a predictor of bleeding and levels of haemostatic markers in patients with currently utilized VADs. METHODS: Sixty-three patients (31 HeartMate II, 15 HeartWare, 17 Thoratec paracorporeal ventricular assist device) implanted 2001–11 were analysed for preoperative liver dysfunction (MELD) and blood product administration. Of these patients, 21 had additional blood drawn to measure haemostatic marker levels. Cohorts were defined based on high (≥18.0, n= 7) and low (

Background Gene expression profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of gene expression profiling test scores within a patient may predict risk of future events of allograft dysfunction or death. Method Patients from the IMAGE study with rejection surveillance gene expression profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene expression profiling score variability was defined as the standard deviation of an individual’s cumulative test scores. Gene expression profiling ordinal score (range, 0–39), threshold score (binary value=1 if ordinal score ≥34), and score variability were studied in multivariate Cox regression models to predict future clinical events. Results Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, gene expression profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were, Supplemental digital content is available in the article.

Anticoagulation in mechanical circulatory support (MCS) patients dictated by local practice, and therefore uniform standards for management are lacking. To characterize the worldwide variance in anticoagulation and antiplatelet therapy in patients with MCS devices, a 42 item survey was created and distributed electronically in August 2014. The survey assessed the center-perceived thromboembolic risk (minimal, low, moderate, or high) and characterized the antiplatelet and anticoagulant strategies for the Thoratec HeartMate II (HMII) and HeartWare HVAD (HVAD). A total of 83/214 centers (39%) responded: North America (60/152), Europe (18/50), Australia (2/4), and Asia (3/8). Although the most common target international normalized ratio (INR) was 2-3 for both devices, significant variability exists. Anticoagulation intensity tended to be lower with the HMII, with more centers targeting INR values of less than 2.5. Aspirin monotherapy was the most common antiplatelet regimen; however, the HVAD patients were more likely to be on daily aspirin doses over 100 mg. In addition, parenteral bridging was more frequent with the HVAD device. While 43.8% of respondents indicated an increase in the perceived risk of HMII device thrombosis in 2014, intensification of anticoagulation (22%) or antiplatelet (11%) therapy was infrequent. Our findings verify the wide variety of anticoagulation practice patterns between MCS centers.

A post-approval (PA) study for destination therapy (DT) was required by the Food and Drug Administration (FDA) to determine whether results with the HeartMate (HM) II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) in a commercial setting were comparable to results during the DT multicenter pivotal clinical trial.New device technology developed in the clinical research setting requires validation in a real-world setting.The PA study was a prospective evaluation of the first 247 HM II patients identified pre-operatively as eligible for DT in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry. Patients were enrolled from January to September 2010 at 61 U.S. centers and followed for 2 years. A historical comparison group included patients (n = 133 at 34 centers) enrolled in the primary data cohort in the DT pivotal trial (TR). Survival rates and adverse events for the PA group were obtained from the INTERMACS registry.Baseline characteristics were similar for PA versus TR. Forty-five percent of PA patients were in INTERMACS profiles 1 to 2 and 28% were in profile 3. Adverse events in the PA group were similar or lower than those in the TR group, including improvements in device-related infection (0.22 vs. 0.47) and post-operative bleeding requiring surgery (0.09 vs. 0.23) events per patient-year. Kaplan-Meier survival at 2 years was 62% (PA group) versus 58% (TR group). PA group survival at 1 and 2 years was 82 ± 5% and 69 ± 6% for INTERMACS profiles 4 to 7 (n = 63) versus 72 ± 3% and 60 ± 4% for profiles 1 to 3 (n = 184). The median length of stay after surgery was reduced by 6 days in the PA group versus the TR group.Results in a commercial patient care setting for the DT population supported the original pivotal clinical trial findings regarding the efficacy and risk profile of the HM II LVAD. Survival was best in patients who were not inotrope-dependent (INTERMACS profiles 4 to 7).

This study investigated how the initial intended strategy at left ventricular assist device (LVAD) implantation influenced patient outcomes.Left ventricular assist device implantation strategy impacts candidate selection, reimbursement, and clinical trial design; however, concepts of device strategy are continuing to evolve.For patients entered in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) receiving a primary continuous flow LVAD between March 2006 and March 2011, initial strategies were bridge to transplant (BTT), bridge to candidacy (BTC) for transplant, and destination therapy (DT). Primary analyses compared BTT, BTC, and DT outcomes at 6, 12, and 24 months.Among 2,816 primary LVAD recipients, implant strategy was 1,060 (38%) BTT, 1,162 (42%) BTC (likely to be listed 796, moderately likely 282, unlikely 84), and 553 (20%) DT. Compared with BTC/DT, those listed at implant (BTT) had similar degrees of ventricular dysfunction and hemodynamic derangement but generally less comorbidity. Survival (alive with LVAD or transplanted) was superior at 24 months for BTT versus BTC versus DT (77.7% vs.70.1% vs. 60.7%, respectively, p0.0001). Strategic intent changed over time, at 2 years 43.5% of BTT patients were no longer listed for transplant, but 29.3% of BTC patients were listed for transplant.The currently accepted indications only account for 58% of LVAD implants. Across indications, patients differ by the number and types of comorbidities rather than the need for hemodynamic support. Regardless of initial implant strategy, patients often have long durations of support, and strategies often change over time, challenging the regulatory categorization of LVAD recipients as either BTT or DT.

Background Continuous flow (CF) left ventricular assist devices (LVAD) are afterload sensitive and therefore pump performance is affected by hypertension. In addition, poorly controlled hypertension may increase the risk of aortic insufficiency (AI) and stroke. Blood pressure regimens after CF LVAD have not been studied and their impact on rates of AI and stroke are unknown. Methods Patients who had CF LVAD at a single center and were supported greater than 30 days were included. Blood pressure was monitored at home by Doppler. Outpatient management of blood pressure was conducted according to a predefined institutional protocol (target mean arterial pressure ≤80 mm Hg). Results A total of 96 patients were included. At the end of follow-up, 25 patients were not on an antihypertensive drug, of these 9 died. Of the 74% receiving antihypertensives, 54% required 1 medication, 34% were on 2, 10% were on 3, and 3% were on 4 or more. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (85% of patients on an antihypertensive) and beta blockers (30%) were the most commonly prescribed medications. There was a significantly higher neurologic event rate in those on no antihypertensives compared with those on antihypertensives ( p = 0.009). Only 3% of patients with no or mild AI at baseline progressed to develop moderate or greater AI after a mean of 201 days of follow-up. Conclusions Blood pressure control can be achieved in patients with CF LVADs, with the majority of patients requiring only 1 or 2 antihypertensives.

Background— Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. Methods and Results— We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump ( P Conclusions— A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00751972.