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In June 2021, HVAD System distribution ceased due to observational data demonstrating increased mortality and neurological events compared to another commercial device, and a device malfunction with delay or failure to restart, especially in certain subpopulations. To assess ongoing risk for patients on support following subsequent device recalls, the manufacturer's Intermacs HVAD System 2022 Quarterly Reports were queried to identify mortality and adverse events trends in a contemporary cohort of 3110 primary HVAD implantations since October 2017, stratified by year-of-implant. Mean duration of support was 21 ± 16 months, with 33% alive on original device, 25% transplanted, 6% undergoing device exchange, 4% recovered, and 32% expired. Kaplan–Meier and event-per-patient-year estimates for survival, freedom from device explant, stroke, and pump thrombus were similar across year-of-implant. Following market withdrawal and recent device recalls, there appears to be no increase in mortality, stroke, pump thrombus, or explant for HVAD-supported patients. Quarterly report monitoring is ongoing. [ABSTRACT FROM AUTHOR]

Aims: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post‐heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non‐CHD patients before (Era‐1) and after (Era‐2) pediatric heart allocation policy implementation. Methods: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era‐1 and Era‐2. Results: 5551 patients were listed for HT, of whom 2447(44%) were in Era‐1 and 3104(56%) were in Era‐2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era‐2, whereas the number of non‐CHD patients listed as status 1A decreased, but status 1B increased. In Era‐2 compared to Era‐1, both temporary (1% to 4%, p <.001) and durable VAD (13.6% to 17.8%, p <.001) utilization increased, and the transplantation rate per 100‐patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p =.06), whereas for non‐CHD patients it decreased from 61 to 54 days (p <.001). Adjusted 90‐day WL survival increased from 84% to 88%, p =.016 in CHD, but there was no significant change in non‐CHD patients (p =.57). There was no significant difference in 1‐year post‐HT survival in CHD and non‐CHD patients between Era‐1 and Era‐2. Conclusions: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non‐CHD cohort, and 90‐day WL survival probability improved in children with CHD without significant change in 1‐year post‐HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post‐HT survival. [ABSTRACT FROM AUTHOR]

Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3. [ABSTRACT FROM AUTHOR]

The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices. (J Thorac Cardiovasc Surg 2022;-:1–8) [ABSTRACT FROM AUTHOR]

Inspired Therapeutics (Merritt Island, FL) is developing a mechanical circulatory support (MCS) system designed as a single driver with interchangeable, extracorporeal, magnetically levitated pumps. The NeoMate system design features an integrated centrifugal rotary pump, motor, and controller that will be housed in a single compact unit. Conceptually, the primary innovation of this technology will be the combination of disposable, low-cost pumps for use with a single, multi-functional, universal controller to support multiple pediatric cardiopulmonary indications. In response to the paucity of clinically available pediatric devices, Inspired Therapeutics is specifically targeting the underserved neonate and infant heart failure (HF) patient population first. In this article, we present the development of the prototype Inspired Therapeutics NeoMate System for pediatric left ventricular assist device (LVAD) support, and feasibility testing in static mock flow loops (H-Q curves), dynamic mock flow loops (hemodynamics), and in an acute healthy ovine model (hemodynamics and clinical applicability). The resultant hydrodynamic and hemodynamic data demonstrated the ability of this prototype pediatric LVAD and universal controller to function over a range of rotary pump speeds (500–6000 RPM), to provide pump flow rates of up to 2.6 L/min, and to volume unload the left ventricle in acute animals. Key engineering challenges observed and proposed solutions for the next design iteration are also presented. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the clinical characteristics, risk factors, and overall survival outcomes in adults with congenital heart disease (ACHD) bridged to transplantation with a ventricular assist device (VAD) versus no‐VAD. Methods: The study included 894 ACHD patients aged ≥18 years listed for primary heart transplantation between 2010 and 2019 from the United Network for Organ Sharing database. Primary outcomes were waitlist and 1‐year post‐transplant mortality between VAD and no‐VAD ACHD patients. Results: Of 894 ACHD patients included in the study, 91(10.1%) had VAD support at the time of listing. Patients who needed VAD support were mostly males, heavier, and had higher pulmonary artery pressure than the no‐VAD group at the listing. The overall waitlist mortality was 38% in the VAD group than 17% in the no‐VAD group (p < 0.01). ECMO use was associated with significantly higher mortality than either group. There was no significant difference in 1‐year post‐transplant mortality between VAD versus no‐VAD at the time of transplant (15% vs. 17%; p = 0.66). Multivariate regression analysis found that BMI <20 kg/m2 (hazard ratio (HR) 1.1; p = 0.01), bilirubin >2 mg/dl (HR 1.1; p = 0.03), creatinine >2 mg/dl (HR 1.3; p = 0.04) and ECMO at transplant (HR 1.4; p = 0.03) increased early post‐transplant mortality. Conclusions: The one‐year post‐transplant mortality rate was no different for ACHD patients that received VAD versus no‐VAD. These findings suggest that a VAD should be considered an option to support ACHD patients as a bridge to heart transplantation. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate annual heart transplant volumes and 3-year post-transplant outcomes since establishment of United Network for Organ Sharing (UNOS) database stratified by race. Methods: The UNOS thoracic transplant database was evaluated for adult patients since 1987. The available database was then stratified by Race: Black, White and Other and era of transplant: group 1(1987–1991), group 2(1992–1996), group 3(1997–2001), group 4(2002–2006), group 5(2007–2011), group 6(2012–2016) and group 7(2017 and later). Demographic and clinical factors were evaluated. Results: A total of 105,266 adults have been listed since 1987 and 67,824 have been transplanted. Of the transplanted patients 11,235 were Black, 48,786 White and 6803 were of Other race. The proportion of Black patients listed increased from 7% in 1987 to 13.4% in 1999 and 25% in 2019 and those transplanted increased from 5% in 1987 to 13.4% in 2001 and 26% in 2019. The survival of Black patients gradually improved. Conclusion: Historically, fewer Black patients received cardiac transplantation however, their access gradually improved over the years and account for over 25% of cardiac transplantations performed in recent years. The historically poor survival of Black patients has recently improved and became comparable to the rest. [ABSTRACT FROM AUTHOR]

Implantable cardioverter‐defibrillators (ICDs) have been shown to have survival advantage in advanced heart failure patients. Few studies have evaluated the role of ICDs in patients supported with continuous‐flow left ventricular assist devices (CFVADs). We aimed to evaluate the impact of ICD and CFVAD on heart transplant (HTx) waiting list survival. We queried the United Network for Organ Sharing (UNOS) thoracic transplant database between years 2007 and 2016 for patients aged ≥ 18 years listed for HTx. Patients receiving devices other than CFVAD were excluded. Patients were divided into groups—with and without CFVAD and further subdivided into groups—with and without ICD use. Kaplan‐Meier curves were used to evaluate the survival outcomes. There were 34 860 patients listed for HTx during study period of which 11 481 (32%) had a CFVAD and 26 139 (75%) had an ICD. Within CFVAD group, patients with ICD were older, more likely male, with higher creatinine and listed as UNOS status 1A. In the No‐CFVAD group, 1‐year waitlist survival was significantly better with ICD use (81% vs. 73%, P <.0001); however, in CFVAD patients, 1‐year survival with ICD use was comparable to No‐ICD use (95% vs. 94%, P =.1). Use of ICD is associated with significantly better heart transplant waitlist survival in patients not supported by CFVAD. In patients supported with CFVAD, the ICD does not offer additional survival benefit. [ABSTRACT FROM AUTHOR]

Aims: Continuous‐flow left ventricular assist devices (LVADs) as destination therapy (DT) are a recommended treatment by National Institute for Health and Care Excellence England for end‐stage heart failure patients ineligible for cardiac transplantation. Despite the fact that DT is frequently used as an LVAD indication across other major European countries and the United States, with consistent improvements in quality‐of‐life and longevity, National Health Service (NHS) England does not currently fund DT, mainly due to concerns over cost‐effectiveness. On the basis of the recently published ENDURANCE Supplemental Trial studying DT patients, we assessed for the first time the cost‐effectiveness of DT LVADs compared with medical management (MM) in the NHS England. Methods and results: We developed a Markov multiple‐state economic model using NHS cost data. LVAD survival and adverse event rates were derived from the ENDURANCE Supplemental Trial. MM survival was based on Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost‐effectiveness ratios (ICERs) were calculated over a lifetime horizon. A discount rate of 3.5% per year was applied to costs and benefits. Deterministic ICER was £46 207 per quality‐adjusted life year (QALY). Costs and utilities were £204 022 and 3.27 QALYs for the LVAD arm vs. £77 790 and 0.54 QALYs for the MM arm. Sensitivity analyses confirmed robustness of the primary analysis. Conclusions: The implantation of the HeartWare™ HVAD™ System in patients ineligible for cardiac transplantation as DT is a cost‐effective therapy in the NHS England healthcare system under the end‐of‐life willingness‐to‐pay threshold of £50 000/QALY, which applies for VAD patients. [ABSTRACT FROM AUTHOR]

Neutrophil to lymphocyte ratio (NLR) can predict mortality/complications in left ventricular assist device (LVAD) patients; however, the prognostic value of longitudinal NLR measurements has not been well studied. Here, we examine the mortality/complication incidence in patients with chronically increased NLR verses patients with acutely elevated NLR as a predictor of patient outcomes. This retrospective analysis included 102 patients who underwent LVAD implantation from 2016 to 2018 at a single center. The NLR was calculated at the time of surgery, and at 30 and 90 days after surgery. The NLR values were grouped into categorical data: low, normal (put in range), and high. Patients were classified in 2 groups based on change in their NLR values from surgery to 90 days; the H90 group had sustained increase of NLR over 90‐days and the N90 group had normalization of NLR at 90‐days. Actuarial survival the between study groups was measured using Kaplan–Meier curves. The N90 group had 50 patients (median age 58 (48–66) years, 21% female) at the time of LVAD placement. Group H90 had 52 patients (median age 64 (52–68) years, 16% female). Median age, body mass index (BMI), bilirubin, creatinine, and BNP at time of implant as well as type of device and implant strategy were comparable between the study groups. The post implant survival for N90 group was significantly better than the H90 group at 1 year (93% vs. 80%) and 2 years (90% vs. 67%) (log‐rank P =.001). Early post LVAD survival in patients with elevated NLR over 90 days postoperatively was significantly worse compared to patients who normalized the NLR at 90 days. [ABSTRACT FROM AUTHOR]

Background: While clinical experience with left ventricular assist devices (LVAD) continues to grow and evolve, little is known regarding the ongoing use of certain medications in this population. We sought to evaluate the utility of digoxin in LVAD recipients and its association with outcomes. Methods: A total of 505 patients who underwent continuous-flow LVAD implantation at 5 centers from 2007–2015 were included. Patients were divided into 4 groups: not on digoxin at any time (ND; n = 257), received digoxin pre implant (PreD; n = 144), received digoxin pre and post implant (ContD; n = 55), and received digoxin only post implant (PostD; n = 49). Survival and all-cause readmission were compared between the 4 groups. Results: There was no difference in survival at 1 year nor at 3 years between groups (ND = 88%, 66%, respectively; PreD = 85%, 66%; ContD = 86%, 57%; PostD = 90%, 51%; p = 0.7). Readmission per 100 days also was not different between groups (ND = 0.5, PreD = 0.6, ContD = 0.5, PostD = 0.7; p = 0.1). Conclusions: In this large, multicenter cohort, use of digoxin was not associated with any significant benefit in regard to mortality or hospitalization in patients supported with a continuous-flow LVAD. Importantly, its discontinuation post implant did not worsen all-cause hospitalization or survival. [ABSTRACT FROM AUTHOR]

Modulation of pump speed has been proposed and implemented clinically to improve vascular pulsatility in continuous flow ventricular assist device patient. The flow dynamics of the HVAD with a promising asynchronous pump speed modulation and its potential risk for device-induced blood trauma was investigated numerically. The boundary conditions at the pump inlet and outlet were defined using the pressure waveforms adapted from the experimentally recorded ventricular and arterial pressure waveforms in a large animal ischemic heart failure (IHF) model supported by the HVAD operated at constant and modulated pump speeds. Shear stress fields and hemolysis indices were derived from the simulated flow fields. The overall features of the computationally generated flow waveforms at simulated constant and pulse-modulated speed operations matched with those of the experimentally recorded flow waveforms. The simulations showed that the shear stress field and hemolysis index vary throughout the cardiac cycle under the constant speed operation, and also as a function of modulation profile under modulated speed operation. The computational model did not demonstrate any differences in the time average hemolysis index between constant and modulated pump speed operations, thereby predicting pulse-modulated speed operation may help to restore vascular pulsatility without any further increased risk of blood trauma. Graphical abstract The streamline inside the HVAD pump and the wall shear stress distribution on the impeller surface at six discrete time instants over one cardiac cycle under constant speed operation (3000 rpm) (a) and under pulse-modulated speed operation (b). c Computationally predicted flow rate waveform under pulse-modulated speed operation. d Computationally predicted time-varying HI generated by the HVAD pump under the two operation modes constant speed (dash line) and pulse-modulated speed (solid line). These figures indicate that the pulse-modulated speed operation may help to restore vascular pulsatility without any further increased risk of blood trauma. [ABSTRACT FROM AUTHOR]

Abstract: In this study, the flow features and device‐associated blood trauma in 4 clinical ventricular assist devices (VADs; 2 implantable axial VADs, 1 implantable centrifugal VAD, and 1 extracorporeal VAD) were computationally analyzed under clinically relevant pulsatile flow conditions. The 4 VADs were operated at fixed pump speed at a mean rate of 4.5 L/min. Mean pressure difference, wall shear stress, volume distribution of scalar shear stress (SSS), and shear‐induced hemolysis index (HI) were derived from the flow field of each VAD and were compared. The computationally predicted mean pressure difference across the 3 implantable VADs was ~70 mmHg, and the extracorporeal VAD was ~345 mmHg, which matched well with their reported pressure‐flow curves. The axial VADs had higher mean wall shear stress and SSS compared with the centrifugal VADs. However, the residence time of the centrifugal VADs was much longer compared with the axial VADs because of the large volume of the centrifugal VADs. The highest SSS was observed in one axial VAD, and the longest exposure time was observed in 1 centrifugal VAD. These 2 VADs generated the highest HI. The shear‐induced HI varied as a function of flow rate within each cardiac cycle. At fixed pump speed, the HI was greatest at low flow rate due to longer exposure time to shear stress compared with at high flow rate. Subsequently, we hypothesize that to reduce the risk of blood trauma during VAD support, shear stress magnitude and exposure time need to be minimized. [ABSTRACT FROM AUTHOR]

The role of oxidative stress and leukocyte activation has not been elucidated in developing systemic inflammatory response syndrome ( SIRS) in heart failure ( HF) patients after continuous-flow left ventricular assist device ( CF-LVAD) implantation. The objective of this study was to investigate the change of plasma redox status and leukocyte activation in CF-LVAD implanted HF patients with or without SIRS. We recruited 31 CF-LVAD implanted HF patients (16 SIRS and 15 non- SIRS) and 11 healthy volunteers as the control. Pre- and postimplant blood samples were collected from the HF patients. Plasma levels of oxidized low-density lipoprotein ( oxLDL), malondialdehyde ( MDA), total antioxidant capacity ( TAC), superoxide dismutase ( SOD) in erythrocyte, myeloperoxidase ( MPO), and polymorphonuclear elastase ( PMN-elastase) were measured. The HF patients had a preexisting condition of oxidative stress than healthy controls as evident from the higher oxLDL and MDA levels as well as depleted SOD and TAC. Leukocyte activation in terms of higher plasma MPO and PMN-elastase was also prominent in HF patients than controls. Persistent oxidative stress and reduced antioxidant status were found to be more belligerent in HF patients with SIRS after the implantation of CF-LVAD when compared with non- SIRS patients. Similar to oxidative stress, the activation of blood leukocyte was significantly highlighted in SIRS patients after implantation compared with non- SIRS. We identified that the plasma redox status and leukocyte activation became more prominent in CF-LVAD implanted HF patients who developed SIRS. Our findings suggest that plasma biomarkers of oxidative stress and leukocyte activation may be associated with the development of SIRS after CF-LVAD implant surgery. [ABSTRACT FROM AUTHOR]

Background There is a paucity of data on the use of induction immunosuppression in patients with active infections undergoing orthotopic heart transplantation (OHT). We hypothesized that induction immunosuppression in patients with ventricular assist device (VAD) undergoing OHT with localized active driveline infection (DLI) does not lead to worse outcomes. Materials and Methods We retrospectively analyzed our database for bridge-totransplant VAD patients who underwent OHT and received induction therapy. Patients were stratified into those with and without active DLI at the time of OHT and followed up till death or at least 30 months after OHT. Posttransplant length of stay (LOS), frequency of infections, and mortality were compared between the two groups. Results Thirty-eight patients (30 males) with mean age of 57.5 ± 13 years with VAD underwent OHT during the study period. Twelve had active DLI. Mean follow-up was 46.4 ± 23.1 months. In the DLI versus non-DLI group, there was no difference in mortality (17 vs. 23%, p = NS), LOS (16.3 ± 5.4 vs. 17.2 ± 13.7, p = NS), postoperative renal function, incidence of hyperacute or late rejection or infection either in the first month (25 vs. 23%, p = NS) or during entire follow-up (92 vs. 88%, p = NS). No patient in the DLI group had infections attributable to the same organism responsible for pretransplant DLI. Conclusion In patients with active DLI, induction immunosuppression after OHT did not increase LOS, infections, or mortality after at least 30 months of follow-up and therefore it appears to be a safe and feasible therapeutic option. [ABSTRACT FROM AUTHOR]

Background Although atrial arrhythmias (AAs) are common in heart failure, the incidence of AAs subsequent to the placement of left ventricular assist devices (LVADs) has not been elucidated. Methods Patients receiving a HeartMate II LVAD in the bridge to transplant (n = 490) and destination therapy (n = 634) trials were included (n = 1125). AAs requiring treatment were recorded, regardless of symptoms. Using Cox models with and without a 60-day blanking period, risk factors for early and late AAs were determined. Results In total, there were 271 AAs in 231 patients (21%), most of which occurred within the first 60 days. Patients with and without AAs had similar survival (p = 0.16). Serum creatinine (hazard ratio [HR] = 1.49 per unit increase, 1.18 to 1.88; p < 0.001) and ejection fraction (HR = 0.98 per 1% increase, 0.95 to 0.999; p = 0.04) were associated with AAs in a multivariable model. Although quality of life (QoL) and functional status improved in all patients, those with AAs had worse unadjusted QoL (p < 0.001) and a decreased rate of improvement in six-minute walk distance over six to 24 months postimplant (p = 0.016). Conclusions Approximately one-fifth of LVAD patients have AAs, most commonly within the first 60 days of support. Preoperative creatinine is a strong risk factor for early and late AAs. Although AAs do not impact survival, they are associated with decreased functional status and QoL improvements during LVAD support. doi: 10.1111/jocs.12336 (J Card Surg 2014;29:572-580) [ABSTRACT FROM AUTHOR]

Background: The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) is the first implantable centrifugal continuous-flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study, we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies, and examine factors pre-disposing to the development of pump thrombus. Methods: The analysis included 382 patients who underwent implantation of the HVAD as part of the HeartWare Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) trial. Descriptive statistics and group comparisons were generated to analyze baseline characteristics, incidence of pump thrombus, and treatment outcomes. A multivariate analysis was performed to assess significant risk factors for developing pump thrombus. Results: There were 34 pump thrombus events observed in 31 patients (8.1% of the cohort) for a rate of 0.08 events per patient-year. The incidence of pump thrombus did not differ between BTT and CAP. Medical management of pump thrombus was attempted in 30 cases, and was successful in 15 (50%). A total of 16 patients underwent pump exchange, and 2 underwent urgent transplantation. Five patients with a pump thrombus died after medical therapy failed, 4 of whom also underwent a pump exchange. Survival at 1 year in patients with and without a pump thrombus was 69.4% and 85.5%, respectively (p = 0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure > 90 mm Hg, aspirin dose ≤ 81 mg, international normalized ratio ≤ 2, and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile level of ≥ 3 at implant. Conclusions: Pump thrombus is a clinically important adverse event in patients receiving an HVAD, occurring at a rate of 0.08 events per patient-year. Significant risk factors for pump thrombosis include elevated blood pressure and sub-optimal anti-coagulation and anti-platelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines. [Copyright &y& Elsevier]

Ventricular assist devices ( VADs) have emerged as a successful treatment option for advanced heart failure. The objective of this study was to develop a clinically relevant model of chronic ischemic cardiomyopathy to investigate functional, histological, and molecular changes during mechanical circulatory support. In calves ( n = 17, 94 ± 7 kg), 90 μm microspheres were injected percutaneously into the left coronary artery. Serial echocardiography was performed weekly to evaluate cardiac function. Sixty days after coronary microembolization, a terminal study was performed via thoracotomy to measure hemodynamics. Regional myocardial and end-organ blood flows were quantified with 15-μm fluorescent-labeled microspheres. Myocardial fibrosis, myocyte size, and myocardial apoptosis were quantified with histological stains. Eleven animals survived coronary microembolization and exhibited clinical and statistically significant echocardiographic and hemodynamic signs of severe systolic dysfunction. Statistically significant decreases in regional myocardial blood flow and increases in myocardial fibrosis, myocyte size, total myocardial apoptosis, and cardiac myocyte-specific apoptosis were observed. End-organ hypoperfusion was observed. Coronary microembolization induced stable and reproducible chronic left ventricular failure in calves. The anatomical size and physiology of the bovine heart and thorax are appropriate to study novel interventions for the clinical management of heart failure. This model is an appropriate physiological substrate in which to test VAD and adjunctive biological therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mechanical circulatory assist devices that provide temporary support in heart failure patients are needed to enable recovery or provide a bridge to decision. Minimizing risk of blood damage (i.e., hemolysis) with these devices is critical, especially if the length of support needs to be extended. Hematologic responses of the RotaFlow (Maquet) and CentriMag (Thoratec) temporary support devices were characterized in an in vitro feasibility study. Paired static mock flow loops primed with fresh bovine blood (700 mL, hematocrit [Hct] = 25 ± 3%, heparin titrated for activated clotting time >300 s) pooled from a single-source donor were used to test hematologic responses to RotaFlow ( n = 2) and CentriMag ( n = 2) simultaneously. Pump differential pressures, temperature, and flow were maintained at 250 ± 10 mm Hg, 25 ± 2°C, and 4.2 ± 0.25 L/min, respectively. Blood samples (3 mL) were collected at 0, 60, 120, 180, 240, 300, and 360 min after starting pumps in accordance with recommended Food and Drug Administration and American Society for Testing and Materials guidelines. The CentriMag operated at a higher average pump speed (3425 rpm) than the RotaFlow (3000 rpm) while maintaining similar constant flow rates (4.2 L/min). Hematologic indicators of blood trauma (hemoglobin, Hct, platelet count, plasma free hemoglobin, and white blood cell) for all measured time points as well as normalized and modified indices of hemolysis were similar (RotaFlow: normalized index of hemolysis [NIH] = 0.021 ± 0.003 g/100 L, modified index of hemolysis [MIH] = 3.28 ± 0.52 mg/mg compared to CentriMag: NIH = 0.041 ± 0.010 g/100 L, MIH = 6.08 ± 1.45 mg/mg). In this feasibility study, the blood trauma performance of the RotaFlow was similar or better than the CentriMag device under clinically equivalent, worst-case test conditions. The RotaFlow device may be a more cost-effective alternative to the CentriMag. [ABSTRACT FROM AUTHOR]

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<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. 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. [ABSTRACT FROM AUTHOR]

The article investigates comparison of outcomes in advanced heart failure (AHF) patients with continuous-flow left ventricular assist devices (LVAD) like HeartMate II (HMII) destination therapy (DT) with outcomes in patients implanted with pulsatile-flow HeartMate XVE. It is reported that LVAD is an accepted treatment for medically refractory AHF, non-transplant eligible patients. Results confirmed DT therapy benefits of HMII in subsequent trial patients with strong survival improvement trend.

The article discusses an assessment study on cost effectiveness of continuous-flow left ventricular assist devices (LVAD) for destination therapy against optimal medical management in advanced heart failure by comparing results with previous estimates for pulsatile devices. Baseline results showed significant improvement of continuous-flow LVADs compared with pulsatile devices. The study showed total LVAD costs were at 391,906 dollars, total QALY at 0.76 and ICER at 802,674 dollars in 2002.

Background: Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure. Methods: HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated. Results: The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5–6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0–30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs. Conclusions: We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis. [ABSTRACT FROM AUTHOR]

Background: Patients listed for heart transplant have a prolonged wait time, with continued deterioration, poor quality of life, and 10% mortality. Although recent bridge to transplant (BTT) studies demonstrated 1-year survival similar to heart transplantation, doubt remains about overall effectiveness as a treatment strategy compared with waiting and implanting a left ventricular device (LVAD) only as a last resort. We evaluated 1-year outcome and effectiveness of LVAD vs heart transplantation. Methods: Patients on the heart transplantation list, either receiving an allograft or LVAD for BTT from January 2009 to December 2009 were evaluated. Of 43 patients treated, 1 received both LVAD and an allograft during same admission was removed from the analysis. All patients but one who received an allograft had prior LVAD. Descriptive and univariate (t test) statistics and Kaplan-Meier survival curve were used for analyses. Results: LVAD for BTT was used in 29 patients (51.4 ± 12.8 years, 6.9% women), and 13 (51.1 ± 11.6 years, 15.38% women) underwent heart transplantation. Initial hospital length of stay was 17.5 ± 14.4 days in BTT group and 14.3 ± 4.6 days in heart transplant group (p = 0.44) At 1 year, the total number of days spent in the hospital (operation and related complications), including index hospitalization was 11.6 ± 14.3 days/100 days in BTT and 7.9 ± 9.0 days/100 days in heart transplantation (p = 0.38). A total of 41% BTT and 46% heart transplant patients had one readmission within 3 months of the index hospitalization. Infection was the most common cause of readmission in both groups. The 1-year survival was similar for both groups (no hospital death in either group; 3 late deaths in the BTT group). Conclusions: One-year outcomes for patients eligible for heart transplantation were similar whether they received an allograft or LVAD for BTT. Heart transplant outcome for patients with LVAD were not adversely affected. Improving outcomes for patients treated with LVAD suggest that current decision models for patients eligible for heart transplantation may need to be reevaluated. [Copyright &y& Elsevier]

The article presents information on a study which analyzed outpatients on chronic support with the HeartMate II assist device and investigated the hemostatic abnormalities and clinical effects for this patient cohort. A review of the related literature on left ventricular assist devices (LVAD) is offered. It describes the design, setting and population of the study, including blood collection and laboratory assays, anticoagulation regimen and screening for bleeding events. A discussion on the findings of the study is detailed.

Left ventricular assist devices (LVADs) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients, whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to the discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective on the practical and technical issues surrounding LVAD deactivation. [ABSTRACT FROM AUTHOR]

The article focuses on physician O.H. Frazier who recently implanted his 1,000th ventricular assist device on a patient with advanced heart failure. It is stated that it is only a small part of Frazier's contributions to the development of mechanical circulatory support (MCS) as a treatment for advanced heart failure although this is monumental and worthy of recognition.

Background--Cardiac valve procedures are commonly performed concurrently during implantation of left ventricular assist devices, but the added procedural risk has not been studied in detail. Methods and Results--Data from patients receiving the HeartWare Ventricular Assist Device in the ADVANCE bridge to transplant (BTT) trial and continued access protocol were reviewed. Of 382 consecutive patients who completed follow-up between August 2008 and June 2013 (mean time on support 389 days, median 271 days), 262 (68.6%) underwent isolated HeartWare Ventricular Assist Device implantation, 75 (19.6%) a concurrent valve procedure, and 45 (11.8%) concurrent nonvalvular procedures. Of the concurrent valve procedures, 56 were tricuspid, 13 aortic, and 6 mitral. Survival was similar between groups (79% for concurrent valve procedures and 85% for HeartWare Ventricular Assist Device only at 1 year; P=0.33). Concurrent valve procedures were also associated with increased unadjusted early right heart failure (RHF). A multivariable analysis for death and RHF (121 total events) identified female sex (odds ratio=2.0 [95% confidence interval, 1.2-3.3; P=0.0053]) and preimplant tricuspid regurgitation severity (odds ratio=2.9 [95% confidence interval, 1.8-4.8, P<0.0001]) as independent predictors while concurrent tricuspid valve procedures (TVP) were not predictors. Furthermore, patients with significant preimplant tricuspid regurgitation who did not receive a TVP experienced an increased rate of late RHF compared with those who received TVP (0.19 versus 0.05 events per patient-year, respectively; P=0.024). Conclusions--Compared with HeartWare Ventricular Assist Device alone, survival was equivalent for the concurrent valve procedure group. Tricuspid regurgitation severity was the most important predictor of increased postoperative RHF, and concurrent TVP was not an independent predictor of RHF overall. Concurrent TVP may reduce the rate of late RHF for patients with significant preimplant tricuspid insufficiency. [ABSTRACT FROM AUTHOR]

Background: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation.Methods: Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months.Results: Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant left ventricular ejection fraction, 57±8%; end-diastolic diameter, 4.81±0.58 cm; end-systolic diameter, 3.53±0.51 cm; pulmonary capillary wedge pressure, 8.1±3.1 mm Hg; pulmonary artery saturations 63.6±6.8% at 6000 rpm). Overall, 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The 15 ongoing explanted patients are now 2.26±0.97 years after explant. After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years.Conclusions: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01774656. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure with reduced ejection fraction. Although these devices effectively improve survival, atrial and ventricular arrhythmias are common, predispose these patients to additional risk, and complicate patient management. However, there is no consensus on best practices for the medical management of these arrhythmias or on the optimal timing for procedural interventions in patients with refractory arrhythmias. Although the vast majority of these patients have preexisting cardiovascular implantable electronic devices or cardiac resynchronization therapy, given the natural history of heart failure, it is common practice to maintain cardiovascular implantable electronic device detection and therapies after LVAD implantation. Available data, however, are conflicting on the efficacy of and optimal device programming after LVAD implantation. Therefore, the primary objective of this scientific statement is to review the available evidence and to provide guidance on the management of atrial and ventricular arrhythmias in this unique patient population, as well as procedural interventions and cardiovascular implantable electronic device and cardiac resynchronization therapy programming strategies, on the basis of a comprehensive literature review by electrophysiologists, heart failure cardiologists, cardiac surgeons, and cardiovascular nurse specialists with expertise in managing these patients. The structure and design of commercially available LVADs are briefly reviewed, as well as clinical indications for device implantation. The relevant physiological effects of long-term exposure to continuous-flow circulatory support are highlighted, as well as the mechanisms and clinical significance of arrhythmias in the setting of LVAD support. [ABSTRACT FROM AUTHOR]

Introduction Oxidative stress and platelet integrin α2bβ3 plays important role in the process of hemostasis and thrombosis. We hypothesized that device-induced patient specific oxidative stress and integrin α2bβ3 shedding may be linked to major bleeding complication (MBC) in heart failure (HF) patients supported by continuous flow left ventricular assist devices (CF-LVADs). Materials and methods We recruited 47patients implanted with CF-LVADs and 15 healthy volunteers. Fourteen patients developed MBC (bleeder group) within one month after implantation while others were considered non-bleeder group (n = 33). Oxidative stresses were evaluated by measuring reactive oxygen species (ROS) in platelets, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) and oxidized low density lipoprotein (oxLDL). Assessments of α2bβ3 were carried out using flow cytometry and ELISA. Results Biomarkers of oxidative stress and α2bβ3 shedding (decreased surface expression and higher plasma levels) were found to be preexisting condition in all HF patients prior to CF-LVAD implantation compared to the healthy volunteers. Significantly elevated levels of ROS and oxLDL; concomitant depletion of SOD and TAC; and α2bβ3 shedding were observed in the bleeder group temporarily in comparison to the non-bleeder group after CF-LVAD implantation. A significantly strong association between α2bβ3 shedding and biomarkers of oxidative stress was observed; suggesting a potential role of oxidative stress in platelet integrin shedding leading to MBC after CF-LVAD implantation. Moreover, a receiver operating characteristic (ROC) analysis indicated that the likelihood of MBC data from Integrin α2bβ3 shedding had a predictive power of MBC in CF-LVAD patients. Conclusions Oxidative stress might play a potential role in accelerating α2bβ3 shedding and platelet dysfunction, resulting in MBC in CF-LVAD patients. Integrin α2bβ3 shedding may be used to refine bleeding risk stratification in CF-LVAD patients. [ABSTRACT FROM AUTHOR]

Background: Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation.Methods: We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal-flow) device or the control (axial-flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points.Results: The intention-to treat-population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups.Conclusions: In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .). [ABSTRACT FROM AUTHOR]

Background Pump thrombosis in durable continuous-flow pumps is a barrier to long-term mechanical circulatory support. Earlier Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data identified an increasing risk of pump thrombosis in recent years with the HeartMate II (HMII) left ventricular assist device. The current analysis examines pump thrombosis in the patient cohort extended through June 2014. Methods The INTERMACS identified 9,808 adult patients from 144 institutions receiving a primary HMII implant between April 2008 and June 30, 2014. Pump thrombosis was identified at time of explant, transplant or death. Risk factors for pump thrombosis were examined by multivariable analysis in the hazard function domain. The association between pump thrombosis and implant year was modeled in the hazard domain. Results Parametric hazard modeling of thrombosis by year of implant identified an increasing risk of pump thrombosis from 2009 through 2013, followed by a decrease in the risk during the first half of 2014 , which was most apparent during the first 3 months post-implant. Risk factors for pump thrombosis included younger age ( p < 0.001), higher body mass index ( p = 0.02), history of non-compliance ( p = 0.004), severe right heart failure ( p = 0.02), later date of implant ( p < 0.0001), and elevated lactate dehydrogenase during the first month post-implant ( p < 0.0001). Subsequent pump thrombosis was more likely if the initial pump exchange indication was pump thrombosis ( p < 0.0001). Conclusions The small, but progressive increase in the incidence of pump thrombosis observed between 2010 and 2013 with the HMII pump had reversed somewhat in the first half of 2014. Identification of marked elevation of lactate dehydrogenase during the first month offers an opportunity for early intervention strategies. [ABSTRACT FROM AUTHOR]

background The Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) Bridge to Transplant (BTT) trial was a multicenter, prospective trial of the HeartWare Ventricular Assist Device (HVAD). The performance of the HVAD in various demographic sub-groups was evaluated. Methods Baseline characteristics, adverse events, and survival were compared for men vs women and whites vs non-whites in the combined ADVANCE BTT and continued access protocol trial. Of 332 patients enrolled in these trials, 236 were men and 96 women, with 228 whites and 104 non-whites. Results At baseline, women had a smaller body surface area (1.8 ± 0.2 vs 2.1 ± 0.3 m 2 , p < 0.0001), less hypertension (50.0% vs 61.9%, p = 0.05), and less ischemic cardiomyopathy (15.6% vs 45.3%, p < 0.0001). Differences in Kaplan-Meier survival were not significant at 180 days (men, 91.8%; women, 91.7%) and 1 year (men, 85.3%; women, 85.1%) despite adjustment for baseline differences. Men had a lower incidence of early right heart failure and renal and respiratory dysfunction, and a shorter length of stay. In the analysis by race, non-whites were younger than whites and had less ischemic heart failure, more hypertension, and lower creatinine levels at baseline. Non-whites had lower rates of arrhythmia, bleeding requiring rehospitalization, and device malfunctions than whites. Survival was high in non-whites and whites, at 94.1% vs 90.4% at 180 days and 89.2% vs 82.8% at 1 year, respectively, despite adjustment for baseline differences. Conclusions Although heart failure etiology differed between men and women and between whites and non-whites, sex and race were not factors that affected survival in patients receiving the HVAD as BTT, which was high in all sub-groups. [ABSTRACT FROM AUTHOR]

Background Drive-line infections and sepsis lead to significant morbidity and even mortality in patients with ventricular assist devices (VADs). The HeartWare HVAD system is unique compared with other VAD systems in that it has a thin, flexible drive-line and is implanted directly into the pericardial space without the need for a pump pocket. We reviewed 332 patients receiving the HVAD in the pivotal ADVANCE Bridge to Transplant (BTT) trial and Continued Access Protocol (CAP) to determine the incidence of drive-line infections and sepsis. Methods Summary statistics of outcomes and Kaplan–Meier freedom-from-event analyses were performed. The Cochran–Mantel–Haenszel test for homogeneity was used to determine whether there was any site effect on rates of either drive-line exit-site or sepsis infections. Results Drive-line exit-site infections occurred in 16.9% (56 of 332) of patients (0.25 event per patient-year [EPPY]). These infections were primarily treated with antibiotics and most occurred >30 days post-implant (88%, or 66 of 75 drive-line infections). Sepsis occurred in 17.2% (57 of 332) of patients (0.23 EPPY), and sepsis events occurred more frequently >30 days post-implant (86%, or 60 of 70 sepsis events). Of patients with sepsis, 17.5% (10 of 57) died due to sepsis-related neurologic events (7 of 10) and multisystem organ failure (2 of 10) and cardiopulmonary failure (1 of 10), whereas there were no deaths related to drive-line infections. In addition, 17.5% (10 of 57) of patients had a stroke event while under treatment for sepsis (7 hemorrhagic and 3 ischemic strokes), and 3.5% (2 of 57 patients with sepsis) had a device exchange for VAD thrombus (4 days before and 1 day after sepsis diagnosis). Patients with drive-line infections or sepsis had a larger body mass index compared to those without infection (29.4 vs 27.6 kg/m 2 , p = 0.015), and were more frequently diabetic (43.7% vs 31.2%, p = 0.034). Although there was no negative impact on survival in patients with drive-line exit-site infections, there was a trend for reduced survival in patients with sepsis events when compared to those patients without sepsis. Conclusions The incidence of drive-line infection and sepsis was low in patients receiving the HVAD pump. Despite a trend toward reduced survival in patients with sepsis events, the overall survival of patients with either drive-line infections or sepsis was excellent. [ABSTRACT FROM AUTHOR]

Continuous-flow ventricular assist devices (CVADs) have gained widespread use as an effective clinical therapy for patients with advanced-stage heart failure. Axial and centrifugal CVADs have been successfully used as bridge-to-transplant and destination therapy. CVADs are smaller, more reliable, and less complex than the first-generation pulsatile-flow ventricular assist devices. Despite their recent clinical success, arteriovenous malformations, gastrointestinal bleeding, hemorrhagic strokes, aortic valve insufficiency, and valve fusion have been reported in heart failure patients supported by CVADs. It has been hypothesized that diminished arterial pressure and flow pulsatility delivered by CVAD may be a contributing factor to these adverse events. Subsequently, the clinical significance of vascular pulsatility continues to be highly debated. Studies comparing pulsatile-flow and continuous-flow support have presented conflicting findings, largely due to variations in device operation, support duration, and the criteria used to quantify pulsatility. Traditional measurements of pulse pressure and pulsatility index are less effective at quantifying pulsatility for mechanically derived flows, particularly with the growing trend of CVAD speed modulation to achieve various pulsatile flow patterns. Kinetic measurements of energy equivalent pressure and surplus hemodynamic energy can better quantify pulsatile energies, yet technologic and conceptual challenges are impeding their clinical adaption. A review of methods for quantifying vascular pulsatility and their application as a research tool for investigating physiologic responses to CVAD support are presented. [ABSTRACT FROM AUTHOR]

The authors discuss a study which has identified that infections from heart assist devices can complicate patient placement in the U.S. They state that Staphylococcus has been suffered by 47% of patients. The authors note that infection has been predicted by a history of mental depression and elevated baseline serum creatinine.

Objectives: The aim of this study was to derive and validate a model to predict survival in candidates for HeartMate II (HMII) (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) support. Background: LVAD mortality risk prediction is important for candidate selection and communicating expectations to patients and clinicians. With the evolution of LVAD support, prior risk prediction models have become less valid. Methods: Patients enrolled into the HMII bridge to transplantation and destination therapy trials (N = 1,122) were randomly divided into derivation (DC) (n = 583) and validation cohorts (VC) (n = 539). Pre-operative candidate predictors of 90-day mortality were examined in the DC with logistic regression, from which the HMII Risk Score (HMRS) was derived. The HMRS was then applied to the VC. Results: There were 149 (13%) deaths within 90 days. In the DC, mortality (n = 80) was higher in older patients (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1 to 1.7 per 10 years), those with greater hypoalbuminemia (OR: 0.49, 95% CI: 0.31 to 0.76 per mg/dl of albumin), renal dysfunction (OR: 2.1, 95% CI: 1.4 to 3.2 per mg/dl creatinine), coagulopathy (OR: 3.1, 95% CI: 1.7 to 5.8 per international normalized ratio unit), and in those receiving LVAD support at less experienced centers (OR: 2.2, 95% CI: 1.2 to 4.4 for <15 trial patients). Mortality in the DC low, medium, and high HMRS groups was 4%, 16%, and 29%, respectively (p < 0.001). In the VC, corresponding mortality was 8%, 11%, and 25%, respectively (p < 0.001). HMRS discrimination was good (area under the receiver-operating characteristic curve: 0.71, 95% CI: 0.66 to 0.75). Conclusions: The HMRS might be useful for mortality risk stratification in HMII candidates and may serve as an additional tool in the patient selection process. [ABSTRACT FROM AUTHOR]

Background: Patterns of weight change after implantation of a continuous-flow left ventricular assist device (CF-LVAD) can affect transplant candidacy and may influence outcomes. We evaluated changes in weight over a 24-month period from a national LVAD clinical trial database. Methods: A retrospective analysis was performed of 896 patients enrolled into the HeartMate II Clinical trials for bridge-to-transplant and destination therapy from March 2005 to January 2009. The patients were divided into 4 groups: underweight (body mass index [BMI] <18.5 [kg/m2]); normal (BMI 18.5 to 29.9); obese (BMI 30 to 34.9); and extremely obese (BMI≥35). Baseline BMI was compared with BMI at 6 months and 24 months after implant. BMI change >10% of baseline was considered clinically significant. Results: At 6 months, underweight and normal-weight patients had significant increases in BMI, with effects sustained up to 24 months (p < 0.01). Underweight patients gained weight most often, with 75% showing clinically meaningful weight gain at 24 months. Obese and extremely obese patients, in contrast, did not experience weight change over the same period. Pre-albumin levels improved from baseline to 6 months in all patients. Conclusions: Underweight and normal-weight patients had an increase in BMI after LVAD implantation, and these changes persisted through 24 months. The BMIs of obese and extremely obese patients remained unchanged. Nutritional status improved in all groups. [ABSTRACT FROM AUTHOR]

Background: Extremes of body mass index (BMI) are often considered contraindications to use of a left ventricular assist device (LVAD), but data regarding outcomes across the spectrum of BMI are limited. We sought to assess the association of BMI with survival and major morbidity after continuous-flow (CF) LVAD implantation. Methods: Patients (n = 896) enrolled in the HeartMate II LVAD bridge-to-transplantation and destination therapy trials were divided into 4 BMI groups: underweight (<18.5 kg/m2); normal (18.5 kg/m2 ≤ BMI < 30 kg/m2); obese (30 kg/m2 ≤ BMI < 35 kg/m2); and extremely obese (≥35 kg/m2). The association of BMI with survival was tested using Kaplan–Meier analysis and proportional hazards regression. Major adverse events were compared using Poisson''s regression and chi-square tests. Results: At implantation, 48 (5%) patients were underweight, 596 (67%) normal weight, 164 (18%) obese and 88 (10%) extremely obese. BMI extremes were associated with differences in creatinine, albumin, age, central venous pressure and etiology. BMI was not associated with survival in the univariate analysis (p = 0.83) or in adjusted models (extremely obese: hazard ratio [HR] 1.29, p = 0.231; obese: HR 0.94, p = 0.723; underweight: HR 1.23, p = 0.452). Underweight patients were more likely to have bleeding events (p < 0.001), whereas extremely obese patients had higher rates of device-related infection (p = 0.041) and rehospitalization (p = 0.014). Conclusions: Overall survival in patients receiving CF LVAD is similar across BMI categories. Carefully selected patients at both extremes of BMI have good mid-term survival after LVAD and should be considered for LVAD implantation relative to overall risk profile. [ABSTRACT FROM AUTHOR]

Introduction: Sustained ventricular arrhythmias (VA) are common in heart failure patients receiving continuous flow left ventricular assist devices (LVAD). Available studies evaluating the impact of VA on clinical outcomes in LVAD recipients have been single center and limited by small sample size Hypothesis: We report the first multicenter study to assess the incidence, predictors, and outcomes associated with VA in LVAD patients Methods: Analysis was performed on 408 patients who underwent LVAD implantation at 5 centers from 2007-2015. VA was defined as sustained ventricular tachyarrhythmias lasting >30 sec or requiring ICD therapy. Effects of pre- and post-LVAD VA on survival was assessed using Kaplan-Meier analysis. Results: Of 408 LVAD patients (Age 60 years), 254 (62%) had pre-LVAD VA (PreVA) and 154 (38%) did not (No-PreVA). At baseline, the PreVA group had greater male sex (85 vs 75%, p=0.02), amiodarone use (44 vs 31%, p=0.01), LV diastolic dimensions (7.1 vs 6.8 cm, p=0.01) and atrial arrhythmias (AA) (57 vs 45%, p=0.03). Compared to the No-PreVA group, the PreVA group had significantly higher incidence of post-LVAD VA (73 vs 37%, p< 0.0001), AA (63 vs 42%, P<0.0001), and ICD shocks (42 vs 32%, p=0.001) but similar rates of hospitalization (0.5 vs 0.5/100 days, p=0.7). During a median follow-up of 478 days, 35% of patients died in both groups. Kaplan-Meier analysis showed no difference in survival between the groups (Log Rank p=0.1: Fig 1). Those who had both pre- and post-LVAD VA had similar survival as patients without any VA (Log rank p=0.1). Conclusions: In this large, multicenter LVAD cohort, PreVA was associated with a significantly higher incidence of post-LVAD VA and ICD shocks. PreVA was not significantly associated with survival or all-cause hospitalizations. [ABSTRACT FROM AUTHOR]

Context: Ventricular assist devices (VADs) improve quality of life in advanced heart failure patients, but there are little data exploring psychological symptoms in this population.Objective: This study examined the prevalence of psychiatric symptoms and disease over time in VAD patients.Methods: This prospective multicenter cohort study enrolled patients immediately before or after VAD implant and followed them up to 48 weeks. Depression and anxiety were assessed with Patient-Reported Outcomes Measurement Information System Short Form 8a questionnaires. The panic disorder, acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) modules of the Structured Clinical Interview for the DSM were used.Results: Eighty-seven patients were enrolled. After implant, depression and anxiety scores decreased significantly over time (P = 0.03 and P < 0.001, respectively). Two patients met criteria for panic disorder early after implantation, but symptoms resolved over time. None met criteria for ASD or PTSD.Conclusions: Our study suggests VADs do not cause serious psychological harms and may have a positive impact on depression and anxiety. Furthermore, VADs did not induce PTSD, panic disorder, or ASD in this cohort. [ABSTRACT FROM AUTHOR]

Context: Ventricular assist devices (VADs) have been shown to improve survival and overall quality of life, but there are limited data on pain control and functional status in this patient population.Objectives: This study examined changes in pain, functional status, and quality of life over time in VAD patients.Methods: Patients were enrolled in this prospective cohort study before or as early after VAD implant as possible and then followed for up to 48 weeks. The Brief Pain Inventory was used to assess pain. The Katz Independent Activities of Daily Living questionnaire was used to assess functional status. The Kansas City Cardiomyopathy Questionnaire, a 23-item questionnaire covering five domains (physical function, symptoms, social function, self-efficacy, and quality of life), was used to assess quality of life and health status.Results: Eighty-seven patients were enrolled at four medical centers. The median Brief Pain Inventory severity score was 2.8 (interquartile range 0.5-5.0) before implantation and 0.0 (interquartile range 0.0-5.3) 48 weeks after implantation (P = 0.0009). Katz Independent Activities of Daily Living summary scores also demonstrated significant improvement over time (P < 0.0001). Kansas City Cardiomyopathy Questionnaire summary scales demonstrated significant improvement with time (P < 0.0016).Conclusion: This study demonstrated that patients with VADs experienced improved pain, functional status, and quality of life over time. These data may be useful to help patients make decisions when they are considering undergoing VAD implantation. [ABSTRACT FROM AUTHOR]