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AIMS Cardiac contractility modulation (CCM) improves symptoms and exercise tolerance and reduces heart failure (HF) hospitalizations over 6-month follow-up in patients with New York Heart Association (NYHA) class III or IV symptoms, QRS

Introduction: Effective AED defibrillation of out of hospital cardiac arrest (OHCA) depends on the safe and effective identification of shockable rhythms, and on delivery of effective defibrillation energy. This report summarizes rhythm detection performance and shock efficacy during OHCA uses of Philips HeartStart Home and OnSite AEDs using non-escalating 150 J therapy. Methods: A convenience sample of 185 OHCA AED patient uses were reviewed by clinical experts. All analysis periods that resulted in AED rhythm advisories (Shock Advised or No Shock Advised) were annotated. Shockable rhythm categories include VF and polymorphic VT/flutter. Non-Shockable rhythm categories include normal sinus rhythm, other rhythms (e.g., atrial fibrillation/flutter, bradycardia, SVT, idioventricular, bundle branch block), and asystole. Intermediate rhythms (benefits of defibrillation are limited or uncertain) were not included. Post-shock rhythm was categorized as shockable, non-shockable, or undeterminable (rhythms corrupted by CPR artifact or pads removal within 5-s of shock delivery). Shock success was defined as conversion to a non-shockable rhythm within 5-s post-shock. Results: A total of 487 analysis periods resulted in AED rhythm advisories, with 175 annotated as Shockable and 312 Non-shockable. Sensitivity and specificity (n/N, Exact 95% CI) were 97.7% (171/175, 94.3%, 99.4%) and 100% (312/312, 98.8%, 100.0%) respectively. A total of 165 shocks were delivered to 100 patients with 5 undeterminable post-shock rhythms. The remaining 160 shocks were delivered to 156 Shockable rhythm episodes. All shock efficacy was 96.9% (155/160, 92.9%, 99.0%): 150 episodes converted to non-shockable rhythms after one shock (96.2% (150/156, 91.8%, 98.6%)); 154 after two shocks (98.7% (154/156, 95.4%, 99.8%)); and 155 after three shocks, the first two of which were undeterminable (99.4% (155/156, 96.5%, 100.0%)). The remaining episode had a failed first shock, followed by an undeterminable second shock, which was the last shock of the use. Conclusion: For these 150J fixed-energy AEDs, OHCA defibrillation is safe (100% specificity), and effective (97.7% sensitivity; 96.2% single shock effectiveness; 98.7% after two shocks; 99.4% after three shocks).

Objectives 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). Background Patients supported with left ventricular assist devices are at risk for both ischemic and hemorrhagic cerebrovascular events. Methods 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. Results 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 pressure >90 mm Hg, aspirin ≤81 mg, and an international normalized ratio >3.0. 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). Conclusions 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)

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.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.At baseline, women had a smaller body surface area (1.8 ± 0.2 vs. 2.1 ± 0.3 m2, p0.0001), less hypertension (50.0% vs. 61.9%, p = 0.05), and less ischemic cardiomyopathy (15.6% vs. 45.3%, p0.0001). 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.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.

Objectives This study evaluated gastrointestinal bleeding (GIB) in patients receiving the HeartWare HVAD System (HeartWare Inc., Framingham, Massachusetts) in the pivotal BTT (Bridge to Transplant) trial and under the continued access protocol (CAP). Background GIB has become a significant problem for recipients of continuous flow device left ventricular assist devices (CF-LVAD). The need for anticoagulation and antiplatelet therapies complicates the management of GIB. Methods Bleeding events from 382 patients with advanced heart failure (140 patients enrolled in the BTT trial, and an additional 242 CAP patients) were analyzed. Post-implant anticoagulation consisted of heparin followed by warfarin at a target international normalized ratio of 2 to 3. Acetylsalicylic acid was recommended at 81 to 325 mg. Results Overall, 59 of 382 (15.4%) patients experienced 108 GIB events (0.27 events per patient year). Mean time to first bleed was 273.1 days and 86.1% of events occurred beyond 30 days. Freedom from GIB was 84.1% at 1 year. Median international normalized ratio at the time of first bleed was 2.4 ± 1.4. The most common etiology of bleeding identified was arteriovenous malformation and the most common site was the small intestine. Repeat bleeding was infrequent, though GIB patients required more readmissions and developed nondevice infections more frequently. No patients required surgical intervention and no deaths directly related to GIB occurred. Conclusions Recipients of the HeartWare Ventricular Assist Device System had an incidence of 0.27 GIB/patient year with a freedom from GIB of 84.1% at 1 year. All patients with GIB events were managed with medical and endoscopic therapies, although 31% of patients experienced a recurrence of GIB. No surgical intervention was required. GIB did not impact survival. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972 )

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.

Background The post-market Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE) is an investigator-initiated registry established to collect post–CE Mark Trial clinical data on patients receiving a HeartWare ventricular assist device (HVAD) in the European Union and Australia. Methods The ReVOLVE is a multi-center, prospective, single-arm registry performed at seven centers in Europe and two in Australia. Herein we describe a total of 254 commercial HVAD implants according to labeled indications between February 2009 and November 2012. Summary statistics included patients’ demographics, adverse events, length of support and outcomes. Results Compared with the clinical trial supporting the CE Mark of the HeartWare system, patient selection differed in that patients were older, and there were higher proportions of females and patients with idiopathic cardiomyopathies in the ReVOLVE cohort. Duration of support ranged from 1 to 1,057 days, with a mean of 363 ± 280 days (median 299.5 days). Transplantation was done in 56 patients (22%), explant for recovery was performed in 3 patients (1%), 43 died while on support (17%), and 152 (60%) remain on the device. Success in patients with the HeartWare system was 87% at 6 months, 85% at 1 year, 79% at 2 years and 73% at 3 years. Adverse event rates were low, comparable or improved when compared to the CE Mark Trial. Conclusion Real-world use of the HeartWare system continues to demonstrate excellent clinical outcomes in patients supported with the device.

Advanced heart failure patients who are classified as bridge to transplant (BTT) often remain on mechanical circulatory support (MCS) for long durations because of the limited supply of donor organs. Here, we present the outcomes of patients who have been supported by the HeartWare ventricular assist device system for more than 2 years. In the HeartWare BTT and continued access protocol trial, 74 of the 382 total patients (19.4%) had more than 2 years of MCS with a mean time of 1,045 days on device. The long-term group was more frequently female, was nonwhite, and had Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7. Postimplant adverse event rates including bleeding, cardiac arrhythmia, infection, stroke, renal dysfunction, and right heart failure were less frequent in the long-term cohort. In addition, the long-term cohort displayed significant improvements in Kansas City Cardiomyopathy Questionnaire Overall Summary Score, EuroQOL-5D Overall Health State Score, and 6 minute walk scores from baseline values. The rate of heart transplantation was lower for the long-term cohort, which may have been a result of their sex and blood type. However, most of these patients are still listed for cardiac transplantation and maintained their quality of life profiles through 3 years of support.

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).

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 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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00751972.

Background The HeartWare Ventricular Assist System (HeartWare Inc, Framingmam, MA) is a miniaturized implantable, centrifugal design, continuous-flow blood pump. The pivotal bridge to transplant and continued access protocols trials have enrolled patients with advanced heart failure in a bridge-to-transplant indication. Methods The primary outcome, success, was defined as survival on the originally implanted device, transplant, or explant for ventricular recovery at 180 days. Secondary outcomes included an evaluation of survival, functional and quality of life outcomes, and adverse events. Results A total of 332 patients in the pivotal bridge to transplant and continued access protocols trial have completed their 180-day primary end-point assessment. Survival in patients receiving the HeartWare pump was 91% at 180 days and 84% at 360 days. Quality of life scores improved significantly, and adverse event rates remain low. Conclusions The use of the HeartWare pump as a bridge to transplant continues to demonstrate a high 180-day survival rate despite a low rate of transplant. Adverse event rates are similar or better than those observed in historical bridge-to-transplant trials, despite longer exposure times due to longer survival and lower transplant rates.

Purpose Cardiac Transplantation remains one of the best therapeutic options for patients with advanced heart failure who fail optimal medical therapy. However, limited donor availability leads to extended wait-list time and the possibility of continued deterioration. We reviewed post-transplant survival following HeartWare® continuous flow ventricular assist device (HVAD) implantation, as well as the impact of several variables on post-transplant survival. Methods and Materials A review of patients with advanced heart failure enrolled in the ADVANCE Bridge to Transplant (BTT, n=140) and an additional 192 patients enrolled under the continued access protocol (CAP) to receive a continuous flow HVAD Pump as BTT revealed a total of 160 patients (48%) who were transplanted or explanted for recovery. Analyses included descriptive statistics, survival by simple proportion and Kaplan-Meier analysis, and a multivariable analysis including 41 risk factor variables. Results Of 160 patients who were transplanted or explanted for recovery, survival was 90% at 180 days and 89% at 1 year. Average time on HVAD support prior to transplant was 251 + 188 days (range 23 to 839 days). Baseline characteristics at HVAD implant revealed 96% of patients with NYHA Stage IV heart failure, 22% female, and 37% having heart failure of ischemic origin. Post-transplant survival was greater in patients ≤60 years (range 22 to 60) than in patients >60 years (range 61 to 69), 94% vs 78% at 180 days ( P =0.011) and 91% vs 66% at 1 year ( P =0.005), respectively. Survival was statistically similar regardless of time on HVAD support prior to transplant. Etiology of heart failure, sex, and bleeding or infection events while on HVAD support did not influence survival. A multivariable analysis revealed BMI≥30 as a predictive factor for survival 6 months post-transplant. Conclusions Post-transplant survival in patients supported with a continuous-flow LVAD such as the HVAD Pump is excellent, suggesting consideration should be given to developing strategies to optimize donor organ allocation.

Purpose The REVOLVE Registry is an investigator-initiated registry established to collect data on the commercial use of the HeartWare® HVAD System in the European Union and Australia. Methods and Materials REVOLVE is a multi-center, prospective, single arm registry. Each patient is followed to device explant, transplantation or death. Data from the first 242 commercial implants performed between February of 2009 and March 2012 from six centers in Europe (4) and Australia (2) is presented. Final data on the total dataset will be available at the time of presentation. Patients receiving the HeartWare System for both labeled and off-label indications were included. Summary statistics are used to describe patient demographics, adverse events, length of support and outcomes. Results When compared to the clinical trial supporting CE Mark of the HVAD Pump, changes in patient selection (older mean age, patients younger than 18 year old and more females), as well as an increase in idiopathic cardiomyopathies are evident in the REVOLVE patients. Implants were performed mostly via sternotomy (96%), and thoracotomy in 4%. Implant was for LVAD support in 91% of cases, biventricular support in 7%, and as right ventricular support in Conclusions Real world use of the HVAD Pump continues to support the excellent outcomes on the device. Complication EPPY (222 years of support) Any INTERMACS Bleeding 0.27 Right Heart Failure 0.16 Stroke 0.09 Driveline Infection 0.08 Sepsis 0.05 Renal Failure 0.03 Pump Thrombus - Overall 0.06 Medically Treated Pump Thrombus 0.02 Pump Thrombus Treated with Exchange 0.04 EPPY=events per patient year.

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.