Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage D Heart Failure]): Medium-Term and Primary End Point Results.

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.

High Transpulmonary Artery Gradient Obtained at the Time of Left Ventricular Assist Device Implantation Negatively Affects Survival After Cardiac Transplantation.

AIM: Preoperatively elevated pulmonary vascular resistance (PVR) is a contraindication to heart transplantation (HT). Transpulmonary pressure gradient (TPG) is one of the main variables used in PVR determination (ie, PVR = TPG/cardiac output). Unlike PVR, which is subject to the shortcoming of cardiac output estimation, TPG is directly measured. We aimed to evaluate the relationship of TPG obtained before left ventricular assist device (LVAD) implantation on post-HT survival. METHODS AND RESULTS: A total of 490 patients were implanted with Heartmate II LVADs in the multicenter Heartmate II Bridge-to-Transplantation clinical trial, and 416/490 had pre-LVAD TPG data available. Outcomes during LVAD support and after HT stratified by both PVR and TPG were studied. The median pre-LVAD TPG was 10 mm Hg. Baseline demographic and clinical characteristics were similar for patients with and without TPG >10 mm Hg. Outcomes during LVAD support (ie, recovery to LVAD explantation, HT, or ongoing device support) for patients below and above the median TPG were similar. However, post-HT 1-year survival rate was significantly higher for patients with TPG ≤10 mm Hg compared with those with TPG >10 mm Hg (91% vs 80%; P = .016). Analysis based on the median PVR of 2.68 Wood units did not stratify post-HTx 1-year survival rates between the groups (89% vs 83%; P = .25). CONCLUSIONS: Elevated TPG, rather than high PVR, before LVAD implantation was associated with increased mortality following HT. Pre-LVAD TPG may be useful to identify a cohort that requires close follow-up with serial hemodynamic monitoring before HT.

Preoperative Determinants of Quality of Life and Functional Capacity Response to Left Ventricular Assist Device Therapy.

BACKGROUND: Left ventricular assist devices (LVADs) improve survival, quality of life (QOL), and functional capacity (FC) among patients with end-stage heart failure. Few data are available regarding characteristics associated with QOL and FC response. METHODS AND RESULTS: Patients enrolled in the Heartmate II clinical trials that were alive with ongoing LVAD support at 6 months were included. QOL response criteria included scoring above the lowest quartile on either the Minnesota Living With Heart Failure Questionnaire or the Kansas City Cardiomyopathy Questionnaire. FC responder criteria included improvement in 6-minute walk distance (6MWD) >70 meters from baseline, a 6MWD >220 meters at 6 months, or New York Heart Association functional class I or II. Independent variables associated with QOL nonresponse included history of diabetes (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.20-2.78), lower mean pulmonary arterial pressure (OR 0.97, 95% CI 0.95-0.99), or a Heartmate II right ventricular risk score >2 (OR 1.77, 95% CI 1.00-3.12). Variables associated with FC nonresponse included history of COPD (OR 1.92, 95% CI 1.22-3.03) or diabetes (OR 1.52, 95% CI 1.01-2.27). Compared with responders, QOL and FC nonresponders had reduced long-term survival. CONCLUSIONS: Preoperative comorbidities, including diabetes, COPD, and right heart failure, may limit the QOL and FC response to LVAD therapy and should be considered during the shared decision-making process.

Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: design and rationale of the ROADMAP clinical trial.

BACKGROUND: Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. OBJECTIVE: The objective of this study is to examine the impact of mechanically assisted circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration-defined criteria for treatment but are not yet receiving intravenous inotropic therapy. METHODS: This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. CLINICAL CONTEXT: This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy.

Principles of HeartMate II implantation to avoid pump malposition and migration.

Proper left ventricular assist device (LVAD) insertion will help maximize LVAD flow and may reduce adverse events such as right heart failure and pump thrombosis. Although no standardized insertion technique has been universally accepted, the goals are: unobstructed inflow cannula, unobstructed outflow graft with avoidance of right ventricular compression, and prevention of pump migration. To achieve these objectives for the HeartMate II LVAD, we delineate four principles: proper pump pocket creation, optimized positioning of inflow cannula and outflow graft, proper pump position in the body, and fixation. These basic principles are easy to implement and have been beneficial in our patients, assuring long-term unobstructed LVAD flow.

Incidence, risk, and consequences of atrial arrhythmias in patients with continuous-flow left ventricular assist devices.

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.

Enhanced Thrombin Formation in Patients With Ventricular Assist Devices Experiencing Bleeding: Insights From the Multicenter PREVENT Study.

The aim of this investigation was to characterize the hemostatic status of heart failure patients with implanted left ventricular assist devices (LVADs) to propose a mechanism associated with bleeding. Patients (n = 300) from 23 US hospitals were enrolled in the PREVENtion of HeartMate II Pump Thrombosis through Clinical Management (PREVENT) study. A biobank was established with serum and plasma samples prospectively collected from a cohort of 175 patients preimplant baseline (BL) and 3 months (3M) postimplant. Outcomes were collected for 6 months. Thrombin (prothrombin fragment 1.2 [F1.2], functional thrombin generation [TG]) and fibrinolytic activity (D-dimer, plasminogen activator inhibitor-1 [PAI-1]), but not contact activation (complement C5a), were elevated in heart failure patients at BL. F1.2, TG, and PAI-1 levels decreased 3M after LVAD implantation ( p < 0.01) but did not revert to normal in all patients; conversely, D-dimer increased BL to 3M ( p < 0.01). Compared with patients without events, thrombin activity (F1.2) was increased in patients with late bleeding (3-4 months postimplant) ( p = 0.06) and in those with late gastrointestinal (GI) bleeding ( p = 0.01). Patients with 3M F1.2 levels above the cohort mean had a higher incidence of bleeding ( p < 0.001) and GI bleeding ( p < 0.001) compared with those with below mean F1.2. Patients experiencing multiple bleeding events were more likely to have 3M F1.2 greater than the cohort mean. Despite anticoagulation with aspirin and warfarin, LVAD implanted patients exhibit hemostatic activation. Excess thrombin formation, particularly shown by increased F1.2, was demonstrated in association with bleeding in LVAD implanted patients.

Association of Angiopoetin-2 and TNF-α With Bleeding During Left Ventricular Assist Device Support: Analysis From the PREVENT Biorepository.

The purpose of this study was to describe the changes in plasma levels of angiogenic and inflammatory biomarkers, specifically Ang-2 and TNF-α, in patients receiving HeartMate II (HMII) left ventricular assist device (LVAD) and correlate them with nonsurgical bleeding. It has been shown that angiopoietin-2 (Ang-2) and tissue necrosis factor-α (TNF-α) may be linked to bleeding in LVAD patients. This study utilized biobanked samples prospectively collected from the PREVENT study, a prospective, multicenter, single-arm, nonrandomized study of patients implanted with HMII. Paired serum samples were obtained in 140 patients before implantation and at 90 days postimplantation. Baseline demographics were as follows: age 57 ± 13 years, 41% had ischemic etiology, 82% male, and 75% destination therapy indication. In the 17 patients with baseline elevation of both TNF-α and Ang-2, 10 (60%) experienced a significant bleeding event within 180 days postimplant compared with 37 of 98 (38%) patients with Ang-2 and TNF-α below the mean ( p = 0.02). The hazard ratio for a bleeding event was 2.3 (95% CI: 1.2-4.6) in patients with elevated levels of both TNF-α and Ang-2. In the PREVENT multicenter study, patients with elevations in serum Angiopoietin-2 and TNF-α at baseline before LVAD implantation demonstrated increased bleeding events after LVAD implantation.

Use of a Pulmonary Artery Pressure Sensor to Manage Patients With Left Ventricular Assist Devices.

BACKGROUND: Hemodynamic-guided management with a pulmonary artery pressure sensor (CardioMEMS) is effective in reducing heart failure hospitalization in patients with chronic heart failure. This study aims to determine the feasibility and clinical utility of the CardioMEMS heart failure system to manage patients supported with left ventricular assist devices (LVADs). METHODS: In this multicenter prospective study, we followed patients with HeartMate II (n=52) or HeartMate 3 (n=49) LVADs and with CardioMEMS PA Sensors and measured pulmonary artery pressure, 6-minute walk distance, quality of life (EQ-5D-5 L scores), and heart failure hospitalization rates through 6 months. Patients were stratified as responders (R) and nonresponders to reductions in pulmonary artery diastolic pressure (PAD). RESULTS: There were significant reductions in PAD from baseline to 6 months in R (21.5-16.5 mm Hg; P<0.001), compared with an increase in NR (18.0-20.3; P=0.002), and there was a significant increase in 6-minute walk distance among R (266 versus 322 meters; P=0.025) compared with no change in nonresponder. Patients who maintained PAD <20 compared with PAD ≥20 mm Hg for more than half the time throughout the study (averaging 15.6 versus 23.3 mm Hg) had a statistically significant lower rate of heart failure hospitalization (12.0% versus 38.9%; P=0.005). CONCLUSIONS: Patients with LVAD managed with CardioMEMS with a significant reduction in PAD at 6 months showed improvements in 6-minute walk distance. Maintaining PAD <20 mm Hg was associated with fewer heart failure hospitalizations. Hemodynamic-guided management of patients with LVAD with CardioMEMS is feasible and may result in functional and clinical benefits. Prospective evaluation of ambulatory hemodynamic management in patients with LVAD is warranted. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03247829.

Advanced heart failure treated with continuous-flow left ventricular assist device.

BACKGROUND: Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy. New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices. METHODS: In this randomized trial, we enrolled patients with advanced heart failure who were ineligible for transplantation, in a 2:1 ratio, to undergo implantation of a continuous-flow device (134 patients) or the currently approved pulsatile-flow device (66 patients). The primary composite end point was, at 2 years, survival free from disabling stroke and reoperation to repair or replace the device. Secondary end points included survival, frequency of adverse events, the quality of life, and functional capacity. RESULTS: Preoperative characteristics were similar in the two treatment groups, with a median age of 64 years (range, 26 to 81), a mean left ventricular ejection fraction of 17%, and nearly 80% of patients receiving intravenous inotropic agents. The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices (62 of 134 [46%] vs. 7 of 66 [11%]; P<0.001; hazard ratio, 0.38; 95% confidence interval, 0.27 to 0.54; P<0.001), and patients with continuous-flow devices had superior actuarial survival rates at 2 years (58% vs. 24%, P=0.008). Adverse events and device replacements were less frequent in patients with the continuous-flow device. The quality of life and functional capacity improved significantly in both groups. CONCLUSIONS: Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device. Both devices significantly improved the quality of life and functional capacity. (ClinicalTrials.gov number, NCT00121485.)

Young patients with nonischemic cardiomyopathy have higher likelihood of left ventricular recovery during left ventricular assist device support.

BACKGROUND: Recovery of ventricular function during left ventricular assist device (LVAD) support allowing device explantation occurs infrequently. We explored the hypothesis that certain patient profiles are more likely to exhibit LV recovery during LVAD support. METHODS AND RESULTS: A retrospective analysis of data from the HeartMate II bridge to transplant (BTT) and destination therapy (DT) trials was conducted, including 490 BTT, 600 DT, and 18 compassionate-use patients. Of the 1,108 patients, 20 (1.8%; 10 BTT, 10 DT) were explanted owing to LV recovery. The median age was 33 years, and 12 patients (60%) were <40 years of age. History of heart failure was <1 year for 11 patients (61%), and the primary etiology was nonischemic (90%). Of the patients with nonischemic etiologies and <1-year history of heart failure, 13% were explanted. Three patients required LVAD reimplantation; of the remaining 17, 16 remain alive. At follow-up (median 510 days), the mean ejection fraction was 42% (20%-67%) and the mean left ventricular end-diastolic diameter was 55 ± 8 mm. At the 2-year follow-up (n = 13), patients were New York Heart Association functional class I or II and overall survival rate was 85 ± 11%. CONCLUSIONS: The results of this study suggest that LV recovery is most likely to occur in young patients (<40 years) with nonischemic cardiomyopathy of <1 year duration. Two-year postexplant survival was excellent.

Low operative mortality with implantation of a continuous-flow left ventricular assist device and impact of concurrent cardiac procedures.

BACKGROUND: The objective of this study was to determine the impact of concurrent cardiac procedures (CCP) on patient outcomes after HeartMate II (HMII) left ventricular assist device implantation. METHODS AND RESULTS: Two hundred eighty-one patients underwent implantation of a HMII as a bridge to transplantation from March 2005 to March 2007. One hundred seventy patients had an HMII implanted only, and 81 patients underwent concurrent cardiac procedures in conjunction with HMII implantation (HMII+CCP). Of these, 47 patients had concurrent valvular procedures, 15 patients had simultaneous closure of patent foramen ovale, and 19 patients had other various cardiac procedures. Patients requiring right ventricular assist device support or noncardiac procedures were excluded. Preoperative characteristics were similar for patients with and without concurrent cardiac procedures. Overall 30-day mortality was 5.8% for the HMII group and 11.3% for the HMII+CCP group. Subgroup analysis demonstrated that simultaneous patent foramen ovale closure was not associated with an increased 30-day mortality rate, but concurrent valvular procedures increased the risk to 8.5%. Patients who underwent an aortic valve procedure had a 30-day mortality rate of 25%, higher than for isolated concurrent mitral (0%) or tricuspid repair (3.3%). Survival at 180 days was 87% for HMII alone and 80% for HMII+CCP. The hazard ratio for concurrent cardiac procedures adjusted for baseline parameters was 1.82 (95% CI, 1.07 to 3.10, P=0.026). CONCLUSIONS: There is a low 5.8% operative mortality rate for patients requiring uncomplicated HMII implantation, with no apparent increased risk for concurrent patent foramen ovale closure or mitral or tricuspid repair. However, concurrent aortic valve and other cardiac procedures are associated with significantly decreased perioperative and long-term survival.

Renal and hepatic function improve in advanced heart failure patients during continuous-flow support with the HeartMate II left ventricular assist device.

BACKGROUND: The effects of continuous blood flow and reduced pulsatility on major organ function have not been studied in detail. METHODS AND RESULTS: We evaluated renal (creatinine and blood urea nitrogen) and hepatic (aspartate transaminase, alanine transaminase, and total bilirubin) function in 309 (235 male, 74 female) advanced heart failure patients who had been supported with the HeartMate II continuous-flow left ventricular assist device for bridge to transplantation. To determine whether patients with impaired renal and hepatic function improve over time with continuous-flow left ventricular assist device support or whether there are any detrimental effects in patients with normal organ function, we divided patients into those with above-normal and normal laboratory values before implantation and measured blood chemistry over time during left ventricular assist device support. There were significant improvements over 6 months in all parameters in the above-normal groups, with values in the normal groups remaining in the normal range over time. Mean blood urea nitrogen and serum creatinine in the above-normal groups decreased significantly from 37+/-14 to 23+/-10 mg/dL (P<0.0001) and from 1.8+/-0.4 to 1.4+/-0.8 mg/dL (P<0.01), respectively. There were decreases in aspartate transaminase and alanine transaminase in the above-normal groups from 121+/-206 and 171+/-348 to 36+/-19 and 31+/-22 IU (P<0.001), respectively. Total bilirubin for the above-normal group was 2.1+/-0.9 mg/dL at baseline; after an acute increase at week 1, it decreased to 0.9+/-0.5 mg/dL by 6 months (P<0.0001). Both renal and liver values from patients in the normal groups remained normal during support with the left ventricular assist device. CONCLUSIONS: The HeartMate II continuous-flow left ventricular assist device improves renal and hepatic function in advanced heart failure patients who are being bridged to transplantation, without evidence of detrimental effects from reduced pulsatility over a 6-month time period.

Use of a continuous-flow device in patients awaiting heart transplantation.

BACKGROUND: The use of left ventricular assist devices is an accepted therapy for patients with refractory heart failure, but current pulsatile volume-displacement devices have limitations (including large pump size and limited long-term mechanical durability) that have reduced widespread adoption of this technology. Continuous-flow pumps are newer types of left ventricular assist devices developed to overcome some of these limitations. METHODS: In a prospective, multicenter study without a concurrent control group, 133 patients with end-stage heart failure who were on a waiting list for heart transplantation underwent implantation of a continuous-flow pump. The principal outcomes were the proportions of patients who, at 180 days, had undergone transplantation, had cardiac recovery, or had ongoing mechanical support while remaining eligible for transplantation. We also assessed functional status and quality of life. RESULTS: The principal outcomes occurred in 100 patients (75%). The median duration of support was 126 days (range, 1 to 600). The survival rate during support was 75% at 6 months and 68% at 12 months. At 3 months, therapy was associated with significant improvement in functional status (according to the New York Heart Association class and results of a 6-minute walk test) and in quality of life (according to the Minnesota Living with Heart Failure and Kansas City Cardiomyopathy questionnaires). Major adverse events included postoperative bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in two patients. CONCLUSIONS: A continuous-flow left ventricular assist device can provide effective hemodynamic support for a period of at least 6 months in patients awaiting heart transplantation, with improved functional status and quality of life. (ClinicalTrials.gov number, NCT00121472 [ClinicalTrials.gov].).

Optical tracking and laser-induced mortality of insects during flight.

Addressing the need for novel insect observation and control tools, the Photonic Fence detects and tracks mosquitoes and other flying insects and can apply lethal doses of laser light to them. Previously, we determined lethal exposure levels for a variety of lasers and pulse conditions on anesthetized Anopheles stephensi mosquitoes. In this work, similar studies were performed while the subjects were freely flying within transparent cages two meters from the optical system; a proof-of-principle demonstration of a 30 m system was also performed. From the dose-response curves of mortality data created as a function of various beam diameter, pulse width, and power conditions at visible and near-infrared wavelengths, the visible wavelengths required significantly lower laser exposure than near infrared wavelengths to disable subjects, though near infrared sources remain attractive given their cost and retina safety. The flight behavior of the subjects and the performance of the tracking system were found to have no impact on the mortality outcomes for pulse durations up to 25 ms, which appears to be the ideal duration to minimize required laser power. The results of this study affirm the practicality of using optical approaches to protect people and crops from pestilent flying insects.

Association of Clinical Outcomes With Left Ventricular Assist Device Use by Bridge to Transplant or Destination Therapy Intent: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) Randomized Clinical Trial.

Importance: Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant. Objective: To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT). Design, Setting, and Participants: This study was a prespecified secondary analysis of the MOMENTUM 3 trial, a multicenter randomized clinical trial comparing the magnetically levitated centrifugal-flow HeartMate 3 (HM3) LVAD to the axial-flow HeartMate II (HMII) pump. It was conducted in 69 centers with expertise in managing patients with advanced heart failure in the United States. Patients with advanced heart failure were randomized to an LVAD, irrespective of the intended goal of therapy (BTT/BTC or DT). Main Outcomes and Measures: The primary end point was survival free of disabling stroke or reoperation to remove or replace a malfunctioning device at 2 years. Secondary end points included adverse events, functional status, and quality of life. Results: Of the 1020 patients with implants (515 with HM3 devices [50.5%] and 505 with HMII devices [49.5%]), 396 (38.8%) were in the BTT/BTC group (mean [SD] age, 55 [12] years; 310 men [78.3%]) and 624 (61.2%) in the DT group (mean [SD] age, 63 [12] years; 513 men [82.2%]). Of the patients initially deemed as transplant ineligible, 84 of 624 patients (13.5%) underwent heart transplant within 2 years of LVAD implant. In the primary end point analysis, HM3 use was superior to HMII use in patients in the BTT/BTC group (76.8% vs 67.3% for survival free of disabling stroke and reoperation; hazard ratio, 0.62 [95% CI, 0.40-0.94]; log-rank P = .02) and patients in the DT group (73.2% vs 58.7%; hazard ratio, 0.61 [95% CI, 0.46-0.81]; log-rank P < .001). For patients in both BTT/BTC and DT groups, there were not significantly different reductions in rates of pump thrombosis, stroke, and gastrointestinal bleeding with HM3 use relative to HMII use. Improvements in quality of life and functional capacity for either pump were not significantly different regardless of preimplant strategy. Conclusions and Relevance: In this trial, the superior treatment effect of HM3 over HMII was similar for patients in the BTT/BTC or DT groups. It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure. Trial Registration: ClinicalTrials.gov identifier: NCT02224755.

Mechanical circulatory support devices for acute heart failure syndromes: considerations for clinical trial design.

Mechanical circulatory support (MCS) devices are a guideline-recommended treatment option for a small subset of advanced heart failure patients. MCS has the potential to become more prominent in the management of Acute Heart Failure Syndromes (AHFS) as device technology advances and as clinical trials consistently discover neutral or harmful effects with pharmacologic therapies hypothesized to be beneficial in this population. While it is now possible to identify AHFS patients who are at high risk of death, the therapeutic options available to improve their long-term outcomes are limited. MCS therapy in this population offers a "bridge to recovery" strategy; these patients may have viable myocardium that responds favorably to the influence of MCS on neurohormones, cytokines, and/or reverse remodeling. Patients at high risk for mortality who have a substantial likelihood of benefiting from MCS can be easily identified using standard clinical criteria developed from large observational databases. MCS technology is rapidly evolving, and risks related to implantation are declining. It is evident that rigorous clinical trial testing of the potential risks, benefits, and economic implications of MCS in patients with AHFS will need to be conducted before the "routine" application of this aggressive therapy. This paper examines the rationale for conducting trials of MCS devices in patients with AHFS, and it explores considerations for patient selection and appropriate endpoints. This manuscript was generated from discussions on this issue during the third international meeting of the International Working Group on AHFS held in Washington, DC, April 8-9, 2006.

Changes in pulmonary artery pressure before and after left ventricular assist device implantation in patients utilizing remote haemodynamic monitoring.

AIMS: The time course of changes in pulmonary artery (PA) pressure due to left ventricular assist devices (LVADs) is not well understood. Here, we describe longitudinal haemodynamic trends during the peri-LVAD implantation period in patients previously implanted with a remote monitoring PA pressure sensor. METHODS AND RESULTS: We retrospectively studied PA pressure trends in patients implanted with CardioMEMS™ PA pressure sensor between October 2007 and March 2017 who subsequently had an LVAD procedure. Data are presented as mean ± standard deviation, and P-values are calculated using standard t-test with equal variance. Among 436 patients in cohort, 108 (age 58 ± 11 years, 82% male) received an LVAD and 328 (age 60 ± 13 years, 70% male) did not. The mean PA pressure at sensor implant was higher by 29% (P < 0.001) among patients who later received LVAD. Mean PA pressure 6 months prior to LVAD implant was 35.5 ± 8.5 mmHg, increasing to 39.4 ± 9.9 mmHg (P = 0.04) at 4 weeks before LVAD, and then decreasing 27% to 28.8 ± 8.4 mmHg (P < 0.001) at 3 months post-implant and stabilizing at 31.0 ± 9.4 mmHg at 1 year. CONCLUSIONS: Patients who later receive LVADs have higher PA pressures at sensor implant and show a further increase leading up to LVAD implantation. There is a significant reduction of PA pressures post-LVAD implantation that persists long term. PA pressure monitoring may aid in the clinical decision making of timing for LVAD implantation and in management of LVAD patients.

Pump Position Impacts HeartMate II Left Ventricular Assist Device Thrombosis.

The PREVENtion of HeartMate II pump Thrombosis through clinical management (PREVENT) study was a multicenter, prospective investigation to evaluate the rate of pump thrombosis (PT) with adoption of a uniform set of surgical and medical practices for left ventricular assist device implantation. We sought to quantify pump position at baseline and retrospectively define a pump position associated with poor clinical outcomes. Chest x-rays at baseline were prospectively obtained per protocol. Pump pocket depth, inflow cannula (IC) angle relative to the pump, and IC angle relative to the vertical were measured. Pumps falling in the tail-ends of the IC angle and pump pocket depth distributions were categorized as having an extreme pump position within the PREVENT study. Patients with extreme pump position had a significantly higher risk of confirmed and suspected PT, hemolysis, and elevated lactate dehydrogenase. In a multivariable analysis of survival free of confirmed PT, extreme pump position was an independent risk factor (hazard ratio = 3.6; 95% confidence interval = 1.5-8.9; p = 0.006) when adjusting for differences in pump speed and anticoagulation level. Our analysis shows that HeartMate II pump position at implant can significantly impact event-free survival and the incidence of adverse events at 6 months.

Hemodynamic and exercise performance with pulsatile and continuous-flow left ventricular assist devices.

BACKGROUND: Continuous-flow rotary pumps with axial design are increasingly used for left ventricular assist support. The efficacy of this design compared with pulsatile, volume displacement pumps, with respect to characteristics of left ventricular unloading, and exercise performance remains largely unstudied. METHODS AND RESULTS: Thirty-four patients undergoing implantation with a pulsatile, volume displacement pump operating in a full-to-empty cycle (HeartMate XVE; Thoratec Inc, Pleasanton, Calif; n=16) or continuous-flow rotary pump with an axial design operating at a fixed rotor speed (HeartMate II; Thoratec Inc; n=18) were evaluated with right heart catheterization and echocardiography preoperatively and at 3 months postoperatively and cardiopulmonary exercise testing 3 months postoperatively. Support with either the XVE or II resulted in significant (P<0.05) increases in cardiac output and reduction in mean pulmonary artery and pulmonary wedge pressures. Exercise capacity at 3 months was similar between groups (% predicted peak VO2-XVE: 46.8+/-10.2 versus II: 49.1+/-13.6). Echocardiography at 3 months demonstrated a significantly (P<0.05) greater reduction in left ventricular end-diastolic volume (-49+/-16% versus -35+/-20%), left ventricular end-systolic volume (-59+/-20 versus -37+/-21%), and percent mitral valve regurgitant volume (-99+/-2% versus -52+/-56%) for the XVE compared with II, respectively. CONCLUSIONS: The HeartMate XVE or II provided equivalent degrees of hemodynamic support and exercise capacity. The XVE was associated with greater left ventricular volume unloading. Characteristics of left ventricular pressure and volume unloading between these pump designs and mode of operation do not influence early exercise performance.