The GUIDE-HF trial of pulmonary artery pressure monitoring in heart failure: impact of the COVID-19 pandemic.

AIMS: During the coronavirus disease 2019 (COVID-19) pandemic, important changes in heart failure (HF) event rates have been widely reported, but few data address potential causes for these changes; several possibilities were examined in the GUIDE-HF study. METHODS AND RESULTS: From 15 March 2018 to 20 December 2019, patients were randomized to haemodynamic-guided management (treatment) vs. control for 12 months, with a primary endpoint of all-cause mortality plus HF events. Pre-COVID-19, the primary endpoint rate was 0.553 vs. 0.682 events/patient-year in the treatment vs. control group [hazard ratio (HR) 0.81, P = 0.049]. Treatment difference was no longer evident during COVID-19 (HR 1.11, P = 0.526), with a 21% decrease in the control group (0.536 events/patient-year) and no change in the treatment group (0.597 events/patient-year). Data reflecting provider-, disease-, and patient-dependent factors that might change the primary endpoint rate during COVID-19 were examined. Subject contact frequency was similar in the treatment vs. control group before and during COVID-19. During COVID-19, the monthly rate of medication changes fell 19.2% in the treatment vs. 10.7% in the control group to levels not different between groups (P = 0.362). COVID-19 was infrequent and not different between groups. Pulmonary artery pressure area under the curve decreased -98 mmHg-days in the treatment group vs. -100 mmHg-days in the controls (P = 0.867). Patient compliance with the study protocol was maintained during COVID-19 in both groups. CONCLUSION: During COVID-19, the primary event rate decreased in the controls and remained low in the treatment group, resulting in an effacement of group differences that were present pre-COVID-19. These outcomes did not result from changes in provider- or disease-dependent factors; pulmonary artery pressure decreased despite fewer medication changes, suggesting that patient-dependent factors played an important role in these outcomes. Clinical Trials.gov: NCT03387813.

Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial.

BACKGROUND: Previous studies have suggested that haemodynamic-guided management using an implantable pulmonary artery pressure monitor reduces heart failure hospitalisations in patients with moderately symptomatic (New York Heart Association [NYHA] functional class III) chronic heart failure and a hospitalisation in the past year, irrespective of ejection fraction. It is unclear if these benefits extend to patients with mild (NYHA functional class II) or severe (NYHA functional class IV) symptoms of heart failure or to patients with elevated natriuretic peptides without a recent heart failure hospitalisation. This trial was designed to evaluate whether haemodynamic-guided management using remote pulmonary artery pressure monitoring could reduce heart failure events and mortality in patients with heart failure across the spectrum of symptom severity (NYHA funational class II-IV), including those with elevated natriuretic peptides but without a recent heart failure hospitalisation. METHODS: The randomised arm of the haemodynamic-GUIDEed management of Heart Failure (GUIDE-HF) trial was a multicentre, single-blind study at 118 centres in the USA and Canada. Following successful implantation of a pulmonary artery pressure monitor, patients with all ejection fractions, NYHA functional class II-IV chronic heart failure, and either a recent heart failure hospitalisation or elevated natriuretic peptides (based on a-priori thresholds) were randomly assigned (1:1) to either haemodynamic-guided heart failure management based on pulmonary artery pressure or a usual care control group. Patients were masked to their study group assignment. Investigators were aware of treatment assignment but did not have access to pulmonary artery pressure data for control patients. The primary endpoint was a composite of all-cause mortality and total heart failure events (heart failure hospitalisations and urgent heart failure hospital visits) at 12 months assessed in all randomly assigned patients. Safety was assessed in all patients. A pre-COVID-19 impact analysis for the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT03387813. FINDINGS: Between March 15, 2018, and Dec 20, 2019, 1022 patients were enrolled, with 1000 patients implanted successfully, and follow-up was completed on Jan 8, 2021. There were 253 primary endpoint events (0·563 per patient-year) among 497 patients in the haemodynamic-guided management group (treatment group) and 289 (0·640 per patient-year) in 503 patients in the control group (hazard ratio [HR] 0·88, 95% CI 0·74-1·05; p=0·16). A prespecified COVID-19 sensitivity analysis using a time-dependent variable to compare events before COVID-19 and during the pandemic suggested a treatment interaction (pinteraction=0·11) due to a change in the primary endpoint event rate during the pandemic phase of the trial, warranting a pre-COVID-19 impact analysis. In the pre-COVID-19 impact analysis, there were 177 primary events (0·553 per patient-year) in the intervention group and 224 events (0·682 per patient-year) in the control group (HR 0·81, 95% CI 0·66-1·00; p=0·049). This difference in primary events almost disappeared during COVID-19, with a 21% decrease in the control group (0·536 per patient-year) relative to pre-COVID-19, virtually no change in the treatment group (0·597 per patient-year), and no difference between groups (HR 1·11, 95% CI 0·80-1·55; p=0·53). The cumulative incidence of heart failure events was not reduced by haemodynamic-guided management (0·85, 0·70-1·03; p=0·096) in the overall study analysis but was significantly decreased in the pre-COVID-19 impact analysis (0·76, 0·61-0·95; p=0·014). 1014 (99%) of 1022 patients had freedom from device or system-related complications. INTERPRETATION: Haemodynamic-guided management of heart failure did not result in a lower composite endpoint rate of mortality and total heart failure events compared with the control group in the overall study analysis. However, a pre-COVID-19 impact analysis indicated a possible benefit of haemodynamic-guided management on the primary outcome in the pre-COVID-19 period, primarily driven by a lower heart failure hospitalisation rate compared with the control group. FUNDING: Abbott.

Aspirin and left ventricular assist devices: rationale and design for the international randomized, placebo-controlled, non-inferiority ARIES HM3 trial.

AIMS: Over decades, left ventricular assist device (LVAD) technology has transitioned from less durable bulky pumps to smaller continuous-flow pumps which have substantially improved long-term outcomes and quality of life. Contemporary LVAD therapy is beleaguered by haemocompatibility-related adverse events including thrombosis, stroke and bleeding. A fully magnetically levitated pump, the HeartMate 3 (HM3, Abbott, USA) LVAD, has been shown to be superior to the older HeartMate II (HMII, Abbott, USA) pump by improving haemocompatibility. Experience with the HM3 LVAD suggests near elimination of de-novo pump thrombosis, a marked reduction in stroke rates, and only a modest decrease in bleeding complications. Since the advent of continuous-flow LVAD therapy, patients have been prescribed a combination of aspirin and anticoagulation therapy on the presumption that platelet activation and perturbations to the haemostatic axis determine their necessity. Observational studies in patients implanted with the HM3 LVAD who suffer bleeding have suggested a signal of reduced subsequent bleeding events with withdrawal of aspirin. The notion of whether antiplatelet therapy can be avoided in an effort to reduce bleeding complications has now been advanced. METHODS: To evaluate this hypothesis and its clinical benefits, the Antiplatelet Removal and Hemocompatibility Events with the HeartMate 3 Pump (ARIES HM3) has been introduced as the first-ever international prospective, randomized, double-blind and placebo-controlled, non-inferiority trial in a patient population implanted with a LVAD. CONCLUSION: This paper reviews the biological and clinical role of aspirin (100 mg) with LVADs and discusses the rationale and design of the ARIES HM3 trial.

Impact of left ventricular assist device implantation on mitral regurgitation: An analysis from the MOMENTUM 3 trial.

BACKGROUND: Mitral regurgitation (MR) determines pathophysiology and outcome in advanced heart failure. The impact of left ventricular assist device (LVAD) placement on clinically significant MR and its contribution to long-term outcomes has been sparsely evaluated. METHODS: We evaluated the effect of clinically significant MR on patients implanted in the MOMENTUM 3 trial with either the HeartMate II (HMII) or the HeartMate 3 (HM3) at 2 years. Clinical significance was defined as moderate or severe grade MR determined by site-based echocardiograms. RESULTS: Of 927 patients with LVAD implants without a prior or concomitant mitral valve procedure, 403 (43.5%) had clinically significant MR at baseline. At 1-month of support, residual MR was present in 6.2% of patients with HM3 and 14.3% of patients with HMII (relative risk = 0.43; 95% CI, 0.22-0.84; p = 0.01) with a low rate of worsening at 2 years. Residual MR at 1-month post-implant did not impact 2-year mortality for either the HM3 (hazard ratio [HR],1.41; 95% CI, 0.52-3.89; p = 0.50) or HMII (HR, 0.91; 95% CI, 0.37-2.26; p = 0.84) LVAD. The presence or absence of baseline MR did not influence mortality (HM3 HR, 0.86; 95% CI, 0.56-1.33; p = 0.50; HMII HR, 0.81; 95% CI, 0.54-1.22; p = 0.32), major adverse events or functional capacity. In multivariate analysis, severe baseline MR (p = 0.001), larger left ventricular dimension (p = 0.002), and implantation with the HMII instead of the HM3 LVAD (p = 0.05) were independently associated with an increased likelihood of persistent MR post-implant. CONCLUSIONS: Hemodynamic unloading after LVAD implantation improves clinically significant MR early, sustainably, and to a greater extent with the HM3 LVAD. Neither baseline nor residual MR influence outcomes after LVAD implantation.

Left ventricular assist systems and infection-related outcomes: A comprehensive analysis of the MOMENTUM 3 trial.

BACKGROUND: In a randomized controlled trial (MOMENTUM 3), the HeartMate 3 (HM3) fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) demonstrated superiority over the HeartMate II (HMII) axial-flow LVAD. These findings were driven by hemocompatibility-related outcomes, but infection-related outcomes were not altered by device choice. In this trial-level analysis, we analyzed the clinical patterns of infection-related outcomes over 2 years of support. METHODS: In MOMENTUM 3, 1,020 patients were implanted with either the HM3 (n = 515) or HMII (n = 505) pump. Clinical characteristics and morbidity- and mortality-related outcomes were evaluated to identify predictors associated with major infectious complications, using univariable and multivariable models. RESULTS: The cumulative number of infections at 2 years was 1,213 (634 HM3 and 579 HMII), and major infection occurred in 58% of patients with the HM3 and 56% of patients with the HMII (p = 0.57). Infections of a local nature unrelated to pump components were most common (n = 681/1,213; 56%), followed by driveline-associated infection (n = 329/1,213; 27%), sepsis (n = 194/1,213; 16%), and other events (n = 9/1,213; 0.7%). Bacterial pathogens were implicated in 806 of 1,213 events (66%); significant predictors of infection included sex (women vs men; hazard ratio [HR]: 1.38, p = 0.003), pre-implant use of intra-aortic balloon pump (HR: 1.33, p = 0.02), pre-implant history of cardiac surgery (HR: 1.28, p = 0.01), and body mass index ≥ 30 (HR: 1.40, p < 0.0001). Most deaths in those with infection occurred owing to non-infectious causes. CONCLUSION: Infection is the most common adverse effect in patients implanted with contemporary continuous-flow LVADs, with most such events unrelated to the pump or its peripheral components. Whether chronic mechanical circulatory devices confer an immunomodulatory effect pre-disposing to infection warrants closer scrutiny to understand and ameliorate this morbidity.

Effect of aspirin dose on hemocompatibility-related outcomes with a magnetically levitated left ventricular assist device: An analysis from the MOMENTUM 3 study.

BACKGROUND: Aspirin (ASA) anti-platelet therapy is mandated with left ventricular assist devices (LVADs) to prevent hemocompatibility-related adverse events (HRAEs). However, the optimal dose of ASA with HeartMate 3 (HM3) LVAD is unknown. METHODS: In an exploratory analysis of HM3-supported patients in the MOMENTUM 3 study (NCT02224755), 2 groups were analyzed: usual-dose (325 mg) and low-dose (81 mg) ASA with anti-coagulation targeted to an international normalized ratio of 2.0 to 3.0. Exclusion criteria included patients not receiving either ASA 81 mg or 325 mg, those with HRAEs ≤7 days after device implantation, and those receiving >1 anti-platelet agent. The primary end-point was survival free from HRAEs (non-surgical bleeding, pump thrombosis, stroke, and peripheral arterial thromboembolic events) at 2 years. RESULTS: Overall, 321 HM3 patients (usual-dose: n = 141, low-dose: n = 180) were included in this analysis. Usual-dose group patients were younger (57 ± 13 vs 60 ± 12 years, p = 0.035) and less often assigned destination therapy (55% vs 67%, p = 0.029) than low-dose ASA. At 2 years, a similar proportion of patients in the usual- and low-dose groups (43.4% vs 45.3%, p = 0.94) met the primary end-point. There were no differences in survival free from hemorrhagic (usual-dose: 54.4% vs low-dose: 51.7%, p = 0.42) or thrombotic (usual-dose: 76.8% vs low-dose: 75.7%, p = 0.92) events. CONCLUSIONS: Usual- and low-dose ASA revealed similar rates of bleeding and thrombotic events in HM3 LVAD-supported patients within the MOMENTUM 3 trial. Whether ASA therapy provides any meaningful therapeutic effect in patients treated by the HM3 LVAD remains to be determined.

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.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Long-term evaluation of a fully magnetically levitated circulatory support device for advanced heart failure-two-year results from the HeartMate 3 CE Mark Study.

AIM: This study aimed to assess safety and outcomes of patients, 2 years after implantation with the HeartMate 3 Left Ventricular Assist System. METHODS AND RESULTS: This study included 50 adults with New York Heart Association (NYHA) class IIIB or IV symptoms or American College of Cardiology/American Heart Association stage D heart failure with an ejection fraction ≤25% and a cardiac index ≤2.2 L/min/m2 without inotropes, or inotrope-dependent with optimal medical management, or listed for heart transplant. The median duration of left ventricular assist device support was 694 days (range: 19-833 days). At baseline, cardiac index was 1.8 ±0.5 L/min/m2 , 58% of patients were receiving inotropes, and 92% were INTERMACS profiles 2-4. At 2 years, Kaplan-Meier survival was 74 ±6%, 5 (10%) patients were transplanted, and 32 patients (64%) remain with support. Adverse event rates include bleeding requiring surgery (16%), gastrointestinal bleeding (20%), driveline infection (24%), ischaemic stroke (16%), haemorrhagic stroke (8%), right heart failure (14%), and outflow graft thrombosis (2%). Notably, no haemolysis, pump thrombosis, or pump malfunction events occurred. At 2 years, 47% of patients remained in NYHA class I and 41% in NYHA class II (P <0.0001). From baseline to 2 years, the mean six-minute walk distance increased from 239 m to 347 m (P <0.0001), and the mean EQ-5D quality of life score improved from 48.2 to 70.6 (P < 0.0001). CONCLUSIONS: Two years post-HeartMate 3 implantation, results show expected and acceptable survival, enhanced haemocompatibility, improved patient functional status and quality of life. This corroborates the success of HeartMate 3 since its first-in-man implantation case in Germany. ClinicalTrials.gov: NCT02170363.

Echocardiographic Changes in Patients Implanted With a Fully Magnetically Levitated Left Ventricular Assist Device (Heartmate 3).

BACKGROUND: The Heartmate 3 (HM3) is a Conformiteé Européenne mark-approved left ventricular (LV) assist device (LVAD) with fully magnetically levitated rotor and features consisting of a wide range operational speeds, wide flow paths, and artificial pulse. We performed a hemodynamic-echocardiographic speed optimization evaluation in HM3-implanted patients to achieve optimal LV- and right ventricular (RV) shape. METHODS AND RESULTS: Sixteen HM3 patients underwent pump speed ramp tests with right heart catheterization. Three-dimensional echocardiographic (3DE) LV and RV datasets (Philips) were acquired, and volumetric (Tomtec) and shape (custom software) analyses were performed (LV: sphericity, conicity; RV: septal and free-wall curvatures). Data were recorded at up to 13 speed settings. Speed changes were in 100-rpm steps, starting at 4600 rpm and ramping up to 6200 rpm. 3DE was feasible in 50% of the patients. Mean original speed was 5306 ± 148 rpm. LV end-diastolic (ED) diameter (-0.15 ± 0.09 cm/100 rpm) and volumes (ED: 269 ± 109 mL to 175 ± 90 mL; end-systolic [ES]: 234 ± 111 mL to 146 ± 81 mL) progressively decreased as the shape became less spherical and more conical; RV volumes initially remained stable, but at higher speeds increased (ED: from 148 ± 64 mL to 181 ± 92 mL; ES: 113 ± 63 mL to 130 ± 69 mL). On average, the RV septum became less convex (bulging toward the LV) at the highest speeds. CONCLUSIONS: LV and RV shape changes were noted in HM3-supported patients. Although a LV volumetric decrease and shape improvement was consistently noted, RV volumes grew in response to increase in speed above a certain point. A next concern would be whether understanding of morphologic and function changes in LV and RV during LVAD speed change assessed with the use of 3DE helps to optimize LVAD speed settings and improve clinical outcomes.

Healthcare Resource Use and Cost Implications in the MOMENTUM 3 Long-Term Outcome Study.

BACKGROUND: The MOMENTUM 3 trial compares the centrifugal HeartMate 3 (HM3) with the axial HeartMate II (HMII) continuous-flow left ventricular assist system in patients with advanced heart failure, irrespective of the intended goal of therapy. The trial's 2-year clinical outcome (n=366) demonstrated superiority of the HM3 for the primary end point (survival free of a disabling stroke or reoperation to replace or remove a malfunctioning pump). This analysis evaluates health resource use and cost implications of the observed differences between the 2 devices while patients were enrolled in the trial. METHODS: We analyzed all hospitalizations and their associated costs occurring after discharge from the implant hospitalization until censoring (study withdrawal, heart transplantation, and pump exchange with a nonstudy device or death). Each adjudicated episode of hospital-based care was used to calculate costs (device-attributable and non-device-attributable event costs), estimated by using trial data and payer administrative claims databases. Cost savings stratified by subgroups (study outcome [transplant, death, or ongoing on device], intended goal of therapy, type of insurance, or sex) were also assessed. RESULTS: In 366 randomly assigned patients, 361 comprised the as-treated group (189 in the HM3 group and 172 in the HMII group), of whom 337 (177 in the HM3 group and 160 in the HMII group) were successfully discharged following implantation. The HM3 arm experienced fewer total hospitalizations per patient-year (HM3: 2.1±0.2 versus HMII: 2.7±0.2; P=0.015) and 8.3 fewer hospital days per patient-year on average (HM3: 17.1 days versus HMII: 25.5 days; P=0.003). These differences were driven by patients hospitalized for suspected pump thrombosis (HM3: 0.6% versus HMII: 12.5%; P<0.001) and stroke (HM3: 2.8% versus HMII: 11.3%; P=0.002). Controlled for time spent in the study (average cumulative cost per patient-year), postdischarge HM3 arm costs were 51% lower than with the HMII (HM3: $37 685±4251 versus HMII: $76 599±11 889, P<0.001) and similar in either bridge to transplant or destination therapy intent. CONCLUSIONS: In this 2-year outcome economic analysis of the MOMENTUM 3 trial, the HM3 demonstrated a reduction in rehospitalizations, hospital days spent during rehospitalizations, and a significant cost savings following discharge in comparison with the HMII left ventricular assist system, irrespective of the intended goal of therapy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02224755.

Evaluation of low-intensity anti-coagulation with a fully magnetically levitated centrifugal-flow circulatory pump-the MAGENTUM 1 study.

BACKGROUND: The HeartMate 3 left ventricular assist system is engineered to avoid pump thrombosis, yet bleeding complications persist. We investigated the safety of low-intensity anti-coagulation in patients with the HeartMate 3. METHODS: The Minimal AnticoaGulation EvaluatioNTo aUgment heMocompatibility (MAGENTUM 1) pilot study is a prospective, single-arm study of low-intensity warfarin anti-coagulation in patients implanted with the HeartMate 3 pump. After standard warfarin anti-coagulation (international normalized ratio [INR] 2.0 to 3.0) and aspirin for 6 weeks post-implant, patients were transitioned to a lower INR target range of 1.5 to 1.9. The primary end-point was a composite of survival free of pump thrombosis, disabling stroke (modified Rankin score [MRS] >3), or major bleeding (excluding peri-operative bleeding) with at least 6-month post-implant follow-up. Time in therapeutic range (TTR) was measured to assess anti-coagulation target efficacy using the Rosendaal method. A safety algorithm to monitor for signs of pump thrombosis was developed and implemented. RESULTS: We enrolled 15 patients (mean age 57.3 ± 13.3 years), 13 men with advanced heart failure (67% with INTERMACS Profiles 2 or 3), irrespective of therapeutic goal of bridge-to-transplant or destination therapy. The primary end-point was met in 14 of 15 (93 ± 6%) patients; 1 patient developed recurrent gastrointestinal bleeding. The TTR during the reduced anti-coagulation phase (6 weeks to 6 months) was 75.3 ± 8.6%. No thrombotic events occurred. CONCLUSIONS: This pilot study suggests low-intensity anti-coagulation targeting an INR between 1.5 and 1.9 is achievable and safe with the HeartMate 3 cardiac pump in the short-term phase, 6-months post-implant. A large-scale trial is now warranted.

Efficacy and Safety of the HeartMate Percutaneous Heart Pump During High-Risk Percutaneous Coronary Intervention (from the SHIELD I Trial).

This study aimed to evaluate the use of the HeartMate percutaneous heart pump, a catheter-based axial flow pump designed to provide partial left ventricular support, in patients who underwent high-risk percutaneous coronary intervention (PCI). Patients who are hemodynamically unstable, or at risk of being hemodynamically unstable, while undergoing PCI may require mechanical circulatory support. Fifty high-risk patients were enrolled in a prospective, nonrandomized, multicenter, open-label trial. Primary end points were freedom from hemodynamic compromise during PCI and a composite measure of major adverse events. Patients were followed for 30 days. No patient met the primary performance end point. Six safety end points in 5 patients occurred, including 1 access site complication requiring intervention, 1 cerebrovascular accident, 2 major bleeding complications, and 2 cases of new or worsening aortic insufficiency. No cardiac deaths, myocardial infarctions, or surgical interventions occurred. In conclusion, initial results of the HeartMate percutaneous heart pump for mechanical circulatory support during high-risk PCI are encouraging. Hemodynamic stability was achieved in all patients with a low incidence of adverse events.

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure.

BACKGROUND: In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. METHODS: In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points. RESULTS: Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). CONCLUSIONS: In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months: A Randomized Controlled Study of a Fully Magnetically Levitated Pump in Advanced Heart Failure.

BACKGROUND: The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy). This investigation reported its primary outcome in the short-term cohort (n=294; 6-month follow-up), demonstrating superiority of the HM3 for the trial primary end point (survival free of a disabling stroke or reoperation to replace the pump for malfunction), driven by a reduced need for reoperations. The aim of this analysis was to evaluate the aggregate of hemocompatibility-related clinical adverse events (HRAEs) between the 2 LVAS. METHODS: We conducted a secondary end point evaluation of HRAE (survival free of any nonsurgical bleeding, thromboembolic event, pump thrombosis, or neurological event) in the short-term cohort (as-treated cohort n=289) at 6 months. The net burden of HRAE was also assessed by using a previously described hemocompatibility score, which uses 4 escalating tiers of hierarchal severity to derive a total score for events encountered during the entire follow-up experience for each patient. RESULTS: In 289 patients in the as-treated group (151 the HM3 and 138 the HMII), survival free of any HRAE was achieved in 69% of the HM3 group and in 55% of the HMII group (hazard ratio, 0.62; confidence interval, 0.42-0.91; P=0.012). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 36 points, P<0.001) or medically managed pump thrombosis (0 versus 5 points, P=0.02), and fewer nondisabling strokes (6 versus 24 points, P=0.026) than the control HMII LVAS. The net hemocompatibility score in the HM3 in comparison with the HMII patients was 101 (0.67±1.50 points/patient) versus 137 (0.99±1.79 points/patient) (odds ratio, 0.64; confidence interval, 0.39-1.03; P=0.065). CONCLUSIONS: In this secondary analysis of the MOMENTUM 3 trial, the HM3 LVAS demonstrated greater freedom from HRAEs in comparison with the HMII LVAS at 6 months. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02224755.

Clinical hemodynamic evaluation of patients implanted with a fully magnetically levitated left ventricular assist device (HeartMate 3).

BACKGROUND: The HeartMate 3 (HM3) is a Conformiteé Européenne (CE) mark-approved left ventricular assist device (LVAD) with a fully magnetically levitated rotor with features consisting of a wide range of operational speeds, wide flow paths and an artificial pulse. We performed a hemodynamic and echocardiographic evaluation of patients implanted with the HM3 LVAD to assess the speed range for optimal hemodynamic support. METHODS: Sixteen HM3 patients underwent pump speed ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP] and blood pressure [BP]) and 3-dimensional echocardiography (3DE). Data were recorded at up to 13 speed settings. Speed changes were in steps of 100 revolutions per minute (rpm), starting at 4,600 rpm and ramping up to 6,200 rpm. RESULTS: Mean original speed was 5,306 ± 148 rpm, with a majority of patients (10 of 16, 62.5%) having normal CVPs and PCWPs at their original rpm settings. Going from lowest to highest speeds, cardiac output improved at the rate of 0.08 ± 0.08 liter/min per 100 rpm (total change 1.25 ± 1.20 liters/min) and PCWP decreased at the rate of -0.48 ± 0.27 mm Hg per 100 rpm (total change -6.13 ± 3.72 mm Hg). CVP and systolic BP did not change significantly with changes in rpm. Left ventricular end-diastolic dimension (LVEDD) decreased at a rate of -0.15 ± 0.09 cm per 100 rpm. Number of rpm was adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in 13 (81.3%) patients. For the remaining 3 patients, medical management was pursued to optimize hemodynamic support. CONCLUSION: Hemodynamic normalization of pressures was achieved in the majority of patients implanted with the HM3 pump within a narrow speed range.