Will the Heartmate 3 Left Ventricular Assist Device Gain Momentum With New Study Results?
Editor's Note: This Expert Analysis is part of a series presenting perspectives on major ACC.19 trials. Please follow this link for the companion articles.
One of the more eagerly awaited late-breaking clinical trials in heart failure presented at ACC.19 was the MOMENTUM 3 Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) trial. MOMENTUM 3 reported the results of a fully magnetically levitated left ventricular assist device (LVAD), namely the HeartMate 3, used for the treatment of advanced heart failure (HF). The HeartMate 3 device is a pulsatile-flow system without mechanical bearings, as opposed to the HeartMate II device which is a continuous-flow system with mechanical bearings which has carried the burden of hemocompatibility related complications, including pump thrombosis, stroke, and gastrointestinal bleeding. The presentation, given by Dr. Mandeep R. Mehra, outlined the two-year results of the HeartMate 3 LVAD compared to the HeartMate II device. The goal of the study was to randomize, in a one-to-one fashion, patients with advanced HF, regardless of the final goals of therapy (e.g., bridge to transplant or destination therapy), to either a HeartMate II or HeartMate 3 device. The initial short-term follow-up cohort was 294 patients who were followed for 6 months before enrolling an additional 72 patients for the initial long-term cohort. An additional 662 patients were enrolled in the long-term cohort, comprising the full cohort of 1028 patients to be followed for 2 years. Of the full cohort, 999 patients completed the study follow-up (Heartmate 3, n = 509; Heartmate II, n = 490).
The baseline characteristics of the two populations were similar with regards to mean age, ischemic cause of HF, need for intravenous inotropic agents, need for intra-aortic balloon pump, serum creatinine, serum sodium and mean arterial pressures. However, there were significant differences in race between groups. The INTERMACS profile at the time of implant was similar in both populations. The intended goal of pump support was similar between groups, with approximately 61% of patients in both groups undergoing implantation for destination therapy and approximately 22% in both groups undergoing device implantation as a bridge to transplant.
In the initial short-term feasibility cohort, there was significant superiority of the HeartMate 3 device over the HeartMate II with regards to event-free survival which was predominantly driven by a reduction in pump thrombosis. In the initial long-term outcome cohort consisting of 366 patients at 2 years, there was a statistically significant decrease in non-disabling strokes in the HeartMate 3 population over the HeartMate II population.
The primary endpoint of event-free survival at 2 years was significantly better in the HeartMate 3 group. 74.7% of the HeartMate 3 patients were free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years compared to only 60.6% in the HeartMate II population (p < 0.0001). Furthermore, there were significantly fewer pump exchanges, a secondary endpoint, in the HeartMate 3 group compared to the HeartMate II group at 2 years (2.3% vs. 11.3%, p < 0.0001). In addition, with regards to hemocompatibility-related adverse events, the HeartMate 3 was better overall, as there were significantly fewer episodes of suspected pump thrombosis, any type of stroke, as well as surgical, non-surgical and gastrointestinal bleeding complications. In regard to stroke specifically, 88.6% of Heartmate 3 patients were free from all stroke at 2 years compared to 75.8% in the HeartMate II group (p < 0.0001), and there was a significantly lower severity of these strokes in the Heartmate 3 group (p < 0.0001).
While other adverse events were similar between groups with regards to transient ischemic events, major infections including driveline infections, right HF, need for right ventricular assist support, respiratory failure, renal dysfunction and liver dysfunction, there were fewer arrhythmias (35.9% vs. 41%, p = 0.02), as well as specifically ventricular arrhythmias (20.8% vs. 25.3%, p = 0.01), in the HeartMate 3 group as compared to the HeartMate II group.
Also, while the overall survival at 2 years (81% for HeartMate 3 vs. 80% for Heartmate II) and median length of stay was similar between groups (19 days for HeartMate 3 vs. 17 for HeartMate II), the rates of rehospitalization, median duration of rehospitalization when such events occurred and mean duration (in days) of LVAD support outside of the hospital were all significantly lower in the HeartMate 3 group.
With regards to functional status and quality of life, there were significant improvements in the 6-minute walk test, percentage of patients in New York Heart Association class I or II, KCCQ overall summary score and EQ-5D-5L visual analogue scale scores within each treatment arm over time. However, there were no significant differences between the two treatment arms in regards to any of these indicators.
Additional subgroup analyses of the primary endpoint of event-free survival at 2 years demonstrated that the benefits of the HeartMate 3 over the well-established HeartMate II device were seen in both younger patients (<65 years), older patients (≥65 years), men, women, Caucasians, bridge to transplant candidates and those receiving devices as destination therapy. INTERMACS profile 2 or 3 patients also had significantly increased event-free survival with a HeartMate 3. Though there was a trend towards improved event-free survival at 2 years in non-Caucasians and INTERMACS profiles 4 or 5 patients, these did not reach statistical significance.
This study demonstrated that the centrifugal-flow HeartMate 3 LVAD performed significantly better than the axial-flow HeartMate II system with regards to reductions in pump thrombosis and the need for device replacement, reductions in all types and severity of stroke, reductions in any bleeding (especially gastrointestinal), reductions in cardiac arrhythmias (particularly ventricular arrhythmias), and reductions in re-hospitalizations and total number of days spent in the hospital when readmitted. Additionally, the number needed to treat over 2 years to prevent at least one hemocompatibility-related adverse event was less than one. And, over this same time period, 108 such events are averted for every 100 patients treated with HeartMate 3 over HeartMate II. These data demonstrate the significant strides that have been made in mechanical circulatory support. In the original REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial published in 2001, the two-year survival was 23% in the device group whereas the two-year survival was 81% in the current study. Nevertheless, while there are considerable improvements in device-related complications, there undoubtedly remains tremendous opportunities for improving quality of life and event-free survival in patients implanted with long-term durable mechanical assist devices. The technological advances of the HeartMate 3 LVAD, which include wide blood flow passages to reduce shear stress, a frictionless pump design to reduce wear and tear, and probably most importantly, an intrinsic pulse designed to reduce blood stasis, have all contributed to a reduction in the risk of thrombosis and embolic complications. Hopefully, parallel to improved device design and technology will come improvements in patient selection and pre-and post-LVAD management.
The advances of a fully magnetically levitated LVAD, namely the HeartMate 3, will continue to raise the bar with regards to improved overall outcomes in a very sick and challenging patient population. While the ultimate goal of long-term, durable and safe mechanical cardiac support devices that provide comparable outcomes to heart transplantation remain in the distance, the excellent results of the MOMENTUM 3 trial demonstrate a potential for durable mechanical support eventually replacing transplantation as the preferred therapy for end-stage heart failure and also opportunities for potentially considering earlier institution of mechanical circulatory support in advanced heart failure patients.
Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Valvular Heart Disease, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Heart Transplant, Mechanical Circulatory Support, Pulmonary Hypertension, Interventions and ACS, Interventions and Imaging, Interventions and Structural Heart Disease, Interventions and Vascular Medicine, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging, Hypertension, Smoking, Mitral Regurgitation
Keywords: Acute Coronary Syndrome, Acute Kidney Injury, Aneurysm, Dissecting, Aortic Aneurysm, Aorta, Aortic Valve Insufficiency, Aortic Valve, Aortic Valve Stenosis, Arrhythmias, Cardiac, Arterial Pressure, Atherosclerosis, Atrial Appendage, Atrial Fibrillation, Bicuspid, Biomarkers, Cardiac Surgical Procedures, Constriction, Pathologic, Constriction, Pathologic, Conversion to Open Surgery, Coronary Artery Bypass, Coronary Disease, Creatinine, Diagnosis, Differential, Disease-Free Survival, Dilatation, Echocardiography, Endovascular Procedures, Factor VII, Follow-Up Studies, Heart Defects, Congenital, Heart Transplantation, Heart Failure, Heart Valve Diseases, Heart Valve Prosthesis, Heart-Assist Devices, Hemodynamics, Hemorrhage, Hospital Mortality, Hospitalization, Hypertension, Hypertension, Pulmonary, Length of Stay, Liver Diseases, Mitral Valve, Mitral Valve Stenosis, Mitral Valve Insufficiency, Pacemaker, Artificial, Patient Selection, Percutaneous Coronary Intervention, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Pulmonary Embolism, Pulmonary Veins, Pulsatile Flow, Quality Improvement, Quality of Life, Referral and Consultation, Registries, Reoperation, Renal Insufficiency, Research Personnel, Respiratory Insufficiency, Risk Factors, Smoking, Sodium, Spinal Cord Ischemia, Stroke, Stroke Volume, Surgeons, Surgical Instruments, Thrombosis, Tomography, X-Ray Computed, Transcatheter Aortic Valve Replacement, Treatment Outcome, Tricuspid Valve Insufficiency, Ventricular Dysfunction, Left, ACC Annual Scientific Session, ACC19
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