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.

Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial.

Importance: Although durable left ventricular assist device (LVAD) therapy has emerged as an important treatment option for patients with advanced heart failure refractory to pharmacological support, outcomes, including survival, beyond 2 years remain poorly characterized. Objective: To report the composite end point of survival to transplant, recovery, or LVAD support free of debilitating stroke (Modified Rankin Scale score >3) or reoperation to replace the pump 5 years after the implant in participants who received the fully magnetically levitated centrifugal-flow HeartMate 3 or axial-flow HeartMate II LVAD in the MOMENTUM 3 randomized trial and were still receiving LVAD therapy at the 2-year follow-up. Design, Setting, and Participants: This observational study was a 5-year follow-up of the MOMENTUM 3 trial, conducted in 69 US centers, that demonstrated superiority of the centrifugal-flow LVAD to the axial-flow pump with respect to survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump at 2 years. A total of 295 patients were enrolled between June 2019 to April 2021 in the extended-phase study, with 5-year follow-up completed in September 2021. Exposures: Of 1020 patients in the investigational device exemption per-protocol population, 536 were still receiving LVAD support at 2 years, of whom 289 received the centrifugal-flow pump and 247 received the axial-flow pump. Main Outcomes and Measures: There were 10 end points evaluated at 5 years in the per-protocol population, including a composite of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump between the centrifugal-flow and axial-flow pump groups and overall survival between the 2 groups. Results: A total of 477 patients (295 enrolled and 182 provided limited data) of 536 patients still receiving LVAD support at 2 years contributed to the extended-phase analysis (median age, 62 y; 86 [18%] women). The 5-year Kaplan-Meier estimate of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump in the centrifugal-flow vs axial-flow group was 54.0% vs 29.7% (hazard ratio, 0.55 [95% CI, 0.45-0.67]; P < .001). Overall Kaplan-Meier survival was 58.4% in the centrifugal-flow group vs 43.7% in the axial-flow group (hazard ratio, 0.72 [95% CI, 0.58-0.89]; P = .003). Serious adverse events of stroke, bleeding, and pump thrombosis were less frequent in the centrifugal-flow pump group. Conclusions and Relevance: In this observational follow-up study of patients from the MOMENTUM 3 randomized trial, per-protocol analyses found that receipt of a fully magnetically levitated centrifugal-flow LVAD vs axial-flow LVAD was associated with a better composite outcome and higher likelihood of overall survival at 5 years. These findings support the use of the fully magnetically levitated LVAD. Trial Registration: ClinicalTrials.gov Identifier: NCT02224755 and NCT03982979.

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 .).

A principal components analysis of factors associated with successful implementation of an LVAD decision support tool.

BACKGROUND: A central goal among researchers and policy makers seeking to implement clinical interventions is to identify key facilitators and barriers that contribute to implementation success. Despite calls from a number of scholars, empirical insights into the complex structural and cultural predictors of why decision aids (DAs) become routinely embedded in health care settings remains limited and highly variable across implementation contexts. METHODS: We examined associations between "reach", a widely used indicator (from the RE-AIM model) of implementation success, and multi-level site characteristics of nine LVAD clinics engaged over 18 months in implementation and dissemination of a decision aid for left ventricular assist device (LVAD) treatment. Based on data collected from nurse coordinators, we explored factors at the level of the organization (e.g. patient volume), patient population (e.g. health literacy; average sickness level), clinician characteristics (e.g. attitudes towards decision aid; readiness for change) and process (how the aid was administered). We generated descriptive statistics for each site and calculated zero-order correlations (Pearson's r) between all multi-level site variables including cumulative reach at 12 months and 18 months for all sites. We used principal components analysis (PCA) to examine any latent factors governing relationships between and among all site characteristics, including reach. RESULTS: We observed strongest inclines in reach of our decision aid across the first year, with uptake fluctuating over the second year. Average reach across sites was 63% (s.d. = 19.56) at 12 months and 66% (s.d. = 19.39) at 18 months. Our PCA revealed that site characteristics positively associated with reach on two distinct dimensions, including a first dimension reflecting greater organizational infrastructure and standardization (characteristic of larger, more established clinics) and a second dimension reflecting positive attitudinal orientations, specifically, openness and capacity to give and receive decision support among coordinators and patients. CONCLUSIONS: Successful implementation plans should incorporate specific efforts to promote supportive and mutually informative interactions between clinical staff members and to institute systematic and standardized protocols to enhance the availability, convenience and salience of intervention tool in routine practice. Further research is needed to understand whether "core predictors" of success vary across different intervention types.

Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study.

BACKGROUND: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. METHODS: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. RESULTS: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1-733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181-730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08-0.63; P=0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). CONCLUSIONS: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.

A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure.

BACKGROUND: Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis. METHODS: We randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end point (noninferiority margin, -10 percentage points). RESULTS: Of 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 131 patients (86.2%) in the centrifugal-flow pump group and in 109 (76.8%) in the axial-flow pump group (absolute difference, 9.4 percentage points; 95% lower confidence boundary, -2.1 [P<0.001 for noninferiority]; hazard ratio, 0.55; 95% confidence interval [CI], 0.32 to 0.95 [two-tailed P=0.04 for superiority]). There were no significant between-group differences in the rates of death or disabling stroke, but reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (1 [0.7%] vs. 11 [7.7%]; hazard ratio, 0.08; 95% CI, 0.01 to 0.60; P=0.002). Suspected or confirmed pump thrombosis occurred in no patients in the centrifugal-flow pump group and in 14 patients (10.1%) in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes at 6 months than was implantation of an axial-flow pump, primarily because of the lower rate of reoperation for pump malfunction. (Funded by St. Jude Medical; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Impact of Socioeconomic Factors on Patient Desire for Early LVAD Therapy Prior to Inotrope Dependence.

BACKGROUND: Worsening heart failure (HF) and health-related quality of life (HRQOL) have been shown to impact the decision to proceed with left ventricular assist device (LVAD) implantation, but little is known about how socioeconomic factors influence expressed patient preference for LVAD. METHODS AND RESULTS: Ambulatory patients with advanced systolic HF (n=353) reviewed written information about LVAD therapy and completed a brief survey to indicate whether they would want an LVAD to treat their current level of HF. Ordinal logistic regression analyses identified clinical and demographic predictors of LVAD preference. Higher New York Heart Association (NYHA) class, worse HRQOL measured by Kansas City Cardiomyopathy Questionnaire, lower education level, and lower income were significant univariable predictors of patients wanting an LVAD. In the multivariable model, higher NYHA class (OR [odds ratio]: 1.43, CI [confidence interval]: 1.08-1.90, P = .013) and lower income level (OR: 2.10, CI: 1.18 - 3.76, P = .012 for <$40,000 vs >$80,000) remained significantly associated with wanting an LVAD. CONCLUSION: Among ambulatory patients with advanced systolic HF, treatment preference for LVAD was influenced by level of income independent of HF severity. Understanding the impact of socioeconomic factors on willingness to consider LVAD therapy may help tailor counseling towards individual needs.

Successful venoplasty of superior vena cava stenosis in a patient with a total artificial heart after orthotopic heart transplantation due to primary graft failure.

BACKGROUND: With the limited number of available suitable donor hearts resulting in plateaued numbers of heart transplantations, short- and long-term mechanical circulatory support devices, including the implantation of total artificial hearts (TAHs) are modalities that are increasingly being used as treatment options for patients with end-stage heart failure. The superior vena cava syndrome has been described in this context in various disease processes. We report successful venoplasty for superior vena cava syndrome in a patient with a TAH. CASE PRESENTATION: A 65-year-old man with a history of nonischemic cardiomyopathy had received a left ventricular assist device, and then 2 years later, underwent orthotopic heart transplantation using the bicaval anastomosis technique. The postprocedural course was complicated by primary graft failure, resulting in the need for implantation of a TAH. About 5 months after TAH implantation, he started to develop complications such as volume retention, swelling of the upper extremities, and was diagnosed to have a superior vena cava syndrome. The patient underwent a successful venoplasty of his superior vena cava by interventional radiology with resolution of upper body edema, normalization of renal, and liver function. CONCLUSION: Potential fatal complications caused by catheter or wire entrapment in the right-sided mechanical valve of a TAH have been reported. We describe a safe method for the treatment of superior vena cava syndrome in patients with TAH.

Percutaneous venoarterial extracorporeal membrane oxygenation as a bridge to double valve implantation in acute biventricular heart failure with profound cardiogenic shock.

A 71-year-old woman was admitted with acute hypoxic and hypercapnic respiratory failure and cardiogenic shock, secondary to acute on chronic biventricular systolic and diastolic congestive heart failure and severe aortic and mitral valve stenosis. She further presented with pulmonary hypertension and moderate-to-severe tricuspid regurgitation requiring high and increasing doses of vasopressors. The patient was percutaneously cannulated for venoarterial extracorporeal membrane oxygenation (VA-ECMO) and stabilized on ECMO, with a urine output of 17.3 L within the following 8 days. Balloon valvuloplasty and/or transcatheter aortic valve replacement were discussed but ruled out by the multidisciplinary team considering the mitral valve could not be fully addressed. Though lung function was not fully optimized, a window of opportunity was identified and used for double valve replacement on day 8 of VA-ECMO support. After a 24-hour vasoplegic period, the patient was extubated to continuous positive airway pressure and further transitioned to nasal cannula, following which she recovered well.

A Multisite Randomized Controlled Trial of a Patient-Centered Ventricular Assist Device Decision Aid (VADDA Trial).

BACKGROUND: Studies indicate that decision making and informed consent among patients considering left ventricular assist device (LVAD) support for advanced heart failure could be improved. In the VADDA (Ventricular Assist Device Decision Aid) trial, we tested a patient-centered decision aid (DA) to enhance the quality of decision making about LVAD therapy. METHODS: After an extensive user-centered design process, we conducted a multisite randomized trial of the DA compared with standard education (SE) among inpatients considering LVAD treatment for advanced heart failure The main outcome was LVAD knowledge at 1 week and 1 month after administration of the DA versus the SE, according to a validated scale. Secondary measures included prespecified quality decision making measures recommended by the International Patient Decision Aid Standards collaboration. RESULTS: Of 105 eligible patients, 98 consented and were randomly assigned to the DA and SE arms. Patients receiving the VADDA exhibited significantly greater LVAD knowledge than the SE group at 1 week of follow-up (P = .01) but not at 1 month (P = .47). No differences were found between DA and SE patients in rates of acceptance versus decline of LVAD treatment (85% vs 78%; P = .74). Recipients in the DA arm reported greater satisfaction with life after implantation compared with nonrecipients (28 vs 23 out of 30; P = .008), although both arms reported high satisfaction. Patients rated the DA high in acceptability and usability. CONCLUSIONS: The VADDA enhances LVAD knowledge, particularly in the short term (1 week) during the peak period of decision making. The DA does not encourage decision direction and reflects patient, caregiver, and physician preferences for content and format. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02248974. The trial is registered with clinicaltrials.gov (NCT02248974).

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.

Factors Related to Pump Thrombosis With the Heartmate II Left Ventricular Assist Device.

BACKGROUND: Recent reports suggested that HeartMate II (HMII) thrombosis rates may be higher in implants after 2011. We characterize events at HMII centers (>100 HMII implants) whose device thrombosis rates are equivalent or lower than reported by INTERMACS. METHODS: Seven centers pooled implants from 2011 through June 2013 to examine pump thrombus and identify characteristics and clinical strategies that potentially mitigate the risk. A total of 666 patients (age 59 ± 13 years; 81% male) were studied (support duration: 13.7 ± 8.3 months, cumulative: 759 patient years). Median target INR was 2.25 (range 2.0 to 2.5), and median pump speed was 9200 rpm (range 8600 to 9600). Pump thrombus was suspected with clinical evidence (e.g., hemolysis, positive ramp test) requiring intervention (e.g., anticoagulation therapy, pump exchange) or patient death. RESULTS: Suspected pump thrombus occurred in 24/666 (3.6%) patients within three months of implant. At six months, 38/666 (5.7%) had suspected pump thrombus including 24 (3.6%) resulting in pump exchange or death. Stroke (hemorrhagic: 0.049, and ischemic: 0.048 events/patient year) and survival (six months: 88 ± 1%; 1 year: 81 ± 2%) were consistent with national averages. Suspected pump thrombus patients were younger (55 ± 13 vs. 59 ± 13, p = 0.046) and had more females (31.6% vs. 18.3%, p = 0.054). There was no difference in indication, etiology of heart failure, or body size. CONCLUSIONS: This analysis demonstrates low HMII thrombus events. Minimization of risk factors by uniform implant techniques and consistent post-op management may reduce device thrombosis. A larger scale multicenter evaluation may better elucidate the difference in thrombus events between centers.

Concurrent valvular procedures during left ventricular assist device implantation and outcomes: A comprehensive analysis of the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 trial portfolio.

BACKGROUND: Correction of valvular disease is often undertaken during left ventricular assist device (LVAD) implantation with uncertain benefit. We analyzed clinical outcomes with HeartMate 3 (HM3; Abbott) LVAD implantation in those with various concurrent valve procedures (HM3+VP) with those with an isolated LVAD implant (HM3 alone). METHODS: The study included 2200 patients with HM3 implanted within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial portfolio who underwent 820 concurrent procedures among which 466 (21.8%) were HM3+VP. VPs included 101 aortic, 61 mitral, 163 tricuspid; 85 patients had multiple VPs. Perioperative complications, major adverse events, and survival were analyzed. RESULTS: Patients who underwent HM3+VP had higher-acuity Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles (1-2: 41% vs 31%) compared with no VPs (P < .05). The cardiopulmonary bypass time (124 vs 76 minutes; P < .0001) and hospital length of stay (20 vs 18 days; P < .0001) were longer in HM3+VP. A higher incidence of stroke (4.9% vs 2.4%), bleeding (33.9% vs 23.8%), and right heart failure (41.5% vs 29.6%) was noted in HM3+VP at 0 to 30 days (P < .01), with no difference in 30-day mortality (3.9% vs 3.3%) or 2-year survival (81.7% vs 80.8%). Analysis of individual VP showed no differences in survival compared to HM3 alone. No differences were noted among patients with either significant mitral (moderate or worse) or tricuspid (moderate or worse) regurgitation with or without corrective surgery. CONCLUSIONS: Concurrent VPs, commonly performed during LVAD implantation, are associated with increased morbidity during the index hospitalization, with no effect on short- and long-term survival. There is sufficient equipoise to consider a randomized trial on the benefit of commonly performed VPs (such as mitral or tricuspid regurgitation correction), during LVAD implantation.

Predictors of 5-Year Mortality in Patients Managed With a Magnetically Levitated Left Ventricular Assist Device.

BACKGROUND: In advanced heart failure patients implanted with a fully magnetically levitated HeartMate 3 (HM3, Abbott) left ventricular assist device (LVAD), it is unknown how preimplant factors and postimplant index hospitalization events influence 5-year mortality in those able to be discharged. OBJECTIVES: The goal was to identify risk predictors of mortality through 5 years among HM3 LVAD recipients conditional on discharge from index hospitalization in the MOMENTUM 3 pivotal trial. METHODS: This analysis evaluated 485 of 515 (94%) patients discharged after implantation of the HM3 LVAD. Preimplant (baseline), implant surgery, and index hospitalization characteristics were analyzed individually, and as multivariable predictors for mortality risk through 5 years. RESULTS: Cumulative 5-year mortality in the cohort (median age: 62 years, 80% male, 65% White, 61% destination therapy due to transplant ineligibility) was 38%. Two preimplant characteristics (elevated blood urea nitrogen and prior coronary artery bypass graft or valve procedure) and 3 postimplant characteristics (hemocompatibility-related adverse events, ventricular arrhythmias, and estimated glomerular filtration rate <60 mL/min/1.73 m2 at discharge) were predictors of 5-year mortality. In 171 of 485 patients (35.3%) without any risk predictors, 5-year mortality was reduced to 22.6% (95% CI: 15.4%-32.7%). Even among those with 1 or more predictors, mortality was <50% at 5 years (45.7% [95% CI: 39.0%-52.8%]). CONCLUSIONS: Long-term survival in successfully discharged HM3 LVAD recipients is largely influenced by clinical events experienced during the index surgical hospitalization in tandem with baseline factors, with mortality of <50% at 5 years. In patients without identified predictors of risk, long-term 5-year mortality is low and rivals that achieved with heart transplantation, even though most were implanted with destination therapy intent. (MOMENTUM 3 IDE Clinical Study Protocol, NCT02224755; MOMENTUM 3 Pivotal Cohort Extended Follow-up PAS, NCT03982979).

Outcomes of COVID-19 in heart failure, LVAD, and heart transplant patients in an advanced heart failure practice.

Background: Patients with heart failure face increased morbidity and mortality when infected with COVID-19. The objective of this study was to evaluate the outcomes of patients with Heart Failure (HF), Left Ventricular Assist Devices (LVADs), or Heart Transplants (HTx) diagnosed with COVID-19 within an advanced HF practice. Methods: Out of 2635 patients followed, 96 patients were diagnosed with COVID-19 between March 2020 and January 2021. Median hospital length of stay (LOS), requirement for mechanical ventilation (MV), and mortality rate were evaluated. Results: The distribution of COVID-19 among the 96 patients was: HF = 43 (45 %), LVAD = 16 (17 %) and HTx = 37 (38 %). Among 43 HF patients, 5 (12 %) died, 18 (42 %) required hospitalization with an LOS of 7 days, 5 (12 %) required ICU and 4 (9 %) required MV. Of the 16 LVAD patients, 2 (13 %) died, 8 (50 %) required hospitalization with an LOS of 11 days, 3 (19 %) required ICU and 3 (19 %) required MV. Among 37 HTx patients, 7 (19 %) died, 23 (62 %) required hospitalization with an LOS of 9 days, 6 (16 %) required ICU and 6 (16 %) required MV. Conclusion: This report is among the first to describe the impact of COVID-19 on a diverse advanced HF practice. It highlights the risks associated with COVID-19 faced by the HF, LVAD and HTx patients. A 90-day mortality rate of 19 % with HTx patients acquiring COVID-19 is ominous as is a mortality rate of 12 % each for HF and LVAD patients. This clinical impact should serve as a reminder of unique challenges with these populations.

Oncostatin M: a Potential Biomarker to Predict Infection in Patients with Left Ventricular Assist Devices.

Infection is a serious adverse event limiting left ventricular assist device (LVAD) therapy in advanced heart failure patients, but a reliable means to identify patients at increased risk of infection is still lacking. We hypothesized that preoperative elevated levels of plasma Oncostatin M (OSM), a cytokine marker of leukocyte activation and inflammation, would be predictive of subsequent infection. We measured plasma OSM in 41 LVAD patients one day before LVAD implantation and postoperatively over two months. Preoperative plasma OSM levels were normal in 27 patients (group A, 4.9 ± 3.2 pg/ml) but elevated in 14 patients (group B, 1649.0 ± 458.9 pg/ml) ( p = 0.003). Early postoperative levels rose in both groups and declined rapidly in group A, with group B declining slowly over two months. Significantly more infections developed in group B than group A patients over two months postimplantation ( p = 0.004). No other routine clinical assessment or laboratory testing afforded this differentiation. These findings suggest that preoperative plasma OSM levels may assist in identifying patients at increased risk of infections after LVAD implantation.

Outcomes in Smaller Body Size Adults After HeartMate 3 Left Ventricular Assist Device Implantation.

BACKGROUND: Outcomes in patients with smaller body size after HeartMate 3 left ventricular assist device (HM3) implantation are not well characterized. We sought to evaluate outcomes in smaller vs larger body surface area (BSA) patients in the MOMENTUM 3 pivotal trial and its Continued Access Protocol cohort. METHODS: The analysis cohort included 1015 HM3 patients divided into 2 groups: BSA ≤1.70 m2 (small patients, n = 82) and BSA >1.70 m2 (large patients, n = 933). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or to remove a malfunctioning device. Adverse events were compared between groups. RESULTS: Smaller patients were more frequently women (56.1% vs 17.7%; P < .001) and had lower prevalence of diabetes (28.1% vs 43.9%; P = .005) and hypertension (51.2% vs 71.9%; P < .001), larger median indexed LVEDD (normalized by BSA, 40 vs 33 mm/m2; P < .001), and lower median serum creatinine concentration (1.1 vs 1.3 mg/dL; P < .001). The proportion of patients achieving the composite end point at 2 years was 77% in both groups (adjusted hazard ratio, 1.14; 95% CI, 0.68-1.91; P = .62). Two-year adverse event rates were also similar between groups except for sepsis (6.1% vs 14.9%; P = .029) and cardiac arrhythmias (24.4% vs 35.3%; P = .005), which were higher in the larger patients. CONCLUSIONS: Outcomes after HM3 implantation were comparable between small and large patients. Smaller body size should not be used to deny HM3 implantation in patients who are otherwise suitable candidates for durable mechanical circulatory support.

Primary results of long-term outcomes in the MOMENTUM 3 pivotal trial and continued access protocol study phase: a study of 2200 HeartMate 3 left ventricular assist device implants.

AIM: The MOMENTUM 3 pivotal trial established superiority of the HeartMate 3 (HM3) left ventricular assist device (LVAD), a fully magnetically levitated centrifugal-flow pump, over the HeartMate II axial-flow pump. We now evaluate HM3 LVAD outcomes in a single-arm prospective continuous access protocol (CAP) post-pivotal trial study. METHODS AND RESULTS: We enrolled 2200 HM3 implanted patients (515 pivotal trial and 1685 CAP patients) and compared outcomes including survival free of disabling stroke or reoperation to replace or remove a malfunctioning device (primary composite endpoint), overall survival and major adverse events at 2 years. The 2-year primary endpoint [76.7% vs. 74.8%; adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.71-1.08, P = 0.21] and overall survival (81.2% vs. 79.0%) were similar among CAP and pivotal cohorts despite sicker patients (more intra-aortic balloon pump use and INTERMACS profile 1) in CAP who were more often intended for destination therapy. Survival was similar between the CAP and pivotal trial in transplant ineligible patients (79.1% vs. 76.7%; adjusted HR 0.89, 95% CI 0.68-1.16, P = 0.38). In a pooled analysis, the 2-year primary endpoint was similar between INTERMACS profiles 1-2 ('unstable' advanced heart failure), profile 3 ('stable' on inotropic therapy), and profiles 4-7 ('stable' ambulatory advanced heart failure) (75.7% vs. 77.6% vs. 72.9%, respectively). The net burden of adverse events was lower in CAP (adjusted rate ratio 0.93, 95% CI 0.88-0.98, P = 0.006), with consequent decrease in hospitalization. CONCLUSIONS: The primary results of accumulating HM3 LVAD experience suggest a lower adverse event burden and similar survival compared to the pivotal MOMENTUM 3 trial.

Clinical outcomes and healthcare expenditures in the real world with left ventricular assist devices - The CLEAR-LVAD study.

BACKGROUND: Several distinctly engineered left ventricular assist devices (LVADs) are in clinical use. However, contemporaneous real world comparisons have not been conducted, and clinical trials were not powered to evaluate differential survival outcomes across devices. OBJECTIVES: Determine real world survival outcomes and healthcare expenditures for commercially available durable LVADs. METHODS: Using a retrospective observational cohort design, Medicare claims files were linked to manufacturer device registration data to identify de-novo, durable LVAD implants performed between January 2014 and December 2018, with follow-up through December 2019. Survival outcomes were compared using a Cox proportional hazards model stratified by LVAD type and validated using propensity score matching. Healthcare resource utilization was analyzed across device types by using nonparametric bootstrap analysis methodology. Primary outcome was survival at 1-year and total Part A Medicare payments. RESULTS: A total of 4,195 de-novo LVAD implants were identified in fee-for-service Medicare beneficiaries (821 HeartMate 3; 1,840 HeartMate II; and 1,534 Other-VADs). The adjusted hazard ratio for mortality at 1-year (confirmed in a propensity score matched analysis) for the HeartMate 3 vs HeartMate II was 0.64 (95% CI; 0.52-0.79, p< 0.001) and for the HeartMate 3 vs Other-VADs was 0.51 (95% CI; 0.42-0.63, p < 0.001). The HeartMate 3 cohort experienced fewer hospitalizations per patient-year vs Other-VADs (respectively, 2.8 vs 3.2 EPPY hospitalizations, p < 0.01) and 6.1 fewer hospital days on average (respectively, 25.2 vs 31.3 days, p < 0.01). The difference in Medicare expenditures, conditional on survival, for HeartMate 3 vs HeartMate II was -$10,722, p < 0.001 (17.4% reduction) and for HeartMate 3 vs Other-VADs was -$17,947, p < 0.001 (26.1% reduction). CONCLUSIONS: In this analysis of a large, real world, United States. administrative dataset of durable LVADs, we observed that the HeartMate 3 had superior survival, reduced healthcare resource use, and lower healthcare expenditure compared to other contemporary commercially available LVADs.

Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (P=0.007) and less burden by both time spent (P<0.0001) and difficulty (P=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (P=0.034) and being a married caregiver (P=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03-1.99; P=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29-6.96; P=0.011). Conclusions Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient-caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.