Cardiogenic Shock in Older Adults: A Focus on Age-Associated Risks and Approach to Management: A Scientific Statement From the American Heart Association.

Cardiogenic shock continues to portend poor outcomes, conferring short-term mortality rates of 30% to 50% despite recent scientific advances. Age is a nonmodifiable risk factor for mortality in patients with cardiogenic shock and is often considered in the decision-making process for eligibility for various therapies. Older adults have been largely excluded from analyses of therapeutic options in patients with cardiogenic shock. As a result, despite the association of advanced age with worse outcomes, focused strategies in the assessment and management of cardiogenic shock in this high-risk and growing population are lacking. Individual programs oftentimes develop upper age limits for various interventional strategies for their patients, including heart transplantation and durable left ventricular assist devices. However, age as a lone parameter should not be used to guide individual patient management decisions in cardiogenic shock. In the assessment of risk in older adults with cardiogenic shock, a comprehensive, interdisciplinary approach is central to developing best practices. In this American Heart Association scientific statement, we aim to summarize our contemporary understanding of the epidemiology, risk assessment, and in-hospital approach to management of cardiogenic shock, with a unique focus on older adults.

The Future of Durable Mechanical Circulatory Support: Emerging Technological Innovations and Considerations to Enable Evolution of the Field.

The field of durable mechanical circulatory support (MCS) has undergone an incredible evolution over the past few decades, resulting in significant improvements in longevity and quality of life for patients with advanced heart failure. Despite these successes, substantial opportunities for further improvements remain, including in pump design and ancillary technology, perioperative and postoperative management, and the overall patient experience. Ideally, durable MCS devices would be fully implantable, automatically controlled, and minimize the need for anticoagulation. Reliable and long-term total artificial hearts for biventricular support would be available; and surgical, perioperative, and postoperative management would be informed by the individual patient phenotype along with computational simulations. In this review, we summarize emerging technological innovations in these areas, focusing primarily on innovations in late preclinical or early clinical phases of study. We highlight important considerations that the MCS community of clinicians, engineers, industry partners, and venture capital investors should consider to sustain the evolution of the field.

Impact of Right Ventricular Dysfunction on Outcomes in Acute Myocardial Infarction and Cardiogenic Shock: Insights from the National Cardiogenic Shock Initiative.

BACKGROUND: Right ventricular dysfunction (RVD) complicates 30%-40% of cases in acute myocardial infarction (AMI) and cardiogenic shock (CS). There are sparse data on the effects of RVD on outcomes and the impact of providing early left ventricular (LV) mechanical circulatory support (MCS) on RV function and hemodynamics. METHODS AND RESULTS: Between July 2016 and December 2020, 80 sites participated in the study. All centers agreed to treat patients with AMI-CS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of LV-MCS. RVD was defined as a right atrial (RA) pressure of >12 mm Hg and a pulmonary artery pulsatility index (PAPI) of <1 within 24 hours of the index procedure. The primary outcome was survival to discharge. In a subgroup analysis, data available from the Automated Impella Controller console was used to analyze diastolic suction alarms from LV placement signal and its relation to RVD. A total of 361 patients were included in the analysis, of whom 28% had RVD. The median age was 64 years (interquartile range 55-72 years), 22.7% were female and 75.7% were White. There was no difference in age, sex, or comorbidities between those with or without RVD. Patients with RVD had a higher probability of active CPR during LV-MCS implant (14.7% vs 6.3%), Society for Cardiovascular Angiography and Interventions stage E shock (39.2% vs 23.2%), and higher admission lactate levels (5.1 mg/dL vs 3.0 mg/dL). Survival to discharge was significantly lower among those with RVD (61.8% vs 73.4%, odds ratio 0.89, 95% confidence interval 0.36-0.95, P = .031). This association remained significant in the multivariate analysis. There was no significant difference in hemodynamic variables within 24 hours of LV-MCS support among those with or without RVD. At 24 hours, patients with a CPO of >0.6 W and a PAPi of >1 had a trend toward better survival to discharge compared with those with a CPO of ≤0.6 W and a PAPi of ≤1 (77.1% vs 54.6%, P = .092). Patients with RVD were significantly more likely to have diastolic suction alarms within 24 hours of LV-MCS initiation. CONCLUSIONS: RVD in AMI-CS is common and associated with worse survival to discharge. Early LV-MCS decreases filling pressures rapidly within the first 24 hours and decreases the rate of RVD. Achieving a CPO of >0.6 W and a PAPi of >1 within 24 hours is associated with high survival. Diastolic suction alarms may have usefulness as an early marker of RVD.

Use of percutaneous mechanical circulatory support for right ventricular failure.

BACKGROUND: Utilization of right ventricular mechanical circulatory support (RV-MCS) devices has been limited by a lack of recognition of RV failure as well as a lack of availability and experience with RV-MCS. AIMS: We report a single-center experience with the use of percutaneous RV-MCS and report predictors of adverse outcomes. METHODS: This was a single-center retrospective cohort study. Data from consecutive patients who received RV-MCS for any indication between June 2015 and January 2022 were included. Data on baseline comorbidities, hemodynamics, and laboratory values were collected. The primary outcome was in-hospital mortality analyzed as a logistic outcome in a multivariable model. These variables were further ranked by their predictive value. RESULTS: Among 58 consecutive patients enrolled, the median age was 66 years, 31% were female and 53% were white. The majority of the patients (48%) were hospitalized for acute on chronic heart failure. The majority of the patients were SCAI SHOCK Stage D (67%) and 34 (64%) patients had MCS placed within 24 h of the onset of shock. Before placement of RV-MCS, median central venous pressure (CVP) and RV stroke work index were 20 mmHg and 8.9 g m/m2, respectively. Median serum lactate was 3.5 (1.6, 6.2) mmol/L. Impella RP was implanted in 50% and ProtekDuo in the remaining 50%. Left ventricular MCS was concomitantly used in 66% of patients. Twenty-eight patients (48.3%) died. In these patients, median serum lactate was significantly higher (4.1 [2.3, 13.0] vs. 2.2 [1.4, 4.0] mmol/L, p = 0.007) and a trend toward higher median CVP (24 [18, 31] vs. 19 [14, 24] mmHg, p = 0.052). In the multivariable logistic model, both serum lactate and CVP before RV-MCS placement were independent predictors of in-hospital mortality. Serum lactate had the highest predictive value. CONCLUSION: In our real-world cohort, 52% of patients treated with RV-MCS survived their index hospitalization. Serum lactate at presentation and CVP were the strongest predictors of in-hospital mortality.

HFSA Expert Consensus Statement on the Medical Management of Patients on Durable Mechanical Circulatory Support.

The medical management of patients supported with durable continuous flow left ventricular assist device (LVAD) support encompasses pharmacological therapies administered in the preoperative, intraoperative, postoperative, and chronic LVAD support stages. As patients live longer on LVAD support, the risks of LVAD-related complications and progression of cardiovascular and other diseases increase. Using existing data from cohort studies, registries, randomized trials, and expert opinion, this Heart Failure Society of America Consensus Document on the Medical Management of Patients on Durable Mechanical Circulatory Support offers best practices on the management of patients on durable mechanical circulatory support, focusing on pharmacological therapies administered to patients on continuous flow LVADs. Although quality data in the LVAD population are few, the use of guideline-directed heart failure medical therapies and the importance of blood pressure management, right ventricular preload and afterload optimization, and antiplatelet and anticoagulation regimens are discussed. Recommended pharmacological regimens used to mitigate or treat common complications encountered during LVAD support, including arrhythmias, vasoplegia, mucocutaneous bleeding, and infectious complications, are addressed. Finally, this document touches on important potential pharmacological interactions from antidepressants and herbal and nutritional supplements of relevance to providers of patients on LVAD support.

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

BACKGROUND: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management. METHODS: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System. CONCLUSION: The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, and PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

Exploring Physician Perceptions of the 2018 United States Heart Transplant Allocation System.

BACKGROUND: After the implementation of the 2018 US heart transplant allocation system, the experience and perceptions of heart transplant clinicians have not been well-cataloged. METHODS AND RESULTS: This web-based survey of both heart failure cardiologists and surgeons examined physician perspectives about the policy changes and whether the system is meeting its intended goals. The majority of participants (94%, n = 113) responded that the 2018 heart allocation system requires modification. Eighty-four percent reported using more temporary mechanical circulatory support to achieve higher status and 86% were concerned about the change in physician behavior and practices under the new system. CONCLUSIONS: Suggestions for possible improvement included higher status for patients on durable left ventricular assist device support, changes to criteria for status 2, modification of status exceptions, and advocacy for a heart allocation score.

Outcomes in Patients With Chronic Kidney Disease and End-stage Renal Disease and Durable Left Ventricular Assist Device: Insights From the United States Renal Data System Database.

BACKGROUND: There is paucity of data regarding durable left ventricular assist device (LVAD) outcomes in patients with chronic kidney disease (CKD) stages 3-5 and CKD stage 5 on dialysis (end-stage renal disease [ESRD]). METHODS AND RESULTS: We conducted a retrospective study of Medicare beneficiaries with ESRD and a 5% sample of patients with CKD with an LVAD (2006-2018) to determine 1-year outcomes using the United States Renal Data System database. The LVAD implantation, comorbidities, and outcomes were identified using appropriate International Classification of Diseases, 9th and 10th edition codes. We identified 496 patients with CKD and 95 patients with ESRD who underwent LVAD implantation. The patients with ESRD were younger (59 years vs 66 years; P < .001), had more Blacks (40% vs 24.6%, P = .009), compared with the CKD group. The 1-year mortality (49.5% vs 30.9%, P < .001) and index mortality (27.4% vs 16.7%, P = .014) rates were higher for patients with ESRD. A subgroup analysis showed significantly higher mortality in ESRD vs CKD 3 (49.5% vs 30.2%, adjusted P = .009), but no significant difference in mortality between stage 3 vs 4/5 (30.2% vs 30.8%, adjusted P = .941). There was no significant difference in secondary outcomes (bleeding, stroke, and sepsis/infection) during follow-up between the 2 groups. CONCLUSIONS: Patients with ESRD undergoing LVAD implantation had significantly higher index and 1-year mortality rates compared with patients with CKD.

Center Variability in Patient Outcomes Following HeartMate 3 Implantation: An Analysis of the MOMENTUM 3 Trial.

BACKGROUND: As left ventricular assist device (LVAD) survival rates continue to improve, evaluating site-specific variability in outcomes can facilitate identifying targets for quality-improvement initiative opportunities in the field. METHODS: Deidentified center-specific outcomes were analyzed for HeartMate 3 (HM3) patients enrolled in the MOMENTUM 3 pivotal and continued access protocol trials. Centers < 25th percentile for HM3 volumes were excluded. Variability in risk-adjusted center mortality was assessed at 90 days and 2 years (conditional upon 90-day survival). Adverse event (AE) rates were compared across centers. RESULTS: In the 48 included centers (1958 patients), study-implant volumes ranged between 17 and 106 HM3s. Despite similar trial-inclusion criteria, patient demographics varied across sites, including age quartile ((Q)1-Q3:57-62 years), sex (73%-85% male), destination therapy intent (60%-84%), and INTERMACS profile 1-2 (16%-48%). Center mortality was highly variable, nadiring at ≤ 3.6% (≤ 25th percentile) and peaking at ≥ 10.4% (≥ 75th percentile) at 90 days and ≤ 10.2% and ≥ 18.7%, respectively, at 2 years. Centers with low mortality rates tended to have lower 2-year AE rates, but no center was a top performer for all AEs studied. CONCLUSIONS: Mortality and AEs were highly variable across MOMENTUM 3 centers. Studies are needed to improve our understanding of the drivers of outcome variability and to ascertain best practices associated with high-performing centers across the continuum of intraoperative to chronic stages of LVAD support.

The genetics of cardiac amyloidosis.

Heritable cardiac amyloidosis (CA) is an underrecognized cause of morbidity and mortality in the USA. It results from the accumulation of the misfolded protein transthyretin within the myocardium, resulting in amyloid transthyretin-associated cardiomyopathy (ATTR-CM). Over 150 different pathologic point mutations within the transthyretin gene have been identified, each carrying variable clinical phenotypes and penetrance. In the USA, the most common cause of hereditary ATTR is the Val122Ile point mutation, with a prevalence of 3.4-4.0% in North Americans of African and Caribbean descent. Among Caucasians with hereditary ATTR-CM, the V30M mutation is the most commonly identified variant. Overall, the incidence of ATTR disease in the USA has been increasing, likely due to an increase in practitioner awareness, utilization of new non-invasive imaging technologies for ATTR diagnosis, and the growth of multidisciplinary amyloid programs across the country. Yet significant numbers of patients with evidence of left ventricular thickening on cardiac imaging, senile aortic stenosis, and/or symptoms of heart failure with preserved ejection fraction likely have undiagnosed CA, especially within the African American population. With the emergence of new disease-modifying therapies for ATTR, recognition and the prompt diagnosis of CA is important for patients and their potentially affected progeny. Herein, we review the genetics of heritable CA as well as the importance of genetic counseling and testing for patients and their families.

Quality of life metrics in LVAD patients after hemocompatibility-related adverse events.

BACKGROUND: Hemocompatibility-related adverse events (HRAE) negatively influence survival. However, no study has examined the impact of these events on health-related quality of life (HRQOL) and functional outcomes following continuous-flow left ventricular assist device implantation (CF-LVAD). We assessed the impact of HRAE events on HRQOL and hypothesized that HRAE's adversely impact HRQOL and functional outcomes. METHODS: INTERMACS database identified patients undergoing primary CF-LVAD implantation from 2008 to 2017. HRAEs included stroke, non-surgical bleeding, hemolysis, and pump thrombosis and were identified as defined in the literature. HRAEs were further stratified as Tier 1-2 and disabling stroke events. Time-series analysis was executed for HRAE patients with values pre-HRAE, post-HRAE, and closest to 12 months follow up. Local polynomial regression curves modeling individual patients were superimposed into "spaghetti" plots. RESULTS: All HRQOL and functional metrics improved in patients over time, despite HRAE complications. However, these patient metrics were significantly reduced compared to the non-HRAE cohort. Advanced data visualization techniques noted a decline after experiencing an HRAE with a subsequent recovery to baseline levels or higher. Six-minute walk test (6MWT) was noted to be most affected in the post-HRAE period but recovered similar to other metrics. CONCLUSIONS: The burden of HRAE following CF-LVAD implantation did not negatively impact the quality of life. However, the 6MWT did not increase in the post-HRAE period in all HRAE patients. Improvement of heart failure symptoms after CF-LVAD coupled with optimal management following the HRAE act to preserve the enhanced quality of life.

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.

Mechanical circulatory support in acute myocardial infarction and cardiogenic shock: Challenges and importance of randomized control trials.

BACKGROUND: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is associated with significant morbidity and mortality. METHODS: We provide an overview of previously conducted studies on the use of mechanical circulatory support (MCS) devices in the treatment of AMI-CS and difficulties which may be encountered in conducting such trials in the United States. RESULTS: Well powered randomized control trials are difficult to conduct in a critically ill patient population due to physician preferences, perceived lack of equipoise and challenges obtaining informed consent. CONCLUSIONS: With growth in utilization of MCS devices in patients with AMI-CS, efforts to perform well-powered, randomized control trials must be undertaken.

Health-Related Quality of Life in Patients With a Left Ventricular Assist Device (QOLVAD) Questionnaire: Initial Psychometrics of a New Instrument.

BACKGROUND: Patients with a left ventricular assist device are a unique and growing population who deserve their own valid, reliable instrument for health-related quality of life. OBJECTIVE: We developed and tested the Health-Related Quality of Life with a Left Ventricular Assist Device (QOLVAD) questionnaire. METHODS: In a prospective, descriptive study, patients from 7 sites completed the QOLVAD and comparator questionnaires. Construct validity was tested using confirmatory factor analysis. Convergent validity was tested using correlations of QOLVAD scores to well-established measures of subjective health status, depression, anxiety, and meaning/faith. Reliability and test-retest reliability were quantified. RESULTS: Patients (n = 213) were 58.7 ± 13.9 years old; 81.0% were male, 73.7% were White, and 48.0% had bridge to transplant. Questionnaires were completed at a median time of 44 weeks post ventricular assist device. The 5 QOLVAD domains had acceptable construct validity (root mean square error of approximation = 0.064, comparative and Tucker-Lewis fit indices > 0.90, weighted root mean square residual = 0.95). The total score and domain-specific scores were significantly correlated with the instruments to which they were compared. Internal consistency reliability was acceptable for all subscales (α = .79-.83) except the cognitive domain (α = .66). Unidimensional reliability for the total score was acceptable (α = .93), as was factor determinacy for multidimensional reliability (0.95). Total test-retest reliability was 0.875 (P < .001). CONCLUSION: Our analysis provided initial support for validity and reliability of the QOLVAD for total score, physical, emotional, social, and meaning/spiritual domains. The QOLVAD has potential in research and clinical settings to guide decision making and referrals; further studies are needed.

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.

Heart transplant recipients with confirmed 2019 novel coronavirus infection: The Detroit experience.

A chronic immunosuppressed state as in solid organ transplant recipients is a reported risk factor for the novel 2019 coronavirus infection. Patients with a history of orthotopic heart transplant (OHT) at a tertiary care transplant center in Detroit, Michigan were retrospectively reviewed from March until May 2020. Clinical parameters and outcomes of 5 OHT recipients and one combined heart-lung recipient with confirmed SARS-CoV-2 were obtained. The cohort was predominately African American males with median age of 59 years (interquartile range, 48.25-73.25). All patients were classified as having mild-moderate disease; none required intubation or ICU admission with no deaths. The most common presenting symptoms were fever and shortness of breath 83% (n = 5), followed by cough and chills 67% (n = 4). All admitted patients (n = 5) received hydroxychloroquine and 3 received high-dose steroids. Antimetabolites were held for 2 patients (33.3%). The calcineurin inhibitor trough goal was decreased in only 1 patient; 3 other patients, without change in goal, required calcineurin inhibitor dosage reduction. Two patients requiring readmission presented 7 and 23 days after initial symptoms onset. In conclusion, our experience with OHT patients infected by the SARS-CoV-2 virus did not have an elevated risk of severe infection. Impact of modifying immunosuppression remains unclear.

Impact of QRS Duration and Ventricular Pacing on Clinical and Arrhythmic Outcomes in Continuous Flow Left Ventricular Assist Device Recipients: A Multicenter Study.

OBJECTIVES: Wide QRS duration and ventricular pacing are common in recipients of continuous-flow left ventricular assist devices (CF-LVADs) but their impact on outcomes remains unclear. We assessed the clinical and arrhythmic outcomes of CF-LVAD patients with wide QRS or right ventricular (RV) pacing at baseline, compared with those with narrow QRS and those with continued cardiac resynchronization therapy (CRT). METHODS AND RESULTS: A total of 520 patients (57 ± 13 years) with an implantable cardioverter-defibrillator (ICD) (n = 240) or CRT-defibrillator (n = 280) who underwent CF-LVAD implantation at 5 centers in 2007-2015 were studied. Patients were divided into 3 groups: ICD-N (QRS ≤120 ms; n = 134), ICD-W (QRS >120 ms; n = 106), and CRT (n = 280). Mortality, hospitalization, and ventricular arrhythmia (VA) incidence were compared among the groups. Baseline QRS duration was different among the groups (100 ± 13 [ICD-N] vs 155 ± 26 [ICD-W] vs 159 ± 29 ms [CRT]; P < .0001). In the ICD-W group, 37 (35%) had >80% RV pacing at baseline. Median biventricular pacing in the CRT group was 96%. Over 523 days of CF-LVAD support, Kaplan-Meier analysis showed no difference in survival among groups (log rank P = .9). According to multivariate Cox regression, wide QRS duration and RV pacing were not associated with survival. QRS narrowed during CF-LVAD support in the ICD-W and CRT groups but was not associated with improved survival (P = .9). No differences were noted among the groups in hospitalizations (P = .9), VA (P = .2), or ICD shocks (P = .06). CONCLUSIONS: In this large CF-LVAD cohort, a wide QRS duration, high percentage of RV pacing at baseline, and changes in QRS duration after LVAD implantation were not associated with survival. Continued CRT after CF-LVAD implantation also was not associated with improved survival or HF hospitalizations.