Clonal Hematopoiesis of Indeterminate Potential and Long-term Outcomes in Heart Transplantation.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) mutations, a trait of aging, has been associated with the progression of cardiovascular disease and the development of malignancy. Uncertainty prevails regarding a robust association between CHIP and heart-transplantation (HT) outcomes. OBJECTIVES: To determine the prevalence of CHIP mutations in HT and their association with long-term outcomes, including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. METHODS: We conducted a mixed retrospective-prospective observational study of HT recipients with targeted sequencing for CHIP mutations (variant allele frequency [VAF] of ≥ 2%). The primary composite outcome was the first occurrence of CAV grade ≥ 2, graft failure, malignancy, cardiac retransplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. RESULTS: Among 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%), followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%), and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP mutations were not associated with the primary outcome, which occurred in 44 (46.3%) patients (HR = 0.487; 95% CI:0.197-1.204; P = 0.119), nor were they associated with mlalignancy alone, or death. CONCLUSION: We demonstrated no association between CHIP mutations and post-transplant outcomes, including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence about the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after HT.

Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.3 years (30%). With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS has the potential for immediate improvement in healthspan and lifespan. However, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. An international group of experts in HGPS, pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to identify strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases that typify HGPS clinical pathology. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. These breakthrough interventions for treating critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have high impact on treatment success.

Ventricular assist device using a thoracotomy-based implant technique: Multi-Center Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy (HM3 SWIFT).

OBJECTIVES: The HeartMate 3 (Abbott) left ventricular assist device provides substantial improvement in long-term morbidity and mortality in patients with advanced heart failure. The Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study compares thoracotomy-based implantation clinical outcomes with standard median sternotomy. METHODS: We conducted a prospective, multicenter, single-arm study in patients eligible for HeartMate 3 implantation with thoracotomy-based surgical technique (bilateral thoracotomy or partial upper sternotomy with left thoracotomy). The composite primary end point was survival free of disabling stroke (modified Rankin score >3), or reoperation to remove or replace a malfunctioning device, or conversion to median sternotomy at 6-months postimplant (elective transplants were treated as a success). The primary end point (noninferiority, -15% margin) was assessed with >90% power compared with a propensity score-matched cohort (ratio 1:2) derived from the Multi-Center Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 continued access protocol. RESULTS: The study enrolled 102 patients between December 2020 and July 2022 in the thoracotomy-based arm at 23 North American centers. Follow-up concluded in December 2022. In the Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study group, noninferiority criteria was met (absolute between-group difference, -1.2%; Farrington Manning lower 1-sided 95% CI, -9.3%; P < .0025) and event-free survival was not different (85.0% vs 86.2%; hazard ratio, 1.01; 95% CI, 0.58-2.10). Length of stay with thoracotomy-based implant was longer (median, 20 vs 17 days; P = .03). No differences were observed for blood product utilization, adverse events (including right heart failure), functional status, and quality of life between cohorts. CONCLUSIONS: Thoracotomy-based implantation of the HeartMate 3 left ventricular assist device is noninferior to implantation via standard full sternotomy. This study supports thoracotomy-based implantation as an additional standard for surgical implantation of the HeartMate 3 left ventricular assist device.

Outcomes of untreated subclinical antibody-mediated rejection after heart transplantation.

Subclinical antibody-mediated rejection (AMR) is represented by histopathological and/or immunopathological manifestations in the absence of significant cardiac allograft dysfunction. Treatment remains uncertain as there is a lack of data on asymptomatic heart transplant (HT) recipients (HTR) with a positive cardiac biopsy. We sought to determine the impact of untreated subclinical biopsy-proven AMR, regardless of circulating donor-specific antigen (DSA) expression, when diagnosed on surveillance biopsies in the first year after HT. This retrospective case control study evaluated 260 HTR between May 2004 and February 2021. These comprised 231 controls and 29 patients with untreated subclinical AMR. The mortality event rate was higher in controls (2.63 events per 100 person-years) compared to the scAMR Group (1.71 events per 100 person-years), a difference that did not reach statistical significance (hazard ratio 0.66, CI: 0.18-2.36). The combined event rate of cardiac allograft vasculopathy (CAV), graft dysfunction, or mortality was higher in the subclinical AMR group (5.60 events per 100 person-years) than in controls (3.89 events per 100 person-years) but did not reach statistical significance (hazard ratio 1.63, CI: 0.07-40.09). Our results suggest that subclinical AMR diagnosed in the first year after HT on surveillance biopsy is not associated with decreased survival. This may sway the management of subclinical AMR towards a more conservative approach in transplant-capable institutions that currently prioritize treatment, though prospective, randomized studies of such a management strategy are required.

Clinical Outcomes With a Fully Magnetically Levitated Left Ventricular Assist Device Among Women and Men.

BACKGROUND: Left ventricular assist devices (LVADs) are underused among women with advanced heart failure, but reasons remain unclear. Outcomes in women compared with men with contemporary fully magnetically levitated LVADs remain uncertain. OBJECTIVES: The authors examined differences in characteristics, 2-year outcomes, and risk for key adverse events among women and men. METHODS: In 2,200 HeartMate3 (HM3) (Abbott Cardiovascular) LVAD recipients in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3), survival free of disabling stroke or reoperation to replace or remove a malfunctioning pump at 2 years was analyzed between women and men. Other outcomes included overall 2-year survival, adverse events, and functional measures. RESULTS: Women comprised 20.4% (n = 448 of 2,200) of the study population and were younger, with nonischemic cardiomyopathy, and more often were Black persons compared with men. The primary endpoint (women 79.4% vs men 75.5% (adjusted [a]HR: 0.96 [95% CI: 0.75-1.24]; P = 0.66) or survival at 2 years (women 82.4% vs men 80.2%; aHR: 1.06 [95% CI: 0.81-1.40]; P = 0.66) was no different. Women had an increased rate of stroke (adjusted incidence rate ratio [aIRR]: 1.52 [95% CI: 1.09-2.11]; P = 0.012), major bleeding (aIRR: 1.28 [95% CI: 1.15-1.42]; P < 0.0001) and infection (aIRR 1.14 [95% CI: 1.03-1.55]; P = 0.01), but these differences were not seen among older (>65 years) patients. Both groups had similar gains in 6-minute walk distance and quality-of-life measurements. CONCLUSIONS: There were no differences in the primary composite endpoint or overall survival in women compared with men at 2 years of support. Reasons underlying increase in hemocompatibility-related events and infection-related morbidity in younger women deserves further study. (MOMENTUM 3 IDE [HM3], NCT02224755; MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP], NCT02892955).

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).

Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer.

BACKGROUND: Body wasting in patients with cancer can affect the heart. OBJECTIVES: The frequency, extent, and clinical and prognostic importance of cardiac wasting in cancer patients is unknown. METHODS: This study prospectively enrolled 300 patients with mostly advanced, active cancer but without significant cardiovascular disease or infection. These patients were compared with 60 healthy control subjects and 60 patients with chronic heart failure (ejection fraction <40%) of similar age and sex distribution. RESULTS: Cancer patients presented with lower left ventricular (LV) mass than healthy control subjects or heart failure patients (assessed by transthoracic echocardiography: 177 ± 47 g vs 203 ± 64 g vs 300 ± 71 g, respectively; P < 0.001). LV mass was lowest in cancer patients with cachexia (153 ± 42 g; P < 0.001). Importantly, the presence of low LV mass was independent of previous cardiotoxic anticancer therapy. In 90 cancer patients with a second echocardiogram after 122 ± 71 days, LV mass had declined by 9.3% ± 1.4% (P < 0.001). In cancer patients with cardiac wasting during follow-up, stroke volume decreased (P < 0.001) and resting heart rate increased over time (P = 0.001). During follow-up of on average 16 months, 149 patients died (1-year all-cause mortality 43%; 95% CI: 37%-49%). LV mass and LV mass adjusted for height squared were independent prognostic markers (both P < 0.05). Adjustment of LV mass for body surface area masked the observed survival impact. LV mass below the prognostically relevant cutpoints in cancer was associated with reduced overall functional status and lower physical performance. CONCLUSIONS: Low LV mass is associated with poor functional status and increased all-cause mortality in cancer. These findings provide clinical evidence of cardiac wasting-associated cardiomyopathy in cancer.

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.

Incidence and clinical correlates of de-novo aortic regurgitation with a fully magnetically levitated left ventricular assist device: a MOMENTUM 3 trial portfolio analysis.

AIMS: We assessed the incidence, predictors and clinical correlates of de-novo aortic regurgitation (AR), which physiologically reduces left ventricular assist device (LVAD) effectiveness due to recirculation syndrome, in the MOMENTUM 3 trial portfolio of the fully magnetically levitated HeartMate 3 (HM3) pump using the randomized pivotal trial (PT) and post-trial continued access protocol (CAP). METHODS AND RESULTS: De-novo aortic regurgitation incidence at 2 years was analysed in the randomized PT and validated in the first 1000 implanted patients of the CAP. Patients with concomitant/prior aortic valve surgery or without baseline or post-implant echocardiograms were excluded from this analysis. AR severity was assessed qualitatively by site-adjudicated echocardiograms (significant AR was defined as moderate or severe grade on echocardiogram). Of 1028 patients enrolled in the PT, 918 were eligible for inclusion in this analysis (HM3, n = 465; HMII, n = 453). At 2 years of LVAD support, freedom from significant AR was greater in the HM3 (92%) than HMII (82%) (hazard ratio 0.45, 95% confidence interval 0.27-0.75, p < 0.01). Of 907 HM3 patients analysed from the first 1000 implanted CAP patients, the rate of freedom from significant AR was 90%, consistent with the PT (p = 0.3). In the combined HM3 group (n = 1372), multivariable Cox modelling identified increasing age and female sex as significant predictors. Survival free of urgent transplant or AR corrective procedure was similar between HM3 patients with and without significant de-novo AR. CONCLUSIONS: The development of moderate or severe grade de-novo AR is reduced with the fully magnetically levitated HM3 LVAD compared to the axial-flow HMII pump. The occurrence of significant de-novo AR with the HM3 pump is not associated with a worse outcome at 2 years of follow-up.

Prediction of Survival After Implantation of a Fully Magnetically Levitated Left Ventricular Assist Device.

BACKGROUND: Clinical trials inform on average efficacy, but individualized risk assessments for outcome prediction are important in guiding treatment implementation. OBJECTIVES: The authors developed and validated a patient-specific risk score to predict survival at 1 and 2 years after HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation. METHODS: The MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial includes 2,200 HM3 LVAD patients in the pivotal trial and Continued Access Protocol study (2014-2018). The authors randomly assigned all patients to a derivation cohort (n = 1,540) or validation cohort (n = 660). Univariate mortality predictors were screened for potential model inclusion, stepwise selection was used to build the multivariable Cox proportional hazards regression model, and performance (discrimination and calibration) was evaluated. RESULTS: Age, prior cardiac surgery (coronary artery bypass grafting [CABG] or valve procedure), lower serum sodium, higher blood urea nitrogen (BUN), small left ventricular size, and right atrial pressure-to-pulmonary capillary wedge pressure (RAP/PCWP) ratio >0.6 were significant risk factors for mortality. Receiver-operating characteristic (ROC) analysis in the validation cohort demonstrated an area under the curve (AUC) of 0.76 (95% CI: 0.70-0.81) at 1 year and 0.71 (95% CI: 0.66-0.77) at 2 years. Calibration between predicted and observed survival of the risk quintiles was high, with Pearson correlation coefficients of 0.986 and 0.994 at 1 and 2 years, respectively. Patients were successfully stratified into tertiles with higher-than-average, average, and lower-than-average survival, and observed mortality risk increased by 2-fold from one tertile to the next. CONCLUSIONS: A practical, easy-to-use HM3 Survival Risk Score with 6 components was developed to accurately predict 1- and 2-year survival after HM3 LVAD implantation. The survival risk score can be used to provide individual survival estimates to facilitate shared decision making when considering HM3 LVAD therapy. (MOMENTUM 3 Trial Portfolio; NCT02224755, NCT02892955).

A multicenter evaluation of external outflow graft obstruction with a fully magnetically levitated left ventricular assist device.

BACKGROUND: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study. METHODS: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases. RESULTS: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%). CONCLUSIONS: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant.

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.

Heart transplantation: focus on donor recovery strategies, left ventricular assist devices, and novel therapies.

Heart transplantation is advocated in selected patients with advanced heart failure in the absence of contraindications. Principal challenges in heart transplantation centre around an insufficient and underutilized donor organ pool, the need to individualize titration of immunosuppressive therapy, and to minimize late complications such as cardiac allograft vasculopathy, malignancy, and renal dysfunction. Advances have served to increase the organ donor pool by advocating the use of donors with underlying hepatitis C virus infection and by expanding the donor source to use hearts donated after circulatory death. New techniques to preserve the donor heart over prolonged ischaemic times, and enabling longer transport times in a safe manner, have been introduced. Mechanical circulatory support as a bridge to transplantation has allowed patients with advanced heart failure to avoid progressive deterioration in hepato-renal function while awaiting an optimal donor organ match. The management of the heart transplantation recipient remains a challenge despite advances in immunosuppression, which provide early gains in rejection avoidance but are associated with infections and late-outcome challenges. In this article, we review contemporary advances and challenges in this field to focus on donor recovery strategies, left ventricular assist devices, and immunosuppressive monitoring therapies with the potential to enhance outcomes. We also describe opportunities for future discovery to include a renewed focus on long-term survival, which continues to be an area that is under-studied and poorly characterized, non-human sources of organs for transplantation including xenotransplantation as well as chimeric transplantation, and technology competitive to human heart transplantation, such as tissue engineering.

Impact of Race on Clinical Outcomes After Implantation With a Fully Magnetically Levitated Left Ventricular Assist Device: An Analysis From the MOMENTUM 3 Trial.

BACKGROUND: Heart failure disproportionately affects Black patients. Whether differences among race influence outcomes in advanced heart failure with use of a fully magnetically levitated continuous-flow left ventricular assist device remains uncertain. METHODS: We included 515 IDE (Investigational Device Exemption) clinical trial patients and 500 Continued Access Protocol patients implanted with the HeartMate 3 left ventricular assist device in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3). Outcomes were compared between Black and White left ventricular assist device recipients for the primary end point of survival free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years, overall survival, adverse events, 6-minute walk distance, and quality of life scores. RESULTS: Of 1015 HeartMate 3 patients, 675 were self-identified as White and 285 as Black individuals. The Black patient cohort was younger, more obese and with a history of hypertension, and more nonischemic cause of heart failure, relative to the White patient group. Black and White patients did not experience a difference in the primary end point (81.1% versus 77.9%; hazard ratio, 1.08 [95% CI, 0.76-1.54], P=0.6568). Black patients were at higher risk of adverse events (calculated as events per 100 patient-years), including bleeding (75.4 versus 63.5; P<0.0001), stroke (9.5 versus 7.2; P=0.0183), and hypertension (10.1 versus 3.2; P<0.0001). The 6-minute walk distance was not different at baseline and 6 months between the groups, however, the absolute change from baseline was greater for White patients (median: +183.0 [interquartile range, 42.0-335.3] versus +163.8 [interquartile range, 42.3-315.0] meters, P=0.01). The absolute quality of life measurement (EuroQoL group, 5-dimension, 5-level instrument visual analog scale) at baseline and 6 months was better in the Black patient group, but relative improvement from baseline to 6 months was greater in White patients (median: +20.0 [interquartile range, 5.0-40.0] versus +25.0 [interquartile range, 10.0-45.0]; P=0.0298). CONCLUSIONS: Although the survival free of disabling stroke or reoperation to replace/remove a malfunctioning device at 2 years with the HM 3 left ventricular assist device did not differ by race, Black HeartMate 3 patients experienced a higher morbidity burden and smaller gains in functional capacity and quality of life when compared with White patients. These findings require efforts designed to better understand and overcome these gaps through systematic identification and tackling of putative factors. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02224755 and NCT02892955.

Early aspirin use, allograft rejection, and cardiac allograft vasculopathy in heart transplantation.

BACKGROUND: Early aspirin (ASA) use after orthotopic heart transplantation (OHT) has been associated with lower rates of cardiac allograft vasculopathy (CAV). We hypothesized that the inverse association between ASA use and CAV incidence may be most pronounced in patients with allograft rejection. METHODS: Patients receiving OHT at a single center 2004-2010 (n = 120) were categorized by early ASA use post-transplant (ASA use for > 6 months in the first year) and the presence of biopsy-defined acute cellular rejection (ACR) and/or antibody-mediated rejection (AMR) during 5-year follow-up. Propensity scores for ASA treatment were estimated using boosting models and applied by inverse probability of treatment weighting. The association between ASA use and time to moderate/severe CAV (ISHLT ≥ 2) was investigated. RESULTS: Among patients with ACR or AMR, ASA therapy was associated with significantly lower rates of CAV≥ 2 (3.3 vs. 30.1%; P = .001; HRadj .07; 95% CI .01-.52), whereas ASA therapy was not associated with lower rates of CAV in patients with no rejection (5.6 vs. 5.3%; P = .90; HRadj 1.26; 95% CI .08-20.30; pinteraction  = .09). CONCLUSIONS: Early ASA use after OHT was associated with lower rates of moderate to severe CAV only in those patients with episodes of allograft rejection.

Heart Failure Association, Heart Failure Society of America, and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.