What If the Destination Is Transplant? Outcomes of Destination Therapy Patients Who Were Transplanted

We sought to characterize patients who underwent heart transplant (HTx) following destination therapy (DT) implant in the combined ENDURANCE/ENDURANCE Supplemental Trials (DT/DT2). A post hoc analysis of the DT/DT2 trials was performed. Baseline characteristics and adverse events between the HTx and no-HTx cohorts were analyzed. Reasons for transplant were examined. Time to HTx was compared with contemporaneous HVAD BTT trial patients. Of the 604 DT/DT2 HVAD patients, 80 (13%) underwent HTx. The HTx cohort was younger (53.6 ± 11.1 vs. 65.2 ± 10.8, P \u3c 0.0001) with fewer Caucasians (60.0% vs. 76.5%, P = 0.002), less ischemic cardiomyopathy (42.5% vs. 58.8%, P = 0.01), and atrial fibrillation (38.8% vs. 54.4%, P = 0.01). The HTx cohort had longer 6-minute walk distances (183.6 vs. 38.0 m, P = 0.02). Most HTx in DT/DT2 were categorized as elective (n = 63, 79%) and, of these, 70% were due to modification of behavioral issues and weight loss. Adverse events were the main indication for urgent HTx (n = 17, 21%). Median times to HTx were longer in DT/DT2 (550.0 days) versus BTT/lateral (285.2 days). In this post hoc analysis of the DT/DT2 trials, over 1 in 10 underwent heart transplantation within 3 years of HVAD support. In DT therapy patients, consideration for transplant following DT VAD implant may be feasible

Extended criteria donor organ use for heart-lung transplantation in the modern era

Background: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. Methods and results: : The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynamics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. Conclusions: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population

Adult cardiac surgery during the COVID-19 Pandemic: A Tiered Patient Triage Guidance Statement

In the setting of the current novel coronavirus pandemic, this document has been generated to provide guiding statements for the adult cardiac surgeon to consider in a rapidly evolving national landscape. Acknowledging the risk for a potentially prolonged need for cardiac surgery procedure deferral, the authors have created this proposed template for physicians and interdisciplinary teams to consider in protecting their patients, institution and their highly specialized cardiac surgery team. In addition, recommendations on the transition from traditional in-person patient assessments and outpatient follow-up are provided. Lastly, we advocate that the cardiac surgeon must continue to serve as leaders, experts, and relevant members of our medical community, shifting our role as necessary in this time of need

Ramping up Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from The Society of Thoracic Surgeons COVID-19 Task Force

The COVID-19 pandemic has had a profound global impact. Its rapid transmissibility has transformed healthcare delivery and forced countries to adopt strict measures to contain its spread. The vast majority of U.S. cardiac surgical programs have deferred all but truly emergent/urgent operative procedures in an effort to reduce the burden on the healthcare system and to mobilize resources to combat the pandemic surge. While the number of COVID-19 cases continues to increase worldwide, the incidence of new cases has begun to decline in many North American cities. This flattening of the curve has prompted interest in re-opening the economy, relaxing public health restrictions, and resuming non-urgent health care delivery

Concordance of Treatment Effect: An Analysis of The Society of Thoracic Surgeons Intermacs Database

BACKGROUND: The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations. METHODS: Patients (aged \u3e 19 years) enrolled into STS Intermacs between August 2017 - June 2019 were stratified by device type (centrifugal device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by three statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis). RESULTS: Of 4,448 patients, 2,012 (45.2%) received CF-HL and 2,436 (54.8%) received CF-FML. One-year survival for CF-FML was 88% vs. 79% for CF-HL (overall p \u3c .001), with a hazard ratio for mortality of 3.18 for CF-HL (p\u3c0.0001) after risk adjustment. With propensity score matching (n=1400 each cohort), 1-year survival was 87% for CF-FML vs. 80% for CF-HL, with a hazard ratio of 3.20 for mortality with CF-HL (p\u3c0.0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving CF-HL was associated with a hazard ratio of 3.11 (p\u3c0.0001). CONCLUSIONS: Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of CF-FML versus CF-HL

Natural history of coexistent tricuspid regurgitation in patients with degenerative mitral valve disease: Implications for future guidelines

ObjectiveThe management of coexistent tricuspid regurgitation in patients with mitral regurgitation remains controversial. We sought to define the incidence and natural history of coexistent tricuspid regurgitation in patients undergoing isolated mitral surgery for degenerative mitral regurgitation, as well as the effect of late secondary tricuspid regurgitation on cardiovascular symptom burden and survival.MethodsTo minimize confounding, analysis was limited to 495 consecutive patients who underwent isolated mitral surgery for degenerative mitral valve disease between 2002 and 2011. Patients with coexistent severe tricuspid regurgitation were excluded because such patients typically undergo concomitant tricuspid intervention.ResultsGrade 1 to 3 coexistent tricuspid regurgitation was present in 215 patients (43%) preoperatively. Actuarial freedom from grade 3 to 4 tricuspid regurgitation 1, 5, and 9 years after surgery was 100% ± 0%, 90% ± 2%, and 64% ± 7%, respectively. Older age (P < .001) and grade of preoperative tricuspid regurgitation (P = .006) independently predicted postoperative progression of tricuspid regurgitation on multivariable analysis. However, when limited to patients with mild or absent tricuspid regurgitation, indexed tricuspid annular diameter was the only significant risk factor for late tricuspid regurgitation (P = .04). New York Heart Association functional class and long-term survival did not worsen with development of late secondary tricuspid regurgitation (P = .4 and P = .6, respectively). However, right ventricular dysfunction was significantly more common in patients with more severe late tricuspid regurgitation (P = .007).ConclusionsDespite durable correction of degenerative mitral regurgitation, less than severe tricuspid regurgitation is likely to progress after surgery if uncorrected. Given the low incremental risk of tricuspid annuloplasty, a more aggressive strategy of concomitant tricuspid repair may be warranted

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\u3c 0.001) and for the HeartMate 3 vs Other-VADs was 0.51 (95% CI; 0.42-0.63, p \u3c 0.001). The HeartMate 3 cohort experienced fewer hospitalizations per patient-year vs Other-VADs (respectively, 2.8 vs 3.2 EPPY hospitalizations, p \u3c 0.01) and 6.1 fewer hospital days on average (respectively, 25.2 vs 31.3 days, p \u3c 0.01). The difference in Medicare expenditures, conditional on survival, for HeartMate 3 vs HeartMate II was -$10,722, p \u3c 0.001 (17.4$17,947, p \u3c 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

Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy

ObjectiveIschemic heart failure is an increasingly prevalent global health concern with major morbidity and mortality. Currently, therapies are limited, and novel revascularization methods might have a role. This study examined enhancing endogenous myocardial revascularization by expanding bone marrow-derived endothelial progenitor cells with the marrow stimulant granulocyte-monocyte colony-stimulating factor and recruiting the endothelial progenitor cells with intramyocardial administration of the potent endothelial progenitor cell chemokine stromal cell-derived factor.MethodsIschemic cardiomyopathy was induced in Lewis rats (n = 40) through left anterior descending coronary artery ligation. After 3 weeks, animals were randomized into 4 groups: saline control, granulocyte-monocyte colony-stimulating factor only (GM-CSF only), stromal cell-derived factor only (SDF only), and combined stromal cell-derived factor/granulocyte-monocyte colony-stimulating factor (SDF/GM-CSF) (n = 10 each). After another 3 weeks, hearts were analyzed for endothelial progenitor cell density by endothelial progenitor cell marker colocalization immunohistochemistry, vasculogenesis by von Willebrand immunohistochemistry, ventricular geometry by hematoxylin-and-eosin microscopy, and in vivo myocardial function with an intracavitary pressure-volume conductance microcatheter.ResultsThe saline control, GM-CSF only, and SDF only groups were equivalent. Compared with the saline control group, animals in the SDF/GM-CSF group exhibited increased endothelial progenitor cell density (21.7 ± 3.2 vs 9.6 ± 3.1 CD34+/vascular endothelial growth factor receptor 2–positive cells per high-power field, P = .01). There was enhanced vascularity (44.1 ± 5.5 versus 23.8 ± 2.2 von Willebrand factor-positive vessels per high-power field, P = .007). SDF/GM-CSF group animals experienced less adverse ventricular remodeling, as manifested by less cavitary dilatation (9.8 ± 0.1 mm vs 10.1 ± 0.1 mm [control], P = .04) and increased border-zone wall thickness (1.78 ± 0.19 vs 1.41 ± 0.16 mm [control], P = .03). (SDF/GM-CSF group animals had improved cardiac function compared with animals in the saline control group (maximum pressure: 93.9 ± 3.2 vs 71.7 ± 3.1 mm Hg, P < .001; maximum dP/dt: 3513 ± 303 vs 2602 ± 201 mm Hg/s, P < .05; cardiac output: 21.3 ± 2.7 vs 13.3 ± 1.3 mL/min, P < .01; end-systolic pressure-volume relationship slope: 1.7 ± 0.4 vs 0.5 ± 0.2 mm Hg/μL, P < .01.)ConclusionThis novel revascularization strategy of bone marrow stimulation and intramyocardial delivery of the endothelial progenitor cell chemokine stromal cell-derived factor yielded significantly enhanced myocardial endothelial progenitor cell density, vasculogenesis, geometric preservation, and contractility in a model of ischemic cardiomyopathy

Computational Protein Design to Re-Engineer Stromal Cell-Derived Factor-1α (SDF) Generates an Effective and Translatable Angiogenic Polypeptide Analog

BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy