Should there be an age limit for advanced therapies?

Combined heart lung transplant has become a rare procedure. However, there is a significant number of patients potentially benefitting from replacement of both heart and lungs. This represents a quite diverse patient population. Decisions in patient selection have to be adjusted to individual needs and distinct constellation of the patient. Age may be a risk factor, but should be carefully integrated into the evaluation of perioperative and long term risks.

Evaluation of the Safety and Efficacy of a Novel Thrombin Containing Combination Hemostatic Powder Using a Historical Control.

This clinical study compares 2 hemostatic agents, a novel combination powder (CP) (HEMOBLAST™ Bellows) and an established polysaccharide starch powder (PP) (Arista™ AH) to assess the usefulness of CP. Retrospective comparative analysis of CP (July 2018 to July 2019, 68 patients) to PP (January 2011 to January 2013, 94 patients) in cardiothoracic patients was performed using linear regression models adjusting for age, sex, and procedure type for the endpoints: blood loss; protamine to skin closure time (hemostasis time); chest tube output and blood products required 48 hours postoperatively; ICU stay; postoperative comorbidities; and 30 day mortality. 162 patients (108 M: 54 F) underwent 162 cardiothoracic surgical procedures including: transplantation (n = 44), placement of ventricular assist device (n = 87), and others (n = 31). Use of CP compared to PP (Estimated Mean Difference [95% CI], P-value) produced significant reductions: blood loss (mL) (-886.51 [-1457.76, -312.26], P = 0.003); protamine to skin closure time (min) (-16.81 [-28.03, -5.59], P = 0.004); chest tube output (48 hrs, mL) (-445.76 [-669.38, -222.14], P < 0.001); packed red blood cell transfusions (units) (-0.98 [-1.56, -0.4], P = 0.001); and postoperative comorbidities (-0.31 [-0.55, -0.07], P = 0.012). There were no differences in the ICU stay (4.07 [-2.01, 10.15], P = 0.188) or 30-day mortality (0.57 [0.20, 1.63], P = 0.291). The use of CP in complex cardiothoracic operations resulted in improved hemostasis and significant clinical benefits in blood loss, transfusion requirements, morbidity, and time in operating room.

Prospective, multicenter, randomized, controlled trial evaluating the performance of a novel combination powder vs hemostatic matrix in cardiothoracic operations.

AIM: This trial compared the hemostatic performance of a novel combination powder (CP) to a control hemostatic matrix (HM) in cardiothoracic operations. METHODS: Patients meeting eligibility criteria were enrolled after providing informed consent. Subjects were randomized intraoperatively to receive CP (HEMOBLAST Bellows; Biom'up, France) or HM (FLOSEAL Hemostatic Matrix; Baxter Healthcare Corporation, Hayward, CA). Bleeding was assessed using a clinically validated, quantitative bleeding severity scale. The primary endpoint was total time to hemostasis (TTTH), from the start of device preparation, as an indicator of when a surgeon asks for a surgical hemostat until hemostasis was achieved. TTTH at 3 minutes was utilized for the primary analysis, while TTTH at 5 minutes was considered as a secondary endpoint. RESULTS: A total of 105 subjects were enrolled across four institutions. The primary efficacy endpoint for the superiority of CP relative to HM for success at achieving hemostasis within 3 minutes was met, with 64.2% of the CP group achieving hemostasis compared with 9.6% of the HM group, a difference of 54.54% (37.4%-71.6%; P < .001 for superiority). The secondary efficacy endpoint was also met, with 92.5% of the CP group achieving hemostasis at 5 minutes versus 44.2% in the HM group, a difference of 48.2% (31.1%-65.4%; P < .001 for noninferiority). There were no device-related adverse events. CONCLUSIONS: In this multicenter, randomized, controlled trial, comparison of CP to HM revealed CP superiority and noninferiority for TTTH at 3 and 5 minutes, respectively.

Application techniques of a novel hemostat in cardiac operations: HEMOBLAST.

BACKGROUND: Postoperative bleeding complications are associated with less favorable outcomes in cardiac surgery and contribute to excessive overall healthcare costs. HEMOBLAST (Biom'up, Lyon, France) (HB) is a novel ready-to-use hemostatic powder that consists of porcine collagen, bovine chondroitin sulfate, and human pooled plasma thrombin that may help reduce surgical bleeding. AIMS: The aim of this study was to describe the techniques of application for this new combination powder-based hemostat, HB, and demonstrate its use employing photographs of application methods during cardiac procedures. MATERIALS AND METHODS: The initial 24 procedures in which HB was used at our institution included: left ventricular assist device (LVAD) insertions, lung transplants, heart transplants, aortic valve replacements, coronary artery bypass grafting, and mitral valve repair. RESULTS: Hemostasis was achieved in all cases and there were no instances of mediastinitis, sternal infections, allergic reactions, or 30-day mortality. DISCUSSION: This report describes the best methods of application of HB including use for treatment of mediastinal bleeding in a re-operative procedure in a patient on antiplatelet agents and sternal bleeding during an LVAD insertion. Proper application can facilitate excellent hemostasis using this powder. CONCLUSION: HB is a novel powder-based multiple component hemostatic agent that promotes focal or large area hemostasis. We have presented the techniques of use that are important to the successful application of HB to facilitate hemostasis.

Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis.

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004-2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart-kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8-32.9 months) post-HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart-lung transplantation. A strategy of delayed ASCT 1-year post-HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.

Implication of Ventricular Assist Devices in Extracorporeal Membranous Oxygenation Patients Listed for Heart Transplantation.

The new allocation criteria classify patients on veno-arterial extracorporeal membranous oxygenation (VA-ECMO) as the highest priority for receiving orthotopic heart transplantation (OHT) especially if they are considered not candidates for ventricular assist devices. The outcomes of patients who receive ventricular assist devices (VADs) after being listed for heart transplantation with VA-ECMO is unknown. We analyzed 355 patients listed for OHT with VA-ECMO from the United Network for Organ Sharing database from 2006 to 2014. Univariate and multivariate Cox proportional-hazards models were used to determine the contribution of prognostic variables to the outcome. Thirty-three patients (9.3%) received VADs (15 dischargeable, 7 non-dischargeable VADs). The VAD and non-VAD groups had similar listing characteristics except that the VAD group were more likely to have non-ischemic cardiomyopathy (48.5% vs. 25.2%), and less likely to be obese (6.1% vs. 25.2%) or have a history of prior organ transplant (3% vs. 31.1%). Patients who underwent VAD implantation had more days on the list (median 189 vs. 14 days) compared to the non-VAD group. Amongst the patients who had VADs, (25/33) 75.5% patients were subsequently transplanted with similar post-transplant survival compared to the non-VAD group (72% vs. 60.5%; p = 0.276). Predictors of one-year post-transplant mortality included panel reactive antibodies (PRA) class I ≥ 20%, recipient smoking history, increased serum creatinine and total bilirubin. Therefore, a small proportion of patients listed for transplantation with VA ECMO undergo VAD implantation. Their waitlist survival is better than non-VAD group but with similar post-transplant survival.

Adenosine and hyaluronan promote lung fibrosis and pulmonary hypertension in combined pulmonary fibrosis and emphysema.

Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that predominantly affects male smokers or ex-smokers and it has a mortality rate of 55% and a median survival of 5 years. Pulmonary hypertension (PH) is a frequently fatal complication of CPFE. Despite this dismal prognosis, no curative therapies exist for patients with CPFE outside of lung transplantation and no therapies are recommended to treat PH. This highlights the need to develop novel treatment approaches for CPFE. Studies from our group have demonstrated that both adenosine and its receptor ADORA2B are elevated in chronic lung diseases. Activation of ADORA2B leads to elevated levels of hyaluronan synthases (HAS) and increased hyaluronan, a glycosaminoglycan that contributes to chronic lung injury. We hypothesize that ADORA2B and hyaluronan contribute to CPFE. Using isolated CPFE lung tissue, we characterized expression levels of ADORA2B and HAS. Next, using a unique mouse model of experimental lung injury that replicates features of CPFE, namely airspace enlargement, PH and fibrotic deposition, we investigated whether 4MU, a HAS inhibitor, was able to inhibit features of CPFE. Increased protein levels of ADORA2B and HAS3 were detected in CPFE and in our experimental model of CPFE. Treatment with 4MU was able to attenuate PH and fibrosis but not airspace enlargement. This was accompanied by a reduction of HAS3-positive macrophages. We have generated pre-clinical data demonstrating the capacity of 4MU, an FDA-approved drug, to attenuate features of CPFE in an experimental model of chronic lung injury.This article has an associated First Person interview with the first author of the paper.

Cleavage factor 25 deregulation contributes to pulmonary fibrosis through alternative polyadenylation.

Idiopathic pulmonary fibrosis (IPF) is a chronic and deadly disease with a poor prognosis and few treatment options. Pathological remodeling of the extracellular matrix (ECM) by myofibroblasts is a key factor that drives disease pathogenesis, although the underlying mechanisms remain unknown. Alternative polyadenylation (APA) has recently been shown to play a major role in cellular responses to stress by driving the expression of fibrotic factors and ECMs through altering microRNA sensitivity, but a connection to IPF has not been established. Here, we demonstrate that CFIm25, a global regulator of APA, is down-regulated in the lungs of patients with IPF and mice with pulmonary fibrosis, with its expression selectively reduced in alpha-smooth muscle actin (α-SMA) positive fibroblasts. Following the knockdown of CFIm25 in normal human lung fibroblasts, we identified 808 genes with shortened 3'UTRs, including those involved in the transforming growth factor-ß signaling pathway, the Wnt signaling pathway, and cancer pathways. The expression of key pro-fibrotic factors can be suppressed by CFIm25 overexpression in IPF fibroblasts. Finally, we demonstrate that deletion of CFIm25 in fibroblasts or myofibroblast precursors using either the Col1a1 or the Foxd1 promoter enhances pulmonary fibrosis after bleomycin exposure in mice. Taken together, our results identified CFIm25 down-regulation as a novel mechanism to elevate pro-fibrotic gene expression in pulmonary fibrosis.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Technologies for intrapericardial delivery of therapeutics and cells.

The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to increase therapeutic myocardial retention, efficacy, and bioactivity, while decreasing undesired systemic effects. Here, we provide a literature review of various approaches for intrapericardial delivery of agents. Emphasis is given to sustained delivery approaches (pumps and catheters) and localized release (patches, drug eluting stents, and support devices and meshes). Further, minimally invasive access techniques, pericardial access devices, pericardial washout and fluid analysis, as well as therapeutic and cell delivery vehicles are presented. Finally, several promising new therapeutic targets to treat heart diseases are highlighted.

Retransplantation Outcomes at a Large Lung Transplantation Program.

BACKGROUND: With the increase of primary lung transplantation across major centers worldwide, over the last several years the need of lung retransplant (ReTX) is likely to increase. Therefore, characterization of ReTX patients is prudent and necessary. Our study aimed to investigate and characterize the covariates and outcomes associated with lung ReTX survival in a single large U.S. transplant center. METHODS: Demographic, clinical diagnoses, and comorbidities were analyzed. Kaplan-Meier statistics were used to calculate and predict survival for 30 days and up to 3 years. Cox proportional modeling was used to determine the variables associated with mortality. RESULTS: Of included 684 lung transplants performed at the Houston Methodist Hospital between January 2009 and December 2015, 49 were lung ReTX. Median age of primary lung transplant (non-ReTX) and ReTx recipients was 62 and 49 years, respectively. Chronic graft rejection in the form of restrictive chronic lung allograft dysfunction and bronchiolitis obliterans syndrome was the main indications for ReTX. Compared with non-ReTX patients, ReTX patients had higher median lung allocation score (46.2 vs 37.0, respectively) and higher mortality after 6 months posttransplant. ReTX, older age, female sex, hospitalization 15 days or longer, estimated glomerular filtration rate less than 60, 6-minute walk distance less than 400 ft, and donor/recipient height ratio less than 1 were significantly associated with decreased 1-year patient and graft survival. Chronic graft rejection was still the major cause of death in the long-term follow-up recipients. CONCLUSIONS: Our findings suggested that lung ReTX recipients have poor long-term survival outcomes. Lung ReTX should only be offered to carefully selected patients.

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).

Switching-Off Adora2b in Vascular Smooth Muscle Cells Halts the Development of Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a devastating and progressive disease characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and remodeling of the lung vasculature. Adenosine signaling through the ADORA2B receptor has previously been implicated in disease progression and tissue remodeling in chronic lung disease. In experimental models of PH associated with chronic lung injury, pharmacological or genetic inhibition of ADORA2B improved markers of chronic lung injury and hallmarks of PH. However, the contribution of ADORA2B expression in the PASMC was not fully evaluated. Hypothesis: We hypothesized that adenosine signaling through the ADORA2B receptor in PASMC mediates the development of PH. Methods: PASMCs from controls and patients with idiopathic pulmonary arterial hypertension (iPAH) were characterized for expression levels of all adenosine receptors. Next, we evaluated the development of PH in ADORA2Bf/f-Transgelin (Tagln)cre mice. These mice or adequate controls were exposed to a combination of SUGEN (SU5416, 20 mg/kg/b.w. IP) and hypoxia (10% O2) for 28 days (HX-SU) or to chronic low doses of bleomycin (BLM, 0.035U/kg/b.w. IP). Cardiovascular readouts including right ventricle systolic pressures (RVSPs), Fulton indices and vascular remodeling were determined. Using PASMCs we identified ADORA2B-dependent mediators involved in vascular remodeling. These mediators: IL-6, hyaluronan synthase 2 (HAS2) and tissue transglutaminase (Tgm2) were determined by RT-PCR and validated in our HX-SU and BLM models. Results: Increased levels of ADORA2B were observed in PASMC from iPAH patients. ADORA2Bf/f-Taglncre mice were protected from the development of PH following HX-SU or BLM exposure. In the BLM model of PH, ADORA2Bf/f- Taglncre mice were not protected from the development of fibrosis. Increased expression of IL-6, HAS2 and Tgm2 was observed in PASMC in an ADORA2B-dependent manner. These mediators were also reduced in ADORA2Bf/f- Taglncre mice exposed to HX-SU or BLM. Conclusions: Our studies revealed ADORA2B-dependent increased levels of IL-6, hyaluronan and Tgm2 in PASMC, consistent with reduced levels in ADORA2Bf/f- Taglncre mice exposed to HX-SU or BLM. Taken together, our data indicates that ADORA2B on PASMC mediates the development of PH through the induction of IL-6, hyaluronan and Tgm2. These studies point at ADORA2B as a therapeutic target to treat PH.

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 .).

Long-Term Survival in Bilateral Lung Transplantation for Scleroderma-Related Lung Disease.

BACKGROUND: Lung disease is the leading cause of morbidity and death in scleroderma patients, but scleroderma is often considered a contraindication to lung transplantation because of concerns for worse outcomes. We evaluated whether 5-year survival in scleroderma patients after lung transplantation differed from other patients with restrictive lung disease. METHODS: This was a single-center, retrospective cohort study of all patients undergoing bilateral lung transplantation for scleroderma-related pulmonary disease between January 2006 and December 2014. This cohort was compared with patients undergoing bilateral lung transplantation for nonscleroderma group D restrictive disease. Primary outcomes reported were 1-year and 5-year survival. Diagnoses were identified by United Network of Organ Sharing listing and were confirmed by clinical examination and prelisting workup. RESULTS: We compared 26 patients who underwent BLT for scleroderma and 155 patients who underwent BLT for group D restrictive disease. Overall, the nonscleroderma cohort was younger, with lower lung allocation score but no difference in functional status. Donor characteristics were not different between the cohorts. Survival at 1 year was not different (73.1% vs 80.0%, p = 0.323). Long-term survival at 5 years was also not significantly different (65.4% vs 66.5%, p = 0.608). Multivariate Cox proportional hazards analysis found no differences in survival between scleroderma and nonscleroderma group D restrictive disease (hazard ratio, 2.19; p = 0.122). CONCLUSIONS: Despite being at high risk for extrapulmonary complications, patients undergoing bilateral lung transplantation for scleroderma have similar 1-year and 5-year survival as those with restrictive lung disease. Transplantation is a reasonable treatment option for a carefully selected population of candidates.

Impact of age, sex, therapeutic intent, race and severity of advanced heart failure on short-term principal outcomes in the MOMENTUM 3 trial.

BACKGROUND: Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. METHODS: Cox proportional hazard models were used to analyze patients enrolled in the "as-treated cohort" (n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. RESULTS: Baseline characteristics were well balanced among HM3 (n = 151) and HMII (n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. CONCLUSIONS: This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned.

Melding a High-Risk Patient for Continuous Flow Left Ventricular Assist Device into a Low-Risk Patient.

The model for end-stage liver disease (MELD) has been used as a predictor of mortality after left ventricular assist device (LVAD) placement. However, improvement or worsening of MELD and how those changes affect outcomes is unknown. We performed a retrospective analysis of 244 patients implanted with a continuous flow (CF) LVAD. Patients were dichotomized at admission into low- or high-risk categories using a cutoff of MELD ≥ 19, and they were reclassified at day of implant forming four groups: Group LL (low to low, remained low risk), LH (low to high, worsened to high risk), HH (high to high, remained high risk), and HL (high to low, improved to low risk). Patients who improved to a low risk (group HL) had the same 1 year survival as those that remained low risk (group LL; 80% vs. 77%; p = 0.6). However, patients who were initially classified as low risk and worsened to a high risk (group LH) had a survival that was worse than those that were consistently high risk (group HH; 55% vs. 10%; p = 0.01). Model for end-stage liver disease reclassification after adjusting for commonly attributed risk factors remained an independent predictor for mortality, including patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 and 2. In conclusion, our MELD score reclassification is an independent and powerful predictor of mortality in patients undergoing LVAD implantation.

Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients: The ROADMAP Study 2-Year Results.

OBJECTIVES: The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years. BACKGROUND: The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients. METHODS: The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m. RESULTS: Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p < 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 ± 5% vs. 41 ± 5%; p < 0.001), but there was no difference in intent-to-treat survival (70 ± 5% vs. 63 ± 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias. CONCLUSIONS: Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802).

Improved Outcomes With the Evolution of a Neoadjuvant Chemotherapy Approach to Right Heart Sarcoma.

BACKGROUND: Right-side heart sarcomas tend to be bulky, infiltrative, and difficult to treat. We have previously examined our outcomes with right heart sarcomas. Surgical resection with R0 margins showed better survival than positive margins but in only one third of cases could R0 status be achieved. The hypothesis for this study was that preoperative neoadjuvant chemotherapy would shrink the tumor margins and allow an increase in R0 resection, and hence, better survival. METHODS: Review of our cardiac tumor database from 1990 to 2015 yielded 133 primary cardiac sarcoma cases. Of these, we identified 44 patients with primary right-side heart sarcomas. Prospective database and retrospective data collection and clinical outcomes were evaluated for all 44 patients. Primary outcomes included 30-day mortality and morbidity and long-term survival. We used univariate and multivariate analyses to identify independent predictors of overall survival. RESULTS: There were 27 male and 17 female patients with a mean age of 41 ± 12.7 years (range, 15 to 67). Seventy-three percent of the patients (32 of 44) received neoadjuvant chemotherapy. The most common tumor histology was angiosarcoma in 30 of 44 (68%). Thirty-day mortality was 4.5%, and statistically similar between the two groups. The median survival of patients who had R0 resection was 53.5 months compared with 9.5 months for R1. Neoadjuvant chemotherapy led to a doubling of survival (20 versus 9.5 months). CONCLUSIONS: Neoadjuvant chemotherapy followed by radical surgery is a safe and effective strategy in patients with primary right-side heart sarcoma. This multimodality treatment enhances resectability (R0 resection) that translates into improved patient survival.

Caregivers of Patients With Left Ventricular Assist Devices: Possible Impacts on Patients' Mortality and Interagency Registry for Mechanically Assisted Circulatory Support-Defined Morbidity Events.

BACKGROUND: How caregivers contribute to positive or negative outcomes for left ventricular assist device (LVAD) patients remains unclear. Our primary study objectives were to (1) identify caregiver support attributes through a retrospective chart review of social workers' psychosocial assessments for LVAD patients and (2) determine how these attributes associated with patients' post-LVAD placement mortality and Interagency Registry for Mechanically Assisted Circulatory Support-defined morbidity events. METHODS AND RESULTS: We retrospectively reviewed and recorded social workers' clinical assessments of adult patients implanted with durable continuous-flow LVADs as bridge to transplant, destination therapy, or bridge to decision from January 2010 to December 2014. Associations between caregiver characteristics and patient mortality and morbidity events were analyzed using Kaplan-Meier curves and Cox proportional hazards regression. Patient follow-up time was calculated as the time from hospital discharge until the earliest among death with LVAD, transplant, or the last day of the study (December 31, 2015). Patients were censored for death with LVAD at the time of transplant or the last day of the study. A total of 96 LVAD recipients were included in this study. Having a caregiver who understands the severity of the illness and options available to the patient (as determined and documented by the social worker; P=0.01), a caregiver who has identified a backup plan (P=0.02), and a caregiver who is able to provide logistical support (P=0.04) significantly mitigated risk of death. The risk of death for an LVAD patient was also significantly lower among those who have at least 1 adult child who lives within 50 miles (P=0.03) and those who have an extended family who can care for the patient (P=0.03). The risk of death was 3.1× more likely among patients who live alone compared with those who do not live alone (P=0.04). No caregiver characteristics were significantly associated with morbidity. CONCLUSIONS: This exploratory, hypothesis-generating study suggests that mortality after LVAD placement is impacted by caregiver understanding of patient severity of illness and caregiver presence. This study provides initial evidence to support further work in understanding the associations between caregivers and LVAD patients, as well as interventions that may improve patient outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02248974.