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Background--Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. Methods and Results--We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. Conclusions--A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of echocardiographic indices of right ventricular dysfunction(RVD) in left sided valve surgery has not been well described. The main objective of this study is to evaluate preoperative RV echocardiographic parameters associated with adverse outcomes after left sided valve surgery. Methods: Pre-operative echocardiographic data, perioperative adverse outcomes(POAO) and 30-day mortality were retrospectively analyzed in a total of 359 patients who underwent left sided valve surgery (198 aortic and 161 mitral respectively) at a single academic medical center from 2006 to 2014. RVD was defined as 2 or more abnormal RV echocardiographic parameters: RV fractional area change, RV dp/dt, TAPSE, tissue doppler S' and RIMP(Tei index). Results: 359 patients with left sided valvular surgery (average age: 67 ±15, 60.6 % male). The most common POAO were atrial fibrillation and prolonged ventilation time as shown in Figure. After adjustment for age, sex, ejection fraction and admission with heart failure, patients with preexisting RVD undergoing aortic valve surgery were associated with 30-day composite outcome(POAO) [adjusted odds ratio(OR): 2.92, 95 % confidence interval(CI): 1.46 to 5.8; P< 0.05]. Patients with preexisting RVD undergoing mitral valve surgery were also observed to have 30-day composite outcome(POAO) [OR: 2.2, 95 % CI: 1.08 to 4.6; P<0.05]. Pre and post echocardiographic parameters which significantly changed after surgery are listed in Table. Conclusion: Preoperative RVD is associated with increased peri-operative complications after left sided valve surgery. A comprehensive assessment of RV function with multiple echocardiographic parameters can help with better estimation of surgical risk. [ABSTRACT FROM AUTHOR]

Introduction: Among asymptomatic patients, the value of stress imaging at 1 year following successful CABG for predicting long-term adverse outcomes has not been shown. Hypothesis: Among patients enrolled in a VA cooperative study to detect graft patency at 1-year post-CABG, SPECT-MPI predicts long-term risk of adverse cardiovascular events. Methods: At a single center participating in a VA Cooperative Study on long-term graft patency, enrolled patients underwent both coronary angiography and stress imaging at 1-year following CABG. Stress imaging was performed on the same day as the coronary angiogram and interpretation was blinded to the coronary angiogram. SPECT results were categorized according to the size of the perfusion defect, and graded as none, small or moderate to large. Results of the graft studies were categorized as either none or 1 or more grafts with a significant stenosis. Long-term adverse end-points include the composite of death and new diagnosis of heart failure. Results: Eighty-four participants underwent SPECT-MPI and coronary angiogram at one-year post-CABG. Graft disease was identified in 39 patients involving 56 of 251 potential graft sites (22%) and compared to those individuals with no graft disease, did not predict long-term adverse outcomes (31% vs 38% p=0.51). Those individuals with a poor long-term outcome failed to increase their LVEF at 1-year compared with pre-CABG (Figure 1). In addition, a moderate or larger sized defect on SPECT (N=18) was associated with a significant increased risk of adverse outcomes compared with those individuals with either no defect (N=57) or a small defect (N=27) (56% Versus 30%; Odds Ratio = 1.8, P<0.05) (Figure 2). Conclusions: Among asymptomatic patients at 1-year following CABG, assessment of LVEF and defect size with SPECT-MPI was a predictor of long-term risk of death and heart failure. Use of stress imaging, as a means of risk-stratification following bypass surgery, even among those patients without clinical symptoms, may have value. [ABSTRACT FROM AUTHOR]

Introduction: Significant variability in morbidity and mortality persists for children with single ventricle congenital heart disease (SV-CHD) despite standardization in medical and surgical care. Multiple risk factors for poor outcomes have been described, but they only explain a fraction of the disparity in outcomes. The Developmental Origins of Health and Disease (DOHaD) theory proposes that fetal adaptation to an adverse in utero environment alters the ability to respond to post-natal stressors and may explain additional risk for poor outcomes. This study assessed maternal risk factor association with disparate outcomes following SV palliation. Hypothesis: Maternal factors related to weight, diabetes, hypertension, and smoking may be associated with an increased risk of poor outcomes in children with SV-CHD. Methods: This retrospective observational cohort study included all term maternal-infant pairs with a diagnosis of SV-CHD who underwent surgical palliation from 2006-2015 at Primary Children's Hospital. Pairs lacking maternal variables of interest or infant follow-up data up to 1 year were excluded. The association of death or transplant with maternal risk factors [abnormal pre-pregnancy BMI, abnormal weight gain during pregnancy (≤ 7 kg or ≥ 20 kg), any type of hypertension or diabetes and smoking] was analyzed using a multivariable logistic regression model. Results: Of 190 infants who qualified, 135 (71%) maternal-infant dyads had complete data for inclusion. Systemic right ventricular morphology was present in 69% and 31% had systemic left ventricular morphology. Death or transplant occurred in 48 infants (36%) during an average follow-up of 2.2 years (0.1-11.7 years). Abnormal weight gain during pregnancy was present in 34 (25%) mothers, of which 24 had excessive (>20 kg) and 10 had inadequate (<7 kg) weight gain. Prevalence of other risk factors was 53% with an abnormal pre-pregnancy BMI, 10% for diabetes, 6% for hypertension and 8% for smoking. Abnormal weight gain during pregnancy was associated with an increased risk of death or transplant in offspring with SV-CHD. (OR=2.55, 95%CI:1.11-5.84, p=0.027). Conclusions: Abnormal maternal weight gain (excessive or inadequate) during pregnancy is a novel risk factor that may contribute to worse outcomes in SV-CHD. [ABSTRACT FROM AUTHOR]

Introduction: Partial leaflet resection followed by ring annuloplasty is a reliable and reproducible mitral valve (MV) repair technique for the treatment of severe mitral regurgitation (MR) due to posterior chordal rupture. Hypothesis: We have developed a novel computational virtual MV repair strategy to predict the biomechanical and physiologic characteristics of post-repair MV dynamics to help with optimal surgical planning. Methods: Computational MV models were created using pre- and post-repair 3D echocardiographic data of a patient having posterior chordal rupture and severe MR. Virtual resection was designed by removing a pre-defined triangle-shaped leaflet portion in the P2 scallop and merging the excised leaflet edges. Virtual ring annuloplasty with the same ring size as the post-repair MV was performed following the triangular leaflet resection. Computational simulations of MV function (pre-repair, virtual repair, and post-repair) were performed using dynamic finite element methods. Leaflet coaptation across the MVs were quantitatively determined and compared. Results: The pre-repair MV with P2 chordal rupture showed severe P2 prolapse and leaflet malcoaptation. The post-repair MV demonstrated markedly reduced prolapse and sufficiently restored leaflet coaptation. The virtually repaired MV revealed a similar coaptation ratio as the post-repair MV indicating effective restoration of normal MV function. Both virtual repair and post-repair MVs showed improved coaptation not only in the P2 region but also in the A1-P1 and A3-P3 regions. Conclusions: We have quantitatively evaluated patient-specific MV function before and after potential MV repair using a novel virtual MV repair protocol. Both virtual repair and post-repair MVs decreased posterior leaflet prolapse and restored normal coaptation. This virtual MV repair strategy has the potential for improved pre-surgical planning to predict and optimize post-repair MV function. [ABSTRACT FROM AUTHOR]

Introduction: Dysregulation of endothelial nitric oxide synthase (eNOS) and generation of nitric oxide (NO) are critical early indicators for diabetes-induced endothelial dysfunction and cardiovascular complications. We hypothesize that levels of NO production and eNOS expression by endothelial cells are decreased in DM subjects when compared to non-DM subjects. Methods: The study cohort consisted of 9 non-DM subjects and 6 DM subjects undergoing myocardial biopsy at the time of coronary artery bypass grafting surgery. The non-myocyte cell suspensions from the left ventricle (LV), right atrial appendages (RAA), and skeletal muscle (SKM) tissue were analyzed by flow cytometry to measure production of nitric oxide in subpopulations of endothelial and non-endothelial cells. Cells in suspension were incubated with DAF-2DA in the presence or absence of NO synthase inhibitor, L-NAME. Flow cytometry was used to determine production of NO in subpopulations of endothelial and non-endothelial cells from biopsies. Measurements of eNOS and phospho-eNOS (ser1177) were performed using western blot. Results: Basal Nitric oxide production was measurable in non-diabetic subjects \ in 55%, 80% and 65% of unstimulated endothelial cells obtained from RAA, LV and SKM biopsies, compared to 40%, 40%, and 66%, respectively in diabetic subjects (P < 0.02, DM vs Non-DM). No differences were found in the number of NO-producing non-endothelial cells between DM and non-DM subjects. The level of eNOS showed a trend towards decreased protein expression in DM subjects compared to non-DM. Conclusions: Generation of NO by endothelial cells and level of eNOS expression are decreased in left ventricular endothelial cells of DM patients compared to non-DM. Left ventricular biopsies can be used safely for assessment of NO dysregulation and endothelial dysfunction, and whether these can be improved with interventions targeting diabetic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Introduction: Neochordoplasty is an important repair technique, though the optimal anchoring position is unknown. While typically anchored at papillary muscles, new percutaneous devices anchor the chordae at or near the ventricular apex, which we hypothesize will result in significantly higher forces on the chordae and neochord. Methods: Porcine mitral valves were dissected (n=3) and mounted in a custom 3D printed left heart simulator generating physiological pressure and flow. Hemodynamic and echocardiographic data were collected, and chordal forces were measured using Fiber Bragg Grating (FBG) strain gauge sensors. Isolated MR was induced by cutting P2 primary chordae resulting in prolapse. Regurgitant valves were then repaired with a PTFE neochord with transapical fixation, followed by papillary fixation for comparison. In both cases, the neochord was anchored to a customized force-sensing post positioned to mimic in vivo placement (Fig. A). Results: Hemodynamic and echocardiographic data confirmed that both techniques resulted in elimination of MR in all valves and restoration of physiologic hemodynamics. Peak forces on the chordae and neochord were lower for papillary than the transapical fixation (p=0.04). Force tracings were compiled for each class of chordae at baseline, after prolapse, and after both repair techniques (Fig. B). The maximum dF/dt for the neochord suture was 30.6 N/s with the papillary fixation and 51.7 N/s with the transapical fixation. These may translate into increased stress on the mitral valve apparatus. Conclusions: Transapical fixation results in higher peak forces on the chordae and noechord suture as well as an increased rate of loading on the neochord when compared to the papillary muscle fixation and may influence repair durability. [ABSTRACT FROM AUTHOR]

Background: The use of contemporary advanced cardiovascular interventions (ACI) has dramatically increased. Concurrently, survivorship from cancer continues to improve, and cardiovascular disease (CVD) is quickly becoming a leading cause of death. Hypothesis: There is underutilization of ACIs among patients with cancer compared to general population. Methods: Hospitalizations were identified by querying the National Inpatient Sample from 2003-2015. Hospitalizations included were adults with diagnosis of acute coronary syndrome (dx1), heart failure (dx1) or diagnosis of valve disease (dx1-30). ACI was defined as percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), cardiac valvular surgeries and percutaneous interventions (valves) and cardiac implanted electronic devices (combination of defibrillator, resynchronization therapy and pacemaker, CIED). Metastatic cancer was excluded from analysis. Trends of ACI and in-hospital mortality were plotted across time and compared using Rao-White Chi-Square test. Adjusted analysis was performed with age < 65 years, white race, Medicare insurance and Elixhauser's comorbidity (ELI) <= 2. Results: Over the 13 years considered there were 7,889,166 ACIs (50.8% PCI, 17.5% CABG, 16.7% valves and 15% CIED), of which 631,293 (8.8%, table) were performed in cancer patients. Overall, cancer patients were older, and more often male, smokers, had Medicare insurance. The performance of ACIs is lower in those with cancer compared to those without in the whole cohort with increasing trend of utilization of ACI (p-trend <0.0001, figure 1). Further, cancer cohort has a lower rate of in-hospital mortality following an ACI compared to those who are free of cancer (2.6% vs 2.9%, 1.6% vs 1.9% (adjusted), p<0.0001 for both) with overall decreasing in-hospital mortality in non-cancer cohort (figure 2, p-trends <0.0001) and no change in in-hospital mortality trends in cancer cohort (p-trend not significant, figure 2). Conclusions: Cancer patients have experienced a disproportionate lower but increasing use of ACI. In-hospital mortality is has not changed in the last 13 years and is lower compared to the non-cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Elevated wall stress (WS) from chamber dilatation and wall thinning drive cause congestive heart failure(CHF) after a myocardial infarction(MI). Reducing WS by reshaping the left ventricle (LV) could decelerate or halt CHF progression, delaying need for ventricular assist devices or transplantation. In this study, we sought to investigate if a transventricular reshaping device (TRD - Fig 1A,B) can preserve cardiac function and inhibit adverse remodeling in a rodent model of chronic ischemic cardiomyopathy. Hypothesis: Reducing left ventricular WS and sphericity index (SI) can preserve cardiac function and inhibit adverse remodeling in ischemic cardiomyopathy. Methods: Rats (n=18) were induced with an MI by left coronary artery ligation. 3 weeks post-MI, TRD was implanted on a beating heart in 9 rats (MI+TRD) (Fig 2A-C) and no surgery in others (MI only).TRD was tightened with echo, for 25% reduction in end-diastolic diameter and in WS. All rats were survived for another 3 weeks, with echo at 0, 2, 4, 6 weeks post-MI, and invasive hemodynamics at termination. Tissue was snap frozen for RNA-seq analysis. Results: Cardiac dysfunction were confirmed in both groups prior to TRD implantation (%EF in MI+TRD: 77.4±1.2vs. 59.6±2.1; p<0.0001; %EF in MI: 74.7±1.8 vs. 57.0±3.3; p=0.0002). TRD implantation and tightening, reduced LVEDD from 8.7±0.2mm to 6.7±0.2mm (23% change, p <0.0001), reduced sphericity index from 0.74±0.04 to 0.54±0.05 (27% reduction, p<0.0001), and WS from 19.9±2.0 to 14.5±1.7 (27% decrease, p=0.0662) (Fig 3A-B). At termination, EDV and ESV were significantly reduced in MI+TRD compared to MI alone (EDV: 647.5±39.0μl vs 500.1±14.4μl; p=0.0032; 317.5±16.9 μl vs 218.1±14.7 μl; p=0.0021), indicating halted adverse remodeling with TRD (Fig 4A-B). Infarct border zone wall thickness was preserved in MI+TRD, but significantly reduced/thinned in MI (Fig 5A), containing infarct expansion. Pre-load adjusted LV dp/dt(max), was significantly higher in MI+TRD compared to MI only ( Fig 5B ). Conclusions: Reshaping and reducing the ischemic LV with the transventricular restraint, improves cardiac contractility, preserves ventricular wall thickness and inhibits infarct expansion in this chronic rodent model of cardiomyopathy. [ABSTRACT FROM AUTHOR]

Introduction: Durable ventricular assist device (VAD) therapy is a highly specialized surgical treatment that has experienced rapid growth. To date, there is limited understanding of its dissemination and use compared to heart transplantation. Hypothesis: Use of durable VAD therapy varies by geography and race in patterns that are distinct from heart transplantation. Methods: Durable VAD implant volume was assessed from 2008 to 2014 using data compiled from INTERMACS and Medicare to maximize capture of VADs. State-level U.S. Census data consisting of population estimates stratified by age (>20 years) and race (white vs. minority) were obtained from the Center for Disease Control WONDER database. Implant rates (using implant volume) and heart transplant rates (using data from 2008-2014 from the United Network for Organ Sharing, UNOS) were calculated using the stratified census population data. Results: Overall, 16,607 patients received a VAD implant. The total number of VAD implants increased over time (1,159 in 2008 to 3,390 in 2014). The rate of VAD implants (per 1M) increased for whites from 4.5 in 2008 to 12.2 in 2014 and for minorities from 8.3 in 2008 to 22.79 in 2014. Per capita implant rates varied by UNOS region with relative increases for minorities greatest in UNOS regions 7, 11, 8 and 2 (FIG). Modest increases in transplant rates (<5%) were observed in most UNOS regions for whites and were accompanied by only modest rate increases in VAD implants (<10%). In contrast, most UNOS regions demonstrated a large increase in minority VAD implant rates (>10%) with only modest increases in transplantation rates (<5%). Conclusion: Rates of VAD use increased appreciably over time and varied by race and geography in patterns distinct from rates of heart transplantation. While the reasons underlying a higher rate of VAD use in minority populations are unclear, our findings have implication for ensuring equitable dissemination of this therapy. [ABSTRACT FROM AUTHOR]

Introduction: Purpura fulminans (PF) is a hematologic emergency that can occur in the setting of severe septic shock. It is an uncommon and severe manifestation of disseminated intravascular coagulation (DIC) in which multiple coagulation factors are consumed, including the endogenous inhibitors antithrombin and protein C (PC). Case: A 30-year-old female with a history of treatment-naïve Hepatitis C and intravenous drug abuse that was complicated by methicillin-resistant Staphylococcus aureus (MRSA) tricuspid valve (TV) endocarditis status post bioprosthetic TV replacement presented with altered mental status. She was febrile, hypotensive, and tachycardic on presentation. Admission blood cultures grew MRSA. Electrocardiogram revealed sinus tachycardia with rightward axis deviation and right atrial enlargement. Transesophageal echocardiogram demonstrated severely thickened TV leaflets with severe stenosis and a large mobile echodensity consistent with vegetation. Chest CT demonstrated subpleural nodules. She stabilized however subsequently developed large purpuric plaques with central bulla formation throughout her distal extremities. Further work-up noted depressed function of PC, Protein S, and antithrombin. This constellation of findings was consistent with DIC and PF. Intravenous human PC concentrate was initiated and her purpuric plaques rapidly resolved (Figure). Operative findings noted an obstructive vegetation involving all three TV leaflets with an abscess cavity around the annulus. She underwent a bioprosthetic TV replacement and was discharged to a skilled nursing facility after completion of ceftaroline for six weeks. Conclusion: In this case report, we describe the first patient with PF secondary to MRSA endocarditis who was successfully treated with PC concentrate and surgical valve replacement. Future studies to determine whether administration of PC concentrate can reduce mortality in this setting are indicated. [ABSTRACT FROM AUTHOR]