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There has been a significant expansion of the use of mechanical circulatory support (MCS) devices for patient with acute coronary syndromes (ACS) with cardiogenic shock (CS) and in patients undergoing high-risk percutaneous interventions (PCI). The purpose of this review is to provide an overview of the indications and outcomes of these devices in high-risk cardiac patients.Early revascularization of the culprit-lesion is the immediate goal in ACS patients with CS and the use of pulmonary artery catheters has been associated with improved outcomes in patients with cardiogenic shock. The MCS devices that are used for myocardial support include the intra-aortic balloon pump (IABP), the left ventricle (LV) to aorta pumps, left atrium (LA) to arterial pumps, and right atrial (RA) to arterial pumps. This review provides an overview on the use of these devices in patients with ACS and CS and those undergoing high-risk PCI. Attention is focused on the IABP, the Impella (LV-aorta pump), the TandemHeart (LA-arterial pump), and veno-arterial extracorporeal membrane oxygenation (RA-arterial pump). The indications, evidence, and complications of each device are reviewed. Each device varies in its physiological effect on native heart function, complexity in insertion, and complications. The use of MCS devices for high-risk PCI and CS has increased in recent years and have demonstrated efficacy in supporting a vulnerable myocardium. Although recommendations can be made for use of each device in certain clinical scenarios, further evidence through registries and clinical trials is necessary to guide appropriate device utilization.

Background Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.Methods In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged >= 40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033.Findings Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1.0 [95% CI 0.8-1.2]; p=0.85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (p(interaction)=0.002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (p(interaction)=0.012 [>= 29.7 mL/m(2), worse outcomes]), and sex (p(interaction=)0.02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0.11).Interpretation Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

The purpose of this article is to inform nurse practitioners and other healthcare professionals regarding the utilization of CardioMEMs, a wireless pulmonary artery pressure monitoring device, in reducing heart failure-related hospital readmission rates. This article will briefly explain how CardioMEMs also helps to reduce the risk of Covid-19 in patients with heart failure.

Identifying ischemic etiology of cardiomyopathy carries prognostic and therapeutic significance. Clinical and electrocardiographic parameters can predict ischemic cardiomyopathy. Positive T wave polarity in lead aVR (TPaVR) has been associated with adverse cardiac events and severity of coronary artery disease. Medical records of adults evaluated in an advanced heart failure referral clinic for cardiomyopathy with systolic dysfunction (ejection fraction ≤ 40%) were retrospectively reviewed. Patients with ventricular pacing were excluded. Significant predictors of ischemic cardiomyopathy from a univariate logistic regression model were entered simultaneously into a multivariate logistic regression model. A total of 180 patients met study inclusion criteria. Mean age of the population was 52.5 ± 15.3 years old and 65% were men. Ischemic cardiomyopathy was present in 52 patients (29%). Positive TPaVR was present in 57 patients (32%). Ischemic cardiomyopathy was more common in patients with positive TPaVR (63% vs 13%, plt; 0.001). Ischemic cardiomyopathy was independently predicted by male gender, diabetes, hyperlipidemia, absence of family history of cardiomyopathy, echocardiographic regional wall motion abnormality, and positive TPaVR. The strongest association was with positive TPaVR (odds ratio 30.5, 95% confidence interval 6.47 to 214; plt; 0.001). T wave amplitude of +0.025 mV in lead aVR was the optimal cutoff to distinguish ischemic and nonischemic cardiomyopathy in receiver operating characteristic analysis (sensitivity 69.2%, specificity 83.6%, area under curve = 0.747, 95% confidence interval 0.658 to 0.836). In conclusion, positive TPaVR was a strong predictor of ischemic etiology of cardiomyopathy.

Warfarin is standard anticoagulation therapy for patients with a continuous-flow left ventricular assist device (CF-LVAD). However, warfarin requires regular monitoring and dosage adjustments and fails for many patients, causing thromboembolic and bleeding events. Factor Xa inhibitors have been shown to be noninferior to warfarin in preventing strokes and are associated with less intracranial hemorrhage in patients with atrial fibrillation. We evaluated treatment safety and effectiveness in CF-LVAD patients who switched from warfarin to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin failure. This was a retrospective, single-center study of patients treated between 2008 and 2018. We assessed the occurrence of stroke, non-central nervous system (CNS) embolism, pump thrombosis, and major gastrointestinal bleeding and intracranial hemorrhage during therapy. We identified seven patients: five were male, the average body mass index was 30 kg/m2, and average age was 56 years. Preimplantation comorbidities included hypertension (all patients) and diabetes mellitus, ischemic cardiomyopathy, atrial fibrillation, and previous myocardial infarction (four patients each). Overall, patients received warfarin for 3968 days and apixaban/rivaroxaban for 1459 days. The warfarin group was within the therapeutic INR range (2.0–3.0) 30% of the time. Complication rates did not differ between warfarin and apixaban/rivaroxaban: strokes, 0.20 vs none, non-CNS embolism, 0.54 vs none; pump thrombosis, 0.27 vs none; major gastrointestinal bleeding, 0.20 vs 0.50; intracranial hemorrhage, 0.13 vs none. Factor Xa inhibitors may be viable treatment options for CF-LVAD patients for whom warfarin therapy has failed. Large prospective studies are necessary to confirm these results.

Background: In patients with pulmonary hypertension (PHT), the assessment of left ventricular (LV) diastolic function by echocardiography may not be reliable. PHT can affect Doppler parameters of LV diastolic function such as mitral inflow velocities and mitral annular velocities. The current guidelines for the assessment of LV diastolic function do not recommend specific adjustments for patients with PHT. Methods: We analyzed 36 patients from the PHT clinic that had an echocardiogram and right heart catheterization performed within 6 months of each other. Early mitral inflow velocity (E), lateral mitral annular velocity (lateral e’), septal mitral annular velocity (septal e’), tricuspid free wall annular velocity (RV e’) were measured and compared to the invasively measured intracardiac pressures including pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure, and right ventricular end-diastolic pressure. Results: Among patients with PHT, the specificity of the septal e’ for LV diastolic dysfunction was 0.19, and the positive predictive value was 0.13 (lower than the lateral e’ or E/average e’). By receiver-operating characteristic curve analysis, the area under the curve (AUC) of lateral and septal e’ was just 0.64 (p = 0.9) and 0.53 (p = 0.6), respectively, while the AUC of average E/e’ was 0.94 (p < 0.001). The septal e’ was paradoxically lower at 6.5 ± 1.9 cm/s for normal PCWP compared to 6.9 ± 1.7 cm/s for elevated PCWP (p = 0.04). 81 versus 40% (p = 0.017) of patients with normal versus elevated PCWP had an abnormal septal e’ Conclusion: Our study suggests E/average e’ may be the only reliable tissue Doppler parameter of LV diastolic dysfunction in patients with PHT, and that septal e’ is paradoxically decreased in patients with PHT and normal left-sided filling pressures.

Implantable continuous-flow left ventricular assist devices (CF-LVADs) are used for long-term LV support in bridging patients to heart transplantation or as destination therapy. With prolonged support times, some patients will have repeat complications necessitating multiple device exchanges. To elucidate the safety and efficacy of repeat device exchange, we retrospectively reviewed data from 25 patients who underwent two or more CF-LVAD implantations between July 2005 and August 2017. Indications for exchange were thrombus/hemolysis (n = 8, 32%), electromechanical device malfunction (n = 14, 56%), and infection (n = 3, 12%). The implanted devices were the HeartMate II (n = 13, 52%), the HeartWare HVAD (n = 11, 44%), and the Jarvik 2000 (n = 1, 4%). Average hospital length of stay was 44 days (range 4-221 days), and 17 patients (68%) survived to discharge. Average duration of support after the most recent LVAD implantation was 802 days (range 1-3,229 days). Overall survival was 72% at 1 year and 60% at 2 years. Postoperative complications included respiratory failure in five patients (20%), device infection in five (20%), bleeding requiring reoperation in four (16%), neurologic dysfunction in four (16%), and acute renal failure in two (8%). Overall, our data suggest that repeat LVAD exchange is a feasible option for patients with recurrent device-related complications.

Hyponatremia is associated with adverse outcomes in heart failure and after cardiac surgery. We hypothesized that hyponatremia is associated with poorer short-term and longer term survival in patients after continuous-flow left ventricular assist device (CF-LVAD) placement.We reviewed a single-center database of patients who received a CF-LVAD during 2012-2017. Sodium (Na) values obtained within 14 days before CF-LVAD insertion were averaged; patients (n = 332) were divided into hyponatremia (mean Na135 mEq/L; n = 160; 48.2%) and normonatremia groups (mean Na 135-145 mEq/L; n = 172; 51.8%). Patients requiring preoperative dialysis or pump exchange were excluded. We compared outcomes between preoperative hyponatremia and normonatremia groups.The two groups' baseline characteristics were similar, although hyponatremia patients more often had preoperative mechanical circulatory support (44.4% vs. 31.4%, p = 0.002). Although hyponatremic and normonatremic patients did not differ in 30-day mortality (7.5% vs. 6.5%, p = 0.7), preoperative hyponatremia was associated with greater 5-year mortality (61% vs. 44%, p = 0.03). On binary logistic regression analysis, the strongest independent predictors of late mortality were hyponatremia (odds ratio [OR] 1.88, 95% CI [1.07-3.31], p = 0.02), older age (OR 1.03, 95% CI [1.01-1.05], p = 0.01), and elevated mean right atrial pressure/pulmonary capillary wedge pressure ratio (OR 4.69, 95% CI [1.76-12.47], p = 0.002).Hyponatremia was not associated with greater early mortality but was associated with poorer late survival. The optimal timing of LVAD implantation in relation to hyponatremia, and whether correcting hyponatremia perioperatively improves long-term survival, should be investigated.

106 Background: Apalutamide plus androgen deprivation therapy(ADT) has been approved as a treatment option for castrate resistant non metastatic prostate cancer (nmCRPC) with a high risk of developing metastatic disease. It has also demonstrated benefit in patients with metastatic, castration-sensitive prostate (mHSPC) cancer, with improvement in overall and radiographic progression–free survival. Here we report our first experience of using Apalutamide in real life clinical practice. Methods: A cohort of 108 patients from 5 UK centres were included, among them 68 were metastatic and 40 non metastatic. All patients were treated with Apalutamide 240 mg along with ADT until disease progression. The primary endpoint was objective rate (ORR) and secondary endpoints included treatment duration and safety. Results: The median age for the whole cohort was 71 years (interquartile range 43-91), 73 years for nmCRPC and 69 years for mHSPC respectively. 81% had biopsy proven malignancy. A total of 11.7% with mHSPC had received prior radical treatment (prostatectomy or radiotherapy for localised disease), compared to 92.5% patients in the non-metastatic cohort. PSA reached undetectable levels (

The role of targeted hypothermia in patients with coma after cardiac arrest has been challenged in a recent randomized clinical trial.We performed a computerized search of MEDLINE, EMBASE, and Cochrane databases through July 2021 for randomized trials evaluating the outcomes of targeted hypothermia vs normothermia in patients with coma after cardiac arrest with shockable or non-shockable rhythm. The main study outcome was mortality at the longest reported follow-up.The final analysis included 8 randomized studies with a total of 2927 patients, with a weighted follow-up period of 4.9 months. The average targeted temperature in the hypothermia arm in the included trials varied from 31.7°C to 34°C. There was no difference in long-term mortality between the hypothermia and normothermia groups (56.2% vs 56.9%, risk ratio [RR] 0.96; 95% confidence interval [CI], 0.87-1.06). There was no significant difference between hypothermia and normothermia groups in rates of favorable neurological outcome (37.9% vs 34.2%, RR 1.31; 95% CI, 0.99-1.73), in-hospital mortality (RR 0.88; 95% CI, 0.77-1.01), bleeding, sepsis, or pneumonia. Ventricular arrhythmias were more common among the hypothermia vs normothermia groups (RR 1.36; 95% CI, 1.17-1.58; P = .42). Sensitivity analysis, excluding the Targeted Hypothermia vs Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial, showed favorable neurological outcome with hypothermia vs normothermia (RR 1.45; 95% CI, 1.17-1.79).Targeted temperature management was not associated with improved survival or neurological outcomes compared with normothermia in comatose patients after cardiac arrest. Further studies are warranted to further clarify the value of targeted hypothermia compared with targeted normothermia.

Heart failure represents a major growing health problem in developed world. This article aims to review recent heart failure trials that have significantly impacted the management of heart failure.Despite advances in heart failure, mortality and morbidity remains elevated amongst patients. Recent clinical trials demonstrate promising treatment strategies that likely impact clinical practice; including heart failure prevention with the use of SGLT2-inhibitors in patients with diabetes and cardiovascular risk, new treatments that may abrogate disease progression in cardiac amyloidosis, intravenous iron therapy in iron deficiency anemia in chronic systolic heart failure, predischarge treatment with angiotensin receptor blocker with neprilysin inhibition (ARNi) in patients hospitalized for acute decompensated heart failure, and newer continuous flow left ventricular assist device with increased durability and efficacy in patients with Stage D heart failure.Recent clinical trials with SGLT2 inhibitors, therapies targeting transthyretin cardiac amyloidosis, iron, angiotensin receptor blocker with neprilysin inhibition and newer mechanical circulatory support devices are very promising as practice changing new treatment strategies in prevention and treatment of heart failure. This article presents a summary of important trials and should be of practical value to both clinicians and researchers.

Polymers are extensively applied to protect fluorescent molecules and nanomaterials against photooxidation. However, the chemical conjugation of nanomaterials such as semiconductor quantum dots to polymers is important for long-term stability, avoiding aggregation, and finding device application of polymer-nanomaterial hybrids. The chemical conjugation of polymers provides quantum dots with superior physical stability than those prepared by physical blending. Here, we report a single step conjugation of an environment-friendly, biocompatible polymer to the surface of CdSe/ZnS core shell quantum dots. The direct conjugation of a polymer to the quantum dot surface helps us to avoid phase segregation of quantum dots and the polymer host, without adversely affecting the photoluminescence properties of quantum dots. Here, N-isopropyl acrylamide-maleic anhydride random copolymer is directly attached to the core-shell quantum dots through the amide linkage. The amino-functionalized quantum dots are employed in the conjugation reaction with maleic anhydride units in the polymer. Quantum dots in the resultant conjugate retain resistance to photooxidation in the solution phase or film state. The properties of the conjugate, including photostability, are studied using fluorescence spectroscopy and microscopy methods.

Recent researches focus on the development of lubricants from non-edible vegetable oil which are environment friendly and renewable. In the current work, an industrial lubricant is formulated from a non-edible vegetable oil viz. pongamia oil (PO) by blending it suitable additives. The additives such as silicon dioxide (SiO2) nanoparticles, tert-butylhydroquinone (TBHQ) and styrene butadiene rubber (SBR) were selected as antiwear, antioxidant and viscosity improver additives respectively for the study. Various lubricant properties of the formulated oil (FO) are studied and comparisons were made against neat PO and popularly available mineral oil lubricant viz. SAE 20W40. It is found that the FO possesses superior viscosity index, and lower coefficient of friction than the commercial SAE 20W40. Moreover, the viscosity range, oxidative stability and the wear scar diameter of the FO is also in the range of SAE 20W40. This work is done with an aim of promoting Pongamia agriculture and reducing soil pollution.

Visual Abstract, There is ongoing debate as to whether cardiac complications of coronavirus disease 2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome, which accounts for about 50% of patients with heart failure (HF). The morbidity and mortality associated with HFpEF is similar to HFrEF. Clinical trials to date have failed to show a benefit of medical therapy for HFpEF, which may due to lack of uniform phenotypes and heterogeneous population. In addition, medical therapy proven for HFrEF may not address the pathophysiologic basis for HFpEF. Left atrial remodeling and dysfunction is central to HFpEF and accounts for secondary pulmonary hypertension and pulmonary vascular congestion that frequently occurs with exertion. Interatrial shunts represent a novel treatment modality for HFpEF. These shunts allow for left atrial decongestion and a reduction in pulmonary venous hypertension during exercise leading to improvements in hemodynamics, functional status and quality of life. Trials to date have demonstrated safety and short-term efficacy of these devices for HFpEF. The long-term benefits are currently being evaluated in ongoing trials. If effective, the use of interatrial shunts may be a new therapeutic paradigm for the treatment of HFpEF.

Left ventricular assist devices (LVADs) are increasingly used as destination therapy or as a bridge to future cardiac transplant in patients with end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) can be used to bridge patients in cardiogenic shock or with decompensated heart failure to durable mechanical circulatory support. We assessed outcomes in patients in critical cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1) who underwent implantation of a continuous-flow (CF)-LVAD, with or without preoperative ECMO bridging. For this retrospective study, we selected INTERMACS profile 1 patients who underwent CF-LVAD implantation at our institution between Sep 1, 2004 and Nov 30, 2018. Of 768 patients identified, 133 (17.3%) were INTERMACS profile 1; 26 (19.5%) received preoperative ECMO support, and 107 (80.5%) did not. Postimplantation outcomes were compared between the ECMO and no-ECMO groups. No significant differences were found in 30-day mortality (15.4 vs. 15.9%, P = 0.95) or survival at 1 year (53.8 vs. 60.9%, P = 0.51). Three patients who received ECMO before CF-LVAD implantation subsequently underwent cardiac transplant. In the ECMO group, the lactate level 1 day after ECMO initiation was lower in survivors than nonsurvivors (2.7 ± 2.2 vs. 7.4 ± 4.2 mmol/L, P = 0.02; area under the curve = 0.85, P = 0.01) after CF-LVAD implantation. Bridging with ECMO to CF-LVAD implantation in carefully selected INTERMACS profile 1 patients (those who are at the highest risk for critical cardiogenic shock and for whom palliation may be the only other option) produced acceptable postoperative outcomes. Field of research: Artificial lung/ECMO.

Purpose of review Pulmonary arterial hypertension (PAH) is a disease that carries a significant mortality left untreated. This article aims to review pharmacotherapeutics for PAH. Recent findings PAH-specific therapies have evolved over the last three decades and have expanded from one therapy in the 1990s to 14 FDA-approved medications. Current therapies are directed at restoring the imbalance of vasoactive mediators that include nitric oxide, endothelin and prostacyclin. Although these agents are effective as monotherapy, recent trials have promulgated the strategy of upfront combination therapy. The availability of oral prostacyclin agonists has also allowed for expanded treatment options. Risk assessment is vital in guiding therapy for PAH patients. There is ongoing focus on targeting pathological mechanisms of the disease via novel therapies and repurposing existing drugs. Summary There is an array of medications available for the treatment of PAH. Prudent combination of therapies to maximize treatment effect can improve morbidity and mortality. This article reviews the data supporting these therapies and attempts to outline an approach to patient management.

Renal replacement therapy (RRT) after continuous flow left ventricular assist device (CF-LVAD) implantation significantly affects patients' quality of life and survival. To identify preoperative prognostic markers in patients requiring RRT after CF-LVAD implantation, we retrospectively reviewed data from patients who underwent implantation of a CF-LVAD at our institution during 2012-2017. Patients who required preoperative RRT were excluded. Preoperative and operative characteristics, as well as survival and adverse events, were compared between 74 (22.2%) patients requiring any duration of postoperative RRT and 259 (77.8%) not requiring RRT. Patients requiring RRT experienced more postoperative complications than patients who did not, including respiratory failure necessitating tracheostomy (35.7% vs 2.5%, p 0.001), reoperation for bleeding (34.3% vs 11.7%, p 0.001), and right heart failure necessitating perioperative mechanical circulatory support (32.4% vs 6.9%, p 0.001). Patients requiring postoperative RRT also had poorer survival at 30 days (74.7% vs 98.8%), 6 months (48.2% vs 95.1%), and 12 months (45.3% vs 90.2%) (p 0.001). Significant predictors of RRT after CF-LVAD implantation included urine proteinuria (odds ratio [OR] 3.6, 95% confidence interval [CI] [1.7-7.6], p = 0.001), estimated glomerular filtration rate 45 mL/min/1.73 m

Transthyretin amyloid cardiomyopathy (ATTR-CM) results in a restrictive cardiomyopathy caused by extracellular deposition of transthyretin, normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium. Enthusiasm about ATTR-CM has grown as a result of 3 simultaneous areas of advancement: Imaging techniques allow accurate noninvasive diagnosis of ATTR-CM without the need for confirmatory endomyocardial biopsies; observational studies indicate that the diagnosis of ATTR-CM may be underrecognized in a significant proportion of patients with heart failure; and on the basis of elucidation of the mechanisms of amyloid formation, therapies are now approved for treatment of ATTR-CM. Because therapy for ATTR-CM may be most effective when administered before significant cardiac dysfunction, early identification of affected individuals with readily available noninvasive tests is essential. This scientific statement is intended to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies, as well as unmet needs and areas of active investigation in ATTR-CM.

504 Background: First-line chemotherapy for patients with cisplatin-ineligible metastatic urothelial carcinoma (mUC) is associated with short response duration and high toxicity. Pembrolizumab(PEM) and atezolizumab (ATZ) are associated with long-term, durable remissions as a first-line treatment of cisplatin-ineligible, PD-L1-positive patients with mUC. For patients who progressed during or after platinum-based chemotherapy, Immunotherapy also prolongs survival with less toxicity and better quality of life compared with further lines of chemotherapy. There have been no studies directly comparing the effectiveness of PEM to ATZ in mUC patients. Methods: A cohort of 112 patients from 3 UK centres were included. 62, previously untreated cisplatin ineligible mUC patients who showed PDL1 positivity were given either ATZ or PEM once every 3 weeks until progression. 49 patients who had initial platinum based chemotherapy subsequently had ATZ or PEM as second line treatment following their disease progression The primary endpoint was Overall Survival(OS) and secondary endpoints included objective rate(ORR), response duration and safety. Results: The median age was 69 ( Interquartile range 43-91) and 23% were female and 77% were male. Among, patients who received immunotherapy 1st line, 82% had baseline renal impairment(GFR < 60), and 18% had Eastern Cooperative Oncology Group performance status 2. For chemo naïve patients, median OS was 11.5 months for PEM and 5 months for ATZ respectively. ORR was 22 % for ATZ vs 50% for PEM and median duration of treatment was 4.5 and 2.5 months for PEM and ATZ respectively. When used in 2nd line median OS is 7 months for ATZ irrespective of PDL1 status and not reached for PEM yet. Grade 2 and above toxicities were reported in 18 % ATZ patients vs 10% in PEM patients, commonest were pneumonitis, tiredness, hepatitis and dermatitis. No treatment related deaths were reported. Conclusions: This study suggests that pembrolizumab has higher response rate and better survival compared to atezolizumab in cisplatin-ineligible patients with mUC and also in the 2nd line setting after disease progression following platinum based agents. Both agents were well tolerated.

Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly being used to treat advanced, refractory chronic heart failure. Herein, we sought to determine the incidence of postoperative acute kidney injury (AKI) in axial-flow (HeartMate II; HM-II) and centrifugal-flow (HVAD) CF-LVAD recipients, as well as the effect of AKI on mortality. The study cohort comprised 520 patients who received a HM-II (n = 398) or HVAD (n = 122) at our center between November 2003 and March 2016. Their records were reviewed to determine the incidence of RIFLE-defined AKI after LVAD implantation. We compared the perioperative characteristics, postoperative complications, and survival rates of the patients with and without AKI and differentiated the outcomes based on device type (HM-II or HVAD). Seventy-five patients (14.4%) developed AKI postoperatively. Patients with AKI after LVAD implantation had significantly reduced survival compared to patients without AKI (p = 0.01). Cox proportional hazards models showed that AKI was a significant independent predictor of mortality (HR = 1.54, p = 0.03). Preoperative mechanical circulatory support and prolonged cardiopulmonary bypass time were independent predictors of AKI. The incidence of AKI was similar for HM-II and HVAD recipients (p = 0.25). There was no significant difference in AKI rates for the HM-II and HVAD recipients. Developing AKI adversely affected survival.

Objectives The aim of this study was to evaluate the incidence, predictors, and associated mortality of pre-implantation, early, and late ventricular arrhythmias (VAs) in patients receiving continuous-flow left ventricular assist devices (CFLVADs). Background VAs are common both pre- and post-implantation of left ventricular assist devices. Limited data exist on their prognostic impact in contemporary CFLVADs. Methods A retrospective review was performed to identify patients who underwent CFLVAD implantation between 2000 and 2015 with 2 years of follow-up. All VAs, defined as ventricular fibrillation, ventricular tachycardia lasting >30 s, or a ventricular rhythm requiring defibrillation, were analyzed. VAs occurring within 30 days of implantation were defined as early. Recorded outcomes included death and receipt of cardiac transplant. Results A total of 517 patients were included for analysis. Early VAs were associated with a significant reduction in survival (hazard ratio: 1.83; 95% confidence interval: 1.28 to 2.61; p = 0.001) compared with patients with late or no VAs. Pre-implantation variables independently predictive of early VAs included prior cardiac surgery (odds ratio: 1.90; 95% confidence interval: 1.09 to 3.32; p = 0.023) and pre-CFLVAD ventricular tachycardia storm (odds ratio: 3.15; 95% confidence interval: 1.49 to 6.69; p = 0.003). The incidence of early VAs from 2000 to 2007 was as high as 47%, whereas the highest incidence from 2008 to 2015 was Conclusions VAs within 30 days after CFLVAD implantation are associated with an increased risk for death. Predictors of early VAs include prior cardiac surgery and pre-CFLVAD ventricular tachycardia storm. Temporal trends have shown a decrease in VA from 2000 to 2015. Strategies to reduce arrhythmia burden shortly after CFLVAD implantation warrant further investigation.

Purpose End-stage heart failure is a leading cause of morbidity and mortality in adult congenital heart disease (ACHD) patients; however, advanced therapies such as ventricular assist devices (VADs) are rarely implemented in this population. The aim of this study was to examine the outcomes of ACHD patients supported by durable continuous-flow VADs. Methods We performed a retrospective review of patients with congenital heart disease >18 years of age at time of VAD implantation at Texas Children's Hospital and Baylor St. Luke's Medical Center from 2011-2020. Results In total, 13 patients (median age 34 years [IQR, 24-47]) received a VAD (Table). All devices were implanted in the subaortic ventricle; 2 patients (15%) and 11 patients (85%) had moderate and great complexity congenital heart disease, respectively. Prior to implantation, 11 patients (85%) required inotropic support and 5 patients (38%) required temporary mechanical circulatory support. 12 patients (92%) survived to hospital discharge with a median postoperative LOS of 36 days (IQR, 27-50). Among those who survived to hospital discharge, all (100%) were NYHA class I or II at follow-up and the median duration of support was 816 days (IQR, 160-1629). Patients experienced device-related complications including neurologic events (n = 5; n = 2 disabling stroke), driveline infections (n = 3), presumed device infections requiring chronic antibiotic therapy (n = 4; n = 1 associated pump exchange), GI bleeds (n = 6), and presumed pump thromboses (n = 5; n = 2 associated pump exchanges). Overall survival (heart transplant censored) at 1, 3, and 5 years was 82%, 70%, and 32%, respectively. 2 patients (50%) were successfully bridged to transplant and 1 patient initially implanted as destination therapy eventually received a transplant. Conclusion Our data demonstrate that durable VADs can be used effectively in ACHD patients with end-stage heart failure and support efforts to more readily utilize these therapies in this population.

Purpose We explored if utilization of continuous flow (CF-LVADS) has increased amongst females in the age of new-generation devices, which are smaller and more durable. We also compared outcomes between female and male CF-LVAD recipients. Methods The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) was queried to identify 20,324 CF-LVAD recipients from June 2008 to December 2017, of which 4350 (21.4%) were female and 15,974 (78.6%) were male. Survival was compared after propensity matching for age ≥ 50 yr, heart failure etiology, body surface area, INTERMACS class, co-morbidities, device strategy as destination or bridge to transplant therapy, temporary mechanical circulatory support, and device type. Results In 2008, women made up 22.5% of CF-LVAD recipients but that decreased to 20.9% in 2016 (Figure 1a). After propensity matching, baseline characteristics were comparable between 2463 females and 3925 males with the exception of mean right atrial pressure / pulmonary capillary wedge pressure which was higher in women (0.50 vs 0.45, p Conclusion Women with heart failure are far less likely to receive CF-LVADs and despite propensity matching, women are more likely to present with right heart failure at time of implantation. The higher mortality risk may be due to women presenting with more advanced heart failure at time of referral for CF-LVAD.

Purpose Adult congenital heart disease (ACHD) patients are disproportionally affected by heart failure and cardiogenic shock compared to the general population. Despite a growing and aging cohort, experience with percutaneous continuous flow ventricular assist device (pVAD) use in ACHD patients is rarely described in the literature. Methods Retrospective chart review at Texas Children's Hospital and Baylor St. Luke's Medical Center from 1/2016 to 8/2020 for patients with congenital heart disease who were adult age at time of pVAD placement. Results Six patients with ACHD received 7 pVAD devices with a median age at placement of 34 [IQR 23- 38] years (Table). Five (83%) patients were male and 5 (83%) had complex congenital heart disease. Three (50%) patients had Fontan circulation. Devices included: 4 (57%) Impella CP®, 1 (14%) Impella 5.0® and 2 (29%) Impella 5.5®. Four (57%) devices were placed in patients with INTERMACS profile score 1. Four (57%) devices were placed in patients with acute decompensated heart failure in the setting of chronic heart failure and 3 (43%) devices were placed due to peri-procedural hemodynamic compromise. Three devices (43%) were placed via hybrid-surgical method with axillary artery grafts and 4 (57%) Impella CP® devices were placed percutaneously in the femoral artery. Median duration of patient support was 20 [IQR 3-44] days. Major pVAD-related complications included severe hemolysis requiring replacement of Impella CP® with Impella 5.0 device® and aortic valve replacement at time of Impella® 5.0 removal and durable ventricular assist device implantation in a neo-aortic valve with pre-existing regurgitation. There were no significant limb injuries/ischemia, stroke or bleeding events. Two (33%) patients were bridged to a durable ventricular assist device; all 6 (100%) patients survived to hospital discharge. Conclusion Percutaneous continuous flow ventricular assist devices can be successfully used to hemodynamically support ACHD patients in cardiogenic shock.

BACKGROUND: Type 2 myocardial infarction (MI) is increasingly diagnosed in patients with heart failure (HF). A paucity of data exists pertinent to the contemporary prevalence and impact of type 2 MI in patients with HF. We studied the patient profiles and the prognostic impact of type 2 MI on outcomes of HF hospitalizations. METHODS: The Nationwide Readmission Database 2018 was queried for patients with HF hospitalizations with and without type 2 MI. Baseline characteristics, inpatient outcomes, and 30-day all-cause readmissions between both cohorts were compared. RESULTS: Of 1,072,674 primary HF hospitalizations included in the study, 28,813 (2.7%) had type 2 MI. Patients with type 2 MI were more likely to be males (56.5% vs 51.6%; P < .001) and had a higher prevalence of hypertension (94% vs 92.2%; P < .001), prior myocardial infarction (17.1% vs 14.9%; P < .001), anemia (9.1% vs 8.1%; P < .001), chronic kidney disease (55.7% vs 49.4%; P < .001), neurological disorders (9.4% vs 7.3%; P < .001), and weight loss (7.3% vs 5.6%; P < .001). Compared with their counterparts without type 2 MI, patients with HF with type 2 MI had significantly higher in-hospital mortality (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.37–1.72), hospital costs (adjusted parameter estimate, $1785; 95% CI, 1388–2182), discharge to nursing facility (aOR, 1.22; 95% CI, 1.15–1.29), longer length of stay (adjusted parameter estimate, 0.53; 95% CI, 0.42–0.64), and rate of 30-day all-cause readmissions (aOR, 1.06; 95% CI, 1.01–1.12). CONCLUSION: Type 2 MI in patients hospitalized with HF is associated with higher mortality and resource utilization in the United States.

Anticoagulation with unfractionated heparin is vital to reduce the risk of thromboembolic events during cardiopulmonary bypass and left ventricular assist device placement. However patients with heparin-induced thrombocytopenia are at risk of developing immune-mediated thrombotic events. We describe 2 patients with heparin-induced thrombocytopenia confirmed via serotonin release assay who were successfully treated with plasmapheresis exchange before left ventricular assist device placement.

Purpose Hyponatremia is a recognized risk factor for adverse outcomes in heart failure and after cardiac surgery. We hypothesized that hyponatremia would be associated with poorer short-term and longer-term survival in patients after continuous-flow left ventricular assist device (CF-LVAD) placement. Methods Patients who received a CF-LVAD between January 2012 and December 2017 were identified in a single-center database. Sodium values within 14 days of LVAD insertion were averaged; hyponatremia was defined as Na Results Out of 322 patients, 49.7% (n=160) were found to have hyponatremia prior to LVAD insertion. There were no significant differences in comorbidities between groups. Pre-operative hyponatremia was associated with increased length of post-operative stay (38 vs 30 days, p=0.02). Though there was no difference in short-term (90-day) mortality, hyponatremia was associated with increased long-term, five-year mortality (61% vs 44%, p=0.03) (Figure 1). On binary logistic regression analysis, hyponatremia (OR 1.88 95% CI [1.073-3.315], p=0.03), increased age (OR 1.03 95% CI [1.007-1.053], p=0.01), elevated neutrophil-lymphocyte ratio (OR 1.064 95% CI [1.004-1.128], p=0.037), decreased albumin (OR 0.94 95% CI [0.887-0.992], p=0.03), and elevated mean right atrial pressure/pulmonary capillary wedge pressure ratio (OR 4.69 95% CI [1.762-12.473], p=0.002) were independent risk factors of mortality. Conclusion Pre-operative hyponatremia is associated with increased mortality after LVAD implantation and can be used as a marker or added to existing risk scores to further risk stratify patients. Whether hyponatremia correction improves long-term survival should be investigated.

Pulmonary arterial hypertension (PAH) is a condition associated with substantial morbidity and mortality. Over the last 25 years there has been a significant evolution in the therapies to treat PAH. These therapies are effective for patients with group I PAH and group IV PH [chronic thromboembolic pulmonary hypertension (CTEPH)]. PAH is characterized by an imbalance of nitric oxide, prostacyclin and endothelin levels, and current pharmacotherapy involves these three pathways. Earlier clinical trials involving PAH-specific therapies evaluated improvements in 6-minute walk time as a primary improvement whereas contemporary trials have been larger and focused on morbidity and mortality reductions. While there may be a role for monotherapy in disease management, most patients should be considered for dual or triple therapy.

In this study, we sought to determine the accuracy of several critical care risk scores for predicting survival of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1 patients after continuous-flow left ventricular assist device (CF-LVAD) placement. We retrospectively analyzed the records of 605 patients who underwent CF-LVAD implantation between 2003 and 2016. We calculated the preoperative HeartMate II Risk Score (HMRS) and preoperative Right Ventricular Failure Risk Score (RVFRS) and the following risk scores for postoperative days 1-5: HMRS, RVFRS, Model for End-stage Liver Disease (MELD), MELD-eXcluding International Normalized Ratio, Post Cardiac Surgery (POCAS) risk score, Sequential Organ Failure Assessment (SOFA) risk score, and Acute Physiology and Chronic Health Evaluation III. The preoperative scores and the postoperative day 1, 5-day mean, and 5-day maximum scores were entered into a receiver operating characteristic curve analysis to examine accuracy for predicting 30-day, 90-day, and 1-year survival. The mean POCAS score was the best predictor of 30-day and 90-day survival (area under the curve [AUC] = 0.869 and 0.816). The postoperative mean RVFRS was the best predictor of 1-year survival (AUC = 0.7908). The postoperative maximum and mean RVFRS and HMRS were more accurate than the preoperative scores. Both of these risk score measurements of acuity in the postoperative intensive care unit setting help predict early mortality after LVAD implantation.

Background Elderly metastatic renal cell carcinoma (mRCC) patients are under-represented in clinical trials, whose results are therefore difficult to translate into routine management of older patients. We aimed at exploring treatment outcomes and prognostic factors in our real-life elderly mRCC cohort receiving first-line tyrosine kinase inhibitor (TKI) monotherapy. Patients and Methods We retrospectively analyzed demographic and clinicopathological characteristics, and treatment data of elderly (≥ 70 years old at first-line start) mRCC patients starting either pazopanib or sunitinib as first-line treatment in our institution between March 2012 and April 2018. Baseline characteristics included age-adjusted Charlson comorbidity index (CCI). Results In total, the records of 35 elderly mRCC patients were identified and retrospectively analyzed. Overall response rate, median progression-free survival, and median overall survival were 20%, 9.7 months, and 21.6 months, respectively. Karnofsky performance status ≤ 70%, sarcomatoid features, absolute neutrophil count greater than upper limit of normal, and treatment-related Grade 3 arterial hypertension were independently associated with survival after multivariate analysis. Age-adjusted CCI was significantly associated with survival in univariate analysis only. The overall incidence of Grade 3 to 5 toxicities was 74%. Seven patients (20%) received early crossover to either sunitinib or pazopanib because of toxicity. Dose reduction was applied in 24 (73%) of the 33 patients who completed at least 1 cycle. Conclusion First-line TKI monotherapy provided clinical benefit in our elderly mRCC cohort. Relatively frequent dose reductions helped to maintain an acceptable tolerability profile. Further research is warranted to explore the significance of prognostic factors in elderly mRCC patients.

Introduction: Postoperative atrial fibrillation (POAF) is one of the most common complications after cardiac surgery and is especially hazardous in elderly patients and those with left ventricular dysfunction. Therefore, we sought to find the associated risk factors and predictors for the development of POAF in patients undergoing left ventricular assist device (LVAD) implantation. Materials and methods: We retrospectively reviewed 109 patients with no prior history of atrial fibrillation undergoing continuous flow LVAD implantation at a single center institution from 2013-2017. Results: POAF lasting 24 hours or greater occurred in 29 of 109 patients (26.6%). Early 30-day mortality was higher in POAF patients compared to non-POAF (6.9% vs 0%, p=0.02) (Figure). Patients with POAF had higher rates of pump exchange although this did not reach statistical significance (17.2% vs 6.3%, p=0.08). However, POAF was not associated with stroke (10.3% vs 23.8%, p=0.24) or long-term mortality (27.6% vs 31.3%, p=0.8). The only independent risk factor for POAF was elevated pre-operative creatinine (OR: 2.5 95% CI: 1.3-4.6, p=0.004). Higher mean preoperative CHADS 2 (3.0 +/- 0.01 vs 2.4 +/- 0.5, p=0.01) and mean preoperative R 2 CHADS 2 (5.0 +/- 0.01 vs 4.4 +/- 0.5, p=0.01) scores were associated with POAF as compared to non-POAF. Conclusion: In patients undergoing continuous-flow left ventricular assist device implantation, postoperative atrial fibrillation was associated with higher rates of early mortality but not postoperative stroke or long-term mortality. Furthermore, higher preoperative CHADS 2 and R 2 CHADS 2 scores were associated with postoperative atrial fibrillation. However, the only independent predictor of post-operative atrial fibrillation in this small cohort was elevated preoperative creatinine.

e17034 Background: Studies have shown an improvement in overall survival (OS) and symptom control in metastatic castration-resistant prostate cancer (mCRPC) with Radium-223 treatment. However, there is little information about predicting outcomes using either PSA or Alkaline Phosphatase (ALP) response or comparing bone only disease to bone and lymph node (LN) involvement. Methods: 335 patients receiving Radium 223 at 6 UK centres between March 2014 and June 2020 were included. The primary endpoint was overall survival, secondary endpoints were toxicity, symptomatic benefit and skeletal-related events(SRE) Results: The median age was 75, with 71% having bone only metastases and 29% also having lymph node involvement. Those with PSA response (30%) had a statistically significant improvement in OS, compared to non-responders (18.2 vs 13.8 months, p = 0.026). They also showed highest rate of imaging response/stable disease (54% vs 34%). ALP response was seen in 82%. This did not translate to significantly improved OS, but did correlate with better symptomatic benefit (40% vs 29%). Those with bone only disease showed a survival benefit compared to those with LN involvement (19.4 vs 11.4 months, p = 0.046). Other than anaemia (23.5%), Grade 2 or above toxicities were uncommon including thrombocytopenia and neutropenia(5.5 and 6.2% respectively ) . 14% patients required at-least one blood transfusion. SRE were seen in 24% overall, but lower of in PSA responders(18%). Conclusions: Real life multicentre data suggests that PSA response and bone only disease could be predictors for better survival following Radium-223, whereas ALP response correlates better with symptomatic benefit.

Gas gangrene in a closed pelvic injury is very rare phenomenon and we could not find many reported cases in the literature. Radiographs are not enough for diagnosis and computed tomography (CT) is not widely available yet in primary health center. Basic management includes surgical debridement with incision and drainage of necrotic tissue of the involved area, antibiotic therapy, and surgical intensive care. Delay of the surgical debridement for >12 h is associated with higher overall morbidity. The aerobic and anaerobic bacteria with the indigenous commensal of the pelvis results in the production of exotoxins that leads to severe rapid tissue necrosis and the synthesis of insoluble gases characteristic of subcutaneous emphysema or Fournier's gangrene. Although gas gangrene is often diagnosed clinically, emergency CT can support in early diagnosis with accurate assessment of the disease extent. CT not only helps evaluate the pelvic bony structures but also helps assess the spread of disease in the abdomen and pelvis. The mainstay of the management includes surgical debridement with incision and drainage of necrotic tissue of involved area, antibiotic therapy, and surgical intensive care. Early diagnosis remains the mainstay of the treatment of Gas gangrene. It is important to diagnose these life-threatening conditions and treat them as early as possible. Due to the rarity of such events and the unavailability of gold standard diagnostic and treatment modalities, it is very difficult to prevent the mortality for such patients. There is a need for a better treatment plan to diagnose and manage such patients urgently and not to miss the initial phase of disease progression which is critical for saving the life of the patient.

Purpose Examine gender differences continuous-flow left ventricular assist device (CF-LVAD) recipients. Methods Retrospective review of 695 patients receiving a CF-LVAD from 11/2003 to 08/2017, of which 551 (79.3%) were male and 144 (20.7%) were female. Genders were compared after propensity score matching for age ≥50 yrs, diagnosis, body surface area, INTERMACS class, comorbidities, prior mechanical circulatory support, and prior sternotomy. Survival and outcomes were compared between 139 matched gender pairs. Results After matching, no difference was seen in baseline characteristics (Table 1). A competing risk analysis showed that women had a non-significant increase in mortality (p=0.065) (Figure 1). Women had higher rates of right ventricular assist device support (3.4% vs 0.8%, p=0.03) and there was a trend towards higher rates of stroke, LVAD exchange, and longer length of stay. Additionally, lower rates of drive line infection and transplantation in women were seen (Table 2). Conclusion Larger studies are needed to determine if these single center findings of increased probability of mortality amongst women are reproducible. Additionally, further study should be devoted to risk factors for postoperative right heart failure among women.