Gastrointestinal haemorrhage in extracorporeal membrane oxygenation: insights from the national inpatient sample.

Introduction: Extracorporeal membrane oxygenation (ECMO) is associated with gastrointestinal haemorrhage (GIH), which may result from coagulopathy, systemic inflammation, reduced gastric perfusion, and arteriovenous malformation from non-pulsatile blood flow. Data are limited regarding the burden of this complication in the United States. Material and methods: We analysed the National Inpatient Sample (NIS) database for the years 2007 to 2011 to identify hospitalisations in which an ECMO procedure was performed. Hospitalizations complicated by GIH in this cohort were then identified by relevant codes. Results: Between 2007 and 2011, ECMO hospitalisations increased from 1869 to 3799 (p < 0.01). The proportion of hospitalisations complicated by GIH increased from 2.12% in 2007 to 7.46% in 2011 (p < 0.01). Gastrointestinal haemorrhage was more common in men (56.7%) and in Caucasians (57.4%). Common comorbidities in this population were renal failure (71%), anaemia (55%), and hypertension (26%). All-cause inpatient mortality showed a numerical but nonsignificant increase from 56.7% to 61.9% (p = 0.49). The average cost of care per hospitalisation with GIH associated with ECMO use increased from $132,420 in 2007 to $215,673 in 2011 (p < 0.01). Conclusions: Gastrointestinal haemorrhage during ECMO hospitalisations occurred in small but significantly increasing proportions. The inpatient mortality rate and costs associated with GIH were substantial and increased significantly during the study period.

Left bundle branch area pacing in patients with heart failure and right bundle branch block: Results from International LBBAP Collaborative-Study Group.

Background: Cardiac resynchronization therapy (CRT) using biventricular pacing has limited efficacy in patients with heart failure (HF) and right bundle branch block (RBBB). Left bundle branch area pacing (LBBAP) is a novel physiologic pacing option. Objective: The aim of the study was to assess the feasibility and outcomes of LBBAP in HF patients with RBBB and reduced left ventricular systolic function, and indication for CRT or ventricular pacing. Methods: LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) <50%, RBBB, HF, and indications for CRT or ventricular pacing. Procedural, pacing, and electrocardiographic parameters; clinical response (no HF hospitalization and improvement in NYHA class); and echocardiographic response (≥5% increase in ejection fraction) to LBBAP were assessed. Results: LBBAP was attempted in 121 patients and successful in 107 (88%). Patient characteristics included age 74 ± 12 years, female 25%, ischemic cardiomyopathy 49%, and ejection fraction 35% ± 9%. QRS axis at baseline was normal in 24%, left axis 63%, right axis 13%. LBBAP threshold and R-wave amplitudes were 0.8 ± 0.3 V @ 0.5 ms and 10 ± 9 mV at implant and remained stable during mean follow-up of 13 ± 8 months. LBBAP resulted in narrowing of QRS duration (156 ± 20 ms to 150 ± 24 ms (P = .01) with R-wave peak times in V6 of 85 ± 16 ms. LVEF improved from 35% ± 9% to 43% ± 12% (P < .01). Clinical and echocardiographic response was observed in 60% and 61% of patients, respectively. Female sex and reduction in QRS duration with LBBAP were predictive of echocardiographic response and super-response. Conclusion: LBBAP is a feasible alternative to deliver CRT or physiologic ventricular pacing in patients with RBBB, HF, and LV dysfunction.

Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry.

BACKGROUND: Left bundle branch area pacing (LBBAP) has been shown to be a feasible option for patients requiring ventricular pacing. OBJECTIVE: The purpose of this study was to compare clinical outcomes between LBBAP and RVP among patients undergoing pacemaker implantation METHODS: This observational registry included patients who underwent pacemaker implantations with LBBAP or RVP for bradycardia indications between April 2018 and October 2020. The primary composite outcome included all-cause mortality, heart failure hospitalization (HFH), or upgrade to biventricular pacing. Secondary outcomes included the composite endpoint among patients with a prespecified burden of ventricular pacing and individual outcomes. RESULTS: A total of 703 patients met inclusion criteria (321 LBBAP and 382 RVP). QRS duration during LBBAP was similar to baseline (121 ± 23 ms vs 117 ± 30 ms; P = .302) and was narrower compared to RVP (121 ± 23 ms vs 156 ± 27 ms; P <.001). The primary composite outcome was significantly lower with LBBAP (10.0%) compared to RVP (23.3%) (hazard ratio [HR] 0.46; 95%T confidence interval [CI] 0.306-0.695; P <.001). Among patients with ventricular pacing burden >20%, LBBAP was associated with significant reduction in the primary outcome compared to RVP (8.4% vs 26.1%; HR 0.32; 95% CI 0.187-0.540; P <.001). LBBAP was also associated with significant reduction in mortality (7.8% vs 15%; HR 0.59; P = .03) and HFH (3.7% vs 10.5%; HR 0.38; P = .004). CONCLUSION: LBBAP resulted in improved clinical outcomes compared to RVP. Higher burden of ventricular pacing (>20%) was the primary driver of these outcome differences.

Effects of previous coronary artery bypass graft surgery on in-hospital mortality in ST-segment elevation myocardial infarction: National dataset analysis.

BACKGROUND: Association of history of coronary artery bypass graft surgery (CABG) with clinical outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI) is unclear from current data. METHODS: Using Nationwide Inpatient Sample (NIS) data from 2003 to 2014, adult patients hospitalized with principal diagnosis of STEMI were extracted. The cohort was divided into patients with a history of CABG and those without a history of CABG. The primary outcome measure was in-hospital mortality (IHM). RESULTS: 2,710,375 STEMI patients were included in final analysis of which 110,066 had history of CABG. Patients with history of CABG had higher unadjusted (12.2% vs. 8.8%, P < 0.001) and adjusted (odds ratio [OR]1.16; 95% confidence interval [CI] 1.14 to1.19, P < 0.001) IHM compared to those without previous CABG. Compared to a trend of decreasing IHM in STEMI patients without previous CABG, a trend of increasing IHM was observed over the study period in those with a history of previous CABG. Although patients with previous CABG when treated with primary PCI (PPCI) had a higher unadjusted IHM compared to those without previous CABG, (4.8% vs 4.3%, P < 0.001), after adjusting for comorbidities and in-hospital complications no significant increase in IHM was observed in patients with previous CABG treated with PPCI. CONCLUSION: STEMI patients with previous CABG have a significantly higher IHM compared to those without previous CABG. PPCI improves IHM with no independent mortality disadvantage attributable to previous CABG.

Successful WATCHMAN Device Placement Despite Left Atrial Appendage Perforation in Two Cases.

The WATCHMAN (Boston Scientific, Marlborough, USA) is a device used to occlude the left atrial appendage (LAA) in patients of non-valvular atrial fibrillation (NVAF) with a high CHA2DS2-VASc score who are poor candidates for oral anticoagulation. LAA perforation is a well-known complication of the WATCHMAN device placement. Here we present two cases of NVAF where oral anticoagulation was not advisable due to recurrent bleeding episodes. They underwent the WATCHMAN procedure for stroke prevention. During the placement of the WATCHMAN device into the left atrial appendage (LAA) in both cases, pericardial staining was noted that worsened over the next few minutes. It was decided to deploy the 27 mm WATCHMAN device into the LAA. In one case, satisfactory hemostasis was achieved with the device deployment eliminating the need for cardiothoracic surgery. However, the second case led to pericardial tamponade and was managed by the placement of a pericardial window. To our knowledge, this is the first case series describing the use of a WATCHMAN device upon detection of LAA perforation.

Trends, Outcomes, and Predictive Score For Emergency Coronary Artery Bypass Graft Surgery After Elective Percutaneous Coronary Intervention (from a Nationwide Dataset).

The temporal trends and preprocedural predictors of emergency coronary artery bypass graft surgery (ECABG) after elective percutaneous coronary intervention (PCI) in the contemporary era are largely unknown. From January 2003 to December 2014 elective hospitalizations with PCI as the primary procedure were extracted from the Nationwide Inpatient Sample. ECABG was identified as CABG within 24 hours of elective PCI. Temporal trends of elective PCI, ECABG, comorbidities, and in-hospital mortality were analyzed. Logistic regression model was used to identify preprocedural independent predictors of ECABG and post-PCI ECABG risk score was developed using the regression coefficients from the logistic regression model in the development cohort. The score was then validated in the validation cohort. Of 1,605,641 elective PCI procedures included in the final analysis, 5,561 (0.3%) patients underwent ECABG. The incidence of ECABG, co-morbidities and overall in-hospital mortality increased over the study period, whereas the in-hospital mortality after ECABG remained unchanged. An increasing trend of elective PCI performed at facilities without on-site CABG was noted, with a higher unadjusted in-hospital mortality in this cohort. ECABG risk score, performed well with a significantly higher risk of ECABG in those patients with a score in the highest tertile compared with those with lower ECABG score (0.6% vs 0.3%, p = 0.0005). In conclusion, an increasing trend of adverse outcomes after elective PCI is observed. We describe an easy-to-use predictive score using preprocedural variables that may allow the operator to triage the patient to an appropriate setting in an effort to improve outcomes.

Cardiac troponin release following left bundle branch pacing.

Left bundle branch pacing (LBBP) has emerged as an alternative to His bundle pacing (HBP) to achieve physiologic ventricular stimulation. The extent of myocardial injury during permanent LBBP implantation is currently not known. The aim of the study was to prospectively assess the extent of myocardial injury during LBBP implantation. Cardiac troponin (cTn) levels were measured at baseline and 6-12 h following permanent LBBP. The number of attempts to achieve LBBP was documented. Troponin levels were measured in a control population undergoing other electrophysiology procedures including HBP, other devices involving right ventricular (RV) pacing, radiofrequency ablation for atrial fibrillation (AF) and supraventricular tachycardia (SVT). Significant elevation of troponin (SET) was defined as threefold increase above the upper reference limit (URL) for cTn. Between December 2019 and April 2020, 204 were prospectively enrolled: LBBP in 98 and Control group 106 (SVT, 55; AF, 20; HBP, 17; other devices, 14). SET (>3× URL) was seen in 49.4% of patients in the LBBP group compared to 58.4% in the control group (p = .23). Peak troponin levels were greater in the control group compared to the LBBP group (230.3 ± 320.1 vs. 87.4 ± 71.3 pg/ml; p = .0001). Compared to LBBP (49.4%), SET was observed less frequently following HBP (17.5%; p = .01), and other device implantation (29%; p = .15). Patients requiring >2 attempts (n = 33) had significantly higher incidence of SET compared to <2 attempts (n = 56; 66.7% vs. 39.3%; p = .01). LBBP implantation is associated with myocardial injury. Asymptomatic troponin release following LBBP is less than or comparable to other interventional electrophysiology procedures.

Trends and outcomes of venous thromboembolism in adult hospitalizations with acute myeloid leukemia: analysis of nationwide inpatient sample from 2010 to 2014.

Background: Venous thromboembolism (VTE) occurs frequently in acute myeloid leukemia (AML) patients. There are no population-based studies from the United States (U.S.) analyzing this association. The study aims to analyze the trends, predictors of mortality, and outcomes of VTE in AML patients.Methods: We analyzed the publicly available Nationwide Inpatient Sample (NIS) for years 2010-2014. Hospitalizations due to AML were identified by previously validated International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes as the primary diagnosis. VTE was identified by ICD-9-CM codes as secondary diagnosis. Hospitalizations with age less than 18 years of age were excluded. The trends and outcomes were determined using Chi-squared (χ2) test and multivariate regression models.Results: From 2010 to 2014, there were 313,282 hospitalizations with a primary diagnosis of AML and 1,633 hospitalizations (0.1%) had VTE as a concurrent diagnosis. There was a significant increase in the proportion of AML hospitalizations with VTE from 0.47% in 2010 to 0.56% in 2014 (P = 0.014). Multivariable regression analysis showed that the odds of in-hospital mortality were not higher in AML hospitalizations with VTE (odds ratio [OR] 1.11; 95% confidence interval [CI] 0.81-1.52; P = 0.5) than those without VTE. Age group above 84 years carried the highest risk of mortality (OR 3.20; 95% CI 2.77-3.70; P < 0.0001) in AML-VTE patients. Black (OR 1.23; 95% CI 1.13-1.35; P < 0.0001) and uninsured patients (OR 1.50; 95% CI 1.31-1.73; P < 0.0001) were at significantly higher odds of in-hospital mortality amongst the AML-VTE hospitalizations.Conclusion: The proportion of AML hospitalizations with VTE continues to rise in the U.S. After adjusting for confounders, increasing age, Black race, and lack of insurance were found to have higher risk of in-hospital mortality in the AML-VTE cohort. The odds of in-hospital mortality in AML hospitalizations with VTE are not higher than those without VTE.

Coronary Steal in a Patient With Apical Hypertrophic Cardiomyopathy: A Rare Case of Symptomatic Coronary Artery Fistula.

This report describes a rare case of multiple left coronary artery to pulmonary artery/left atrial fistulae causing a coronary steal phenomenon. A 58-year-old male with apical hypertrophic cardiomyopathy was seen in an outpatient office for exertional chest pain and dyspnea and subsequently had a positive exercise nuclear stress test. Coronary angiogram revealed 70-80% mid-left anterior descending artery stenosis with multiple proximal coronary artery to left atrial/pulmonary artery fistulae. Due to symptomatic coronary artery fistulae with coronary steal phenomenon, the patient underwent surgical correction of fistulae with bypass graft to left anterior descending artery. To our knowledge, this is the first case report on co-existing apical hypertrophic cardiomyopathy and coronary artery-left atrial/pulmonary artery fistulae. This article reviews current guidelines for management of coronary artery fistula.

The effects of exercise on mood and prefrontal brain responses to emotional scenes in smokers.

The benefits of exercise for smokers attempting to quit are partially dependent on physical activity levels prior to cessation. Mood disturbances can manifest within 30 min of smoking a cigarette and contribute to negative reinforcement of smoking behavior over time, whereas a single bout of aerobic exercise can reduce negative mood states and improve affect on a similar timescale in non-smokers. The acute effects of exercise among non-abstaining smokers immediately after a cigarette are unknown but may have clinical implications for smokers considering cessation. The aim of this study was to examine the concurrent effects of exercise on mood disturbance and prefrontal brain hemodynamic response to emotionally arousing scenes 30 min after smoking a cigarette and to test whether prefrontal brain hemodynamic response was correlated with affective ratings of the scenes. Fifteen cigarette smokers, averaging 47.6 cigarettes/week in the year prior to screening, served as participants. Functional near-infrared spectroscopy was used to measure hemodynamic status over the dorsolateral prefrontal cortex (DLPFC). Participants viewed pleasant, unpleasant, and neutral scenes prior to smoking a cigarette and 30 min later after seated rest or exercise at a preferred intensity. Mood disturbance was assessed by the Profile of Mood States-Brief Form four times: before smoking a cigarette, before and after exercise and rest, and after a post-condition (exercise/rest) exposure to emotionally arousing scenes. Compared to seated rest, cycling after a cigarette reduced mood disturbance (p = =.038) and DLPFC hemodynamic response to unpleasant (p = =.003) and pleasant (p = =.021) scenes relative to neutral scenes. DLPFC hemodynamic response was not related to affective ratings of scenes. We report that cycling for 20 min at a preferred intensity reduces mood disturbances which occur shortly after smoking a cigarette and blunts DLPFC hemodynamic response to emotionally arousing scenes. The findings encourage further investigation of exercise for smokers in the maintenance stage of smoking cessation.

Infective endocarditis prophylaxis: current practice trend among paediatric cardiologists: are we following the 2007 guidelines?

BACKGROUND: In 2007, the American Heart Association modified the infective endocarditis prophylaxis guidelines by limiting the use of antibiotics in patients with cardiac conditions associated with the highest risk of adverse outcomes after infective endocarditis. Our objective was to evaluate current practice for infective endocarditis prophylaxis among paediatric cardiologists. METHODS: A web-based survey focussing on current practice, describing the use of antibiotics for infective endocarditis prophylaxis in various congenital and acquired heart diseases, was distributed via e-mail to paediatric cardiologists. The survey was kept anonymous and was distributed twice. RESULTS: Data from 253 participants were analysed. Most paediatric cardiologists discontinued infective endocarditis prophylaxis in patients with simple lesions such as small ventricular septal defect, patent ductus arteriosus, and bicuspid aortic valve without stenosis or regurgitation; however, significant disagreement persists in prescribing infective endocarditis prophylaxis in certain conditions such as rheumatic heart disease, Fontan palliation without fenestration, and the Ross procedure. Use of antibiotic prophylaxis in certain selected conditions for which infective endocarditis prophylaxis has been indicated as per the current guidelines varies from 44 to 83%. Only 44% follow the current guidelines exclusively, and 34% regularly discuss the importance of oral hygiene with their patients at risk for infective endocarditis. CONCLUSION: Significant heterogeneity still persists in recommending infective endocarditis prophylaxis for several cardiac lesions among paediatric cardiologists. More than half of the participants (56%) do not follow the current guidelines exclusively in their practice. Counselling for optimal oral health in patients at risk for infective endocarditis needs to be optimised in the current practice.

The Synergistic Effect of Combination Progesterone and Temozolomide on Human Glioblastoma Cells.

Glioblastoma multiforme (GBM) is the most common and most aggressive malignant brain tumor. Despite optimal treatment and evolving standard of care, the median survival of patients diagnosed with GBM is only 12-15 months. In this study, we combined progesterone (PROG) and temozolomide (TMZ), a standard chemotherapeutic agent for human GBM, to test whether PROG enhances the antitumor effects of TMZ and reduces its side effects. Two WHO grade IV human GBM cells lines (U87MG and U118MG) and primary human dermal fibroblasts (HDFs) were repeatedly exposed to PROG and TMZ either alone or in combination for 3 and 6 days. Cell death was measured by MTT reduction assay. PROG and TMZ individually induced tumor cell death in a dose-dependent manner. PROG at high doses produced more cell death than TMZ alone. When combined, PROG enhanced the cell death-inducing effect of TMZ. In HDFs, PROG did not reduce viability even at the same high cytotoxic doses, but TMZ did so in a dose-dependent manner. In combination, PROG reduced TMZ toxicity in HDFs. PROG alone and in combination with TMZ suppressed the EGFR/PI3K/Akt/mTOR signaling pathway and MGMT expression in U87MG cells, thus suppressing cell proliferation. PROG and TMZ individually reduced cell migration in U87MG cells but did so more effectively in combination. PROG enhances the cytotoxic effects of TMZ in GBM cells and reduces its toxic side effects in healthy primary cells.

U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo.

U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2) and metabotropic glutamate receptor 1 (GRM1), in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv) administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6) indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups) validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases.Molecular Therapy - Nucleic Acids (2013) 2, e92; doi:10.1038/mtna.2013.24; published online 14 May 2013.