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Sex-based disparities have been demonstrated in care delivery for females with cardiogenic shock (CS), including lower use of coronary angiography (CAG), percutaneous intervention (PCI) and mechanical circulatory support (MCS). We evaluated whether sex-based disparities exist and are associated with worse CS outcomes in females. We studied a retrospective cohort of 1498 consecutive, unique adult cardiovascular intensive care unit (CICU) admissions with CS from 2007–2018. Compared to males, females (n = 566, 37.1%) were older (71.7 vs 67.8 years; P < 0.001) but had similar burdens of medical comorbidities. Acute myocardial infarction (AMI) was present in 54.1% of females and 59.1% of males (P = 0.06). There were no sex-based differences in the use of CAG and PCI, but females received temporary MCS less commonly. Specifically, females with non-AMI CS received MCS devices less commonly (17.6% vs 24.4%; P = 0.04). There was no difference in in-hospital or 1-year mortality rates between the sexes. Compared to males, females who received PCI had lower risks of 1-year mortality (unadjusted HR 0.72; P = 0.03), whereas females who received CAG without PCI had higher risks of 1-year mortality (unadjusted HR 1.41; P = 0.02). No sex-based disparities in mortality due to CS were demonstrated in this large, diverse cohort of patients with CICU admissions. Females who underwent PCI demonstrated lower risks of 1-year mortality, whereas females who underwent CAG without PCI demonstrated higher risks of 1-year mortality compared to males. This may reflect underuse of PCI as a mortality-reducing therapy in females. • Females with cardiogenic shock (n = 566/1499; 37.1%) were older but had comorbidities and etiologies similar to those of males. • Females and males received coronary angiography and PCI at similar rates, but females less often received temporary MCS. • In-hospital and 1-year mortality rates were similar in both sexes, both overall and according to the etiologies. • Among patients who received coronary angiography, females who received PCI had better outcomes, and females who did not receive PCI had worse outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

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Heart failure (HF) is associated with both mortality and a significant decline in health status. Interatrial shunting is increasingly being investigated as a novel therapeutic option. The ALT FLOW Early Feasibility Study was designed to evaluate the safety of the Edwards left atrial to coronary sinus APTURE Transcatheter Shunt System in patients with symptomatic HF. A total of 18 centers enrolled patients with symptomatic HF with a pulmonary capillary wedge pressure >15 mm Hg at rest or 25 mm Hg during exercise. Between May 2018 and September 2022, 87 patients underwent attempted APTURE shunt implantation. Mean age was 71 years, and 53% were male. At baseline, mean left ventricular ejection fraction was 59% with 90% of the patients being in NYHA functional class III. Device success was achieved in 78 patients (90%), with no device occlusions or associated adverse events identified after implantation. The primary safety outcome occurred in only 2 patients (2.3%) at 30 days. At 6 months, health status improved: 67% of participants achieved NYHA functional class I to II status, with a 23-point improvement (P < 0.0001; 95% CI: 17-29 points) in the Kansas City Cardiomyopathy Questionnaire overall summary score. Also at 6 months, 20-W exercise pulmonary capillary wedge pressure was 7 mm Hg lower (P < 0.0001; 95% CI: −11 to −4 mm Hg) without change in right atrial pressure or other right heart function indices. In this single-arm experience, the APTURE Transcatheter Shunt System in patients with symptomatic HF was observed to be safe and resulted in reduction in pulmonary capillary wedge pressure and clinically meaningful improvements in HF symptoms and quality of life indices. [Display omitted] [ABSTRACT FROM AUTHOR]

Functional mitral regurgitation (MR) is an important clinical consideration in patients with heart failure. Transcatheter edge-to-edge repair (TEER) has emerged as a useful therapeutic tool for patients with chronic heart failure, however the role of TEER in patients with cardiogenic shock (CS) and MR has not yet been studied in a randomized trial. The Transcatheter Mitral Valve Repair for Inotrope Dependent Cardiogenic Shock (CAPITAL MINOS) trial was therefore designed to determine if TEER improves clinical outcomes in the CS population. The CAPITAL MINOS trial is an open-label, multi-center randomized clinical trial comparing TEER to medical therapy in patients with CS and MR. A total of 144 patients with Society for Cardiovascular Angiography and Interventions (SCAI) class C or D CS and at least 3+ MR will be randomized in a 1:1 ratio to TEER or medical therapy alone. The primary outcome will be a composite of in-hospital all-cause mortality, cardiac transplantation, implantation of durable left ventricular assist device, or discharge on palliative inotropic therapy. Patients will be followed for the duration of their index hospitalization for the primary outcome. Secondary outcomes include 6 month mortality. The CAPITAL MINOS trial will determine whether TEER improves outcomes in patients with CS and MR and will be an important step in optimizing treatment for this high-risk patient population. [ABSTRACT FROM AUTHOR]

Cardiogenic shock (CS) is associated with significant morbidity and mortality; however, there are limited randomized data evaluating the association between sex and clinical outcomes in patients with CS. Patients with CS enrolled in the DObutamine compaREd with MIlrinone (DOREMI) trial were evaluated in this post-hoc analysis. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary outcome. We analyzed the primary and secondary outcomes using unadjusted relative risks and performed adjusted analysis for the primary outcome and all-cause mortality using the covariates mean arterial pressure <70 mmHg at inotrope initiation, age, and acute myocardial infarction CS. Among 192 participants in the DOREMI study, 70 patients (36 %) were female. The primary outcome occurred in 38 female patients (54 %) compared to 61 male patients (50 %) [adjusted relative risk (aRR) 1.23; 95 % CI 0.78–1.95, p = 0.97]. When stratified by inotrope, there was no difference in the primary outcome comparing females to males receiving dobutamine (RR 1.14; 95 % CI 0.79–1.65, p = 0.50) nor milrinone (RR 1.03; 95 % CI 0.68–1.57, p = 0.87). There was no difference in all-cause mortality comparing females to males (aRR 1.51; 95 % CI 0.78–2.94, p = 0.88). Additionally, there were no differences in any secondary outcomes between males and females (p > 0.05 for all endpoints). In patients presenting with CS treated with milrinone or dobutamine, no differences in clinical outcomes were observed between males and females. No sex-based difference in cardiogenic shock: a post-hoc analysis of the DOREMI trial. [Display omitted] • Adverse clinical outcomes in cardiogenic shock (CS) are not associated with sex. • Sex does not influence outcomes in CS when treated with milrinone nor dobutamine. • Women with CS have lower mean arterial pressure, heart rate, and creatinine. [ABSTRACT FROM AUTHOR]

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The objective of this study was to determine the effect of transcatheter mitral valve repair (TMVr) on hospitalization rates by assessing pre- and postprocedural hospitalization patterns. TMVr has emerged as the treatment of choice for selected patients with mitral regurgitation, but the impact of these procedures on hospital utilization remains unclear. All patients who underwent TMVr in Ontario, Canada, between 2011 and 2017 were included in this observational study using population-based data. Hospitalization person-year rates were assessed in the years before and after TMVr and 4 predefined intervals: 1 to 30, 31 to 90, 91 to 182, and 183 to 365 days. Main outcomes of interest were all-cause and heart failure (HF) hospitalizations. Poisson regression models were used to compare incidence rates across all time periods. The study cohort included 523 patients. In the year preceding TMVr, 66.2% of patients were hospitalized compared with 47.4% in the year following. There were stepwise increases in both all-cause and HF hospitalization rates in the periods preceding the index procedure, and all postprocedural periods had significantly lower hospitalization rates. The adjusted rate ratios for all-cause and HF-related hospitalization in the year after TMVr were 0.65 (95% CI: 0.56-0.76) and 0.38 (95% CI: 0.29-0.51), respectively. All time periods had significant reductions in all-cause and HF hospitalization in the adjusted analysis. In this population-based study, significant reductions were observed in both all-cause and HF-related hospitalizations in all time periods after TMVr compared with the year prior. This suggests that TMVr has a sustained effect on hospitalization rates despite a high-risk population. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) complicating primary percutaneous coronary intervention (PCI) is an independent predictor of short- and long-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). Prior studies suggest a lower incidence of AKI in patients undergoing PCI through radial artery compared to femoral artery access; however, no randomized clinical trials have specifically investigated this question in patients presenting with STEMI.Methods: To determine whether radial access (RA) is associated with a reduced frequency of AKI following primary PCI, we performed a substudy of the SAFARI-STEMI trial. The SAFARI-STEMI trial was an open-label, multicenter trial, which randomized patients presenting with STEMI to RA or femoral access (FA), between July 2011 and December 2018. The primary outcome of this post hoc analysis was the incidence of AKI, defined as an absolute (>0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline.Results: In total 2,285 (99.3%) of the patients enrolled in SAFARI-STEMI were included in the analysis-1,132 RA and 1,153 FA. AKI occurred in 243 (21.5%) RA patients and 226 (19.6%) FA patients (RR: 0.91, 95% CI: 0.78-1.07, P = .27). An absolute increase in serum creatinine >0.5 mg/dL was seen in 49 (4.3%) radial and 52 (4.5%) femoral patients (RR: 1.04, 95% CI: 0.71-1.53, P = .83). AKI was lower in both groups when the KDIGO definition was applied (RA 11.9% vs FA 10.8%; RR: 0.90, 95% CI: 0.72-1.13, P = .38).Conclusions: Among STEMI patients enrolled in the SAFARI-STEMI trial, there was no association between catheterization access site and AKI, irrespective of the definition applied. These results challenge the independent association between catheterization access site and AKI noted in prior investigations. [ABSTRACT FROM AUTHOR]

Background: Current LBBB definitions cannot always distinguish LBBB from left ventricular conduction delay. Only patients with LBBB are expected to normalize with His bundle pacing. Patients who develop new LBBB immediately post transcatheter aortic valve replacement (TAVR) provide an excellent model to define electrocardiogram (ECG) features of LBBB. We sought to describe their ECG features and develop a new ECG definition of LBBB.Methods: We screened ECGs from 264 consecutive patients who underwent TAVR at the University of Ottawa Heart Institute. Patients with a baseline QRS of ≤100 ms who developed QRS ≥120 ms immediately after TAVR were included. Two electrocardiologists reviewed all ECG independently. Baseline demographics and echocardiographic data were retrospectively collected.Results: 36 patients were included in the analysis. The median age was 85.5 years (IQR, 81.8-89 years) and 52.8% were males. The minimum QRS duration was 126 ms. The median QRS axis was -18° (IQR, -40-4.5°), which is 18.5° leftward compared to the median QRS axis before TAVR. Fourteen patients (38.9%) had left axis deviation. All patients had a notched/slurred R wave in at least one lateral lead and an R wave duration of ≤20 ms in V1 when present.Conclusion: We developed a new ECG definition of LBBB that includes 2 novel findings: notching/slurring of the R wave in at least one lateral lead and an R wave ≤20 ms in V1. Further larger studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Biological therapies that increase or suppress the expression of transcripts underlying atrial fibrillation (AF) progression are increasingly being explored to create novel treatment paradigms beyond simply suppressing or destroying tissue. To date, there has been no systematic overview of the preclinical evidence exploring manipulation of fundamental biological principles in the treatment of AF. As such, the objective of this study was to establish the effect of biological approaches used in the treatment of AF within large and small animals. We performed a systematic search using predefined terms, which yielded 25 studies. We determined the effect of biological approaches on primary efficacy outcomes and assessed the quality of included studies or possible bias in the treatment of AF. Compared with non-transduced or transduced controls, biological therapies reduced AF inducibility (85% less AF; odds ratio 0.15; 95% confidence interval [CI] 0.07-0.35; P < .01) and atrial scar burden (6.7% smaller scars; 95% CI 4.2-9.2; P < .01) or increased number of days in sinus rhythm (6.4 more days in sinus rhythm; 95% CI 5.83-6.97; P < .01). Similar effects were seen in both large and small animals, while a minor tendency to higher risk of bias was observed in small animal studies. In conclusion, treatment with any biological therapy significantly improved AF in preclinical animal models compared with controls. Although biological therapies target markedly different fundamental mechanisms, we observed a consistent difference in their effect on AF outcomes. [ABSTRACT FROM AUTHOR]

Objectives This study investigated the safety and efficacy of a pharmacoinvasive strategy compared with a primary percutaneous coronary intervention (PCI) strategy for ST-segment elevation myocardial infarction (STEMI) in the context of a real-world system. Background Primary PCI continues to be the optimal reperfusion therapy; however, in areas where PCI centers are not readily available, a pharmacoinvasive strategy has been proposed. Methods The University of Ottawa Heart Institute regional STEMI system provides a primary PCI strategy for patients presenting within a 90-km radius from the PCI center, and a pharmacoinvasive strategy for patients outside this limit. We included all confirmed STEMI patients between April 2009 and May 2011. The primary efficacy outcome was a composite of mortality, reinfarction, or stroke and the primary safety outcome was major bleeding. Results We identified 236 and 980 consecutive patients enrolled in pharmacoinvasive and primary PCI strategies, respectively. The median door-to-needle time was 31 min in the pharmacoinvasive group and the median door-to-balloon time was 95 min in the primary PCI group. In a multivariable model, there was no significant difference in the primary efficacy outcome (odds ratio: 1.54; p = 0.21); however, the propensity for more bleeding with a pharmacoinvasive strategy approached statistical significance (odds ratio: 2.02; p = 0.08). Conclusions Within the context of a STEMI system, a pharmacoinvasive strategy was associated with similar rates of the composite of mortality, reinfarction, or stroke as compared with a primary PCI strategy; however, there was a propensity for more bleeding with a pharmacoinvasive strategy. [ABSTRACT FROM AUTHOR]

Background/objectives Individuals with extreme obesity (EO), defined by a body mass index (BMI) = 40 kg/m², constitute an increasingly prevalent population at higher risk of procedural complications. The implications of increasing weight burdens among this subset of patients in the setting of elective coronary revascularization have yet to be adequately studied. Methods We sought to define major complications in this group at one year following contemporary revascularization strategies by retrospectively analysing a cohort of consecutive EO patients undergoing elective percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The primary endpoint was a composite of peri- and post-procedural complications. Secondary endpoints included a cardiovascular composite and target vessel revascularization (TVR). Results Adjusted event-free survival curves for the primary endpoint among 133 patients differed significantly with higher BMI (> 43.2 kg/m²) associated with greater risk (p = 0.02). The primary endpoint occurred more frequently with CABG compared to PCI (24.2% vs. 5.0%, p < 0.01), which remained significant after adjusting for differences in baseline variables. Rates of the cardiovascular composite and TVR were comparable. Conclusions Increasing BMI was associated with greater risk for major complications among EO patients undergoing elective coronary revascularization. PCI was associated with fewer complications; however, both revascularization strategies demonstrated equivalent rates of death, MI, and/or stroke. Larger studies may permit a better understanding of the associations between increasing BMI and specific outcomes and to evaluate the role for pre-procedural weight loss in this select population. [ABSTRACT FROM AUTHOR]

Objectives This study sought to determine the benefits of adding oral anticoagulation therapy in patients with anterior wall ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PCI). Background Guidelines suggest adding oral anticoagulation to dual-antiplatelet therapy in patients with STEMI when left ventricular apical akinesis or dyskinesis is present to prevent thromboembolic complications. The benefits of this triple therapy remain unknown. Methods We identified patients with anterior STEMI referred (PCI) between July 2004 and June 2010 with apical akinesis or dyskinesis on transthoracic echocardiography. We compared patients who were prescribed warfarin to patients who were not. We excluded patients with left ventricular thrombus, a separate need for oral anticoagulation, and previous intracranial bleeding. The primary outcome was a composite of net adverse clinical events (NACE) consisting of all-cause mortality, stroke, reinfarction, and major bleeding at 180 days. Results Among 460 patients who qualified, 131 were discharged on warfarin therapy and 329 without warfarin therapy. Dual-antiplatelet therapy was prescribed for 99.2% of the patients in the warfarin group and for 97.6% of the patients in the no warfarin group (p = 0.46). Compared with patients in the no warfarin group, patients in the warfarin group had higher rates of NACE (14.7% vs. 4.6%, p = 0.001), death (5.4% vs. 1.5%, p = 0.04), stroke (3.1% vs. 0.3%, p = 0.02), and major bleeding (8.5% vs. 1.8%, p < 0.0001). By propensity score analysis, allocation to warfarin therapy was an independent predictor of NACE (odds ratio [OR]: 4.01, 95% confidence interval: 2.15 to 7.50, p < 0.0001). In a separate multivariable analysis, the OR of NACE remained significantly higher compared with patients who were not prescribed warfarin (OR: 3.13, 95% confidence interval: 1.34 to 7.22, p = 0.007). Conclusions Our results do not support the addition of warfarin therapy after primary PCI in patients with apical akinesis or dyskinesis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease. Background: Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E−/− (ApoE−/−) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection. Methods: Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE−/− mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27. Results: Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551–5,475] vs. 6,200 pg/ml [2,575–9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels (<50th percentile) were predictive of subsequent major adverse cardiovascular events (hazard ratio: 2.93, 95% confidence interval: 1.06 to 8.12; p = 0.04). In experimental murine models of atherosclerosis, increasing serum HSP27 levels both reduced de novo atherosclerotic lesion formation and enhanced features of plaque stability. Conclusions: In humans, low serum HSP27 levels are associated with the presence of coronary artery disease and prognostic of future adverse clinical events. In mouse models of atherosclerosis, increasing HSP27 levels reduced lesion progression and promoted features of plaque stability. Serum HSP27 levels may represent a potential therapeutic target for atherosclerosis. [Copyright &y& Elsevier]

Abstract: Background: Current American Heart Association guidelines recommend against the performance of elective or primary percutaneous coronary intervention (PCI) without on-site surgical backup (i.e. a class III and IIb recommendation respectively). Despite this, numerous centers have already implemented PCI programs with no on-site surgery backup (NSOS). Methods: To evaluate the necessity for on-site surgical backup (SOS) when performing PCI we performed a systematic review and meta-analysis. English-language articles published from 1966 through December 2010 were retrieved using keyword searches of Medline and Scopus, supplemented by letters to authors and reviews of all bibliographies. Article inclusion and data extraction was performed by two independent reviewers. We identified 18 articles published between 1992 and 2009 which contained reported events on 1,150,200 patients. Results: The combined odds ratio calculated using a random effects model for death with NSOS was 0.93 (95% CI, 0.80–1.09). In studies with data reported for primary PCI and elective PCI the OR for death was 0.91 (95% CI, 0.84–1.00) and 1.04 (95% CI, 0.67–1.63). A lack of effect of SOS was maintained when analysis was performed by study type or by either primary or elective PCI. No differences in rates of emergency coronary artery bypass grafting, post procedural myocardial infarction, target vessel revascularization, or cerebrovascular accidents were observed between SOS and NSOS centers. Conclusion: Both primary and elective PCI can safely be performed at NSOS centers without an increase in mortality or PCI related complications. AHA/ACC guidelines should reflect the lack of benefit conferred by on-site surgical backup. In establishing PCI programs, adequate operator/center volumes, patient selection, and geographic/population considerations should take precedence rather than the availability of on-site surgical backup during PCI. [Copyright &y& Elsevier]

Human Immunodeficiency Virus (HIV)-infected individuals have a cardiovascular disease risk that is almost thrice than that of their HIV-uninfected counterparts. Given the critical role of endothelial progenitor cells (EPCs) in vascular homeostasis and arterial repair postinjury, coupled with their strength as biomarkers predictive of cardiovascular events, interest has arisen in characterizing EPCs in the context of HIV infection. We conducted a systematic review of the literature to determine the current state of knowledge on EPCs in the context of HIV infection. Herein, we summarize the pertinent findings of these studies and discuss important differences in the subpopulations of EPCs examined and the methodologies used for their enumeration which likely contributed to the heterogeneity observed across studies. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to evaluate the safety and efficacy of transradial versus transfemoral access for coronary angiography and percutaneous coronary intervention in patients with a body mass index ≥40 kg/m2. Background: Coronary angiography is most commonly performed via femoral artery access; however, the optimal approach in extremely obese (EO) patients remains unclear. Methods: Between January 2007 and August 2010, a cohort of consecutive EO patients who underwent coronary angiography was identified in our center''s registry of angiography and percutaneous coronary intervention procedures. Of 21,103 procedures, 564 (2.7%) were performed in unique EO patients: 203 (36%) via the transradial approach; and 361 (64%) via the transfemoral approach. Results: The primary outcome, a combined endpoint of major bleeding, access site complications, and nonaccess site complications, occurred in 7.5% of the transfemoral group and 2.0% of the transradial group (odds ratio [OR]: 0.30, 95% confidence interval [CI]: 0.10 to 0.88, p = 0.029), an endpoint driven by reductions in major bleeding (3.3% vs. 0.0%, OR: 0.12, 95% CI: 0 to 0.71, p = 0.015), as well as access site injuries (4.7% vs. 0.0%, OR: 0.08, 95% CI: 0 to 0.48, p = 0.002). There were no differences in nonaccess site complications (1.7% vs. 2.0%, OR: 1.50, 95% CI: 0.41 to 5.55), but transradial access procedures were associated with an increase in procedure time and patient radiation dose (p < 0.05). Conclusions: Transfemoral access for coronary angiography and percutaneous coronary intervention was associated with more bleeding and access site complications when compared with a transradial approach. Important reductions in procedural associated morbidity may be possible with a transradial approach in EO patients. [Copyright &y& Elsevier]

The role of catecholamine neuronal input on GABAergic activity in the hypothalamus, telencephalon, optic tectum, and cerebellum was investigated in early recrudescent female goldfish (Carassius auratus). A new quantitative technique was developed and validated, permitting concomitant quantification and correlational analysis of glutamic acid decarboxylase 65 (GAD65), GAD67, and GAD3 mRNA levels and in vivo GABA synthesis. Catecholamine depletion was achieved by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 50 μg/g body weight) and dopamine (DA) depletion verified by HPLC. Endogenous GABA levels were increased by intraperitoneal administration of γ-vinyl GABA (GVG; 300 μg/g body weight), an inhibitor of the GABA catabolic enzyme GABA transaminase. Treatment with MPTP resulted in a greater than twofold increase in GABA synthesis rate in the optic tectum and telencephalon. The increase in GABA synthesis rate was highly correlated with an increase in GAD67, but not GAD65 or GAD3 mRNA levels. These results suggest that catecholaminergic input exerts inhibitory effects on GABA synthesis rates through the modulation of GAD67 in the optic tectum and telencephalon. Together with previously published observations in rodents and primates, it is suggested that catecholaminergic control of GABA synthesis must have evolved more than 200 million years ago, before the emergence of the teleost fishes. [Copyright &y& Elsevier]

Whereas the genesis of an arterial lesion is thought to be the result of migration and proliferation of vascular cells, recent insights into the biology of progenitor cells now question this concept. Specifically, endothelial and smooth muscle cells appear to be derived from multiple sources such as circulating stem and progenitor cells, as well as tissue-resident progenitor cell populations. These cells may engraft at sites of vascular injury and play an integral role in vascular repair. In this review, experimental data from in vitro studies, animal models, and scattered human observations are reviewed in the context of emerging hypotheses regarding the response to vascular injury. [Copyright &y& Elsevier]

Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short-term mortality; however, there are limited data on long-term outcomes and trends. This study sought to examine long-term outcomes of AMI-CS patients. This was a population-based, retrospective cohort study in Ontario, Canada of critically ill adult patients with AMI-CS who were admitted to hospitals between April 1, 2009 and March 31, 2019. Outcome data were captured using linked health administrative databases. A total of 9,789 consecutive patients with AMI-CS from 135 centers were included. The mean age was 70.5 ± 12.3 years, and 67.7% were male. The incidence of AMI-CS was 8.2 per 100,000 person-years, and it increased over the study period. Critical care interventions were common, with 5,422 (55.4%) undergoing invasive mechanical ventilation, 1,425 (14.6%) undergoing renal replacement therapy, and 1,484 (15.2%) receiving mechanical circulatory support. A total of 2,961 patients (30.2%) died in the hospital, and 4,004 (40.9%) died by 1 year. Mortality at 5 years was 58.9%. Small improvements in short- and long-term mortality were seen over the study period. Among survivors to discharge, 2,870 (42.0%) required increased support in care from their preadmission baseline, 3,244 (47.5%) were readmitted to the hospital within 1 year, and 1,047 (15.3%) died within 1 year. The mean number of days at home in the year following discharge was 307.9 ± 109.6. Short- and long-term mortality among patients with AMI-CS is high, with minimal improvement over time. AMI-CS survivors experience significant morbidity, with high risks of readmission and death. Future studies should evaluate interventions to minimize postdischarge morbidity and mortality among AMI-CS survivors. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Data on the efficacy of transcatheter edge-to-edge repair (TEER) in patients with cardiogenic shock (CS) are limited.Objectives: This study investigated the characteristics and outcomes of consecutive patients with significant mitral regurgitation (MR) and CS who underwent TEER.Methods: The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was assessed from November 22, 2013, to December 31, 2021. CS was defined as the coding of: 1) CS; 2) inotrope use; or 3) mechanical circulatory support before TEER. Device success was defined as MR reduction of ≥1 grade and a final MR grade ≤2+. The primary outcome was the impact of device success on 1-year mortality or heart failure (HF) readmissions. Cox proportional hazards models were used to report the risk-adjusted association between device success and 1-year outcomes.Results: A total of 3,797 patients met the inclusion criteria. Mean age was 73.0 ± 11.9 years, and 59.5% were male. Mean Society of Thoracic Surgery score (MV repair) was 14.9% ± 15.3%. MR etiology was degenerative (53.4%) and functional (27.5%). Device success was achieved in 3,249 (85.6%) patients given successful achievement of final MR grade ≤2+ (88.2%) and MR reduction ≥1 absolute grade (91.4%). At 1 year after TEER, device success was associated with significantly lower all-cause mortality (34.6% vs 55.5%; adjusted HR: 0.49; 95% CI: 0.41-0.59; P < 0.001) and a composite of mortality or HF admissions (29.6% vs 45.2%; adjusted HR: 0.51; 95% CI: 0.42-0.62; P < 0.001).Conclusions: Successful MR reduction is achievable in most patients with CS and is associated with significantly lower mortality and HF hospitalization at 1 year. Randomized trials assessing TEER in CS are needed to establish this potential therapeutic approach. [ABSTRACT FROM AUTHOR]

Cardiac arrest (CA) is relatively rare but lethal complication of takotsubo cardiomyopathy (TTC). In most instances, patients are diagnosed with TTC after CA, making it difficult to distinguish if TTC is the precipitant or the consequence of the index event. In this systematic review, patient-level data were obtained to seek out the characteristics of patients in whom the underlying cause of CA is TTC. A comprehensive search of 4 major databases (Embase, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to the last week of September 2014. Of 186 citations, 62 case studies were included in the analysis, providing patient-level data on 77 patients. In 60 patients (78%), the diagnosis of TTC was made after CA. Patients presenting with CA were younger (mean age 49.5 ± 16 vs 64.9 ± 11 years, p <0.0001) and had relatively shorter corrected QT interval (mean 530 ± 101 vs 616 ± 140 ms) on electrocardiography. TTC-related hypotension was the major cause of CA in the acute phase, while a long corrected QT interval triggered CA in the subacute (24- to 72-hour) phase. In 11 patients, CA was not directly instigated by TTC despite a left ventricular appearance matching TTC. In conclusion, in TTC, CA typically develops within the first 3 days of presentation and is the result of long corrected QT intervaleinduced polymorphic ventricular tachycardia. Secondary TTC, in which patients present with typical left ventricular features after CA, likely represents a distinct cohort in which identifiable inheritable arrhythmias or structural heart disease should be sought. [ABSTRACT FROM AUTHOR]

Introduction: Patients admitted with return of spontaneous circulation (ROSC) following out of hospital cardiac arrest (OHCA) are often sedated to facilitate care. Volatile anaesthetics have been proposed as alternative sedatives because of their rapid offset. We performed a systematic review and meta-analysis comparing the use of volatile anaesthetics to conventional sedation in this population.Materials: We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from inception to January 6, 2022. We included randomized trials and observational studies evaluating patients admitted following ROSC. We pooled data and reported summary estimates using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed risk of bias using the Newcastle Ottawa Scale and certainty of evidence using GRADE methodology.Results: Of 1,973 citations, we included three observational studies (n = 604 patients). Compared to conventional sedation, volatile agents had an uncertain effect on delirium (OR 0.96, 95% CI 0.68-1.37), survival to discharge (OR 0.66, 95% CI 0.17-2.61), and ICU length of stay (MD 1.59 days fewer, 95% CI 1.17-4.36, all very low certainty). Patients who received volatile anaesthetic underwent a shorter duration of mechanical ventilation (MD 37.32 hours shorter, 95% CI 7.74-66.90), however this was based on low-certainty evidence. No harms were described with use of volatile anesthetics.Conclusion: Volatile anaesthetics may be associated with a decreased duration of mechanical ventilation in patients admitted with ROSC however this is based on low-certainty evidence. Further data are needed to assess their role in this population. [ABSTRACT FROM AUTHOR]

Abstract: Background: Therapeutic hypothermia (TH) is associated with improved neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). There are currently limited data on the outcomes of patients presenting with resuscitated OHCA in the setting of ST-segment elevation myocardial infarction (STEMI). We conducted a retrospective study to determine the outcomes of patients treated with TH for OHCA in a large regionalized STEMI program. Methods: Patients referred for primary PCI and TH between July 2004 and April 2011 were identified from the University of Ottawa Heart Institute STEMI database. The primary endpoint was survival to hospital discharge with sufficient neurologic recovery to enable discharge home. Results: Among 2467 consecutive patients referred for primary PCI, we identified 50 patients treated with TH following OHCA. Forty-nine underwent PCI, of which 47 (96%) received a stent. Median door-to-balloon time was 113min (IQR 91–151). Patients with good neurologic recovery were younger, mean 51±9 years versus 64±12, p <0.001, and had higher baseline creatinine clearance, 70±19mL/min/1.73m2 versus 53±23mL/min/1.73m2, p =0.007. The primary endpoint of survival with sufficient neurologic recovery to enable discharge home was reached in 30 patients (60%). Four survivors required levels of assistance that precluded discharge home. Conclusions: Therapeutic hypothermia in conjunction with primary PCI is associated with a favorable neurologic outcome in the majority of STEMI patients surviving OHCA. Our results suggest that TH is an important adjunctive therapy for STEMI patients suffering OHCA. [Copyright &y& Elsevier]

Abstract: The regulation of the estrogenic responses may be influenced by the proteins that associate with estrogen receptors (ERs) rather than solely with the receptors themselves. ERβ is expressed in blood vessels and may play an important role in vascular disease. We hypothesized that specific proteins interact with ERβ to modulate its response to estrogens. By means of a yeast two hybrid screen, we discovered that NM23-H2, a multi-faceted protein associates specifically with ERβ. NM23-H2 and ERβ consistently co-localize in a variety of human tissues (e.g. breast tissue), whereas ERα and NM23-H2 did not co-localize. Estrogen response element-mediated transcription increased by 97% when NM23-H2 and ERβ were over-expressed in MCF-7 cells (p ≤0.001). Moreover, there was a synergistic effect of NM23-H2 over-expression with estrogen treatment on the reduction of MCF-7 cell migration (p ≤0.001). These results suggest that NM23-H2 associates with ERβ and is capable of modulating estrogen-induced gene transcription, as well as cell migration. Hence, NM23-H2 may play an important role in modulating the response to endogenous and exogenous estrogens, perhaps even within the context of vascular disease. [Copyright &y& Elsevier]

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a widely used form of mechanical circulatory support in patients with refractory cardiogenic shock. A common drawback of this modality is a resultant increase in left ventricular afterload.Objectives: The purpose of this meta-analysis was to examine the efficacy and safety of left ventricular unloading strategies during VA-ECMO in adult patients with cardiogenic shock.Methods: The authors performed a systematic search of studies examining left ventricular unloading during VA-ECMO in Medline, EMBASE, and the Cochrane library. The primary outcome was all-cause mortality. Secondary outcomes included limb ischemia, bleeding, need for renal replacement therapy, multiorgan failure, stroke or transient ischemic attack, and hemolysis.Results: Of 2,221 publications identified, 17 observational studies met the inclusion criteria. In total, outcomes in 3,997 patients were included with 1,696 (42%) receiving a concomitant left ventricular unloading strategy while on VA-ECMO (intra-aortic balloon pump 91.7%, percutaneous ventricular assist device 5.5%, pulmonary vein or transseptal left atrial cannulation 2.8%). There were 2,412 deaths (60%) in the total cohort. Mortality was lower in patients with (54%) versus without (65%) left ventricular unloading while on VA-ECMO (risk ratio: 0.79; 95% confidence interval: 0.72 to 0.87; p < 0.00001). Hemolysis was higher in patients who underwent VA-ECMO with left ventricular unloading. Otherwise, secondary outcomes were not demonstrably different in patients treated with VA-ECMO with versus without left ventricular unloading.Conclusions: In observational studies, left ventricular unloading was associated with decreased mortality in adult patients with cardiogenic shock treated with VA-ECMO. In the absence of prospective randomized data, left ventricular unloading may be considered for appropriately selected patients undergoing VA-ECMO support. [ABSTRACT FROM AUTHOR]