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Background: Cardiogenic shock remains highly associated with early mortality, with mortality often exceeding 50%. We sought to determine the association between prognostic factors and in-hospital and 30-day mortality in cardiogenic shock., Methods: We performed a systematic review and meta-analysis of prognostic factors in cardiogenic shock, searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for records up to June 5, 2023. English-language studies that investigated prognostic factors and in-hospital and/or 30-day mortality in cardiogenic shock were included. Studies were excluded if they evaluated the pediatric population, were postmortem studies, or included fewer than 100 patients. The primary aim was to identify modifiable and non-modifiable prognostic factors associated with in-hospital and 30-day mortality in cardiogenic shock., Results: We identified 160 studies, including 2,459,703 patients with a median in-hospital mortality of 41.4% (interquartile range, 33.6% to 49.2%). The majority were retrospective cohort studies. Patient factors potentially associated with an increase in early mortality included an age greater than or equal to 75 years of age, peripheral arterial disease, chronic kidney disease, and female sex. Procedural and presentation factors potentially associated with increased mortality included out-of-hospital cardiac arrest, left main culprit artery, left ventricular ejection fraction less than 30%, dialysis, and need for mechanical circulatory support. Revascularization in the form of coronary artery bypass graft and percutaneous coronary intervention were potentially associated with reduced in-hospital mortality., Conclusions: This analysis quantifies the association between patient, presentation, and treatment-related factors and early mortality in cardiogenic shock. Increased certainty in the association of these prognostic factors with cardiogenic shock outcomes can aid in clinical risk assessment, development of risk tools, and analysis of clinical trials.

Objectives: The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scv o2 ) in estimating mixed venous oxygen saturation (Sv o2 ) and cardiac index in critically ill patients., Data Sources: A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024., Study Selection: Studies of patients in the ICU for whom Scv o2 and at least one reference standard test was performed (thermodilution and/or Sv o2 ) were included., Data Extraction: Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Sv o2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments., Data Synthesis: Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Sv o2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Sv o2 was 0.83 (95% CI, 0.75-0.89) with a mean difference of 2.98% toward Scv o2 . The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46-0.48; p < 0.0001)., Conclusions: There is moderate reliability for Scv o2 in predicting Sv o2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scv o2 in predicting cardiac index., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Currently, intravascular optical coherence tomography (IV-OCT) is limited to anatomical imaging, providing structural information about atherosclerotic plaque morphology, thrombus and dissection. Earlier detection and risk stratification would be possible through molecular characterization of endothelium but necessitates a purpose-engineered IV-OCT contrast agent. Here we developed gold superclusters (AuSCs) tailored to clinical instrumentation and integrated into clinically relevant workflows. AuSCs are aqueously dispersible clusters of closely packed small gold nanoparticles, affording plasmon hybridization to maximize light scattering at the IV-OCT laser line (~1,350 nm). A polymer coating fosters AuSC uniformity and provides a functionalizable handle, which we targeted to intravascular P-selectin, an early vascular endothelial marker of inflammation. In a rat model of intravascular inflammation, P-selectin-targeted AuSC facilitated IV-OCT molecular imaging, where the strength of the signal correlates with the severity of vascular inflammation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Electrical storm (ES) is a life-threatening condition of recurrent ventricular arrhythmias (VA) in a short period of time. Percutaneous stellate ganglion blockade (SGB) is frequently used - however the efficacy is undefined. The objective of our systematic review was to determine the efficacy of SGB in reducing VA events and mortality among patients with ES. A search of Medline, EMBASE, Scopus, CINAHL and CENTRAL was performed on February 29, 2024 to include studies with adult patients (≥ 18 years) with ES treated with SGB. Our outcomes of interest were VA burden pre- and post-SGB, and in-hospital/30-day mortality. A total of 553 ES episodes in 542 patients from 15 observational studies were included. Treated VAs pre- and post-SGB were pooled from eight studies including 383 patients and demonstrated a decrease from 3.5 (IQR 2.25-7.25) to 0 (IQR 0-0) events (p = 0.008). Complete resolution after SGB occurred in 190 of 294 patients (64.6%). Despite this, in-hospital or 30-day mortality remained high occurring in 140 of 527 patients (random effects prevalence 22%). Repeat SGB for recurrent VAs was performed in 132 of 490 patients (random effects prevalence 21%). In conclusion, observational data suggests SGB may be effective in reducing VAs in ES. Definitive studies for SGB in VA management are needed. Study protocol: PROSPERO - registration number CRD42023430031., (© 2024. The Author(s).)

Background: 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., Methods: We studied a retrospective cohort of 1498 consecutive, unique adult cardiovascular intensive care unit (CICU) admissions with CS from 2007-2018., Results: 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)., Conclusions: 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

Background: Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly., Aims: Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events., Methods: This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted., Results: A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF., Conclusions: Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population.

Background: Cardiogenic shock due to acute myocardial infarction (AMI-CS) is associated with significant short- and long-term morbidity and mortality. Despite this, little is known about associated cost., Objectives: The purpose of this study was to evaluate the health care costs and resource use associated with AMI-CS using administrative data from the province of Ontario, Canada., Methods: This was a retrospective cohort study of adult patients with AMI-CS from April 2009 to March 2019. One-year costs following index admission were reported at an individual level. We used generalized linear models to identify factors associated with increased cost. We stratified patients by revascularization strategy to compare cost in each group and examined total cost at a patient level per individual fiscal year., Results: We included 9,789 consecutive patients with AMI-CS across 135 centers in Ontario (mean age 70.5 years; 67.7% male). Mortality in-hospital was 30.2%, and mortality at 2 years was 45.9%. The median inpatient cost per patient was $23,912 (IQR: $12,234-$41,833) with a median total 1-year cost of $37,913 (IQR: $20,113-$66,582). The median 1-year cost was $17,730 (IQR: $9,323-$38,379) for those who died in hospital, and $45,713 (IQR: $29,688-$77,683) for those surviving to discharge, with $12,719 (IQR: $4,262-$35,275) occurring after discharge. Patients who received coronary artery bypass grafting incurred the highest cost among revascularization groups. No significant differences were observed in cost per fiscal year from 2009 to 2019., Conclusions: AMI-CS is associated with significant health care costs, both during the index hospitalization and following discharge. To optimize cost-effectiveness, future therapies should aim to reduce disability in addition to improving mortality., Competing Interests: Dr Brodie has received research support from and consulting for 10.13039/100013410LivaNova; is on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos; and he writes for UpToDate. Dr Fan has received personal fees from ALung Technologies, Aerogen, Baxter, GE Healthcare, Inspira, and Vasomune, outside of the submitted work. Dr Slutsky has received personal fees from Baxter and Xenios, outside of the submitted work. Dr Combes has received personal fees from Getinge, Baxter, and Xenios, outside of the submitted work. Dr Tanuseputro is supported by a Physician Services Incorporated Graham Farquharson Knowledge Translation Fellowship. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and Ministry of Long-term Care (MLTC). This document used data adapted from the Statistics Canada Postal CodeOM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario Ministry of Health Postal Code Conversion File, which contains data copied under license from ©Canada Post Corporation and Statistics Canada. Parts of this report are based on Ontario Registrar General (ORG) information on deaths, the original source of which is ServiceOntario. The views expressed therein are those of the author and do not necessarily reflect those of ORG or the Ministry of Public and Business Service Delivery. Parts of this material are based on data and/or information compiled and provided by CIHI, Ontario Health (OH), and the Ontario Ministry of Health. The analyses, conclusions, opinions and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. We thank IQVIA Solutions Canada Inc. for use of their Drug Information File. This study was further supported by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario. The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOH/MLTC is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by the Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, and opinions and statements expressed in the material are those of the authors, and not necessarily those of CIHI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short- and long-term morbidity and mortality. However, there are limited data on mental health sequelae that survivors experience following discharge., Methods: We conducted a retrospective, population-based cohort study in Ontario, Canada of critically ill adult (≥ 18 years) survivors of AMI-CS, admitted to hospital between April 1, 2009 and March 31, 2019. We compared these patients to AMI survivors without shock. We captured outcome data using linked health administrative databases. The primary outcome was a new mental health diagnosis (a composite of mood, anxiety, or related disorders; schizophrenia/psychotic disorders; and other mental health disorders) following hospital discharge. We secondarily evaluated incidence of deliberate self-harm and death by suicide. We compared patients using overlap propensity score-weighted, cause-specific proportional hazard models., Results: We included 7812 consecutive survivors of AMI-CS, from 135 centers. Mean age was 68.4 (standard deviation (SD) 12.2) years, and 70.3% were male. Median follow-up time was 767 days (interquartile range (IQR) 225-1682). Incidence of new mental health diagnosis among AMI-CS survivors was 109.6 per 1,000 person-years (95% confidence interval (CI) 105.4-113.9), compared with 103.8 per 1000 person-years (95% CI 102.5-105.2) among AMI survivors without shock. After propensity score adjustment, there was no difference in the risk of new mental health diagnoses following discharge [hazard ratio (HR) 0.99 (95% CI 0.94-1.03)]. Factors associated with new mental health diagnoses following AMI-CS included female sex, pre-existing mental health diagnoses, and discharge to a long-term hospital or rehabilitation institute., Conclusion: Survivors of AMI-CS experience substantial mental health morbidity following discharge. Risk of new mental health diagnoses was comparable between survivors of AMI with and without shock. Future research on interventions to mitigate psychiatric sequelae after AMI-CS is warranted., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Aortic stenosis (AS) is a progressive disease predominantly affecting elderly patients that carries significant morbidity and mortality without aortic valve replacement, the only proven treatment. Our objective was to determine the cost-effectiveness of AS screening using transthoracic echocardiography (TTE) in a geriatric population from the perspective of the publicly funded healthcare system in Canada., Methods: Markov models estimating the cost-effectiveness ratio (ICER) for AS screening with a one-time TTE were developed. The model included diagnosed and undiagnosed AS health states, hospitalizations, TAVR and post-TAVR health states. Primary analysis included screening at 70 and 80 years of age with intervention at symptom onset, with scenario analysis included for early intervention at the time of severe asymptomatic AS diagnosis. Monte Carlo simulation of 5000 replications was completed with a lifetime horizon and 1.5% discount for costs and outcomes., Results: Screening for AS at the age of 70 years was associated with an ICER of $156,722 and screening at 80 years of age was associated with an ICER of $28,005, suggesting that screening at 80 years of age is cost-effective when willingness-to-pay per QALY is $50,000. Scenario analysis with early intervention was not cost-effective with an ICER of $142,157 at 70 years, and $124,651 at 80 years., Conclusion: Screening for AS at 80 years of age with a one-time TTE, in a Canadian population, improves quality of life and is cost-effective in a publicly funded healthcare system providing TAVR is reserved for symptomatic patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients., Methods and Results: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population., Conclusions: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial., (© 2024 European Society of Cardiology.)

Objective: Open science is a movement and set of practices to conduct research more transparently. Implementing open science will significantly improve public access and supports equity. It also has the potential to foster innovation and reduce duplication through data and materials sharing. Here, we survey an international group of researchers publishing in cardiovascular journals regarding their perceptions and practices related to open science., Methods: We identified the top 100 'Cardiology and Cardiovascular Medicine' subject category journals from the SCImago journal ranking platform. This is a publicly available portal that draws from Scopus. We then extracted the corresponding author's name and email from all articles published in these journals between 1 March 2021 and 1 March 2022. Participants were sent a purpose-built survey about open science. The survey contained primarily multiple choice and scale-based questions for which we report count data and percentages. For the few text-based responses we conducted thematic content analysis., Results: 198 participants responded to our survey. Participants had a mean response of 6.8 (N=197, SD=1.8) on a 9-point scale with endpoints, not at all familiar (1) and extremely familiar (9), when indicating how familiar they were with open science. When asked about where they obtained open science training, most participants indicated this was done on the job self-initiated while conducting research (n=103, 52%), or that they had no formal training with respect to open science (n=72, 36%). More than half of the participants indicated they would benefit from practical support from their institution on how to perform open science practices (N=106, 54%). A diversity of barriers to each of the open science practices presented to participants were acknowledged. Participants indicated that funding was the most essential incentive to adopt open science., Conclusions: It is clear that policy alone will not lead to the effective implementation of open science. This survey serves as a baseline for the cardiovascular research community's open science performance and perception and can be used to inform future interventions and monitoring., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC)., Objectives: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients., Methods: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT., Results: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02)., Conclusions: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT., Competing Interests: Funding Support and Author Disclosures Dr Rodés-Cabau holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions (Laval University, Quebec City, Canada). He also has received institutional research grants from Boston Scientific. Dr Maarse has received an unrestricted grant from Boston Scientific. Dr Pérez de Prado has served as a proctor for Boston Scientific. Dr Gupta has served as a proctor for Abbott. Dr Sanchez has served as a speaker and proctor for Boston Scientific. Dr Wang has served as a consultant for Edwards Lifesciences, Boston Scientific, and Neochord; and received research grant support from Boston Scientific assigned to his employer, the Henry Ford Health System. Dr Demkow has served as a proctor for Abbott and Boston Scientific. Dr Alkhouli has served as a consultant for Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings., (© 2023. The Author(s).)

Percutaneous coronary intervention (PCI) is a management strategy for symptomatic obstructive coronary artery disease (CAD). Despite advancements, in-stent restenosis (ISR) still imparts a 1-2% annual rate of repeat revascularization-a focus of ongoing translational research. Optical coherence tomography (OCT) provides high resolution virtual histology of stents. Our study evaluates the use of OCT for virtual histological assessment of stent healing in a rabbit aorta model, enabling complete assessment of intraluminal healing throughout the stent. ISR varies based on intra-stent location, stent length, and stent type in a rabbit model-important considerations for translational experimental design. Atherosclerosis leads to more prominent ISR proliferation independent of stent-related factors. The rabbit stent model mirrors clinical observations, while OCT-based virtual histology demonstrates utility for pre-clinical stent assessment. Pre-clinical models should incorporate clinical and stent factors as feasible to maximize translation to clinical practice., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Patients undergoing coronary stent implantation incur a 2% annual rate of adverse events, largely driven by in-stent restenosis (ISR) due to neointimal (NI) tissue proliferation, a process in which smooth muscle cell (SMC) biology may play a central role. Dipyridamole (DP) is an approved therapeutic agent with data supporting improved vascular patency rates. Pre-clinical data supports that DP may enact its vasculoprotective effects via adenosine receptor-A2B (ADOR-A2B). We sought to evaluate the efficacy of DP to mitigate ISR in a pre-clinical rabbit stent model., Methods & Results: 24 New Zealand White Rabbits were divided into two cohorts-non-atherosclerosis and atherosclerosis ( n  = 12/cohort, 6 male and 6 female). Following stent implantation, rabbits were randomized 1:1 to control or oral dipyridamole therapy for 6 weeks followed by optical coherence tomography (OCT) and histology assessment of NI burden and stent strut healing. Compared to control, DP demonstrated a 16.6% relative reduction in NI volume (14.7 ± 0.8% vs. 12.5 ± 0.4%, p  = 0.03) and a 36.2% relative increase in optimally healed stent struts (37.8 ± 2.8% vs. 54.6 ± 2.5%, p  < 0.0001). Atherosclerosis demonstrated attenuated effect with no difference in NI burden (15.2 ± 1.0% vs. 16.9 ± 0.8%, p  = 0.22) and only a 14.2% relative increase in strut healing (68.3 ± 4.1% vs. 78.7 ± 2.5%, p  = 0.02). DP treated rabbits had a 44.6% ( p  = 0.045) relative reduction in NI SMC content. In vitro assessment of DP and coronary artery SMCs yielded dose-dependent reduction in SMC migration and proliferation. Selective small molecule antagonism of ADOR-A2B abrogated the effects of DP on SMC proliferation. DP modulated SMC phenotypic switching with ADOR-A2B siRNA knockdown supporting its role in the observed effects., Conclusion: Dipyridamole reduces NI proliferation and improves stent healing in a preclinical model of stent implantation with conventional antiplatelets. Atherosclerosis attenuates the observed effect. Clinical trials of DP as an adjunctive agent may be warranted to evaluate for clinical efficacy in stent outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Simard, Jung, Di Santo, Labinaz, Short, Motazedian, Dhaliwal, Sarma, Rasheed, Ramirez, Froeschl, Labinaz, Holmes, Alkhouli and Hibbert.)

Background: 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., Objectives: This study sought to examine long-term outcomes of AMI-CS patients., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Funding Support and Author Disclosures This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and Ministry of Long-term Care (MLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOH/MLTC is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by the Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, and opinions and statements expressed in the material are those of the authors, and not necessarily those of CIHI. Dr Brodie has received research support from LivaNova outside of the submitted work; and has served on medical advisory boards for LivaNova, Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. Dr Fan has received personal fees from ALung Technologies, Aerogen, Baxter, GE Healthcare, Inspira, and Vasomune outside of the submitted work. Dr Basir has served as a consultant for Abbott Vascular, Abiomed, Boston Scientific, Cardiovascular Systems, Chiesi, Saranas. and Zoll. Dr Combes has received personal fees from Getinge, Baxter, and Xenios outside of the submitted work. Dr Tanuseputro has received support from a Physician Services Incorporated Graham Farquharson Knowledge Translation Fellowship. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Inotropic support is commonly used in patients with cardiogenic shock (CS). High-quality data guiding the use of dobutamine or milrinone among this patient population is limited. We compared the efficacy and safety of these two inotropes among patients with low cardiac output states (LCOS) or CS., Data Sources: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched up to February 1, 2023, using key terms and index headings related to LCOS or CS and inotropes., Data Extraction: Two independent reviewers included studies that compared dobutamine to milrinone on all-cause in-hospital mortality, length of ICU stay, length of hospital stay, and significant arrhythmias in hospitalized patients., Data Synthesis: A total of eleven studies with 21,084 patients were included in the meta-analysis. Only two randomized controlled trials were identified. The primary outcome, all-cause mortality, favored milrinone in observational studies only (odds ratio [OR] 1.19 (95% CI, 1.02-1.39; p = 0.02). In-hospital length of stay (LOS) was reduced with dobutamine in observational studies only (mean difference -1.85 d; 95% CI -3.62 to -0.09; p = 0.04). There was no difference in the prevalence of significant arrhythmias or in ICU LOS., Conclusions: Only limited data exists supporting the use of one inotropic agent over another exists. Dobutamine may be associated with a shorter hospital LOS; however, there is also a potential for increased all-cause mortality. Larger randomized studies sufficiently powered to detect a difference in these outcomes are required to confirm these findings., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed., Research Question: What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA?, Study Design and Methods: In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome., Results: We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85)., Interpretation: Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm., Trial Registry: Center for Open Science: https://osf.io/arxwq., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. S. reports receiving funding from PIPRA AG, outside of the submitted work. B. H. reports receiving research support from Abbott, Edwards Lifesciences, Boston Scientific, and Bayer, outside of the submitted work. L. M. is associate editor of Intensive Care Medicine. E. F. reports receiving personal fees from ALung Technologies, Baxter, Boehringer-Ingelheim, Fresenius Medical Care, MC3 Cardiopulmonary, and Vasomune, outside of the submitted work. D. B. receives research support from ALung Technologies, outside of the submitted work, and has been on the medical advisory boards for Abiomed, Xenios, Medtronic, LivaNova, Inspira, and Cellenkos. S. C. reports receiving research support from Zoll Medical Inc., outside of the submitted work. N. D. F. reports consulting for Baxter and Xenios, outside of the submitted work. C. S. is associate editor of Intensive Care Medicine. G. D. P. receives support from Elsevier for roles as an editor for Resuscitation and editor-in-chief of Resuscitation Plus. J. P. N. receives support from Elsevier for his role as editor-in-chief of Resuscitation. None declared (S. M. F., R. M., B. R., P. D. S., A. T., S. L. M., C. V., D. C. S., S. L., J. S., P. D.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS., Methods and Design: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge., Implication: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction., Objectives: This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function., Methods: In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m 2 and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy., Results: Baseline eGFR <60 ml/min/1.73 m 2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m 2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome ( P  interaction = 0.02) and death ( P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI., Conclusions: In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI., Competing Interests: Funded by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN MEDICAL KNOWLEDGE: Renal dysfunction is a prevalent comorbidity and a common sequelae of end-organ hypoperfusion in patients with cardiogenic shock. Significant renal dysfunction is both an indicator and a mediator of a worse prognosis in patients with cardiogenic shock and an important clinical consideration when choosing pharmacotherapies and timing interventions requiring iodinated-contrast agents. At present, there is a paucity of prospective data examining the relative efficacy and safety of milrinone in patients with cardiogenic shock and renal dysfunction. TRANSLATIONAL OUTLOOK: Future studies should further explore the association between milrinone and outcomes in patients with cardiogenic shock and renal dysfunction., (© 2023 The Authors.)

Background: 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., Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Funding Support and Author Disclosures This study was funded by Edwards Lifesciences, who also directed the design and conduct of the study, the collection, analysis, and interpretation of the data with input from their lead investigators. Dr Hibbert has received institutional research support from Abbott, NXT, Edwards Lifesciences, Boston Scientific, and Occlutech. Dr Zahr is a consultant to Edwards Lifesciences and Medtronic; and has received research and educational grants from Edwards Lifesciences, Medtronic, and Siemens. Dr Simard is a consultant to Boston Scientific; and has received research support from Edwards Lifesciences. Dr Nazer is a consultant to Boston Scientific and Biosense Webster; and has received investigator-initiated research funding from Siemens and Galaxy Medical. Dr Sorajja has served on advisory boards for 4C Medical, Abbott Vascular Structural, Boston Scientific SHV Strategic Advisory Board, Medtronic Structural Advisory Board, and VDyne; and is a consultant to 4C Medical, Anteris, Abbott Structural, Boston Scientific, Edwards Lifesciences, Evolution Medical, Foldax, GLG, Medtronic, Phillips, Siemens, Shifamed, WL Gore, VDyne, and xDot. Dr Pineda is a consultant to Cardiovascular Systems, Inc. Dr Schwartz has been a consultant for Abbott Vascular Structural, Boston Scientific, Edwards Lifesciences, Medtronic, Philips, WL Gore, Cordis; serves on advisory boards for Medtronic, Boston Scientific, Edwards Lifesciences, and Cordis; and has received research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, Philips, WL Gore, and Cordis. Dr Wiley is a consultant to Edwards Lifesciences. Dr Sauer has received speaker or consulting honoraria from Edwards Lifesciences, Abbott, Boston Scientific, Biotronik, Medtronic, Bayer, General Prognostics, Impulse Dynamics, and Story Health. Dr Jorde is a consultant to Abbott, Edwards Lifesciences, and AncoraHeart. Dr Latib is a consultant for Edwards Lifesciences, Abbott Vascular, Medtronic, Boston Scientific, and Philips. Dr Kahwash is a consultant and serves on advisory boards for Medtronic, Cardionomic, and Impulsedynamics. Dr Gafoor is a consultant to Edwards Lifesciences, Abbott Lifesciences, and Boston Scientific. Dr Chaudhry has received speaker honoraria from Medtronic; and consultation fees from Edwards Lifesciences. Dr. Hermiller is a consultant to Edwards Lifesciences. Drs Aldaia and Koulogiannis are members of a cardiovascular core lab, for which they receive no direct compensation, that has agreements with Edwards Lifesciences, Abbott, Medtronic, and NXT Biomedical. Dr Koulogiannis is also a consultant to Edwards Lifesciences and Abbott; and serves on an advisory board for Edwards Lifesciences. Dr Gray is a consultant to Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Transradial access (TRA) has rapidly emerged as the preferred vascular access site for coronary angiography and percutaneous coronary intervention. Radial artery occlusion (RAO) remains as an important complication of TRA as it precludes future ipsilateral transradial procedures. While intraprocedural anticoagulation has been studied extensively, the definitive role of postprocedural anticoagulation has not yet been established., Methods and Analysis: The Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion trial is a multicentre, prospective, randomised, open-label, blinded-endpoint design study investigating the efficacy and safety of rivaroxaban to reduce the incidence of RAO. Eligible patients will undergo randomisation to receive either rivaroxaban 15 mg once daily for 7 days or to no additional postprocedural anticoagulation. Doppler ultrasound to assess radial artery patency will be performed at 30 days., Ethics and Dissemination: The study protocol has been approved by the Ottawa Health Science Network Research Ethics Board (approval number 20180319-01H). The study results will be disseminated via conference presentations and peer-reviewed publications., Trial Registration Number: NCT03630055., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors declare that they have no conflicts of interest.

Background: Inotropic support is widely used in the management of cardiogenic shock (CS). Existing data on the incidence and significance of arrhythmic events in patients with CS on inotropic support is at high risk of bias., Methods: The Dobutamine Compared to Milrinone (DOREMI) trial randomized patients to receive dobutamine or milrinone in a double-blind fashion. Patients with and without arrhythmic events (defined as arrhythmias requiring intervention or sustained ventricular arrhythmias) were compared to identify factors associated with their occurrence, and to examine their association with in-hospital mortality and secondary outcomes., Results: Ninety-two patients (47.9%) had arrhythmic events, occurring equally with dobutamine and milrinone (P = 0.563). The need for vasopressor support at initiation of the inotrope and a history of atrial fibrillation were positively associated with arrhythmic events, whereas predominant right ventricular dysfunction, previous myocardial infarction, and increasing left ventricular ejection fraction were negatively associated with them. Supraventricular arrhythmic events were not associated with mortality (relative risk [RR], 0.97; 95% confidence interval [CI], 0.68-1.40; P = 0.879) but were positively associated with resuscitated cardiac arrests and hospital length of stay. Ventricular arrhythmic events were positively associated with mortality (RR, 1.66; 95% CI, 1.13-2.43; P = 0.026) and resuscitated cardiac arrests. Arrhythmic events were most often treated with amiodarone (97%) and electrical cardioversion (27%), which were not associated with mortality., Conclusions: Clinically relevant arrhythmic events occur in approximately one-half of patients with CS treated with dobutamine or milrinone and are associated with adverse clinical outcomes. Five factors may help to identify patients most at risk of arrhythmic events., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Presentation with ST-segment-elevation myocardial infarction (STEMI) during off-hours may impact timely reperfusion and clinical outcomes. We investigated the association between off-hours presentation, door-to-balloon time, and in-hospital mortality in patients with STEMI referred for primary percutaneous coronary intervention (PCI)., Methods: We included consecutive patients referred for primary PCI at the University of Ottawa Heart Institute between July 2004 and December 2017. The off-hours group included patients presenting on weekends, statutory holidays, or between 18:00 to 07:59 hours on weekdays. The on-hours group included patients presenting between 08:00 and 17:59 hours on weekdays. The primary clinical outcome was the adjusted in-hospital mortality. The primary quality-of-care indicator was door-to-balloon time., Results: A total of 5132 patients were included, with 3152 (61.4%) in the off-hours group and 1980 (38.6%) in the on-hours group. The median door-to-balloon time was longer in the off-hours group compared with the on-hours group (102 minutes vs 77 minutes; P<.001), while the median onset-to-door time was similar (P=.40). There was no difference in the rates of in-hospital mortality (3.5% vs 3.0%; P=.32) or in the adjusted mortality (odds ratio, 1.2; 95% confidence interval, 0.8-1.8; P=.44) between off-hours and on-hours groups. However, door-to-balloon time was an independent predictor of in-hospital mortality (P<.01) and off-hours presentation was an independent predictor of longer door-to-balloon time (P<.001), with an excess of 22.1 minutes., Conclusion: Patients treated with primary PCI during off-hours had longer door-to-balloon times. Treatment during off-hours was an independent predictor of longer door-to-balloon time and longer door-to-balloon times were associated with higher mortality.

Background: Catheter-induced coronary artery dissection (CICAD) is a rare complication of coronary angiography. The association between access site and CICAD remains unclear; however, transradial access (TRA) may be associated with a higher incidence of CICAD due to access vessel tortuosity and the mechanical disadvantage of catheters designed for the transfemoral access (TFA) approach., Methods: In this retrospective study, the reports of consecutive left heart catheterizations between April 2007, and December 2021 were reviewed for CICAD. Patients were excluded if the procedural report did not report an arterial access site. Identified CICAD cases were reviewed in detail., Results: There were 142/89,876 (0.16%) identified cases of CICAD. The access site was not associated with an increased risk of CICAD (0.18% with TRA vs 0.15% with TFA; relative risk [RR], 1.18; 95% CI, 0.84-1.65; P = .34) over the entire study period. With respect to TRA-related CICAD, male sex was associated with a decreased risk of dissection (RR, 0.64; 95% CI, 0.41-0.99; P = .04), but ST-elevation myocardial infarction at presentation was associated with an increased risk (RR, 3.01; 95% CI, 1.86-4.85; P < .01). In the TFA-predominant era, TRA was associated with an increased risk of CICAD (0.48% TRA vs 0.11% TFA; RR, 3.42; 95% CI, 2.05-5.69; P < .01)-an association that was not present in the TRA-predominant era. In-hospital mortality in patients with CICAD was 8.5%., Conclusions: CICAD is a rare complication of coronary angiography. Over a 15-year period, we did not demonstrate an association between access site and an increased risk of CICAD. There is substantial mortality associated with CICAD., (© 2023 The Authors.)

Purpose: To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction., Source: We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality., Principal Findings: We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis., Conclusion: The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding., Study Registration: Center for Open Science ( https://osf.io/ky2gr ); registered 10 November 2020., (© 2022. Canadian Anesthesiologists' Society.)

Background: 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., Methods and Design: 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., Implications: 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., Competing Interests: Conflict of interest None reported., (Copyright © 2022. Published by Elsevier Inc.)

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., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Assessment of the case-fatality rate (CFR) of major bleeding on dual antiplatelet therapy (DAPT) may improve balancing risks and benefits of different durations of DAPT following percutaneous coronary intervention (PCI)., Objectives: To determine the CFR of major bleeding in patients on DAPT after PCI and to compare rates among different durations of DAPT., Methods: Medline, Embase, and CENTRAL were searched from inception to August 2021 for randomized trials that reported fatal bleeding among patients who were randomized to ≥1 month of DAPT following PCI. Summary estimates for CFRs of major bleeding were calculated using the random-effects inverse-variance method. Statistical heterogeneity was evaluated using the I 2 statistic., Results: Of 2777 citations obtained by the search, 15 (48%) of 31 potentially eligible studies were excluded because fatal bleeding was not reported, leaving 16 studies that were included in the analysis. Overall, there were 823 major bleeding events including 91 fatal events in 48,884 patients who were assigned to receive DAPT during study follow-up. The CFR of major bleeding was 10.8% (95% confidence interval [CI], 7.1-16.2; I 2  = 50%) in the entire study population, and 13.8% (95% CI, 6.5-27.1; I 2  = 28%), 11.2% (95% CI, 6.7-18.0; I 2  = 0%), and 5.8% (95% CI, 3.0-11.1; I 2  = 0%) in those on short-term (≤6 months; n  = 16,553), standard-term (12 months; n  = 19,453), and long-term DAPT (>12 months; n  = 10,238), respectively., Conclusion: Fatal bleeding is not reported in many studies evaluating DAPT after PCI. The CFR of major bleeding on DAPT is substantial and may be higher in the first 12 months of DAPT than during long-term DAPT., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objectives: To investigate the real-world implementation of intracoronary assessment (ICA) techniques and evaluate their impact on clinical decisions regarding the management of coronary artery disease (CAD) in contemporary practice., Background: Coronary angiogram is the gold standard used to diagnose vessel stenosis and guide percutaneous coronary intervention (PCI); however, it is limited by its two-dimensional imaging capabilities. ICA techniques like intravascular ultrasound and optical coherence tomography capture the vessel in three-dimensional images. Comparatively, fractional flow reserve provides information on the physiologic significance of coronary stenosis. Both techniques may improve PCI outcomes if they routinely change physician behavior., Methods: Patients who underwent ICA between August 2015 and March 2020 were included in the study. The primary outcome was the clinical impact of ICA on physician clinical decision making of a stenotic vessel. The secondary outcome was the clinical changes that occurred following ICA., Results: A total of 1135 patients were included in the study. Physiologic assessment (PA) and image assessment (IA) were performed in 61.4% and 38.6% respectively. Management plans were changed in 38.1% and 23.9% of patients who received PA and IA. Over half of the management change resulted in physicians deciding to not intervene on the stenotic vessel. One-year outcome of these decisions showed no significant increase in major adverse cardiac events (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.40-1.15; p = 0.15) or unplanned revascularization (HR, 0.78; 95% CI, 0.35-1.74; p = 0.55) suggesting reliance on PA/IA data did not increase risk., Conclusion: Selected ICA alters physician management of CAD in one-third of patients being evaluated for revascularization-typically leading to fewer interventions. All cause death is numerally lower in patients that received a change in management. However, the 1-year outcome of these altered decisions does not appear to be significantly different., (© 2022 Wiley Periodicals LLC.)

Background: 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., Methods: 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., Results: 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)., Conclusion: In patients presenting with CS treated with milrinone or dobutamine, no differences in clinical outcomes were observed between males and females., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)