<div><h4>Angiotensin receptor blockers in patients with hypertrophic cardiomyopathy: A comparison of VANISH and INHERIT randomized trials.</h4><i>Severinsen T, Thune JJ, Gudmundsdottir HL, Vissing CR, ... Bundgaard H, Axelsson Raja A</i><br /><b>Purpose</b><br />To identify the cause of discrepancy between the INHERIT trial and VANISH trial in regards to disease modification of angiotensin receptor II blockers in hypertrophic cardiomyopathy (HCM).<br /><b>Methods</b><br />We replicated the data analysis used in VANISH, converting individual change in each component of the composite endpoint into a z-score and applying this z-score to the INHERIT results.<br /><b>Results</b><br />No significant improvement was identified in the composite z-score between the 2 groups at 12-month follow-up (P = .4). With the exception of tissue Doppler systolic (s\') velocity, we found no significant benefit or harm from losartan compared to placebo for any of the individual components of the composite score at 12-month follow-up. Results were similar in analyses without imputed data or when restricted to patients with sarcomeric HCM.<br /><b>Conclusion</b><br />Despite applying the potentially more sensitive composite z-score endpoint as in the VANISH trial, no statistically significant benefits from the use of losartan compared to placebo could be detected at 12-month follow-up in patients with overt HCM participating in the INHERIT trial.<br /><br />Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 30 Nov 2023; 266:198-200</small></div>

<div><h4>Benefit of cardiac resynchronization therapy among older patients: a patient-level meta-analysis: Short title: CRT in older patients: patient level meta analysis.</h4><i>Zeitler EP, Dalgaard F, Abraham WT, Cleland JGF, ... Sanders GD, Al-Khatib SM</i><br /><b>Background</b><br />Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials.<br /><b>Methods</b><br />Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n=6369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite endpoint of HFH or all-cause mortality or all-cause mortality alone was assessed.<br /><b>Results</b><br />The median age was 67 years with 2436 (38%) being 70+; 1554 (24%) were women; 2586 (41%) had non-ischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay time to the composite endpoint (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66 - 0.85, p = 0.002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69 - 0.96, p = 0.017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either endpoint (p > 0.1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite endpoint (p for interaction = 0.027) with a similar but non-significant trend for mortality (p for interaction = 0.35).<br /><b>Conclusion</b><br />Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 17 Nov 2023; epub ahead of print</small></div>

<div><h4>High-risk admission prior to transcatheter aortic valve replacement and subsequent outcomes: Preceding events and outcomes after TAVR.</h4><i>Strange JE, Nouhravesh N, Schou M, Christensen DM, ... Olesen JB, Fosbøl EL</i><br /><b>Background</b><br />Severe, symptomatic aortic stenosis may cause heart failure, acute myocardial infarction, or syncope; limited data exist on the occurrence of such events before transcatheter aortic valve replacement (TAVR) and their impact on subsequent outcomes. Thus, we investigated the association between a preceding event and outcomes after TAVR.<br /><b>Methods</b><br />From 2014-2021 all Danish patients who underwent TAVR were included. Preceding events up to 180 days before TAVR were identified. A preceding event was defined as a hospitalization for heart failure, acute myocardial infarction, or syncope. The 1-year risk of all-cause death, and cardiovascular or all-cause hospitalization was compared for patients with versus without a preceding event using Kaplan-Meier, Aalen-Johansen, and in Cox regression analyses adjusted for patient characteristics.<br /><b>Results</b><br />Of 5,851 patients included, 759 (13.0%) had a preceding event. Median age was 81 years in both groups. Male sex and frailty were more prevalent in patients with a preceding event (males: 64.7% vs. 55.2%, frailty: 49.6% vs. 40.6%). The most common type of preceding event was a hospitalization for heart failure (n=524). For patients with a preceding event, the 1-year risk of death was 11.7% (95% CI: 9.4%-14.1%) versus 8.0% (95% CI: 7.2%-8.7%) for patients without. The corresponding adjusted hazard ratio (aHR) was 1.29 (95%CI: 1.01-1.64). Mortality was highest for patients with a preceding event of a heart failure admission (1-year risk: 13.5% [95%CI: 10.5%-16.5%]). Comparing patients with a preceding event to those without, the 1-year risk for cardiovascular rehospitalization was 15.0% versus 8.2% (aHR 1.60 [95%CI: 1.29-1.99]) and 57.6% versus 50.6% for all-cause rehospitalization (aHR 1.08 [95%CI: 0.87-1.20]).<br /><b>Conclusion</b><br />A hospitalization for heart failure, myocardial infarction, or syncope prior to TAVR was associated with a poorer prognosis and could represent a group to focus resource management on. Interventions to prevent preceding events and improvements in pre- and post-TAVR optimization of these patients are warranted.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 13 Nov 2023; epub ahead of print</small></div>

<div><h4>LEFT VENTRICULAR EJECTION FRACTION DIGIT BIAS AND RECLASSIFICATION OF HEART FAILURE WITH MILDLY REDUCED VS. REDUCED EJECTION FRACTION BASED ON THE 2021 DEFINITION AND CLASSIFICATION OF HEART FAILURE: Abbreviated title: DIGIT BIAS AND HEART FAILURE RECLASSIFICATION.</h4><i>Savarese G, Gatti P, Benson L, Adamo M, ... Maggioni AP, Und L</i><br /><b>Aims</b><br /><br /><b>Aims:</b><br/>were to evaluate 1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF=40% was considered as HFrEF, 2) role of EF digit bias, i.e. EF reporting favouring 5% increments; 3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry.<br /><b>Methods and results</b><br />. Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was \"exactly\" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF=40-49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF=41-49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF.<br /><b>Conclusions</b><br />. Many patients had reported EF=40%. This led to substantial reclassification of EF from old HFmrEF (40-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 13 Nov 2023; epub ahead of print</small></div>

<div><h4>Testing interventions to reduce clinical inertia in the treatment of hypertension: rationale and design of a pragmatic randomized controlled trial.</h4><i>Haff N, Sreedhara SK, Wood W, Yom-Tov E, ... Fontanet CP, Choudhry NK</i><br /><b>Background</b><br />Clinical inertia, or failure to intensify treatment when indicated, leads to suboptimal blood pressure control. Interventions to overcome inertia and increase antihypertensive prescribing have been modestly successful in part because their effectiveness varies based on characteristics of the provider, the patient, or the provider-patient interaction. Understanding for whom each intervention is most effective could help target interventions and thus increase their impact.<br /><b>Methods</b><br />This three-arm, randomized trial tests the effectiveness of two interventions to reduce clinical inertia in hypertension prescribing compared to usual care. Forty five primary care providers (PCPs) caring for patients with hypertension in need of treatment intensification completed baseline surveys that assessed behavioral traits and were randomized to one of three arms: 1) Pharmacist e-consult, in which a clinical pharmacist provided patient-specific recommendations for hypertension medication management to PCPs in advance of upcoming visits, 2) Social norming dashboards that displayed PCP\'s hypertension control rates compared to those of their peers, or 3) Usual care (no intervention). The primary outcome was the rate of intensification of hypertension treatment. We will compare this outcome between study arms and then evaluate the association between characteristics of providers, patients, their clinical interactions and intervention responsiveness.<br /><b>Results</b><br />Forty-five primary care providers were enrolled and randomized: 16 providers and 173 patients in the social norming dashboards arm, 15 providers and 143 patients in the pharmacist e-consult arm, and 14 providers and 150 patients in the usual care arm. On average, the mean patient age was 64 years, 47% were female, and 73% were white. Baseline demographic and clinical characteristics of patients were similar across arms, with the exception of more Hispanic patients in the usual care arm and fewest in the pharmacist e-consult arm.<br /><b>Conclusions</b><br />This study can help identify interventions to reduce inertia in hypertension care and potentially identify the characteristics of patients, providers, or patient-provider interactions to understand for whom each intervention would be most beneficial.<br /><b>Trial registration</b><br />Clinicaltrials.gov (NCT, Registered: NCT04603560).<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 12 Nov 2023; epub ahead of print</small></div>

<div><h4>Trends in mortality risk of patients with congenital heart disease during the COVID-19 pandemic.</h4><i>Yang Y, Kuo K, Claxton JS, Knight J, ... Oster ME, Kochilas L</i><br /><b>Background</b><br />Cardiovascular conditions are considered risk factors for poor outcomes associated with COVID-19. However, the effect of the COVID-19 pandemic on mortality of patients with congenital heart disease (CHD) is unclear. Our study aims to examine the trends in mortality risk of CHD patients during the COVID-19 pandemic.<br /><b>Methods</b><br />This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a US-based registry of interventions for CHD. We included patients having US residence and direct identifiers; death events were captured by matching with the National Death Index. The observation window (2017-2022) was divided to pre-COVID-19 and COVID-19 era defined around the national onset of COVID-19 disease in 2020. Stratified Cox model was used to assess all-cause mortality between the pre- and the COVID-19 era.<br /><b>Results</b><br />Among 45130 patients with CHD (median age in 2017: 23.3 years, IQR: 19.0-28.4), 503 deaths occurred during the pandemic with 44 deaths (8.7%) attributed to COVID-19 (COVID-19 mortality rate of 0.09%). The overall risk of death for patients with all types of CHD during the pandemic was significantly higher compared to the pre- COVID-19 era (aHR 1.28, 95%CI: 1.08-1.53), with a differential trend towards increased risk in patients with two-ventricle (aHR 1.44, 95% CI: 1.19-1.76) vs. unchanged risk for those with single ventricle CHD (aHR= 0.83, 95% CI: 0.57-1.21). Adjusted subgroup analysis revealed a higher risk of death during the pandemic for CHD patients with male and chromosomal abnormalities. The excess deaths during the pandemic were attributed to the COVID-19 itself rather than CHD or cardiovascular conditions.<br /><b>Conclusion</b><br />In this large CHD cohort study, there was a higher risk of death among CHD patients with male and chromosomal abnormalities. A differential trend towards higher risk for those with two vs. unchanged risk for single ventricle CHD was presented. The excess mortality was attributed to the COVID-19 itself and not to conditions potentially related to deferral of care. These results justify targeted protective measures towards the CHD population and may provide guidance for public health and medical care response in future epidemics.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 12 Nov 2023; epub ahead of print</small></div>

<div><h4>Influenza Vaccination and Use of Lipid Lowering Therapies in Adults with Atherosclerotic Cardiovascular Disease: An Analysis of the Behavioral Risk Factor Surveillance System (BRFSS): Influenza Vaccination and Cholesterol Medication Use.</h4><i>Slavin SD, Berman AN, Gaba P, Hoshi RA, Mittleman MA</i><br /><b>Background</b><br />Influenza vaccination and lipid lowering therapy (LLT) are evidence-based interventions with substantial benefit for individuals with established atherosclerotic cardiovascular disease (ASCVD). However, levels of influenza immunization and LLT use are low, possibly due to pervasive fear-based misinformation uniquely targeting vaccines and LLT. Whether being unvaccinated for influenza predicts lower utilization of LLT is unknown.<br /><b>Objectives</b><br />We tested the hypothesis that American adults with ASCVD who are unvaccinated for influenza have lower use of LLT even after accounting for traditional factors associated with underuse of preventive therapies.<br /><b>Methods</b><br />We pooled 2017, 2019, and 2021 survey data from the Behavioral Risk Factor Surveillance System (BRFSS), and selected respondents aged 40 to 75 years with self-reported ASCVD. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccination and self-reported LLT use. We performed a sensitivity analysis with multiple imputation to account for missing data. All analyses accounted for complex survey weighting.<br /><b>Results</b><br />Of 66,923 participants with ASCVD, 55% reported influenza vaccination in the last year and 76% reported using LLT. Being unvaccinated for influenza was associated with lower odds of LLT use (OR 0.54; 95% CI 0.50, 0.58; p<0.001). In a multivariable regression model adjusting for demographics and co-morbidities, this association remained statistically significant (aOR 0.58, 95% CI 0.52, 0.64, p<0.001). After additional adjustment for preventive care engagement, health care access, and use patterns of other cardiovascular medications this association persisted (aOR 0.66; 95% CI 0.60, 0.74; p<0.001). There were no significant differences across sub-groups, including those with and without hyperlipidemia.<br /><b>Conclusions</b><br />Unvaccinated status for influenza was independently associated with 34% lower odds of LLT use among American adults with ASCVD after adjustment for traditional factors linked to underuse of preventive therapies. This finding identifies a population with excess modifiable ASCVD risk, and supports investigation into non-traditional mechanisms driving underuse of preventive therapies, including fear-based misinformation.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 10 Nov 2023; epub ahead of print</small></div>

<div><h4>Trends and Site-level Variation of Novel Cardiovascular Medication Utilization among Patients Admitted for Heart Failure or Coronary Artery Disease in the US Veterans Affairs System: 2017-2021.</h4><i>Salahuddin T, Hebbe A, Daus M, Essien UR, ... Gilmartin HM, Doll JA</i><br /><b>Objective</b><br />We assessed trends in novel cardiovascular medication utilization in US Veterans Affairs (VA) for angiotensin receptor-neprilysin inhibitors (ARNI), sodium-glucose cotransporter-2 Inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA).<br /><b>Methods</b><br />We retrospectively identified cohorts from 114 VA hospitals with admission for prevalent 1) systolic heart failure (HF, N=82,375) or 2) coronary artery disease and diabetes (CAD+T2D, N=74,209). Site-level data for prevalent filled prescriptions were assessed at hospital admission, discharge, or within 6 months of discharge. Variability among sites was estimated with median odds ratios (mOR), and within-site Pearson correlations of utilization of each medication class were calculated. Site- and patient-level characteristics were compared by high-, mixed-, and low-utilizing sites.<br /><b>Results</b><br />ARNI and SGTL2i use for HF increased from <5% to 20% and 21% respectively, while SGTL2i or GLP-1 RA use for CAD+T2D increased from <5% to 30% from 2017-2021. Adjusted mOR and 95% confidence intervals for ARNI, SGTL2i for HF, and SGTL2i or GLP-1 RA for CAD+T2D were 1.73 (1.64-1.91), 1.72 (1.59-1.81), and 1.53 (1.45-1.62), respectively. Utilization of each medication class correlated poorly with use of other novel classes (Pearson <0.38 for all). Higher patient volume, number of beds, and hospital complexity correlated with high-utilizing sites.<br /><b>Conclusion</b><br />Utilization of novel medications has increased over time but remains suboptimal for US Veterans with HF and CAD+T2D, with substantial site-level heterogeneity despite a universal medication formulary and low out-of-pocket costs for patients. Future work should include further characterization of hospital- and clinician-level practice patterns to serve as targets to increase implementation.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 10 Nov 2023; epub ahead of print</small></div>

<div><h4>Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multi-center registry - \"MYKKE\": Short Title: Pediatric COVID-19 vaccine-associated myocarditis.</h4><i>Rolfs N, Huber C, Schwarzkopf E, Mentzer D, ... Seidel F, MYKKE consortium</i><br /><b>Background</b><br />Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents.<br /><b>Methods</b><br />Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multi-center registry for pediatric myocarditis \"MYKKE\". Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics.<br /><b>Results</b><br />From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (p=0.003), arrhythmias (p=0.031), left ventricular dilatation (p=0.045), lower LVEF (p<0.001) and major cardiac adverse events (p=0.102).<br /><b>Conclusion</b><br />Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 10 Nov 2023; epub ahead of print</small></div>

<div><h4>Opioid Prescription and Risk of Atrial Fibrillation in Younger Veterans: Opioid Use and Risk of Atrial Fibrillation.</h4><i>Chui PW, Khokhar A, Gordon KS, Dziura J, ... Bastian LA, Gandhi PU</i><br /><b>Background</b><br />Opioids may play a part in the development of atrial fibrillation (AF). Understanding the relationship between opioid exposure and AF can help providers better assess the risk and benefits of prescribing opioids.<br /><b>Objective</b><br />To assess the incidence of AF as a function of prescribed opioids and opioid type.<br /><b>Design</b><br />We performed unadjusted and adjusted time-updated Cox regressions to assess the association between opioid exposure and incident AF.<br /><b>Participants</b><br />The national study sample was comprised of Veterans enrolled in the Veterans Health Administration (VHA) who served in support of post-9/11 Operations.<br /><b>Main measures</b><br />The main predictor of interest was prescription opioid exposure, which was treated as a time-dependent variable. The first was any opioid exposure (yes/no). Secondary was opioid type. The outcome, incident AF, was identified through ICD-9-CM diagnostic codes at any primary care visit after the baseline period.<br /><b>Key results</b><br />A total of 609,763 Veterans (mean age: 34 years and 13.24% female) were included in our study. Median follow-up time was 4.8 years. Within this cohort, 124,395 Veterans (20.40%) were prescribed an opioid. A total of 1,455 Veterans (0.24%) were diagnosed with AF. In adjusted time-updated Cox regressions, the risk of incident AF was higher in the Veterans prescribed opioids (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.38-1.57). In adjusted time-updated Cox regressions, both immunomodulating and non-immunomodulating opioid type was associated with increased risk of incident AF (HR: 1.40; 95% CI: 1.25-1.57 and HR: 1.49; 95% CI: 1.39-1.60), compared to no opioid use, respectively.<br /><b>Conclusion</b><br />Our findings suggest opioid prescription may be a modifiable risk factor for the development of AF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 07 Nov 2023; epub ahead of print</small></div>

<div><h4>Realtime Diagnosis from Electrocardiogram Artificial Intelligence-Guided Screening for Atrial Fibrillation with Long Follow-Up (REGAL): Rationale and design of a pragmatic, decentralized, randomized controlled trial.</h4><i>Yao X, Attia ZI, Behnken EM, Hart MS, ... Friedman PA, Noseworthy PA</i><br /><b>Background</b><br />Atrial fibrillation (AF) is associated with increased risks of stroke and dementia. Early diagnosis and treatment could reduce the disease burden, but AF is often undiagnosed. An artificial intelligence (AI) algorithm has been shown to identify patients with previously unrecognized AF; however, monitoring these high-risk patients has been challenging. Consumer wearable devices could be an alternative to enable long-term follow-up.<br /><b>Objectives</b><br />To test whether Apple Watch, used as a long-term monitoring device, can enable early diagnosis of AF in patients who were identified as having high risk based on AI-ECG.<br /><b>Design</b><br />The Realtime diagnosis from Electrocardiogram (ECG) Artificial Intelligence (AI)-Guided Screening for Atrial Fibrillation (AF) with Long Follow-up (REGAL) study is a pragmatic trial that will accrue up to 2,000 older adults with a high likelihood of unrecognized AF determined by AI-ECG to reach our target of 1,420 completed participants. Participants will be 1:1 randomized to intervention or control and will be followed up for two years. Patients in the intervention arm will receive or use their existing Apple Watch and iPhone and record a 30-second ECG using the watch routinely or if an abnormal heart rate notification is prompted. The primary outcome is newly diagnosed AF. Secondary outcomes include changes in cognitive function, stroke, major bleeding, and all-cause mortality. The trial will utilize a pragmatic, digitally-enabled, decentralized design to allow patients to consent and receive follow-up remotely without traveling to the study sites.<br /><b>Summary</b><br />The REGAL trial will examine whether a consumer wearable device can serve as a long-term monitoring approach in older adults to detect AF and prevent cognitive function decline. If successful, the approach could have significant implications on how future clinical practice can leverage consumer devices for early diagnosis and disease prevention.<br /><b>Clinicaltrials</b><br />GOV: : NCT05923359.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 30 Oct 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular Impact of Near Complete Estrogen Deprivation in Premenopausal Women with Breast Cancer: The CROWN Study.</h4><i>Thomas A, O\'Connell NS, Douglas E, Hatcher S, ... D\'Agostino RB, Jordan JH</i><br /><AbstractText>Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and two CCTA scans during the two-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026-2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Effects of Complete Revascularization According to Age in Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Disease (COMPLETE-AGE).</h4><i>Bainey KR, Wood DA, Bossard M, Campo G, ... Mehta SR, COMPLETE trial investigators</i><br /><b>Background</b><br />In ST-segment elevation myocardial infarction (STEMI), complete revascularization with percutaneous coronary intervention (PCI) reduces major cardiovascular events compared with culprit-lesion-only PCI. Whether age influences these results remains unknown.<br /><b>Methods</b><br />COMPLETE was a multinational, randomized trial evaluating a strategy of staged complete revascularization, consisting of angiography-guided PCI of all suitable non-culprit lesions, versus a strategy of culprit-lesion-only PCI. In this pre-specified subgroup analysis, treatment effect according to age (≥65 years versus <65 years) was determined for the first co-primary outcome of cardiovascular (CV) death or new myocardial infarction (MI) and the second co-primary outcome of CV death, new MI, or ischemia-driven revascularization (IDR). Median follow-up was 35.8 months (interquartile range [IQR]: 27.6 to 44.3 months).<br /><b>Results</b><br />Of 4,041 patients randomized in COMPLETE, 1,613 were aged ≥ 65 years (39.9%). Higher event rates were observed for both co-primary outcomes in patients aged ≥ 65 years comparted with those aged < 65 years (11.2% vs. 7.9%, HR 1.49, 95% CI 1.22-1.83; 14.4% vs. 11.8%, HR 1.28, 95% CI 1.07-1.52, respectively). Complete revascularization reduced the first co-primary outcome in patients ≥ 65 years (9.7% vs 12.5%, HR 0.77; 95% CI 0.58-1.04) and < 65 years (6.7% vs 9.1%, HR 0.72; 95% CI 0.54-0.96)(interaction P=0.74). The second co-primary outcome was reduced in those ≥ 65 years (HR 0.56, 95% CI 0.43-0.74) and < 65 years (HR 0.48, 95% CI 0.37-0.61 (interaction P=0.37). A sensitivity analysis was performed with consistent results demonstrated using a 75-year threshold (albeit attenuated).<br /><b>Conclusions</b><br />In patients with STEMI and multivessel CAD, complete revascularization compared with culprit-lesion-only PCI reduced major cardiovascular events regardless of patient age and could be considered as a revascularization strategy in older adults.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 21 Oct 2023; epub ahead of print</small></div>

<div><h4>A randomized trial of expedited intra-arrest transfer versus more extended on-scene resuscitation for refractory Out of Hospital Cardiac Arrest: Rationale and design of the EVIDENCE trial.</h4><i>Burns B, Marschner I, Eggins R, Buscher H, ... Dennis M, EVIDENCE Investigators</i><br /><b>Background</b><br />Refractory Out of Hospital Cardiac Arrest (r-OHCA) is common and the benefit versus harm of intra-arrest transport of patients to hospital is not clear.<br /><b>Objective</b><br />To assess the rate of survival to hospital discharge in adult patients with r-OHCA, initial rhythm pulseless ventricular tachycardia (VT)/ventricular fibrillation (VF) or Pulseless Electrical Activity (PEA) treated with 1 of 2 locally accepted standards of care: (1) expedited transport from scene; or (2) ongoing advanced life support (ALS) resuscitation on-scene.<br /><b>Hypothesis</b><br />We hypothesize that expedited transport from scene in r-OHCA improves survival with favourable neurological status/outcome.<br /><b>Methods/design</b><br />Phase III, multi-center, partially blinded, prospective, intention-to-treat, safety and efficacy clinical trial with contemporaneous registry of patient ineligible for the clinical trial. Eligible patients for inclusion are adults with witnessed r-OHCA; estimated age 18-70, assumed medical cause with immediate bystander cardiopulmonary resuscitation (CPR); initial rhythm of VF/pulseless VT, or PEA; no return of spontaneous circulation following 3 shocks and/or 15 minutes of professional on-scene resuscitation; with mechanical CPR available. Two hundred patients will be randomized in a 1:1 ratio to either expedited transport from scene or ongoing ALS at the scene of cardiac arrest.<br /><b>Setting</b><br />Two urban regions in NSW Australia.<br /><b>Outcomes</b><br />Primary: survival to hospital discharge with cerebral performance category (CPC) 1 or 2. Secondary: safety, survival, prognostic factors, use of ECMO supported CPR and functional assessment at hospital discharge and 4 weeks and 6 months, quality of life, healthcare use and cost-effectiveness.<br /><b>Conclusions</b><br />The EVIDENCE trial will determine the potential risks and benefits of an expedited transport from scene of cardiac arrest.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 21 Oct 2023; epub ahead of print</small></div>

<div><h4>Long-Term Risk of Reintervention after Transcatheter Aortic Valve Replacement.</h4><i>Baron SJ, Ryan MP, Chikermane SG, Thompson C, Clancy S, Gunnarsson CL</i><br /><b>Background</b><br />Transcatheter aortic valve replacement (TAVR) has surpassed surgical aortic valve replacement (SAVR) as the predominant mode of valve replacement for the treatment of severe aortic stenosis (AS). However, the long-term need for valvular reintervention after TAVR remains unknown.<br /><b>Methods</b><br />Using data from the Medicare Fee for Service 100% dataset, all patients receiving TAVR between 7/2011 and 12/2020 were identified. Patients were categorized as receiving a valve reintervention (either surgical or transcatheter) or not using the appropriate International Classification of Diseases 10th Revision Procedure Coding System (ICD-10-PCS). A competing risk regression model was used to estimate the cumulative probability of valve reintervention.<br /><b>Results</b><br />230,644 TAVR patients were identified, of whom 1,880 received a reintervention. Patients receiving a reintervention were younger and more likely to be male. At 10 years, the crude rate of reintervention was 0.59% within a surviving cohort of 341 patients. After adjusting for the competing risk of death and other covariates, the adjusted cumulative incidence of reintervention at 10 years after TAVR was 1.63%. When the rate of reinterventions was compared between early (2011 to 2016) and later (2017 to 2020) time periods, the risk-adjusted rate of reintervention at 4 years had decreased over time (0.85% vs. 0.51%).<br /><b>Conclusion</b><br />The 10-year risk of valve reintervention after TAVR is low and appears to be decreasing over time. Further research is necessary to determine the driving factors contributing to valve reintervention in the current era.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 21 Oct 2023; epub ahead of print</small></div>

<div><h4>Bifurcation PCI With a Hybrid Strategy With Drug- Eluting Balloons Versus a Stepwise Provisional Two- Stent Strategy: Rationale and Design of the Hybrid DEB study.</h4><i>Dillen DMM, Vlaar PJ, Vermeer AJE, Paradies V, ... Tonino PAL, Teeuwen K</i><br /><AbstractText>The optimal treatment strategy for coronary bifurcation lesions by percutaneous coronary intervention is complex and remains a subject of debate. Current guidelines advise a stepwise provisional approach with optional two-stent strategy. However, a two-stent strategy, both upfront and stepwise provisional, is technically demanding. Therefore, there is increasing interest in the use of drug-eluting balloons in bifurcation lesions, mainly after a provisional approach with unsatisfactory result of the side branch. Some small pilot studies already showed that the use of DEB in bifurcation lesions is safe and feasible. However, a randomized comparison of this hybrid DEB strategy to a conventional two-stent strategy is currently lacking. The Hybrid DEB study is a prospective, multicentre, randomized controlled trial investigating non-inferiority of a hybrid DEB approach, using a combination of a drug-eluting stent in the main vessel and drug-eluting balloon in the side branch, compared to stepwise provisional two-stent strategy in patients with true bifurcation lesions. A total of 500 patients with de novo true coronary bifurcation lesions, treated with a stepwise provisional approach and an unsatisfactory result of the side branch after main vessel stenting (≥ 70% stenosis and/or <Thrombolysis in myocardial infarction III flow), will be randomized in a 1:1 ratio to receive either treatment with a drug-eluting balloon or with a second stent in the side branch. The primary endpoint is a composite endpoint of the occurrence of all-cause death, periprocedural or spontaneous myocardial infarction and/or target vessel revascularization at the anticipated median 2 year follow-up.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 06 Oct 2023; epub ahead of print</small></div>

<div><h4>The gut microbiota and coronary artery calcification in Japanese men.</h4><i>Okami Y, Arima H, Kondo K, Hexun Z, ... Ueshima H, Miura K</i><br /><b>Background</b><br />The gut microbiota differs between patients with coronary artery disease (CAD) and healthy controls; however, it currently remains unclear whether these differences exist prior to the onset of CAD. We herein investigated the gut microbiota associated with subclinical coronary artery calcification (CAC) in a Japanese population.<br /><b>Methods</b><br />A total of 663 Japanese men were enrolled in this cross-sectional study. Computed tomography and gut microbiology tests were performed, and CAC scores were calculated using the Agatston method. Participants were categorized into four groups based on their CAC scores: CAC = 0, 0 <CAC ≤100, 100 <CAC, and with a CAD history. The bacterial 16S ribosomal RNA gene was amplified, and DNA sequencing was conducted on a MiSeq System. QIIME2 and LEfSe were used to analyze the gut microbiota, and the results obtained were compared among the four CAC categories.<br /><b>Results</b><br />The mean age of participants was 68.4 years (46-83 years). The numbers of participants in CAC = 0, 0 <CAC ≤100, 100 <CAC, and with a CAD history were 219, 200, 193, and 51, respectively. The medians of the Firmicutes to Bacteroidota ratio were 1.50, 1.52, 1.67, and 1.80 for each CAC category (P = 0.020). One standard deviation higher phylum Firmicutes, class Bacilli, and order Lactobacillales were associated with a 1.3- to 1.4-fold higher risk of CAD. These taxa were also associated with a higher CAC score category. The family Streptococcaceae and genus Streptococcus showed a higher risk of CAD. The order Enterobacterales and family Enterobacteriaceae correlated with CAC scores. The genus Blautia showed a preventive direction for CAD, but did not correlate with CAC scores.<br /><b>Conclusions</b><br />The gut microbiota significantly differed from the phylum to genus level in a manner that was dependent on CAC scores, even before the onset of CAD.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 05 Oct 2023; epub ahead of print</small></div>

<div><h4>Rationale and study protocol for the BRITISH randomised trial (Using cardiovascular magnetic resonance identified scar as the Benchmark Risk Indication Tool for Implantable cardioverter defibrillators in patients with Non-Ischaemic Cardiomyopathy and Severe systolic Heart failure).</h4><i>Flett A, Cebula A, Nicholas Z, Adam R, ... Eminton Z, Curzen N</i><br /><b>Background</b><br />For patients with non-ischaemic cardiomyopathy (NICM), current guidelines recommend implantable cardioverter defibrillators (ICD) when left ventricular ejection fraction (LVEF) is ≤35%, but the DANISH trial failed to confirm that ICDs reduced all-cause mortality for such patients. Circumstantial evidence suggests that scar on CMR is predictive of sudden and arrhythmic death in this population. The presence of myocardial scar identified by cardiac magnetic resonance imaging (CMR) in patients with NICM and an LVEF ≤35% might identify patients at higher risk of sudden arrhythmic death, for whom an ICD is more likely to reduce all-cause mortality.<br /><b>Methods/design</b><br />The BRITISH trial is a prospective, multicentre, randomised controlled trial aiming to enrol 1252 patients with NICM and an LVEF ≤35%. Patients with non-ischaemic scar on CMR will be randomised to either: (A) ICD, with or without cardiac resynchronisation (CRT-D) or (b) implantable loop recorder (ILR) or cardiac resynchronisation (CRT-P). Patients who are screened for the trial but are found not to be eligible, predominantly due to an absence of scar, or those who decline to be randomised will be enrolled in an observational registry. The primary endpoint is all-cause mortality, which we plan to assess at 3 years after last participant is randomised. Secondary endpoints include clinical outcomes, appropriate and inappropriate device therapies, symptom severity and wellbeing, device-related complications, and analysis of the primary endpoint by subgroups with other risk markers. www.<br /><b>Clinicaltrials</b><br />gov: identifier NCT05568069.<br /><b>Conclusion</b><br />The BRITISH trial will assess whether use of CMR-defined scar to direct ICD implantation in patients with NICM and an LVEF ≤35% is associated with a reduction in mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 28 Sep 2023; epub ahead of print</small></div>

<div><h4>Comparison of Tirzepatide and Dulaglutide on Major Adverse Cardiovascular Events in Participants with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: SURPASS-CVOT Design and Baseline Characteristics.</h4><i>Nicholls SJ, Bhatt DL, Buse JB, Prato SD, ... D\'Alessio D, SURPASS-CVOT investigators</i><br /><b>Background</b><br />Tirzepatide, a once weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial.<br /><b>Methods</b><br />Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m<sup>2</sup> were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is non-inferiority for time to first MACE of tirzepatide versus dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority versus a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis).<br /><b>Results</b><br />Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m<sup>2</sup>. Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing.<br /><b>Conclusion</b><br />SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 25 Sep 2023; epub ahead of print</small></div>

<div><h4>Rationale and Design of the Direct Oral Anticoagulants for Prevention of Left Ventricular Thrombus after Anterior Acute Myocardial Infarction (APERITIF) trial.</h4><i>Puymirat E, Soulat G, Fayol A, Mousseaux E, ... Danchin N, APERITIF study investigators</i><br /><b>Background</b><br />Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI.<br /><b>Study design</b><br />APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing \"FRENCHIE\" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into two groups: Dual Anti-Platelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at one month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at one month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power.<br /><b>Conclusion</b><br />The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone.<br /><b>Clinicaltrials</b><br />gov Identifier: NCT05077683.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 14 Sep 2023; epub ahead of print</small></div>

<div><h4>Prophylactic corticosteroids for cardiac surgery in children: A systematic review and meta-analysis.</h4><i>Cheema HA, Khan AA, Ahmad AH, Khan AA, ... Ghelani SJ, Dani SS</i><br /><b>Objective</b><br />Perioperative corticosteroids have been used for pediatric cardiac surgery for decades, but the underlying evidence is conflicting. We aimed to investigate the efficacy and safety of perioperative prophylactic corticosteroids in pediatric heart surgeries.<br /><b>Methods</b><br />We searched electronic databases until March 2023 to retrieve all randomized controlled trials (RCTs) that administered perioperative prophylactic corticosteroids to children undergoing heart surgery. We used RevMan 5.4 to pool risk ratios (RRs) and mean differences (MDs).<br /><b>Results</b><br />A total of 12 RCTs (2209 patients) were included in our review. Corticosteroids administration was associated with a non-significant reduction in all-cause mortality (RR 0.62; 95% CI: 0.37-1.02, I<sup>2</sup>=0%; moderate certainty); however, it was associated with a lower duration of mechanical ventilation (MV) (MD -0.63 days; 95% CI: -1.16 to -0.09 days, I<sup>2</sup>=41%; high certainty). Corticosteroids did not affect the length of ICU and hospital stay but significantly reduced the incidence of postoperative low cardiac output syndrome (LCOS) (RR 0.76; 95% CI: 0.60-0.96, I<sup>2</sup>=0%; moderate certainty) and reoperation (RR 0.37; 95% CI: 0.19-0.74, I<sup>2</sup>=0%; moderate certainty). There was no increase in adverse events except a higher risk of hyperglycemia and postoperative insulin use.<br /><b>Conclusions</b><br />The use of perioperative corticosteroids in pediatric heart surgeries is associated with a trend toward reduced all-cause mortality without attaining statistical significance. Corticosteroids reduced MV duration, and probably decrease the incidence of LCOS, and reoperations. The choice of corticosteroid agent and dose is highly variable and further larger studies may help determine the ideal agent, dose, and patient population for this prophylactic therapy.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 14 Sep 2023; epub ahead of print</small></div>

<div><h4>A Cross-stakeholder Approach to Improving Out-of-Hospital Cardiac Arrest Survival.</h4><i>Guetterman TC, Forman J, Fouche S, Simpson K, ... Nallamothu BK, Abir M</i><br /><b>Background</b><br />Out-of-hospital cardiac arrest (OHCA) affects over 300,000 individuals per year in the U.S. with poor survival rates overall. A remarkable five-fold difference in survival-to-hospital discharge rates exist across U.S. communities.<br /><b>Method</b><br />We conducted a study using qualitative research methods comparing the system of care across sites in Michigan communities with varying OHCA survival outcomes, as measured by return to spontaneous circulation with pulse upon emergency department arrival.<br /><b>Results</b><br />Major themes distinguishing higher performing sites were 1) working as a team, 2) devoting resources to coordination across agencies, and 3) developing a continuous quality improvement culture. These themes spanned the chain of survival framework for OHCA. By examining the unique processes, procedures, and characteristics of higher- relative to lower-performing sites, we gleaned lessons learned that appear to distinguish higher performers. The higher performing sites reported being the most collaborative, due in part to facilitation of system integration by progressive leadership that is willing to build bridges among stakeholders.<br /><b>Conclusion</b><br />Based on the distinguishing features of higher performing sites, we provide recommendations for toolkit development to improve survival in prehospital systems of care for OHCA.<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 12 Sep 2023; epub ahead of print</small></div>

<div><h4>Early Computed Tomography Coronary Angiography and Preventative Treatment in Patients with Suspected Acute Coronary Syndrome A secondary analysis of the RAPID-CTCA trial.</h4><i>Wang KL, Meah MN, Bularga A, Oatey K, ... Gray AJ, RAPID-CTCA Investigators</i><br /><b>Background</b><br />Computed tomography coronary angiography (CTCA) offers detailed assessment of the presence of coronary atherosclerosis and helps guide patient management. We investigated influences of early CTCA on the subsequent use of preventative treatment in patients with suspected acute coronary syndrome.<br /><b>Methods</b><br />In this secondary analysis of a multicentre randomised controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, prescription of aspirin, P2Y<sub>12</sub> receptor antagonist, statin, renin-angiotensin system blocker, and beta-blocker therapies from randomisation to discharge were compared within then between those randomised to early CTCA or to standard of care only. Effects of CTCA findings on adjustment of these therapies were further examined.<br /><b>Results</b><br />In 1743 patients (874 randomised to early CTCA and 869 to standard of care only), prescription of P2Y<sub>12</sub> receptor antagonist, dual antiplatelet, and statin therapies increased more in the early CTCA group (between-group difference: 4.6% (95% confidence interval, 0.3 to 8.9), 4.5% (95% confidence interval, 0.2 to 8.7), and 4.3% (95% confidence interval, 0.2 to 8.5), respectively), whereas prescription of other preventative therapies increased by similar extent in both study groups. Amongst patients randomised to early CTCA, there were additional increments of preventative treatment in those with obstructive coronary artery disease and higher rates of reductions in antiplatelet and beta-blocker therapies in those with normal coronary arteries.<br /><b>Conclusions</b><br />Prescription patterns of preventative treatment varied during index hospitalisation in patients with suspected acute coronary syndrome. Early CTCA facilitated targeted individualisation of these therapies based on the extent of coronary artery disease.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 12 Sep 2023; epub ahead of print</small></div>

<div><h4>Diagnostic and prognostic impact of new pathophysiology-based categorization of type 1 and type 2 myocardial infarction: data from the French RICO survey.</h4><i>Yao H, Cottin Y, Chague F, Maza M, ... Zeller M, Putot A</i><br /><b>Background</b><br />A new classification of type 1 and 2 myocardial infarction (MI) derived from the 4<sup>th</sup> universal definition of MI (UDMI) has been recently proposed, based on pathophysiology of coronary artery disease (CAD). We assessed the impact of this new MI categorization on epidemiology and outcomes, considering type 1 MI and type 2 MI, with and without CAD.<br /><b>Methods</b><br />Retrospective study including all consecutive patients hospitalized for an acute MI in a multicenter database (RICO). MI was defined according to current UDMI. Rates and outcomes of T1MI and T2MI were addressed according to the new classification.<br /><b>Results</b><br />Among the 4573 patients included in our study, 3710 patients (81.1%) were initially diagnosed with T1M1 and 863 (18.9%) with T2MI. After reclassification, 96 T2MI patients were moved into the T1MI category. Out of the remaining 767 patients with T2MI, 567 underwent coronary angiography, and were adjudicated as type 2A MI (68.6%) with obstructive CAD, and type 2B MI (31.4%) without obstructive CAD. When compared with T1MI and T2BMI, T2AMI patients had worse in-hospital outcomes, including severe heart failure (p < 0.001), atrial fibrillation or flutter (p < 0.001) and severe bleeding (p < 0.001). Kaplan-Meier one-year survival curves showed higher all-cause and CV causes mortality in T2AMI patients compared to T1MI and T2BMI (p < 0.001). In multivariate Cox regression analysis, type of MI was independent predictor of death.<br /><b>Conclusion</b><br />Our large observational multicenter study shows major disparities in mortality according to type of MI and support the relevance of the new MI classification to improve risk classification, taking into account CAD in T2MI. Our findings may help identifying specific phenotypes and considering personalized diagnostic and management strategies.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>Randomized Controlled Trial of Mechanical Thrombectomy Versus Catheter-directed Thrombolysis for Acute Hemodynamically Stable Pulmonary Embolism: Rationale and Design of the PEERLESS Study.</h4><i>Gonsalves CF, Gibson CM, Stortecky S, Alvarez RA, ... Tu T, Jaber WA</i><br /><b>Background</b><br />The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient\'s care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the Pulmonary Embolism Response Team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and non-thrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients.<br /><b>Methods</b><br />The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a non-randomized MT cohort for separate analysis. The primary endpoint will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary endpoints. Other key secondary endpoints include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit.<br /><b>Implications</b><br />PEERLESS is the first RCT to compare two different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>The Coronary Microvascular Angina Cardiovascular Magnetic Resonance Imaging Trial: Rationale and Design.</h4><i>Bradley CP, Orchard V, McKinley G, Heggie R, ... McConnachie A, Berry C</i><br /><b>Background</b><br />Coronary microvascular dysfunction may cause myocardial ischemia with no obstructive coronary artery disease (INOCA). If functional testing is not performed INOCA may pass undetected. Stress perfusion cardiovascular MRI (CMR) quantifies myocardial blood flow (MBF) but the clinical utility of stress CMR in the management of patients with suspected angina with no obstructive coronary arteries (ANOCA) is uncertain.<br /><b>Objectives</b><br />First, to undertake a diagnostic study using stress CMR in patients with ANOCA following invasive coronary angiography and, second, in a nested, double-blind, randomized, controlled trial to assess the effect of disclosure on the final diagnosis and health status in the longer term.<br /><b>Design</b><br />All-comers referred for clinically indicated coronary angiography for the investigation of suspected coronary artery disease will be screened in three regional centers in the United Kingdom. Following invasive coronary angiography, patients with ANOCA who provide informed consent will undergo noninvasive endotyping using stress CMR within 3 months of the angiogram.<br /><b>Diagnostic study</b><br />Stress perfusion CMR imaging to assess the prevalence of coronary microvascular dysfunction and clinically significant incidental findings in patients with ANOCA. The primary outcome is the between-group difference in the reclassification rate of the initial diagnosis based on invasive angiography versus the final diagnosis after CMR imaging.<br /><b>Randomized, controlled trial</b><br />Participants will be randomized to inclusion (intervention group) or exclusion (control group) of myocardial blood flow to inform the final diagnosis. The primary outcome of the clinical trial is the mean within-subject change in the Seattle Angina Questionnaire summary score (SAQSS) at 6 months. Secondary outcome assessments include the EUROQOL EQ-5D-5L questionnaire, the Brief Illness Perception Questionnaire (Brief-IPQ), the Treatment Satisfaction Questionnaire (TSQM-9), the Patient Health Questionnaire-4 (PHQ-4), the Duke Activity Status Index (DASI), the International Physical Activity Questionnaire- Short Form (IPAQ-SF), the Montreal Cognitive Assessment (MOCA) and the 8-item Productivity Cost Questionnaire (iPCQ). Health and economic outcomes will be assessed using electronic healthcare records.<br /><b>Value</b><br />To clarify if routine stress perfusion CMR imaging reclassifies the final diagnosis in patients with ANOCA and whether this strategy improves symptoms, health-related quality of life and health economic outcomes.<br /><b>Clinicaltrials</b><br />GOV: NCT04805814.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 30 Aug 2023; epub ahead of print</small></div>

<div><h4>Rationale and design of the ULYSS trial: A randomized multicenter evaluation of the efficacy of early Impella CP implantation in acute coronary syndrome complicated by cardiogenic shock.</h4><i>Delmas C, Laine M, Schurtz G, Roubille F, ... Resseguier N, Bonello L</i><br /><AbstractText>Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLA® CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy. The ULYSS trial is a prospective randomized open label, 2 parallel multicenter clinical trial that plans to enroll patients with AMICS for whom an emergent percutaneous coronary intervention (PCI) is intended. Patients will be randomized to an experimental therapeutic strategy with pre-PCI implantation of an IMPELLA® CP device on top of standard medical therapy or to a control group undergoing PCI and standard medical therapy. The primary objective of this study is to compare the efficacy of this experimental strategy by a composite endpoint of death, need to escalate to ECMO, long-term left ventricular assist device or heart transplantation at 1 month. Among secondary objectives one-year efficacy, safety and cost effectiveness will be assessed.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 30 Aug 2023; epub ahead of print</small></div>