<div><h4>Normative Echocardiographic Left Ventricular Parameters and Reference Intervals in Infants.</h4><i>Vøgg ROB, Sillesen AS, Wohlfahrt J, Pihl C, ... Boyd HA, Bundgaard H</i><br /><b>Background</b><br />In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges.<br /><b>Objectives</b><br />Normative reference intervals and z-scores for 2-dimensional echocardiographic measurements of LV structure and function based on a large group of healthy newborns were developed.<br /><b>Methods</b><br />The study population included 13,454 healthy newborns from the Copenhagen Baby Heart Study who were born at term to healthy mothers, had an echocardiogram performed within 30 days of birth, and did not have congenital heart disease. To develop normative reference intervals, this study modeled 10 LV parameters as a function of body surface area through joint modeling of 4 statistical components.<br /><b>Results</b><br />Infants in the study population (48.5% were female) had a median body surface area of 0.23 m<sup>2</sup> (IQR: 0.22-0.25 m<sup>2</sup>) and median age of 12.0 days (IQR: 8.0-15.0 days) at examination. All normative reference intervals performed well in both sexes without stratification on infant sex. In contrast, creation of separate reference models for infants examined at <7 days of age and those examined at 7-30 days of age was necessary to optimize the performance of the reference intervals.<br /><b>Conclusions</b><br />This study provides normative reference intervals and z-scores for 10 clinical, widely used echocardiographic measures of LV structure and function based on a large cohort of newborns. These results provide highly needed reference material for clinical application by pediatric cardiologists.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Jun 2023; 81:2175-2185</small></div>

<div><h4>Procedure-Related Complications of Catheter Ablation for Atrial Fibrillation.</h4><i>Benali K, Khairy P, Hammache N, Petzl A, ... Andrade JG, Macle L</i><br /><b>Background</b><br />Catheter ablation of atrial fibrillation (AF) is a commonly performed procedure. However, it is associated with potentially significant complications. Reported procedure-related complication rates are highly variable, depending in part on study design.<br /><b>Objectives</b><br />The purpose of this systematic review and pooled analysis was to determine the rate of procedure-related complications associated with catheter ablation of AF using data from randomized control trials and to assess temporal trends.<br /><b>Methods</b><br />MEDLINE and EMBASE databases were searched from January 2013 to September 2022 for randomized control trials that included patients undergoing a first ablation procedure of AF using either radiofrequency or cryoballoon (PROSPERO, CRD42022370273).<br /><b>Results</b><br />A total of 1,468 references were retrieved, of which 89 studies met inclusion criteria. A total of 15,701 patients were included in the current analysis. Overall and severe procedure-related complication rates were 4.51% (95% CI: 3.76%-5.32%) and 2.44% (95% CI: 1.98%-2.93%), respectively. Vascular complications were the most frequent type of complication (1.31%). The next most common complications were pericardial effusion/tamponade (0.78%) and stroke/transient ischemic attack (0.17%). The procedure-related complication rate during the most recent 5-year period of publication was significantly lower than during the earlier 5-year period (3.77% vs 5.31%; P = 0.043). The pooled mortality rate was stable over the 2 time periods (0.06% vs 0.05%; P = 0.892). There was no significant difference in complication rate according to pattern of AF, ablation modality, or ablation strategies beyond pulmonary vein isolation.<br /><b>Conclusions</b><br />Procedure-related complications and mortality rates associated with catheter ablation of AF are low and have declined in the past decade.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 May 2023; 81:2089-2099</small></div>

<div><h4>Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.</h4><i>Fischer U, Koga M, Strbian D, Branca M, ... Dawson J, ELAN Investigators</i><br /><b>Background</b><br />The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.<br /><b>Methods</b><br />We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.<br /><b>Results</b><br />Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.<br /><b>Conclusions</b><br />In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 24 May 2023; epub ahead of print</small></div>

<div><h4>Subepicardial Cardiomyopathy: A Disease Underlying J-Wave Syndromes and Idiopathic Ventricular Fibrillation.</h4><i>Miles C, Boukens BJ, Scrocco C, Wilde AAM, ... Coronel R, Behr ER</i><br /><AbstractText>Brugada syndrome (BrS), early repolarization syndrome (ERS), and idiopathic ventricular fibrillation (iVF) have long been considered primary electrical disorders associated with malignant ventricular arrhythmia and sudden cardiac death. However, recent studies have revealed the presence of subtle microstructural abnormalities of the extracellular matrix in some cases of BrS, ERS, and iVF, particularly within right ventricular subepicardial myocardium. Substrate-based ablation within this region has been shown to ameliorate the electrocardiographic phenotype and to reduce arrhythmia frequency in BrS. Patients with ERS and iVF may also exhibit low-voltage and fractionated electrograms in the ventricular subepicardial myocardium, which can be treated with ablation. A significant proportion of patients with BrS and ERS, as well as some iVF survivors, harbor pathogenic variants in the voltage-gated sodium channel gene, <i>SCN5A</i>, but the majority of genetic susceptibility of these disorders is likely to be polygenic. Here, we postulate that BrS, ERS, and iVF may form part of a spectrum of subtle subepicardial cardiomyopathy. We propose that impaired sodium current, along with genetic and environmental susceptibility, precipitates a reduction in epicardial conduction reserve, facilitating current-to-load mismatch at sites of structural discontinuity, giving rise to electrocardiographic changes and the arrhythmogenic substrate.</AbstractText><br /><br /><br /><br /><small>Circulation: 23 May 2023; 147:1622-1633</small></div>

<div><h4>Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF.</h4><i>Vaduganathan M, Mentz RJ, Claggett BL, Miao ZM, ... Braunwald E, Solomon SD</i><br /><b>Background:</b><br/>and aims</b><br />The PARAGLIDE-HF trial demonstrated reductions in natriuretic peptides with sacubitril/valsartan compared with valsartan in patients with heart failure (HF) with mildly reduced or preserved ejection fraction who had a recent worsening HF event, but was not adequately powered to examine clinical outcomes. PARAGON-HF included a subset of PARAGLIDE-HF-like patients who were recently hospitalized for HF. Participant-level data from PARAGLIDE-HF and PARAGON-HF were pooled to better estimate the efficacy and safety of sacubitril/valsartan in reducing cardiovascular and renal events in HF with mildly reduced or preserved ejection fraction.<br /><b>Methods</b><br />Both PARAGLIDE-HF and PARAGON-HF were multicenter, double-blind, randomized, active-controlled trials of sacubitril/valsartan vs. valsartan in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF >40% in PARAGLIDE-HF and ≥45% in PARAGON-HF). In the pre-specified primary analysis, we pooled participants in PARAGLIDE-HF (all of whom were enrolled during or within 30 days of a worsening HF event) with a \'PARAGLIDE-like\' subset of PARAGON-HF (those hospitalized for HF within 30 days). We also pooled the entire PARAGLIDE-HF and PARAGON-HF populations for a broader context. The primary endpoint for this analysis was the composite of total worsening HF events (including first and recurrent HF hospitalizations and urgent visits) and cardiovascular death. The secondary endpoint was the pre-specified renal composite endpoint for both studies (≥50% decline in estimated glomerular filtration rate from baseline, end-stage renal disease, or renal death).<br /><b>Results</b><br />Compared with valsartan, sacubitril/valsartan significantly reduced total worsening HF events and cardiovascular death in both the primary pooled analysis of participants with recent worsening HF (n=1,088; rate ratio [RR] 0.78; 95% confidence interval [CI] 0.61-0.99; P=0.042) and in the pooled analysis of all participants (n=5,262; RR 0.86; 95% CI: 0.75-0.98; P=0.027). In the pooled analysis of all participants, first nominal statistical significance was reached by day 9 after randomization and treatment benefits were larger in those with LVEF ≤60% (RR 0.78; 95% CI 0.66-0.91) compared with those with LVEF >60% (RR 1.09; 95% CI 0.86-1.40; Pinteraction=0.021). Sacubitril/valsartan was also associated with lower rates of the renal composite endpoint in the primary pooled analysis (hazard ratio [HR] 0.67; 95% CI 0.43-1.05; P=0.080) and the pooled analysis of all participants (HR 0.60; 95% CI 0.44-0.83; P=0.002).<br /><b>Conclusions</b><br />In pooled analyses of PARAGLIDE-HF and PARAGON-HF, sacubitril/valsartan reduced cardiovascular and renal events among patients with HF with mildly reduced or preserved ejection fraction. These data provide support for use of sacubitril/valsartan in patients with HF with mildly reduced or preserved ejection fraction, particularly among those with an LVEF below normal, regardless of care setting.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 21 May 2023; epub ahead of print</small></div>

<div><h4>Efficacy of Pulmonary Artery Pressure Monitoring in Patients with Chronic Heart Failure: A Meta-Analysis of Three Randomized Controlled Trials.</h4><i>Clephas PRD, Radhoe SP, Boersma E, Gregson J, ... de Boer RA, Brugts JJ</i><br /><b>Background:</b><br/>and aims</b><br />Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question.<br /><b>Methods</b><br />A systematic literature search was performed for randomized clinical trials (RCTs) with PA pressure monitoring devices in patients with HF. The primary outcome of interest was the total number of HF hospitalizations. Other outcomes assessed were urgent visits leading to treatment with intravenous diuretics, all-cause mortality, and composites. Treatment effects are expressed as hazard ratios, and pooled effect estimates were obtained applying random effects meta-analyses.<br /><b>Results</b><br />Three eligible RCTs were identified that included 1898 outpatients in New York Heart Association functional class II-IV, either hospitalized for HF in the prior 12 months or with elevated plasma NT-proBNP concentrations. Mean follow-up was 14.7 months, 67.8% of the patients were men, and 65.8% had an ejection fraction ≤40%. Compared to patients in the control group, the hazard ratio (95% confidence interval) for total HF hospitalizations in those randomized to PA pressure monitoring was 0.70 (0.58-0.86) (p=0.0005). The corresponding hazard ratio for the composite of total HF hospitalizations, urgent visits and all-cause mortality was 0.75 (0.61-0.91; p=0.0037) and for all-cause mortality 0.92 (0.73-1.16). Subgroup analyses, including ejection fraction phenotype, revealed no evidence of heterogeneity in the treatment effect.<br /><b>Conclusions</b><br />The use of remote PA pressure monitoring to guide treatment of patients with HF reduces episodes of worsening HF and subsequent hospitalizations.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 21 May 2023; epub ahead of print</small></div>

<div><h4>Novel mechanisms and therapeutic targets in atherosclerosis: inflammation and beyond.</h4><i>Weber C, Habenicht AJR, von Hundelshausen P</i><br /><AbstractText>This review based on the ESC William Harvey Lecture in Basic Science 2022 highlights recent experimental and translational progress on the therapeutic targeting of the inflammatory components in atherosclerosis, introducing novel strategies to limit side effects and to increase efficacy. Since the validation of the inflammatory paradigm in CANTOS and COLCOT, efforts to control the residual risk conferred by inflammation have centred on the NLRP3 inflammasome-driven IL-1β-IL6 axis. Interference with the co-stimulatory dyad CD40L-CD40 and selective targeting of tumour necrosis factor-receptor associated factors (TRAFs), namely the TRAF6-CD40 interaction in macrophages by small molecule inhibitors, harbour intriguing options to reduce established atherosclerosis and plaque instability without immune side effects. The chemokine system crucial for shaping immune cell recruitment and homoeostasis can be fine-tuned and modulated by its heterodimer interactome. Structure-function analysis enabled the design of cyclic, helical, or linked peptides specifically targeting or mimicking these interactions to limit atherosclerosis or thrombosis by blunting myeloid recruitment, boosting regulatory T cells, inhibiting platelet activity, or specifically blocking the atypical chemokine MIF without notable side effects. Finally, adventitial neuroimmune cardiovascular interfaces in advanced atherosclerosis show robust restructuring of innervation from perivascular ganglia and employ sensory neurons of dorsal root ganglia to enter the central nervous system and to establish an atherosclerosis-brain circuit sensor, while sympathetic and vagal efferents project to the celiac ganglion to create an atherosclerosis-brain circuit effector. Disrupting this circuitry by surgical or chemical sympathectomy limited disease progression and enhanced plaque stability, opening exciting perspectives for selective and tailored intervention beyond anti-inflammatory strategies.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 20 May 2023; epub ahead of print</small></div>

<div><h4>Management strategies for heavily calcified coronary stenoses: an EAPCI clinical consensus statement in collaboration with the EURO4C-PCR group.</h4><i>Barbato E, Gallinoro E, Abdel-Wahab M, Andreini D, ... Wijns W, Ribichini F</i><br /><AbstractText>Since the publication of the 2015 EAPCI consensus on rotational atherectomy, the number of percutaneous coronary interventions (PCI) performed in patients with severely calcified coronary artery disease has grown substantially. This has been prompted on one side by the clinical demand for the continuous increase in life expectancy, the sustained expansion of the primary PCI networks worldwide and the routine performance of revascularization procedures in elderly patients; on the other side, the availability of new and dedicated technologies such as orbital atherectomy and intravascular lithotripsy, as well as the optimization of the rotational atherectomy system, have increased operators\' confidence in attempting more challenging PCI. This current EAPCI clinical consensus statement prepared in collaboration with the EURO4C-PCR group describes the comprehensive management of patients with heavily calcified coronary stenoses, starting with how to use non-invasive and invasive imaging to assess calcium burden and inform procedural planning. Objective and practical guidance is provided on the selection of the optimal interventional tool and technique based on the specific calcium morphology and anatomic location. Finally, the specific clinical implications of treating these patients are considered, including the prevention and management of complications, and the importance of adequate training and education.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 19 May 2023; epub ahead of print</small></div>

<div><h4>Vaccine Effectiveness of JYNNEOS against Mpox Disease in the United States.</h4><i>Deputy NP, Deckert J, Chard AN, Sandberg N, ... Gerhart JL, Feldstein LR</i><br /><b>Background</b><br />In the United States, more than 30,000 cases of mpox (formerly known as monkeypox) had occurred as of March 1, 2023, in an outbreak disproportionately affecting transgender persons and gay, bisexual, and other men who have sex with men. In 2019, the JYNNEOS vaccine was approved for subcutaneous administration (0.5 ml per dose) to prevent mpox infection. On August 9, 2022, an emergency use authorization was issued for intradermal administration (0.1 ml per dose); however, real-world effectiveness data are limited for either route.<br /><b>Methods</b><br />We conducted a case-control study based on data from Cosmos, a nationwide Epic electronic health record (EHR) database, to assess the effectiveness of JYNNEOS vaccination in preventing medically attended mpox disease among adults. Case patients had an mpox diagnosis code or positive orthopoxvirus or mpox virus laboratory result, and control patients had an incident diagnosis of human immunodeficiency virus (HIV) infection or a new or refill order for preexposure prophylaxis against HIV infection between August 15, 2022, and November 19, 2022. Odds ratios and 95% confidence intervals were estimated from conditional logistic-regression models, adjusted for confounders; vaccine effectiveness was calculated as (1 - odds ratio for vaccination in case patients vs. controls) × 100.<br /><b>Results</b><br />Among 2193 case patients and 8319 control patients, 25 case patients and 335 control patients received two doses (full vaccination), among whom the estimated adjusted vaccine effectiveness was 66.0% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose (partial vaccination), among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1).<br /><b>Conclusions</b><br />In this study using nationwide EHR data, patients with mpox were less likely to have received one or two doses of JYNNEOS vaccine than control patients. The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection. (Funded by the Centers for Disease Control and Prevention and Epic Research.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 18 May 2023; epub ahead of print</small></div>

<div><h4>The Importance of Timing in Post-Cardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: a Descriptive Multicenter Observational Study.</h4><i>Mariani S, Wang IW, van Bussel BCT, Heuts S, ... Lorusso R, PELS-1 Investigators</i><br /><b>Objectives</b><br />Post-cardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intra-operatively or post-operatively based on indications, settings, patient profile and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patients´ characteristics, in-hospital and long-term survival between intra-operative and post-operative ECMO.<br /><b>Methods</b><br />The retrospective, multicentre, observational Post-cardiotomy Extracorporeal Life Support (PELS-1) Study includes adults requiring ECMO due to post-cardiotomy shock between 2000 and 2020. We compare patients who received ECMO in the operating theatre (intra-operative) with those in the intensive care unit (post-operative) on in-hospital and post-discharge outcomes.<br /><b>Results</b><br />We studied 2003 patients [women:41.1%; median age:65 (IQR:55.0-72.0) years]. Intra-operative (n=1287), compared to post-operative (n=716), ECMO patients had worse pre-operative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for post-operative ECMO initiation, with cannulation occurring after (median) 1 day (IQR:1-3 days). Compared to intra-operative application, post-operative ECMO showed more complications, cardiac reoperations (intra-operative:19.7%; post-operative: 24.8%, p=0.011), percutaneous coronary interventions (intra-operative:1.8%; post-operative: 3.6%, p=0.026), and had higher in-hospital mortality (intra-operative:57.5%; post-operative: 64.5%, p=0.002). Among hospital survivors, ECMO duration was shorter after intra-operative ECMO (median:104, IQR:67.8-164.2 hours) compared to post-operative ECMO (median:139.7, IQR:95.8-192 hours, p<0.001), while post-discharge long-term survival was similar between the two groups (p=0.86).<br /><b>Conclusions</b><br />Intra-operative and post-operative ECMO implantations are associated with different patients\' characteristics and outcomes, with higher complications and in-hospital mortality after post-operative ECMO. Strategies to identify the optimal location and timing of post-cardiotomy ECMO in relation to specific patient\'s characteristics are warranted to optimize in-hospital outcomes.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Thorac Cardiovasc Surg: 16 May 2023; epub ahead of print</small></div>

<div><h4>Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories.</h4><i>Butler J, Packer M, Siddiqi TJ, Böhm M, ... Anker SD, Zannad F</i><br /><b>Background</b><br />Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction.<br /><b>Objectives</b><br />The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively).<br /><b>Methods</b><br />A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively.<br /><b>Results</b><br />In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very-high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved.<br /><b>Conclusions</b><br />The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 May 2023; 81:1902-1914</small></div>

<div><h4>Five-Year Clinical Outcomes After Coronary Bioresorbable Scaffolds and Drug-Eluting Stents: The ABSORB IV Randomized Trial.</h4><i>Stone GW, Kereiakes DJ, Gori T, Metzger DC, ... Ellis SG, ABSORB IV Investigators</i><br /><b>Background</b><br />Bioresorbable vascular scaffolds (BVS) were designed to improve late event-free survival compared with metallic drug-eluting stents. However, initial trials demonstrated worse early outcomes with BVS, in part due to suboptimal technique. In the large-scale, blinded ABSORB IV trial, polymeric everolimus-eluting BVS implanted with improved technique demonstrated non-inferior 1-year outcomes compared with cobalt chromium everolimus-eluting stents (CoCr-EES).<br /><b>Objectives</b><br />To evaluate the long-term outcomes from the ABSORB IV trial.<br /><b>Methods</b><br />We randomized 2,604 patients at 147 sites with stable or acute coronary syndromes to BVS with improved technique vs. CoCr-EES. Patients, clinical assessors and event adjudicators were blinded to randomization. Five-year follow-up was completed.<br /><b>Results</b><br />Target lesion failure (TLF) at 5 years occurred in 216 patients (17.5%) assigned to BVS and 180 patients (14.5%) assigned to CoCr-EES (P=0.03). Device thrombosis within 5 years occurred in 21 (1.7%) BVS and 13 (1.1%) CoCr-EES patients (P=0.15). Event rates were slightly greater with BVS than CoCr-EES through 3-year follow-up and similar between 3-5 years. Angina, also centrally adjudicated, recurred within 5 years in 659 patients (cumulative rate 53.0%) assigned to BVS and 674 patients (53.3%) assigned to CoCr-EES (P=0.63).<br /><b>Conclusions</b><br />In this large-scale, blinded randomized trial, despite improved implantation technique the absolute 5-year rate of TLF was 3% greater after BVS compared with CoCr-EES. The risk period for increased events was restricted to 3 years, the time point of complete scaffold bioresorption; event rates were similar thereafter. Angina recurrence after intervention was frequent during 5-year follow-up but was comparable with both devices.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 13 May 2023; epub ahead of print</small></div>

<div><h4>Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.</h4><i>Gallos I, Devall A, Martin J, Middleton L, ... Hemming K, Coomarasamy A</i><br /><b>Background</b><br />Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle.<br /><b>Methods</b><br />We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle.<br /><b>Results</b><br />A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28).<br /><b>Conclusions</b><br />Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 09 May 2023; epub ahead of print</small></div>

<div><h4>Lipoprotein(a), Oxidized Phospholipids, and Coronary Artery Disease Severity and Outcomes.</h4><i>Gilliland TC, Liu Y, Mohebi R, Miksenas H, ... Januzzi JL, Natarajan P</i><br /><b>Background</b><br />Lipoprotein(a) (Lp[a]) and oxidized phospholipids (OxPLs) are each independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs predict coronary artery disease (CAD) severity and outcomes in a contemporary, statin-treated cohort is not well established.<br /><b>Objectives</b><br />This study sought to evaluate the relationships between Lp(a) particle concentration and OxPLs associated with apolipoprotein B (OxPL-apoB) or apolipoprotein(a) (OxPL-apo[a]) with angiographic CAD and cardiovascular outcomes.<br /><b>Methods</b><br />Among 1,098 participants referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study, Lp(a), OxPL-apoB, and OxPL-apo(a) were measured. Logistic regression estimated the risk of multivessel coronary stenoses by Lp(a)-related biomarker level. Cox proportional hazards regression estimated the risk of major adverse cardiovascular events (MACEs) (coronary revascularization, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) in follow-up.<br /><b>Results</b><br />Median Lp(a) was 26.45 nmol/L (IQR: 11.39-89.49 nmol/L). Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R ≥0.91 for all pairwise combinations). Lp(a) and OxPL-apoB were associated with multivessel CAD. Odds of multivessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI: 1.03-1.18; P = 0.006), 1.18 (95% CI: 1.03-1.34; P = 0.01), and 1.07 (95% CI: 0.99-1.16; P = 0.07), respectively. All biomarkers were associated with cardiovascular events. HRs for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI: 1.03-1.14; P = 0.001), 1.15 (95% CI: 1.05-1.26; P = 0.004), and 1.07 (95% CI: 1.01-1.14; P = 0.02), respectively.<br /><b>Conclusions</b><br />In patients undergoing coronary angiography, Lp(a) and OxPL-apoB are associated with multivessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident cardiovascular events. (Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 May 2023; 81:1780-1792</small></div>

<div><h4>Heart Failure With Preserved Ejection Fraction: JACC Scientific Statement.</h4><i>Borlaug BA, Sharma K, Shah SJ, Ho JE</i><br /><AbstractText>The incidence and prevalence of heart failure with preserved ejection fraction (HFpEF) continue to rise in tandem with the increasing age and burdens of obesity, sedentariness, and cardiometabolic disorders. Despite recent advances in the understanding of its pathophysiological effects on the heart, lungs, and extracardiac tissues, and introduction of new, easily implemented approaches to diagnosis, HFpEF remains under-recognized in everyday practice. This under-recognition presents an even greater concern given the recent identification of highly effective pharmacologic-based and lifestyle-based treatments that can improve clinical status and reduce morbidity and mortality. HFpEF is a heterogenous syndrome and recent studies have suggested an important role for careful, pathophysiological-based phenotyping to improve patient characterization and to better individualize treatment. In this JACC Scientific Statement, we provide an in-depth and updated examination of the epidemiology, pathophysiology, diagnosis, and treatment of HFpEF.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 May 2023; 81:1810-1834</small></div>

<div><h4>Impact of cardiac surgery on left-sided infective endocarditis with intermediate-length vegetations.</h4><i>Scheggi V, Bohbot Y, Tribouilloy C, Trojette F, ... Habib G, Marchionni N</i><br /><b>Objective</b><br />The best strategy to manage patients with left-sided infective endocarditis (IE) and intermediate-length vegetations (10-15 mm) remains uncertain. We aimed to evaluate the role of surgery in patients with intermediate-length vegetations and no other European Society of Cardiology guidelines-approved surgical indication.<br /><b>Methods</b><br />We retrospectively enrolled 638 consecutive patients admitted to three academic centres (Amiens, Marseille and Florence University Hospitals) between 2012 and 2022 for left-sided definite IE (native or prosthetic) with intermediate-length vegetations (10-15 mm). We compared four clinical groups: medically (n=50) or surgically (n=345) treated complicated IE, medically (n=194) or surgically (n=49) treated uncomplicated IE.<br /><b>Results</b><br />Mean age was 67±14 years. Women were 182 (28.6%). The rate of embolic events on admission was 40% in medically treated and 61% in surgically treated complicated IE, 31% in medically treated and 26% in surgically treated uncomplicated IE. The analysis of all-cause mortality showed the lowest 5-year survival rate for medically treated complicated IE (53.7%). We found a similar 5-year survival rate for surgically treated complicated IE (71.4%) and medically treated uncomplicated IE (68.4%). The highest 5-year survival rate was observed in surgically treated uncomplicated IE group (82.4%, log-rank p<0.001). The analysis of the propensity score-matched cohort estimated an HR of 0.23 for uncomplicated IE treated surgically compared with medical therapy (p=0.005, 95% CI: 0.079 to 0.656).<br /><b>Conclusions</b><br />Our results suggest that surgery is associated with lower all-cause mortality than medical therapy in patients with uncomplicated left-sided IE with intermediate-length vegetations even in the absence of other guideline-based indications.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 05 May 2023; epub ahead of print</small></div>

<div><h4>Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer.</h4><i>Partridge AH, Niman SM, Ruggeri M, Peccatori FA, ... International Breast Cancer Study Group, POSITIVE Trial Collaborators</i><br /><b>Background</b><br />Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking.<br /><b>Methods</b><br />We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial.<br /><b>Results</b><br />Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort.<br /><b>Conclusions</b><br />Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 04 May 2023; 388:1645-1656</small></div>

<div><h4>Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation.</h4><i>Ninni S, Dombrowicz D, Kuznetsova T, Vicario R, ... Staels B, Montaigne D</i><br /><b>Background</b><br />On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype.<br /><b>Objectives</b><br />The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery.<br /><b>Methods</b><br />Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes.<br /><b>Results</b><br />The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64<sup>+</sup>CD14<sup>+</sup>CD16<sup>-</sup> circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium.<br /><b>Conclusions</b><br />HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1263-1278</small></div>

<div><h4>Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction.</h4><i>Khan KR, Khan OA, Chen C, Liu Y, ... Langer NB, Elmariah S</i><br /><b>Background</b><br />Afterload from moderate aortic stenosis (AS) may contribute to adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF).<br /><b>Objectives</b><br />The authors evaluated clinical outcomes in patients with HFrEF and moderate AS relative to those without AS and with severe AS.<br /><b>Methods</b><br />Patients with HFrEF, defined by left ventricular ejection fraction (LVEF) <50% and no, moderate, or severe AS were retrospectively identified. The primary endpoint, defined as a composite of all-cause mortality and heart failure (HF) hospitalization, was compared across groups and within a propensity score-matched cohort.<br /><b>Results</b><br />We included 9,133 patients with HFrEF, of whom 374 and 362 had moderate and severe AS, respectively. Over a median follow-up time of 3.1 years, the primary outcome occurred in 62.7% of patients with moderate AS vs 45.9% with no AS (P < 0.0001); rates were similar with severe and moderate AS (62.0% vs 62.7%; P = 0.68). Patients with severe AS had a lower incidence of HF hospitalization (36.2% vs 43.6%; P < 0.05) and were more likely to undergo AVR within the follow-up period. Within a propensity score-matched cohort, moderate AS was associated with an increased risk of HF hospitalization and mortality (HR: 1.24; 95% CI: 1.04-1.49; P = 0.01) and fewer days alive outside of the hospital (P < 0.0001). Aortic valve replacement (AVR) was associated with improved survival (HR: 0.60; CI: 0.36-0.99; P < 0.05).<br /><b>Conclusions</b><br />In patients with HFrEF, moderate AS is associated with increased rates of HF hospitalization and mortality. Further investigation is warranted to determine whether AVR in this population improves clinical outcomes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1235-1244</small></div>