<div><h4>A novel robotic radiation shielding device for electrophysiologic procedures: A prospective study.</h4><i>Laish-Farkash A, Harari E, Rahkovich M, Kogan Y, ... Ben-Assa E, Lev EI</i><br /><b>Background</b><br />A robotic Radiaction Shielding System (RSS) was developed to provide a full-body protection to all medical personnel during fluoroscopy-guided procedures, by encapsulating the imaging beam and blocking scattered radiation.<br /><b>Objectives</b><br />We aimed to evaluate its efficacy in real-world electrophysiologic (EP) laboratory- both during ablations and cardiovascular implantable electronic devices (CIED) procedures.<br /><b>Methods</b><br />A prospective controlled study comparing consecutive real-life EP procedures with and without RSS using highly sensitive sensors in different locations.<br /><b>Results</b><br />Thirty-five ablations and 19 CIED procedures were done without RSS installed and 31 ablations and 24 CIED procedures (17 with usage levels ≥70%) were done with RSS. Overall, there was 95% average usage level for ablations and 88% for CIEDs. For all procedures with ≥70% usage level and for all sensors, the radiation with RSS was significantly lower than radiation without RSS. For ablations, there was 87% reduction in radiation with RSS (76%-97% for different sensors). For CIEDs, there was 83% reduction in radiation with RSS (59%-92%). RSS usage did not increase procedure time and radiation time. User feedback showed a high-level of integration in the clinical workflow and safety profile for all types of EP procedures.<br /><b>Conclusions</b><br />For both CIED and ablation procedures the radiation with RSS was significantly lower than without RSS. Higher usage level brings higher reduction rates. Thus, RSS may have an important role in full-body protection to all medical personnel from scattered radiation during EP and CIED procedures. Until more data is available, it is recommended to maintain existing standard shielding.<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 01 Jul 2023; 261:127-136</small></div>

<div><h4>Does Targeted Positioning of the Left Ventricular Pacing Lead Towards the Latest Local Electrical Activation in Cardiac Resynchronization Therapy Reduce the Incidence of Death or Hospitalization for Heart Failure?</h4><i>Kronborg MB, Frausing MHJP, Svendsen JH, Johansen JB, ... Skals RG, Nielsen JC</i><br /><b>Background</b><br />Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement.<br /><b>Methods</b><br />The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a non-apical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and non-planned HF hospitalization. Patients are followed for a minimum of two years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024.<br /><b>Conclusions</b><br />The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or non-planned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 21 May 2023; epub ahead of print</small></div>

<div><h4>Operational Challenges and Mitigation Measures During the COVID-19 Pandemic - Lessons From DELIVER.</h4><i>Bhatt AS, Lindholm D, Nilsson A, Zaozerska N, ... McMurray JJV, Solomon SD</i><br /><AbstractText>Catastrophic disruptions in care delivery threaten operational efficiency and potentially the validity of clinical research efforts, particularly randomized clinical trials. Most recently, the COVID-19 pandemic affected essentially all aspects of care delivery and clinical research conduct. While consensus statements and clinical guidance documents have detailed potential mitigation measures, few real-world experiences of cardiovascular clinical trial adaptations in the context of the COVID-19 pandemic exist, particularly among, large, global registrational trials. We outline the operational impact of COVID-19 and resultant mitigation measures in the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial, one of the largest and most globally diverse experiences with COVID-19 of any cardiovascular clinical trial to date. Specifically, we address the needed coordination between academic investigators, trial leadership, clinical sites, and the supporting sponsor to ensure the safety of participants and trial staff, to maintain the fidelity of trial operations, and to prospectively adapt statistical analyses plans to understand impact of COVID-19 and the pandemic at large on trial participants. These discussions include key operational issues including ensuring delivery of study medications, adaptations to study visits, enhanced COVID-19 related endpoint adjudication, and protocol and analytical plan revisions. These findings may have important implications for establishing consensus on prospective contingency planning in future clinical trials.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 21 May 2023; epub ahead of print</small></div>

<div><h4>Cardiac Complications in Children with Acute COVID-19 vs. Multisystem Inflammatory Syndrome in Children (MIS-C).</h4><i>Hensley M, Goodman M, Madani R, Jaggi P, ... Zhang Q, Oster ME</i><br /><b>Background</b><br />Cardiac involvement can lead to significant morbidity in children with acute COVID-19 or Multisystem Inflammatory Syndrome in Children (MIS-C). However, the presentation and outcomes of cardiac involvement may differ among these two conditions. We aimed to compare the frequency and extent of cardiac involvement among children admitted with acute COVID-19 vs those with MIS-C.<br /><b>Methods</b><br />We conducted a cross sectional study of patients admitted to our hospital from March 2020 to August 2021 with symptomatic acute COVID-19 or MIS-C. Cardiac involvement was defined by presence of one or more of the following: elevated troponin, elevated brain natriuretic peptide, reduced left ventricular ejection fraction on echocardiogram, coronary dilation on echocardiogram, or abnormal electrocardiogram reading.<br /><b>Results</b><br />Among 346 acute COVID-19 patients with median age of 8.9 years and 304 MIS-C patients with median age of 9.1 years, cardiac involvement was present in 33 acute COVID-19 patients (9.5%) and 253 MIS-C patients (83.2%). The most common cardiac abnormality was abnormal electrocardiogram in acute COVID-19 patients (7.5%) and elevated troponin in MIS-C patients (67.8%). Among acute COVID-19 patients, obesity was significantly associated with cardiac involvement. Among MIS-C patients, non-Hispanic Black race/ethnicity was significantly associated with cardiac involvement.<br /><b>Conclusions</b><br />Cardiac involvement is much more common in children with MIS-C than in those with acute COVID-19. These results reinforce our standardized practice of performing full cardiac evaluations and follow-up in all patients with MIS-C but only in acute COVID-19 patients with signs or symptoms of cardiac involvement.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 20 May 2023; epub ahead of print</small></div>

<div><h4>Prevalence and clinical correlates and characteristics of \"Super Fontan\".</h4><i>Ohuchi H, Mori A, Kurosaki K, Shiraishi I, Nakai M</i><br /><b>Background</b><br />Super-Fontan (SF) is an excellent phenotype of patients with Fontan circulation and normal exercise capacity. This study aimed to clarify the prevalence and clinical correlates and characteristics of SF.<br /><b>Methods</b><br />We reviewed 404 Fontan patients who had undergone cardiopulmonary exercise testing, and the results were compared with clinical profiles.<br /><b>Results</b><br />Seventy-seven (19%) patients had SF, and the post-operative prevalence at 5, 10, 15, 20, and ≥ 25 years was 16 (35%), 30 (39%), 18 (19%), 13 (14%), and 0 (0%), respectively. Compared with non-SF, SF patients were younger (p < 0.001) and were mostly men (p < 0.05). SF was characterized by a current high arterial blood pressure and oxygen saturation (SaO<sub>2</sub>), low systemic ventricle (SV) end-diastolic pressure, favorable body composition, superior pulmonary function, preserved hepatorenal and hemostatic functions, and better glucose tolerance (p < 0.05-0.001). Pre-Fontan better SV function, low pulmonary artery resistance, and high SaO<sub>2</sub> were associated with current SF (p < 0.05-0.01). Furthermore, positive trajectory of exercise capacity and high daily activity during childhood were associated with current adult SF (p < 0.05). During the follow-up, 25 patients died, and 74 patients were unexpectedly hospitalized. There was no death in the SF group, and the rate of hospitalization was 67% lower than that of the non-SF group (p < 0.01-0.001).<br /><b>Conclusions</b><br />The prevalence of SF gradually decreased over time. SF was characterized by preserved multi-end-organ function and an excellent prognosis. Pre-Fontan hemodynamics and post-Fontan childhood daily activity were associated with being adult SF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 19 May 2023; epub ahead of print</small></div>

<div><h4>Clinical Outcomes Associated with Type II Myocardial Infarction Caused by Bleeding.</h4><i>Atallah J, Chiha T, Chen C, Siller-Matula JM, ... Januzzi JL, Wasfy JH</i><br /><b>Background</b><br />T2MI is caused by a mismatch between myocardial oxygen supply and demand. One subset of individuals is T2MI caused by acute hemorrhage. Traditional MI treatments including antiplatelets, anticoagulants, and revascularization can worsen bleeding. In this study, we aim to describe and report clinical outcomes of clinically-adjudicated T2MI patients due to bleeding, stratified by treatment approach.<br /><b>Methods</b><br />The Mass General Brigham Research Patient Data Registry followed by manual physician adjudication was used to identify individuals with T2MI caused by bleeding between 2009 and 2022. We defined 3 treatment groups: (1) an invasively managed group, (2) a pharmacologic group who received antiplatelet and anticoagulant therapy but no procedures, and (3) a conservatively managed group who received no procedures or anticoagulant/antiplatelet therapy. Baseline characteristics, diagnostic testing, treatment regimens, and clinical outcomes for 30-day, mortality, re-bleeding, and readmission were abstracted and outcomes were compared between treatment groups with chi-squared tests.<br /><b>Results</b><br />We identified 5712 individuals coded as having acute bleeding, of which 1017 (17.8%) were coded as having T2MI during their admission. After manual physician adjudication, 73 individuals (7.2%) met the criteria for T2MI caused by bleeding. Among the individuals with T2MI caused by bleeding, 18 were managed invasively, 39 received pharmacologic therapy alone, and 16 were managed conservatively. The invasively managed group experienced lower mortality rates (5.6% vs 37.5%, p = 0.021) yet higher readmission rates (22.2% vs 0%, p = 0.045) than the conservatively managed group. The pharmacologic group experienced lower mortality rates (10.3% vs 37.5%, p= 0.017) yet higher readmission rates (35.9% vs 0%, p = 0.005) than the conservatively managed group. Finally, there were no differences in terms of re-bleeding episodes between the 3 different groups.<br /><b>Conclusion</b><br />Individuals with T2MI associated with acute hemorrhage are a high-risk population. Those patients treated with standard procedures experienced higher readmission but lower mortality rates than patients with conservative management. Although these results are not risk-adjusted and likely reflect treatment-selection bias, they at least raise the possibility of testing ischemia-reduction approaches for such high-risk populations. Future clinical trials are required to validate any treatment strategies for T2MI caused by bleeding.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 16 May 2023; epub ahead of print</small></div>

<div><h4>Generalizability of an EHR-Network Dataset to the United States for Cardiovascular Disease Conditions: Comparison of Cerner Real World Data with the National Inpatient Sample.</h4><i>Shah NP, Peterson ED, Page C, Blanco R, Navar AM</i><br /><b>Background</b><br />Electronic Health Record (EHR) data from health systems are increasingly being combined for clinical research purposes. Yet, it remains unclear whether these large EHR data sources provide a representative assessment of national disease prevalence and treatment. To evaluate this, we compared Cerner RealWorldData (CRWD), a large EHR data source, to those seen in the National Inpatient Sample (NIS) for three cardiovascular conditions (myocardial infarction (MI), congestive heart failure (CHF), and stroke.<br /><b>Methods</b><br />Adult patients (age ≥18 years) hospitalized with MI, CHF, and stroke were identified in both CRWD (86 health systems) and the NIS (4,782 hospitals). Patient demographics, comorbidities, procedures, outcomes (length of stay and in-hospital mortality) and hospital type (teaching or non-teaching) were compared between NIS and CRWD patients.<br /><b>Results</b><br />Of 86 health systems participating in CRWD, 33 were excluded for potential data quality issues which accounted for about 11% of hospitalizations in the dataset, leaving 53 for inclusion in analysis which accounted for about 89% of hospitalizations in the dataset. Between January 1<sup>st</sup> 2017 and December 31<sup>st</sup> 2018, 116,956 MI, 188,107 CHF, and 93,968 stroke hospitalizations were identified in CRWD versus 2,245,300 MI, 4,310,745 CHF, and 1,333,480 stroke hospitalizations in the NIS. Patient demographics were similar among patients in CWRD and the NIS for all three cardiovascular groups except for ethnicity, with underrepresentation of Hispanic individuals in CRWD vs the NIS. Patients hospitalized in CRWD had a slightly higher proportion of coded co-morbidities compared with NIS hospitalizations due to a longer potential look-back period. For patients with MI, hospital mortality, length of stay, coronary artery bypass graft (CABG) rates, and percutaneous coronary intervention (PCI) rates were similar between CRWD and NIS. Additionally, there was similar in hospital mortality and length of stay for those with CHF and stroke hospitalizations between CRWD and NIS.<br /><b>Conclusions</b><br />On aggregate, characteristics of hospitalizations for MI, CHF, and stroke using EHR data from one nationwide EHR-derived database, CRWD, appears similar to characteristics of hospitalizations in the nationally representative NIS. Important limitations of CRWD include lack of geographic representativeness, under-representation of Hispanic adults, and the need to exclude health systems for missing data.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 15 May 2023; epub ahead of print</small></div>

<div><h4>Ultrathin-Strut versus Thin-Strut Drug-Eluting Stents for Multi- and Single-Stent Lesions: A Lesion-Level Subgroup Analysis of Two Randomized Trials.</h4><i>Häner JD, Rohla M, Losdat S, Iglesias JF, ... Windecker S, Pilgrim T</i><br /><b>Background</b><br />Whether ultrathin-strut stents are particularly beneficial for lesions requiring implantation of more than one stent is unknown.<br /><b>Methods</b><br />In a post-hoc lesion-level analysis of two randomized trials comparing ultrathin-strut biodegradable polymer Sirolimus-eluting stents (BP-SES) versus thin-strut durable polymer Everolimus-eluting stents (DP-EES), lesions were stratified into multi stent lesions (MSL) versus single-stent lesions (SSL). The primary endpoint was target lesion failure (TLF), a composite of lesion-related unclear/cardiac death, myocardial infarction (MI), or revascularization, at 24 months.<br /><b>Results</b><br />Among 5328 lesions in 3397 patients, 1492 (28%) were MSL (722 with BP-SES, 770 with DP-EES). At two years, TLF occurred in 63 lesions (8.9%) treated with BP-SES and 60 lesions (7.9%) treated with DP-EES in the MSL-group (subdistibution hazard ratio [SHR], 1.13; 95%CI, 0.77-1.64; p=0.53), and in 121 (6.4%) and 136 (7.4%) lesions treated with BP-SES and DP-EES respectively (SHR, 0.86; 95%CI, 0.62-1.18; p = 0.35) in the SSL-group (p for interaction = 0.241). While the rates of lesion-related MI or revascularization were significantly lower in SSL treated with BP-SES as compared to DP-EES (3.5% vs. 5.2%; SHR, 0.67; 95%CI 0.46-0.97; p=0.036), no significant difference was observed in MSL (7.1% vs. 5.4%; SHR, 1.31; 95%CI 0.85-2.03; p=0.216) with significant interaction between groups (p for interaction=0.014).<br /><b>Conclusions</b><br />Rates of TLF are similar between ultrathin-strut BP-SES and thin-strut DP-EES in MSL and SSL. The use of ultrathin-strut BP-SES versus thin-strut DP-EES did not prove to be particularly beneficial for the treatment of multi-stent lesions.<br /><b>Condensed abstract</b><br />Whether ultrathin-strut stents are particularly beneficial for lesions requiring implantation of more than one stent is unknown. In a post-hoc analysis of two randomized trials comparing ultrathin-strut biodegradable polymer Sirolimus-eluting stents (BP-SES) versus thin-strut durable polymer Everolimus-eluting stents (DP-EES), 5328 lesions in 3397 patients were stratified into multi-stent lesions (MSL) versus single-stent lesions (SSL). At 2 years, rates of target lesion failure were comparable between BP-SES and DP-EES in both MSL and SSL. In the SSL group, lesion-related myocardial infarction or revascularization were significantly lower in BP-SES as compared to DP-EES; in contrast, no significant difference between stents was observed in the MSL group (p for interaction = 0.014).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 14 May 2023; epub ahead of print</small></div>

<div><h4>PROTEUS Study: A Prospective Randomised Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.</h4><i>Woodward G, Bajre M, Bhattacharyya S, Breen M, ... Upton R, Leeson P</i><br /><b>Background</b><br />Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome.<br /><b>Methods/design</b><br />PROTEUS is a randomised, multicentre, two-armed, non-inferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomised 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis.<br /><b>Discussion</b><br />This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 14 May 2023; epub ahead of print</small></div>

<div><h4>Epidemiologic Trends and Risk Factors Associated with the Decline in Mortality from Coronary Heart Disease in the United States, 1990-2019.</h4><i>Ananth CV, Rutherford C, Rosenfeld EB, Brandt JS, ... Kostis WJ, Keyes KM</i><br /><b>Background</b><br />Despite the decline in the rate of coronary heart disease (CHD) mortality, it is unknown how the three strong and modifiable risk factors - alcohol, smoking, and obesity -have impacted these trends. We examine changes in CHD mortality rates in the United States and estimate the preventable fraction of CHD deaths by eliminating CHD risk factors.<br /><b>Methods</b><br />We performed a sequential time-series analysis to examine mortality trends among females and males aged 25-84 years in the United States, 1990-2019, with CHD recorded as the underlying cause of death. We also examined mortality rates from chronic ischemic heart disease (IHD), acute myocardial infarction (AMI), and atherosclerotic heart disease (AHD). All underlying causes of CHD deaths were classified based on the International Classification of Disease 9<sup>th</sup> and 10<sup>th</sup> revisions. We estimated the preventable fraction of CHD deaths attributable to alcohol, smoking, and high body-mass index (BMI) through the Global Burden of Disease.<br /><b>Results</b><br />Among females (3,452,043 CHD deaths; mean [standard deviation, SD] age 49.3 [15.7] years), the age-standardized CHD mortality rate declined from 210.5 in 1990 to 66.8 per 100,000 in 2019 (annual change -4.04%, 95% CI -4.05, -4.03; incidence rate ratio [IRR] 0.32, 95% CI, 0.41, 0.43). Among males (5,572,629 CHD deaths; mean [SD] age 47.9 [15.1] years), the age-standardized CHD mortality rate declined from 442.4 to 156.7 per 100,000 (annual change -3.74%, 95% CI, -3.75, -3.74; IRR 0.36, 95% CI, 0.35, 0.37). A slowing of the decline in CHD mortality rates among younger cohorts was evident. Correction for unmeasured confounders through a quantitative bias analysis slightly attenuated the decline. Half of all CHD deaths could have been prevented with the elimination of smoking, alcohol, and obesity, including 1,726,022 female and 2,897,767 male CHD deaths between 1990-2019.<br /><b>Conclusions</b><br />The decline in CHD mortality is slowing among younger cohorts. The complex dynamics of risk factors appear to shape mortality rates, underscoring the importance of targeted strategies to reduce modifiable risk factors that contribute to CHD mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 11 May 2023; epub ahead of print</small></div>

<div><h4>Patient Characteristics and Long-term Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation in a Failed Surgical Prosthesis versus in a Native Valve: A Danish nationwide study.</h4><i>Begun X, Butt JH, Kristensen SL, Weeke PE, ... Køber L, Fosbøl EL</i><br /><b>Background</b><br />Valve-in-valve-transcatheter aortic valve implantation (TAVI) is a feasible and increasingly used treatment option for failed surgical aortic prosthesis, but data from clinical practice are limited.<br /><b>Objectives</b><br />We aimed to examine patient characteristics and outcomes of patients undergoing TAVI in a surgical valve (valve-in-valve TAVI) compared with patients undergoing TAVI in a native valve.<br /><b>Methods</b><br />Using nationwide registries, we identified all Danish citizens, who underwent TAVI from January 1, 2008, to December 31, 2020.<br /><b>Results</b><br />A total of 6070 patients undergoing TAVI were identified; 247 (4%) patients had a history of SAVR (The valve-in-valve cohort). The median age of the study population was 81 (25<sup>th</sup>-75<sup>th</sup> percentile 77-85) and 55% were men. Patients with valve-in-valve-TAVI were younger but had a greater burden of cardiovascular comorbidities compared with patients with native-valve-TAVI. Within 30 days post-procedure, 11 (0.2%) and 748 (13.8%) patients who underwent valve-in-valve-TAVI and native-valve-TAVI, respectively, had a pacemaker implantation. The cumulative 30-day risk of death among patients with valve-in-valve-TAVI was 2.4% (95% CI: 1.0% to 5.0%) and 2.7% (95% CI: 2.3% to 3.1%) in patients with native-valve-TAVI, respectively. Correspondingly, the cumulative 5-year risk of death was 42.5% (95% CI: 34.2% to 50.6%) and 44.8% (95% CI: 43.2% to 46.4%), respectively. In multivariable Cox proportional hazard analysis, valve-in-valve-TAVI was not associated with a significantly different risk of death at 30 days (Hazard ratio (HR)= 0.95, 95% CI 0.41-2.19) and 5 years (HR=0.79, 95% CI 0.62-1.00) post-TAVI compared with native-valve-TAVI.<br /><b>Conclusions</b><br />TAVI in a failed surgical aortic prosthesis as compared to TAVI in a native valve, was not associated with significantly different short- and long-term mortality, suggesting that valve-in-valve-TAVI is a safe procedure.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 11 May 2023; epub ahead of print</small></div>

<div><h4>Attributable mortality benefit of digoxin treatment in hypoplastic left heart syndrome after the Norwood operation: An instrumental variable-based analysis using data from the Pediatric Health Information Systems Database.</h4><i>O\'Byrne ML, Song L, Huang J, Lemley B, ... Rome JJ, Glatz AC</i><br /><b>Introduction</b><br />Observational studies have demonstrated an association between use of digoxin and reduced interstage mortality after Norwood operation for hypoplastic left heart syndrome (HLHS). Digoxin use has increased significantly but remains variable between different hospitals, independent of case-mix. Instrumental variable analyses have the potential to overcome unmeasured confounding, the major limitation of previous observational studies and to generate an estimate of the attributable benefit of treatment with digoxin.<br /><b>Methods</b><br />A cohort of neonates with HLHS born from 1/1/2007 to 12/31/2021 who underwent Norwood operation at Pediatric Health Information Systems Database hospitals and survived >14 days after operation were studied. Using hospital-specific, 6-month likelihood of administering digoxin as an instrumental variable, analyses adjusting for both unmeasured confounding (using the instrumental variable) and measured confounders with multivariable logistic regression were performed.<br /><b>Results</b><br />The study population included 5,148 subjects treated at 47 hospitals of which 63% were male and 46% non-Hispanic white. Of these, 44% (n=2,184) were prescribed digoxin. Treatment with digoxin was associated with superior 1-year transplant-free survival in unadjusted analyses (85% vs. 82%, p=0.02). This survival benefit persisted in an instrumental-variable analysis (OR: 0.71, 95% CI: 0.54-0.94, p=0.01), which can be converted to an absolute risk reduction of 5% (number needed to treat of 20).<br /><b>Conclusion</b><br />In this observational study of patients with HLHS after Norwood using instrumental variable techniques, a significant benefit in one-year transplant-free survival attributable to digoxin was demonstrated. In the absence of clinical trial data, this should encourage the use of digoxin in this vulnerable population.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 09 May 2023; epub ahead of print</small></div>

<div><h4>Contemporary Use of Cardiovascular Risk Reduction Strategies in Type 2 Diabetes. Insights from The Diabetes Collaborative Registry.</h4><i>Arnold SV, Gosch K, Kosiborod M, Wong ND, ... Rajpura J, Vaduganathan M</i><br /><b>Background</b><br />Cardiovascular disease remains the primary source of morbidity and mortality in type 2 diabetes (T2D). We characterized the change over time in the use of evidence-based therapies to reduce cardiovascular risk in US patients with T2D.<br /><b>Methods</b><br />Data from a longitudinal outpatient diabetes registry were used to calculate the prescription of SGLT2i or GLP-1RA over time and among those with high-risk comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], chronic kidney disease [CKD]) and a diabetes cardiovascular composite score (DCCS; calculated as: #eligible medications prescribed/#eligible medications x 100 for SGLT2i, GLP-1RA, statin, antiplatelet/anticoagulant therapy, ACEi/ARB/ARNI). Scores ranged from 0% to 100% (higher=more optimal care).<br /><b>Results</b><br />Among 1,001,542 outpatients from 391 US sites, 51.7% patients had ASVCD, 17.7% HF, and 23.0% CKD. The percentage of patients prescribed an SGLT2i or GLP-1RA increased over time (7.3% in 2013 to 28.8% in 2019), and 18.3% of patients with ASCVD, HF, or CKD were on at least one of these medications at last follow-up vs. 25.5% of patients without any of these comorbidities. Mean DCCS was 54±36%; 54±25% in patients with ASCVD, HF, or CKD vs. 52±50% in patients without any of these comorbidities (p<0.001 for both). In a hierarchical linear model, male sex, and a diagnosis of CKD were independently associated with higher DCCS whereas a diagnosis of HF or ASCVD was associated with a lower DCCS.<br /><b>Conclusions</b><br />In a large, contemporary cohort of patients with T2D, we found improvement in the use of SGLT2i and GLP-1RA but unexpectedly lower use in patients with ASCVD, heart failure, and CKD, highlighting a treatment-risk paradox. Further education is needed to shift the understanding of these medications as tools for glucose-lowering to cardiovascular risk reduction and to improve their implementation in clinical practice.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 08 May 2023; epub ahead of print</small></div>

<div><h4>Effects of COVID-19 on Heart Failure Admissions.</h4><i>Chouairi F, Pinsker B, Miller PE, Fudim M</i><br /><AbstractText>Despite significant investigation into the effects of COVID-19 on cardiovascular disease, there is a paucity of national data specifically examining its effects on heart failure (HF) hospitalizations. Previous cohort study data demonstrate worsened outcomes in HF patients with recent COVID-19 infection. To better understand this association, this study aimed to utilize a nationally representative database to examine demographics, outcomes, and healthcare utilization in hospitalizations for HF with a co-diagnosis of COVID-19.</AbstractText><br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 06 May 2023; epub ahead of print</small></div>

<div><h4>Determinants and prognostic value of albuminuria in adult patients with congenital heart disease.</h4><i>Ohuchi H, Mori A, Fujita A, Kurosaki K, Shiraishi I, Nakai M</i><br /><b>Background</b><br />The determinants and prognostic value of albuminuria remain unclear in patients with adult congenital heart disease (ACHD), especially in those with Fontan circulation (FC).<br /><b>Methods</b><br />We retrospectively reviewed 512 consecutive ACHD patients and investigated the determinants of urinary albumin-to-creatinine ratio (ACR) and albuminuria (MAU) and their association with all-cause mortality. Demographic data and laboratory and hemodynamic parameters were collected. Regression analysis and Cox proportional hazard models were used to identify the relationship between log ACR and variables, and clinical factors and all-cause mortality, respectively.<br /><b>Results</b><br />Body mass index, aortic systolic blood pressure (ASP), arterial oxygen saturation (SaO<sub>2</sub>), glycated hemoglobin (HbA1c), B-type natriuretic peptide, and diuretic use were independently associated with log ACR. ASP, SaO<sub>2</sub>, and HbA1c were independently associated with MAU (p < 0.05 - 0.001). The prevalence of MAU was highest in unrepaired patients with low SaO<sub>2</sub> (50%; p < 0.0001). Log ACR and MAU were associated with exercise capacity and all-cause mortality (p < 0.0001 for both) independent of renal function. Patients with ACHD, MAU, and renal dysfunction (n = 23) had the highest risk of all-cause mortality, while those without MAU or renal dysfunction had the lowest risk (p < 0.0001). These prognostic values remained significant in separate analyses of Fontan and biventricular circulation (p < 0.0001).<br /><b>Conclusions</b><br />ASP, SaO<sub>2</sub>, and HbA1c levels were independently associated with MAU in ACHD patients. MAU and log ACR were associated with all-cause mortality in patients with Fontan and biventricular circulation, independent of renal dysfunction.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 04 May 2023; epub ahead of print</small></div>

<div><h4>Mortality in patients with chronic obstructive pulmonary disorder undergoing TAVR: the importance of COPD exacerbation.</h4><i>Lauridsen MD, Valentin JB, Strange JE, Jacobsen PA, ... Johnsen SP, Fosbøl E</i><br /><b>Background</b><br />Severe chronic obstructive pulmonary disease (COPD) has been associated with futile outcome after transcatheter aortic valve replacement (TAVR). Data on outcomes according to COPD severity are warranted to aid identification of patients who may not benefit from TAVR. We aimed to examine the association between risk of COPD exacerbation and 1-year mortality after TAVR.<br /><b>Methods</b><br />Using Danish nationwide registries we identified patients undergoing first-time TAVR during 2008‒2021 by COPD status. COPD severity levels were defined as low or high risk of acute exacerbation of COPD (AE-COPD) and treatment intensity levels (none or short-term, mono/dual, triple therapy, or home oxygen). Kaplan-Meier functions and adjusted Cox regression models were used to assess 1-year mortality comparing COPD severity groups with patients without COPD.<br /><b>Results</b><br />We identified 7,047 patients with TAVR of whom 644 had a history of COPD (low risk of AE-COPD: 439, high risk of AE-COPD: 205). The median age of the TAVR cohort was 81.4 years (IQR: 76.8‒85.1) and 55.8% were males. One-year mortality for TAVR patients without COPD was 8.5% (95% CI: 7.8‒9.2) and 15.4% (95% CI: 12.5‒18.2) for those with COPD (adjusted HR: 1.63 (95% CI: 1.28‒2.07)). Patients with low or high risk of AE-COPD had 1-year mortality of 13.1% (95% CI: 9.8‒16.3) and 20.2% (95% CI: 14.6‒25.8) corresponding to adjusted HRs of 1.31 (95% CI: 0.97‒1.78) and 2.44 (95% CI: 1.70‒3.50) compared with patients without COPD. Patients with high risk of AE-COPD and no/short term therapy or use of home oxygen represented the subgroups of patients with the highest 1-year mortality (31.6% (95% CI: 14.5‒48.7) and 30.9% (95% CI: 10.3‒51.6)).<br /><b>Conclusion</b><br />Among patients undergoing TAVR, increasing risk of exacerbation with COPD was associated with increasing 1-year mortality compared with non-COPD patients. Patients with a high risk of exacerbation with COPD not using any guideline recommended COPD medication and those using home oxygen had the highest 1-year mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 26 Apr 2023; epub ahead of print</small></div>

<div><h4>Electronic Health Record Characterization and Outcomes of Heart Failure with Preserved Ejection Fraction.</h4><i>Rao VN, Cyr D, Wruck L, Sanders G, ... Parikh K, Felker GM</i><br /><b>Background</b><br />Electronic health record (EHR)-based identification of heart failure with preserved ejection fraction (HFpEF) in the clinical setting may facilitate screening for clinical trials by improving the understanding of its epidemiology and outcomes; yet, previous data have yielded variable results. We sought to characterize groups identified with HFpEF by different EHR screening strategies and their associated long-term outcomes across a large and diverse population.<br /><b>Methods</b><br />We retrospectively analyzed 116,499 consecutive patients from an academic referral center who underwent echocardiography, and 9,263 patients who underwent echocardiography within 6 months of right heart catheterization (RHC), between 2008-2018. EHR-based screening strategies identified patients with HFpEF using 1) International Classification of Diseases (ICD)-9/10 codes, 2) H<sub>2</sub>FpEF score ≥6 and ejection fraction (EF) ≥50%, or 3) RHC wedge pressure ≥15 mmHg and EF ≥50%, when available. Primary outcomes were 1) cumulative incident heart failure hospitalization (HFH), and 2) death, over 10 years.<br /><b>Results</b><br />There were 33,461 (29%) patients who met either ICD or H<sub>2</sub>FpEF-HFpEF definition, of whom 5,310 (16%) met both criteria. Compared to ICD-HFpEF, patients with H<sub>2</sub>FpEF-HFpEF were more likely older (median age 72 vs. 67), White (78% vs. 64%), and had atrial fibrillation (97% vs. 41%). Among those also with RHC, 6,353 (69%) patients met any HFpEF criteria, of whom only 783 (12%) satisfied all three criteria. Female sex was more common among RHC-HFpEF (55%) compared to other methods (H<sub>2</sub>FpEF-HFpEF, 47%; ICD-HFpEF, 43%). Atrial fibrillation was substantially higher among HFpEF identified by the H<sub>2</sub>FpEF score (97%) compared to other methods (49% for ICD and 47% for RHC). Across HFpEF screening methods, 10-year cumulative incidence rates for HFH was 32 to 45% for echocardiography only and 43 to 52% for echocardiography and RHC populations; 10-year risk of death was 54 to 56% for echocardiography only and 52 to 57% for echocardiography and RHC populations.<br /><b>Conclusions</b><br />Different EHR-based HFpEF definitions identified cohorts with modest overlap and varying baseline characteristics. Yet, long-term risk for HFH and death were similarly high for cohorts identified among both populations undergoing echocardiography only or echocardiography and RHC. These data aid in identifying relevant subgroups in clinical trials of HFpEF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 26 Apr 2023; epub ahead of print</small></div>

<div><h4>Prognostic significance of serial NT-proBNP levels in patients with acute myocardial infarction: A prospective study.</h4><i>Li N, Chen R, Li J, Zhao X, ... Zhao H, Yan H</i><br /><b>Objects</b><br />This study aimed to investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at different sampling times and prognosis in patients with acute myocardial infarction (AMI) undergoing emergency percutaneous coronary intervention (PCI).<br /><b>Methods and results</b><br />Between March 2017 and January 2020, 1105 patients with AMI who underwent emergency PCI were included. NT-proBNP levels were measured on days 0, 1, 2, 3, and 7. A composite of all-cause death, MI recurrence (reMI), and rehospitalization due to heart failure, known as major adverse cardiovascular events (MACE), was recorded. During the 36.8-month follow-up, 175 patients (15.8%) experienced MACEs. When patients were grouped based on quartiles of NT-proBNP levels on days 0 and 7, the results demonstrated that patients in quartile 4 showed a substantially increased MACE risk compared to those in quartile 1 [hazard ratio (HR) 2.27, 95% confidence interval (CI):1.27-4.08, P = 0.006; HR 2.20, 95%CI:1.23-3.94, P = 0.008]. There were U-shaped relationships between the HR for MACE and NT-proBNP levels on days 2, 3, and 7, as well as peak NT-proBNP (P <sub>for nonlinearity</sub> = 0.007, 0.006, 0.004, and 0.009, respectively). A similar relationship was observed in the HR for reMI and NT-proBNP levels on days 2 and 3. For MACE at 3 years, serial NT-proBNP levels improved the predictive accuracy of the Global Registry of Acute Coronary Events risk (GRACE) score [concordance index (C-index): 0.711; continuous net reclassification improvement (NRI): 0.192, 95% CI: 0.022-0.445; integrated discrimination improvement (IDI): 0.034, 95% CI: 0.016-0.064]. For all-cause death at 3 years, the combination of NT-proBNP and GRACE score showed excellent performance, with C-index, continuous NRI, and IDI values of 0.801, 0.373 (95%CI: 0.072-0.853), and 0.051 (95%CI: 0.025-0.091), respectively.<br /><b>Conclusions</b><br />Early and sequential measurement of NT-proBNP levels could assist in predicting MACE risk. Moreover, the relationship between MACE risk and NT-proBNP levels was U-shaped.<br /><b>Clinical trial registration</b><br />clinicaltrials.gov NCT: 03593928.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 26 Apr 2023; epub ahead of print</small></div>

<div><h4>The Remote Exercise SWEDEHEART study - Rationale and design of a multicenter registry-based cluster randomized crossover clinical trial (RRCT).</h4><i>Bäck M, Leosdottir M, Ekström M, Hambraeus K, ... Östlund O, James S</i><br /><b>Background</b><br />Despite proven benefits of exercise-based cardiac rehabilitation (EBCR), few patients with myocardial infarction (MI) participate in and complete these programs.<br /><b>Study design and objectives</b><br />The Remote Exercise SWEDEHEART study is a large multicenter registry-based cluster randomized crossover clinical trial with a planned enrollment of 1500 patients with a recent MI. Patients at intervention centers will be offered supervised EBCR, either delivered remotely, center-based or as a combination of both modes, as self-preferred choice. At control centers, patients will be offered supervised center-based EBCR, only. The duration of each time period (intervention/control) for each center will be 15 months and then cross-over occurs. The primary aim is to evaluate if remotely delivered EBCR, offered as an alternative to center-based EBCR, can increase participation in EBCR sessions. The proportion completers in each group will be presented in a supportive responder analysis. The key secondary aim is to is to investigate if remote EBCR is as least as effective as center-based EBCR, in terms of physical fitness and patient-reported outcome measures. Follow-up of major adverse cardiovascular events (cardiovascular- and all-cause mortality, recurrent hospitalization for acute coronary syndrome, heart failure hospitalization, stroke, and coronary revascularization) will be performed at 1 and 3 years. Safety monitoring of serious adverse events will be registered, and a cost-effectiveness analysis will be conducted to estimate the cost per quality-adjusted life-year (QALY) associated with the intervention compared with control.<br /><b>Conclusions</b><br />The cluster randomized crossover clinical trial Remote Exercise SWEDEHEART study is evaluating if participation in EBCR sessions can be increased, which may contribute to health benefits both on a group level and for individual patients including a more equal access to health care.<br /><b>Trial registration</b><br />The study is registered at ClinicalTrials.gov (Identifier: NCT04260958).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 25 Apr 2023; epub ahead of print</small></div>

<div><h4>Incidence, Source, and Prognostic Impact of Major Bleeding Across the Spectrum of Aortic Stenosis.</h4><i>Coisne A, Aghezzaf S, Butruille L, Woitrain E, ... Montaigne D, Bauters C</i><br /><b>Background</b><br />Severe aortic stenosis (AS) has been associated with bleeding. However, there is a lack of prospective assessment of bleeding events and their clinical significance in a large population of outpatients with variable degree of AS severity.<br /><b>Objectives</b><br />To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with variable degree of AS severity.<br /><b>Methods</b><br />Between May 2016 and December 2017, consecutive outpatients were included. Major bleeding was defined as type ≥3 bleed using the Bleeding Academic Research Consortium (BARC) definition. Cumulative incidence was calculated with death as the competing event. Data was censored at time of aortic valve replacement (AVR).<br /><b>Results</b><br />Among 2,830 patients, 46 major bleeding events occurred (0.7%/year) during a median follow-up of 2.1 years (IQR 1.4 to 2.7). Most frequent sites of bleeding were gastrointestinal (50%) and intracranial (30.4%). Major bleeding was significantly associated with all-cause mortality (hazard ratio: 5.93 (95% confidence interval 3.64 to 9.65); P<0.001). AS severity was associated with major bleedings (P=0.041). By multivariable analysis, severe AS was an independent determinant of major bleeding (hazard ratio vs mild AS: 3.59 (95% confidence interval 1.56 to 8.29); P=0.003). The increased risk of bleeding associated with severe AS was significantly exacerbated in patients using oral anticoagulation.<br /><b>Conclusion</b><br />In AS patients, major bleeding is rare but a strong independent predictor of death. AS severity is a determinant of bleeding events. Severe AS and oral anticoagulation should be identified as an association at very high risk of major bleeding.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 24 Apr 2023; epub ahead of print</small></div>

<div><h4>The Seventh Prevention of Syncope Trial (POST VII) - a randomized clinical trial of atomoxetine for the prevention of vasovagal syncope: Rationale and study design.</h4><i>Sandhu RK, Raj SR, Hamzeh R, Sheldon RS</i><br /><b>Background</b><br />Vasovagal syncope (VVS) is common, recurs, and is associated with markedly reduced quality of life, anxiety, and frequent injuries. The few pharmacological therapies for VVS proven to have a moderate benefit in reducing recurrences are limited to patients without coexisting conditions such as hypertension or heart failure. Although there is some data to suggest Atomoxetine, a norepinephrine reuptake transport inhibitor (NET), may be a promising treatment option, an adequately powered randomized placebo-controlled trial is needed.<br /><b>Study design</b><br />POST VII is a multicenter, randomized, double-blind, placebo-controlled, crossover study that will randomize 180 patients with VVS and at least 2 syncopal spells in the preceding year to a target daily dose of atomoxetine 80 mg daily or to a matching placebo, with an observation period of 6 months in each phase and with a 1-week washout period between phases. The primary endpoint will be the proportion of patients with at least one syncope recurrence in each arm analyzed with an intention-to-treat approach. The secondary endpoints include total syncope burden, quality of life, cost, and cost-effectiveness.<br /><b>Power calculations</b><br />Assuming a 33% relative risk reduction in syncope recurrence with atomoxetine, and a dropout rate of 16%, the enrollment of 180 patients will give an 85% power of reaching a positive conclusion about atomoxetine, with p=0.05.<br /><b>Conclusion</b><br />This will be the first adequately powered trial to determine whether atomoxetine is effective in preventing VVS. If proven effective, atomoxetine might become the first-line pharmacological treatment for recurrent VVS.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 24 Apr 2023; epub ahead of print</small></div>

<div><h4>Inotrope versus Placebo Therapy in Cardiogenic Shock: Rationale and Study Design of the CAPITAL DOREMI2 Trial.</h4><i>Parlow S, Santo PD, Sterling LH, Goodliffe L, ... Hibbert B, Mathew R</i><br /><b>Background</b><br />Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS.<br /><b>Methods and design</b><br />This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge.<br /><b>Implication</b><br />This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 22 Apr 2023; epub ahead of print</small></div>

<div><h4>Fatal, ischemic and bleeding risk of patients meeting the selection criteria of the TWILIGHT trial: insights from a large PCI registry.</h4><i>Spirito A, Koh WJ, Sartori S, Vogel B, ... Dangas G, Mehran R</i><br /><b>Aims</b><br />The TWILIGHT trial (NCT02270242) demonstrated that in selected high-risk patients undergoing percutaneous coronary intervention (PCI) ticagrelor monotherapy significantly reduced bleeding complications without ischemic harm as compared to ticagrelor plus aspirin after 3 month of dual antiplatelet therapy. The aim of this analysis was to assess the applicability of the findings TWILIGHT trial to a real-world population.<br /><b>Methods and results</b><br />Patients undergoing PCI at a tertiary center between 2012 and 2019 and not meeting any TWILIGHT exclusion criterion (oral anticoagulation treatment, ST-segment elevation myocardial infarction [MI], cardiogenic shock, dialysis, prior stroke, or thrombocytopenia) were included. We stratified patients into 2 groups based on whether they fulfilled the TWILIGHT inclusion criteria (high-risk) or not (low-risk). The primary outcome was all-cause death; the key secondary outcomes were MI and major bleeding at 1 year after PCI. Out of 13,136 included patients, 11,018 (83%) were at high risk. At 1-year, these patients had an approximately 3 folds greater hazard of death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70-7.77) and MI (1.8% vs 0.6%, HR 2.81, 95% CI 1.56-5.04) and a nearly 2 folds higher risk of major bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32-2.62) as compared to low-risk patients.<br /><b>Conclusion</b><br />Among patients not meeting the TWILIGHT exclusion criteria from a large PCI registry, the high-risk inclusion criteria of the TWILIGHT trial were met by the majority of patients and were associated with an increased risk of mortality and myocardial infarction and a moderately elevated risk of bleeding.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 22 Apr 2023; epub ahead of print</small></div>

<div><h4>Pre-Percutaneous Coronary Intervention Zalunfiban Dose-Response Relationship to Target Vessel Blood Flow at Initial Angiogram in ST-Elevation Myocardial Infarction - A Post Hoc Analysis of the Cel-02 Phase IIa Study.</h4><i>Rikken SA, Bor WL, Selvarajah A, Zheng KL, ... Van \'t Hof A, Berg JT</i><br /><b>Background</b><br />Zalunfiban (RUC-4) is a novel, subcutaneously administered glycoprotein IIb/IIIa inhibitor (GPI) designed for pre-hospital treatment to initiate reperfusion in the infarct-related artery (IRA) before primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI). Since GPIs have been reported to rapidly reperfuse IRAs, we assessed whether there was a dose-dependent relationship between zalunfiban treatment and angiographic reperfusion indices and thrombus grade of the IRA at initial angiogram in patients with STEMI.<br /><b>Methods</b><br />This was a post hoc analysis from the open-label Phase IIa study that investigated the pharmacodynamics, pharmacokinetics, and tolerability of three doses of zalunfiban - 0.075, 0.090 and 0.110 mg/kg - in STEMI patients. This analysis explored dose-dependent associations between zalunfiban and three angiographic indices of the IRA, namely coronary and myocardial blood flow and thrombus burden. Zalunfiban was administered in the cardiac catheterization laboratory prior to vascular access, ∼10-15 minutes before the initial angiogram. All angiographic data were analyzed by a blinded, independent, core laboratory.<br /><b>Results</b><br />24 out of 27 STEMI patients were evaluable for angiographic analysis (0.075 mg/kg [n=7], 0.090 mg/kg [n=9], and 0.110 mg/kg [n=8]). TIMI flow grade 2 or 3 was seen in 1/7 patients receiving zalunfiban at 0.075 mg/kg, in 6/9 patients receiving 0.090 mg/kg, and in 7/8 patients receiving 0.110 mg/kg (p<sub>trend</sub> = 0.004). A similar trend was observed based on TIMI flow grade 3. Myocardial perfusion was also related to zalunfiban dose (p<sub>trend</sub> = 0.005) as reflected by more frequent TIMI myocardial perfusion grade 3. Consistent with the dose-dependent trends in greater coronary and myocardial perfusion, TIMI thrombus ≥4 grade was inversely related to zalunfiban dose (p<sub>trend</sub> = 0.02).<br /><b>Conclusion</b><br />This post hoc analysis found that higher doses of zalunfiban administered in the cardiac catheterization lab prior to vascular access were associated with greater coronary and myocardial perfusion, and lower thrombus burden at initial angiogram in patients with STEMI undergoing primary percutaneous coronary intervention.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 21 Apr 2023; epub ahead of print</small></div>

<div><h4>Adipose tissue n-3/n-6 fatty acids ratios versus n-3 fatty acids fractions as predictors of myocardial infarction.</h4><i>Chiusolo S, Bork CS, Gentile F, Lundbye-Christensen S, ... Schmidt EB, De Caterina R</i><br /><b>Background</b><br />Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions.<br /><b>Methods</b><br />Subcutaneous adipose tissue biopsies were obtained in a random sample (n=3,500) of the Diet, Cancer and Health cohort (n=57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid (LA) was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design.<br /><b>Results</b><br />A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA+DHA, EPA, EPA/AA, DHA/AA and (EPA+DPA+DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel\'s C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA+DHA)/AA and (EPA+DPA+DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake.<br /><b>Conclusions</b><br />Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 20 Apr 2023; epub ahead of print</small></div>

<div><h4>Physician Responses to Apple Watch-Detected Irregular Rhythm Alerts.</h4><i>Demkowicz PC, Dhruva SS, Spatz ES, Beatty AL, Ross JS, Khera R</i><br /><b>Background</b><br />While the US Food and Drug Administration (FDA) has cleared smartwatch software for detecting atrial fibrillation (AF), there is lack of guidance on management by physicians. We sought to evaluate the approach to management of Apple Watch alerts for AF by physicians and assess whether respondent and case characteristics were associated with their approach.<br /><b>Methods</b><br />We conducted a case-based survey of physicians practicing primary care, emergency medicine, and cardiology at 2 large academic centers (Yale and University of California San Francisco) between September to December 2021. Cases described asymptomatic patients receiving Apple Watch AF alerts; cases varied in sex, race, medical history, and notification frequency. We evaluated physician responses among prespecified diagnostic testing, referral, and treatment options.<br /><b>Results</b><br />We emailed 636 physicians, of whom 95 (14.9%) completed the survey, including 39 primary care, 25 emergency medicine, and 31 cardiology physicians. Among a total of 192 cases (16 unique scenarios), physicians selected at least one diagnostic test in 191 (99.5%) cases and medications in 48 (25.0%). Physicians in primary care, emergency medicine, and cardiology reported varying preference for patient referral (14%, 30%, and 16%, respectively; P=.048), rhythm monitoring (84%, 46%, and 94%, respectively; P<.001), measurement of BNP (8%, 20%, and 2%; P=.003), and use of antiarrhythmics (16%, 4%, and 23%; P=.023). There were few physician differences in reported practices across patient demographics (sex and race), clinical complexity, and alert frequency of the clinical case.<br /><b>Conclusions</b><br />In hypothetical cases of patients presenting without clinical symptoms, physicians opted for further diagnostic testing and often to medical intervention based on Apple Watch irregular rhythm notifications. There was also considerable variation across physician specialties, suggesting a need for uniform clinical practice guidelines. Additional study is required before irregular rhythm notifications should be used in clinical settings.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 19 Apr 2023; epub ahead of print</small></div>

<div><h4>Design of A Multi-Institutional Neurocognitive Discovery Study in Adult Congenital Heart Disease (MINDS-ACHD).</h4><i>Cohen S, Gurvitz M, Burns KM, Wheaton O, ... Zaidi AN, Pediatric Heart Network Investigators and the Alliance for Adult Research in Congenital Cardiology</i><br /><b>Background</b><br />Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD.<br /><b>Methods</b><br />The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD. This multicenter cross-sectional pilot study is enrolling 500 young adults between 18 and 30 years with moderate or severe complexity CHD at 14 centers in North America. Enrollment includes 4 groups (125 participants each): 1) d-looped Transposition of the Great Arteries (d-TGA); 2) Tetralogy of Fallot (TOF); 3) single ventricle (SV) physiology; and 4) \"other moderately or severely complex CHD.\" Participants complete the standardized tests from the NIH Toolbox Cognitive Battery, the NeuroQoL, the Hospital Anxiety and Depression Scale, and the PROMIS Global QoL measure. Clinical and demographic variables are collected by interview and medical record review, and an optional biospecimen is collected for genetic analysis. Due to the COVID-19 pandemic, participation may be done remotely. Tests are reviewed by a Neurocognitive Core Laboratory.<br /><b>Conclusions</b><br />MINDS-ACHD is the largest study to date characterizing NCD in young adults with moderate or severely complex CHD in North America. Its results will provide valuable data to inform screening and management strategies for NCD in ACHD and improve lifelong care.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 19 Apr 2023; epub ahead of print</small></div>

<div><h4>Validation of the ARIC prediction model for sudden cardiac death in the European population: The ESCAPE-NET project: Predicting sudden cardiac death in European adults.</h4><i>Welten SJGC, Remmelzwaal S, Blom MT, van der Heijden AA, ... Elders PJM, for ESCAPE-NET investigators</i><br /><b>Background</b><br />Sudden cardiac death is responsible for 10-20% of all deaths in Europe. The current study investigates how well the risk of sudden cardiac death can be predicted. To this end, we validated a previously developed prediction model for sudden cardiac death from the Atherosclerosis Risk in Communities study (USA).<br /><b>Methods</b><br />Data from participants of the Copenhagen City Heart Study (CCHS) (n=9988) was used to externally validate the previously developed prediction model for sudden cardiac death. The model\'s performance was assessed through discrimination (C-statistic) and calibration by the Hosmer-Lemeshow goodness-of-fit (HL) statistics suited for censored data and visual inspection of calibration plots. Additional validation was performed using data from the Hoorn Study (N=2045), employing the same methods.<br /><b>Results</b><br />During ten years of follow-up of CCHS participants (mean age: 58.7 years, 56.2% women), 425 experienced SCD (4.2%). The prediction model showed good discrimination for sudden cardiac death risk (C-statistic: 0.81, 95% CI:0.79-0.83). Calibration was robust (HL statistic: p=0.8). Visual inspection of the calibration plot showed that the calibration could be improved. Sensitivity was 89.8%, and specificity was 60.6%. The positive and negative predictive values were 10.1% and 99.2%. Model performance was similar in the Hoorn Study (C-statistic: 0.81, 95% CI: 0.77-0.85 and the HL statistic: 1.00).<br /><b>Conclusion</b><br />Our study showed that the previously developed prediction model in North American adults performs equally well in identifying those at risk for sudden cardiac death in a general North-West European population. However, the positive predictive value is low.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 19 Apr 2023; epub ahead of print</small></div>

<div><h4>Moderate Intensity Exercise in Pregnant Patients with Cardiovascular Disease: A Pilot Study.</h4><i>Brown JY, Drakeley S, Duncan M, Knapp WP, ... Valente AM, Economy KE</i><br /><b>Background</b><br />Exercise in pregnancy has proven health benefits, yet the safety of exercise in patients with pre-existing cardiovascular disease (CVD) has not been established. Our aim was to determine the feasibility and safety profile of moderate intensity exercise during pregnancy in patients with CVD, compared with those without CVD.<br /><b>Methods</b><br />This is a prospective single center pilot study of a moderate intensity exercise regimen, with data collection through wearable fitness trackers and personal exercise logs in pregnant patients with and without pre-existing CVD. The primary outcome was Doppler umbilical artery systolic to diastolic (S/D) ratio measured between 32-34 weeks\' gestation. The secondary outcomes were adverse maternal and fetal events, trends in wearable fitness tracker data, C-reactive protein levels, and weight changes.<br /><b>Results</b><br />At baseline, the CVD group (62% congenital heart disease) took part in more pre-pregnancy walking, less weightlifting, and had a higher body mass index compared to the control group, and on average walked 539 fewer steps per day during pregnancy than the control group. Resting heart rate (HR) was found to increase in both groups up to 30 weeks\' gestation. The cardiovascular disease group displayed an overall lower exercise intensity, as measured by the ability to increase HR with exercise over resting heart rate one hour prior to exercise at study baseline (45% vs. 59% P<0.001). Umbilical artery S/D ratio was normal in both groups. No differences were seen in adverse events between groups.<br /><b>Conclusions</b><br />This pilot study of moderate intensity exercise in pregnant individuals with pre-existing CVD demonstrated that patients with CVD were not able to increase their HR during exercise throughout pregnancy compared to those in the control group. Although a small study group, this data supports the hypothesis that exercise interventions during pregnancy for patients with CVD are feasible without evidence abnormal fetal Doppler profiles. Further studies using wearable fitness trackers may provide the opportunity to understand how to safely tailor exercise programs to pregnant individuals with CVD.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 16 Apr 2023; epub ahead of print</small></div>

<div><h4>Coronary Angiography-Derived Index for Assessing Microcirculatory Resistance in Patients with Non-Obstructed Vessels: The FLASH IMR Study.</h4><i>Huang D, Gong Y, Fan Y, Zheng B, ... Huo Y, Ge J</i><br /><b>Background</b><br />Assessing index of microcirculatory resistance (IMR) is customarily performed using intracoronary wires fitted with sensors by at least 3 intracoronary injections of 3-4 ml of room-temperature saline during sustained hyperemia, which is time- and cost-consuming.<br /><b>Methods</b><br />The FLASH IMR study is a prospective, multicenter, randomized study to assess the diagnostic performance of coronary angiography-derived IMR (caIMR) in patients with suspected myocardial ischemia with non-obstructive coronary arteries using wire-based IMR as a reference. The caIMR was calculated by an optimized computational fluid dynamics model simulating hemodynamics during diastole based on coronary angiograms. TIMI frame count and aortic pressure were included in computation. caIMR was determined onsite in real time and compared blind to wire-based IMR by an independent core laboratory, using wire-based IMR ≥25 units as indicative of abnormal coronary microcirculatory resistance. The primary endpoint was the diagnostic accuracy of caIMR, using wire-based IMR as a reference, with a pre-specified performance goal of 82%.<br /><b>Results</b><br />A total of 113 patients underwent paired caIMR and wire-based IMR measurements. Order of performance of tests was based on randomization. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values of caIMR were 93.8% (95% CI: 87.7 -97.5%), 95.1% (95% CI: 83.5 - 99.4%), 93.1% (95% CI: 84.5 - 97.7%), 88.6% (95% CI: 75.4 - 96.2%) and 97.1% (95% CI: 89.9 - 99.7%). The receiver-operating curve for caIMR to diagnose abnormal coronary microcirculatory resistance had area under the curve of 0.963 (95% CI: 0.928 - 0.999).<br /><b>Conclusions</b><br />Angiography-based caIMR has a good diagnostic yield with wire-based IMR.<br /><b>Trial registration</b><br />Clinicaltrials.gov, Unique Identifier: NCT05009667.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 11 Apr 2023; epub ahead of print</small></div>

<div><h4>Left ventricular remodeling in end-stage liver disease and post-transplant mortality assessed using end-diastolic pressure-volume relation analysis: observational retrospective study.</h4><i>Shin WJ, Kwon HM, Kim SH, Jang HY, ... Song JG, Hwang GS</i><br /><b>Background</b><br />Diastolic dysfunction is regarded as an important predictor of outcome after liver transplantation (LT). We investigated the influence of liver disease severity on left ventricular diastolic properties using end-diastolic pressure-volume relationship (EDPVR) analysis in patients with end-stage liver disease (ESLD). Association between alterations of the EDPVR and mortality after LT was evaluated.<br /><b>Methods</b><br />In this observational retrospective cohort study, 3211 patients who underwent LT for ESLD were included in analysis. Variables derived from single-beat EDPVR (diastolic stiffness-coefficient [β] and end-diastolic volume at an end-diastolic pressure of 20 mmHg [EDVI<sub>20</sub>] indicating ventricular capacitance) were estimated using preoperative echocardiographic data. Alterations in EDPVR with increased stiffness (β >6.16) were categorized into 3 groups; leftward-shifted (EDVI<sub>20</sub> <51 mL/m<sup>2</sup>), rightward-shifted (EDVI<sub>20</sub> >69.7 mL/m<sup>2</sup>), and intermediate (EDVI<sub>20</sub> 51-69.7 mL/m<sup>2</sup>).<br /><b>Results</b><br />As the model for ESLD score increases, both EDVI<sub>20</sub> and β gradually increased, which indicated ventricular remodeling with larger capacitance and higher diastolic stiffness. Among patients with increased stiffness (β >6.16, n=1090), survival rates after LT were lower in leftward-shifted EDPVR than in rightward-shifted EDPVR (73.7% vs 82.9%; log-rank P=0.002). In the adjusted Cox proportional hazard model, risk of cumulative all-cause mortality at 11 years was the highest in leftward-shifted EDPVR (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.27-2.92), followed by intermediate EDPVR (HR: 1.55; 95% CI: 1.12-2.26), compared with rightward-shifted EDPVR. The SHapley Additive exPlanation model revealed that the variables associated with leftward-shifted EDPVR were diabetes, female sex, old age, and hypertension.<br /><b>Conclusions</b><br />As ESLD advances, diastolic ventricular properties are characterized by increased EDVI<sub>20</sub> and β on rightward-shifted EDPVR, indicating larger capacitance and higher stiffness. However, leftward-shifted EDPVR with left ventricle remodeling failure is associated with poor post-LT survival.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 10 Apr 2023; epub ahead of print</small></div>

<div><h4>Scale up of implementation of a multidimensional intervention to enhance hypertension and diabetes care at the primary care setting: a protocol for a cluster-randomized study in Brazil.</h4><i>da Fonseca SF, Pinho Ribeiro AL, Rodrigues Cimini CC, de Castro Soares TB, ... Batchelor J, Marcolino MS</i><br /><b>Background</b><br />Hypertension and diabetes mellitus (DM) are highly prevalent in low and middle-income countries (LMICs), and the proportion of patients with uncontrolled diseases is higher than in high-income countries. Innovative strategies are required to surpass barriers of low sources, distance and quality of healthcare. Our aim is to assess the uptake and effectiveness of the implementation of an integrated multidimensional strategy in the primary care setting, for the management of people with hypertension and diabetes mellitus in Brazil.<br /><b>Methods</b><br />This scale up implementation study called Control of Hypertension and diAbetes in MINas Gerais (CHArMING) Project has mixed-methods, and comprehends four steps: (1) needs assessment, including a standardized structured questionnaire and focus groups with healthcare practitioners; (2) baseline period, three months before the implementation of the intervention; (3) cluster randomized controlled trial (RCT) with a 12-month follow-up period; and (4) a qualitative study after the end of follow-up. The cluster RCT will randomize 35 centers to intervention (n= 18) or usual care (n= 17). Patients ≥18 years old, with diagnosis of hypertension and/or DM, of five Brazilian cities in a resource-constrained area will be enrolled. The intervention consists of a multifaceted strategy, with a multidisciplinary approach, including telehealth tools (decision support systems, short message service, telediagnosis), continued education with an approach to issues related to the care of people with hypertension and diabetes in primary care, including pharmacological and non-pharmacological treatment and behavioral change. The project has actions focused on professionals and patients.<br /><b>Conclusions</b><br />This study consists of a multidimensional strategy with multidisciplinary approach using digital health to improve the control of hypertension and/or DM in the primary health care setting. We expect to provide the basis for implementing an innovative management program for hypertension and DM in Brazil, aiming to reduce the present and future burden of these diseases in Brazil and other LMICs.<br /><b>Clinical trial identifier</b><br />This study was registered in ClinicalTrials.gov. (NCT05660928).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 10 Apr 2023; epub ahead of print</small></div>

<div><h4>Rationale and design of the Dynamic Coronary Roadmap for Contrast Reduction (DCR4Contrast) in PCI randomised controlled trial.</h4><i>Hennessey B, Messenger JC, Kirtane AJ, Parikh M, ... Eshuis P, Escaned J</i><br /><b>Background</b><br />The clinical and anatomic complexity of patients undergoing percutaneous coronary interventions (PCI) has increased significantly over the past two decades. Contrast induced nephropathy (CIN) significantly impacts prognosis after PCI, therefore minimising the risk of CIN is important in improving clinical outcomes. Dynamic Coronary Roadmap (DCR) is a PCI navigation support tool which may decrease CIN by projecting a virtual coronary roadmap on the moving angiogram, potentially reducing iodinated contrast volume during PCI.<br /><b>Study design and objectives</b><br />The Dynamic Coronary Roadmap for Contrast Reduction trial (DCR4Contrast) is a multi-center, prospective, unblinded, stratified 1:1 randomised controlled trial investigating if DCR use reduces the total contrast volume administered during PCI compared to PCI performed without DCR guidance. DCR4Contrast aims to recruit 394 patients undergoing PCI. The primary endpoint is the total undiluted iodinated contrast volume administered during the PCI, performed with or without DCR. As of November 14, 2022, 346 subjects have been enrolled.<br /><b>Conclusions</b><br />The DCR4Contrast study will investigate the potential contrast-sparing effect of the DCR navigation support tool in patients undergoing PCI. By reducing iodinated contrast administration, DCR has the potential to contribute to reduced risk of CIN and thus increase PCI safety.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 09 Apr 2023; epub ahead of print</small></div>

<div><h4>Relationship between the volume of cases and in-hospital mortality in patients with cardiogenic shock receiving short-term mechanical circulatory support.</h4><i>Araki T, Kondo T, Imaizumi T, Sumita Y, ... Petrie MC, Murohara T</i><br /><b>Background</b><br />We examined the relationship between annual case volume at each hospital and outcome in cardiogenic shock (CS) patients receiving mechanical circulatory support (MCS) devices.<br /><b>Methods</b><br />This cross-sectional study used the Japanese nationwide database to identify patients receiving short-term MCS for CS between April 2012 and March 2020. Of 65,837 patients, three sub-cohorts were created; the intra-aortic balloon pump (IABP) alone (n=48,643), the extracorporeal membrane oxygenation (ECMO) (n=16,871), and the Impella cohorts (n=696).<br /><b>Results</b><br />The median annual case volume was 13.5 (7.4-22.1) in the IABP alone cohort, 6.4 (3.4-11.0) in the ECMO cohort, and 7.5 (4.0-10.7) in the Impella cohort. The highest quintile for the volume of cases in the IABP alone and ECMO had the lowest in-hospital mortality (IABP alone, 25.1% in quintile 1 vs. 15.2% in quintile 5; ECMO, 73.7% in quintile 1 in 67.4% in quintile 5). Adjusted ORs for in-hospital mortality decreased as case volume increased (IABP alone, 0.63 [0.58-0.68] in quintile 5; ECMO, 0.73 [0.65-0.82] in quintile 5, with the lowest quintile as reference) but did not decrease significantly in the Impella (0.90 [0.58-1.39] in tertile 3, with the lowest tertile as reference). In the continuous models with the case volume as a continuous variable, adjusted ORs for in-hospital mortality decreased to 28 IABP cases/year and 12 ECMO/cases/year. They did not decrease or became almost flat above that.<br /><b>Conclusions</b><br />Higher volumes of IABP and ECMO are associated with a lower mortality. There is an upper limit to the decline. Centralizing patients with refractory CS in a particular hospital might improve patient outcomes in each region.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 07 Apr 2023; epub ahead of print</small></div>

<div><h4>Digital Health Nudging to increase physical activity in pediatric patients with congenital heart disease: A randomized controlled trial.</h4><i>Willinger L, Oberhoffer-Fritz R, Ewert P, Müller J</i><br /><b>Objective</b><br />Digital nudging is a modern e-health approach to increase physical activity (PA) in younger age groups. As activity promotion is particularly important in adolescents with congenital heart disease (CHD) this randomized-controlled trail examines if Digital Health Nudging via daily smartphone messages increases PA, activity-related self-efficacy (ArSE) and health-related quality of life (HrQoL) in adolescents with CHD.<br /><b>Methods</b><br />From May 2021 to April 2022, 97 patients (15.1 ± 2.0 years, 50% girls) with moderate or severe CHD were randomly allocated 1:1 to intervention (IG) or control group (CG). Daily PA was objectively assessed in minutes of moderate-to-vigorous PA (MVPA) by the wearable \"Garmin Vivofit jr. 2®\" over the entire study period. The IG received daily smartphone messages based on Bandura\'s social cognitive theory on the subject of PA over a period of 12-weeks.<br /><b>Results</b><br />According to the linear mixed model, the change of MVPA over the study period did not significantly differ between IG and CG when taking baseline MVPA into account (b=0.136, 95%-CI [-0.355; 0.627], p=0.587). Activity level was comparably high and showed only minor variability in both groups with 73.7 [62.3; 78.8] min/day in IG and 78.4 [66.6; 93.9] min/day in CG throughout the whole 12-weeks. Emotional well-being significantly increased over the study period in the IG (IG: Δ1.60 [-0.2; 6.3] vs. CG: Δ0.0 [-12.5; 6.3], p=0.043), but not total HrQoL (p=0.518) and ArSE (p=0.305).<br /><b>Conclusion</b><br />12-weeks of Digital Health Nudging did not increase PA, but improved feelings of emotional well-being in adolescents with CHD.<br /><b>Trial registration</b><br />Clinical Trials Identifier NCT04933786.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 06 Apr 2023; epub ahead of print</small></div>

<div><h4>Association of CHADS-VASc and HAS-BLED to Frailty and Frail Outcomes: From the TREAT-AF Study.</h4><i>Pundi K, Perino AC, Fan J, Din N, ... Heidenreich P, Turakhia MP</i><br /><b>Background</b><br />Morbidity and mortality associated with high CHA<sub>2</sub>DS<sub>2</sub>-VASc and HAS-BLED scores is not specific to atrial fibrillation (AF). Frailty could be an important contributor to this morbidity and mortality while being mechanistically independent from AF. We sought to evaluate the association of stroke and bleeding risk to non-cardiovascular frail events and the association of stroke prevention therapy to outcomes in frail patients with atrial fibrillation.<br /><b>Methods</b><br />Using the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the Veterans Health Administration, we identified patients with newly diagnosed AF from 2004-2014. Baseline frailty was identified using a previously validated claims-based index requiring ≥2 of 12 ICD-9 diagnoses. Logistic regressions modeled the association between CHA<sub>2</sub>DS<sub>2</sub>-VASc and modified HAS-BLED and frailty. Cox proportional hazard regressions were used to evaluate the association between CHA<sub>2</sub>DS<sub>2</sub>-VASc and modified HAS-BLED and a composite of non-cardiovascular frail events (fractures, urinary tract infections, bacterial pneumonia, or dehydration). We also evaluated the association of oral anticoagulant (OAC) use with stroke, bleeding, and 1-year mortality in frail patients and non-frail patients.<br /><b>Results</b><br />In 213,435 patients (age 70 ± 11; 98% male; CHA<sub>2</sub>DS<sub>2</sub>-VASc 2.4±1.7) with AF, 8498 (4%) were frail. CHA<sub>2</sub>DS<sub>2</sub>-VASc > 0 and HAS-BLED > 0 were strongly associated with frailty (Odds Ratio [OR] 13.3 (95% CI: 11.6-15.2) for CHA<sub>2</sub>DS<sub>2</sub>-VASc 4+ and OR 13.4 (10.2 - 17.5) for HAS-BLED 3+). After adjusting for covariates, CHA<sub>2</sub>DS<sub>2</sub>-VASc and HAS-BLED > 0 were associated with higher risk of non-cardiovascular frail events (Hazard Ratio [HR] 2.1 (95% CI: 2.0-2.2) for CHA<sub>2</sub>DS<sub>2</sub>-VASc 4+ and HR 1.4 (95% CI: 1.3-1.5) for HAS-BLED 3+). In frail patients, OAC use was associated with significantly lower risk of 1-year mortality (HR 0.82; 95% CI 0.72 - 0.94, p = 0.0031) but did not reach significance for risk of stroke (HR 0.80; 95% CI 0.55 - 1.18, p = 0.26) or major bleeding (HR 1.08; 95% CI 0.93 - 1.25, p = 0.34).<br /><b>Conclusion</b><br />High CHA<sub>2</sub>DS<sub>2</sub>-VASc and HAS-BLED scores are strongly associated with frailty. However, in frail patients, OAC use was associated with reduction in 1-year mortality. For this challenging clinical population with competing risks of frailty and frail events, focused prospective studies are needed to support clinical decision-making. Until then, careful evaluation of frailty should inform shared decision-making.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>Evaluation of obstructive sleep apnea among consecutive patients with all patterns of atrial fibrillation using WatchPAT home sleep testing.</h4><i>Mills EW, Cassidy M, Sofer T, Tadros T, ... Antman EM, Javaheri S</i><br /><b>Abbreviations</b><br />Obstructive sleep apnea (OSA), atrial fibrillation (AF), home sleep test (HST), apnea-hypopnea index (AHI), continuous positive airway pressure (CPAP), Epworth Sleepiness Scale (ESS), Center of Excellence (COE), Mayo AF-Specific Symptom Inventory (MAFSI), Atrial Fibrillation Effect Quality of Life (AFEQT), body-mass index (BMI), oxygen desaturation index (ODI) BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is associated with significant morbidity, mortality, and financial burden. Obstructive sleep apnea (OSA) is more common in individuals with AF and may impair the efficacy of rhythm control strategies including catheter ablation. However, the prevalence of undiagnosed OSA in all-comers with AF is unknown.<br /><b>Design</b><br />This pragmatic, phase IV prospective cohort study will test 250-300 consecutive ambulatory AF patients with all patterns of atrial fibrillation (paroxysmal, persistent, and long-term persistent) and no prior sleep testing for OSA using the WatchPAT system, a disposable home sleep test (HST). The primary outcome of the study is the prevalence of undiagnosed OSA in all-comers with atrial fibrillation.<br /><b>Results</b><br />Preliminary results from the initial pilot enrollment of approximately 15% (N=38) of the planned sample size demonstrate a 79.0% prevalence of at least mild (AHI≥5) OSA or greater in consecutively enrolled patient with all patterns of AF.<br /><b>Conclusions</b><br />We report the design, methodology, and preliminary results of our study to define the prevalence of OSA in AF patients. This study will help inform approaches to OSA screening in patients with AF for which there is currently little practical guidance.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 03 Apr 2023; epub ahead of print</small></div>

<div><h4>Cost to Medicare of Acute Kidney Injury in Percutaneous Coronary Intervention.</h4><i>Griffiths RI, Cavalcante R, McGovern AM, Bhave A, ... Solid CA, Amin AP</i><br /><b>Background</b><br />. Acute kidney injury (AKI), including contrast-induced AKI (CI-AKI), is an important complication of percutaneous coronary intervention (PCI), resulting in short- and long-term adverse clinical outcomes. While prior research has reported an increased cost burden to hospitals from CI-AKI, the incremental cost to payers remains unknown. Understanding this incremental cost may inform decisions and even policy in the future. The objective of this study was to estimate the short- and long-term cost to Medicare of AKI overall, and specifically CI-AKI, in PCI.<br /><b>Methods</b><br />. Patients undergoing inpatient PCI between January 2017 and June 2020 were selected from Medicare 100% fee-for-service data. Baseline clinical characteristics, PCI lesion/procedural characteristics, and AKI/CI-AKI during the PCI admission, were identified from diagnosis and procedure codes. Poisson regression, generalized linear modelling, and longitudinal mixed effects modelling, in full and propensity-matched cohorts, were used to compare PCI admission length of stay (LOS) and cost (Medicare paid amount inflated to 2022 US$), as well as total costs during one-year following PCI, between AKI and non-AKI patients.<br /><b>Results</b><br />. The study cohort included 509,039 patients, of whom 104,033 (20.4%) were diagnosed with AKI and 9,691 (1.9%) with CI-AKI. In the full cohort, AKI was associated with + 4.12 (95% confidence interval = 4.10, 4.15) days index PCI admission LOS, +$11,313 ($11,093, $11,534) index admission costs, and +$14,800 ($14,359, $15,241) total one-year costs. CI-AKI was associated with + 3.03 (2.97, 3.08) days LOS, $6,566 ($6,148, $6,984) index admission costs, and +$13,381 ($12,118, $14,644) cumulative one-year costs (all results are adjusted for baseline characteristics). Results from the propensity-matched analyses were similar.<br /><b>Conclusions</b><br />. AKI, and specifically CI-AKI, during PCI is associated with significantly longer PCI admission LOS, PCI admission costs, and long-terms costs.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 02 Apr 2023; epub ahead of print</small></div>

<div><h4>Systolic blood pressure time in target range and long-term outcomes in patients with ischemic cardiomyopathy.</h4><i>Fu G, Zhou Z, Jian B, Huang S, ... Chen G, Wu Z</i><br /><b>Background</b><br />The relationship between the degree of systolic blood pressure (SBP) control and outcomes remains unclear in patients with ischemic cardiomyopathy (ICM). Current control metrics may not take into account the potential effects of SBP fluctuations over time on patients.<br /><b>Methods</b><br />This study was a post-hoc analysis of the surgical treatment of ischemic heart failure trial which enrolled 2,136 participants with ICM. Our SBP target range was defined as 110 to 130 mm Hg and the time in target range (TTR) was calculated by linear interpolation.<br /><b>Results</b><br />A total of 1,194 patients were included. Compared with the quartile 4 group (TTR 77.87%-100%), the adjusted hazard ratios and 95% confidence intervals of all-cause mortality were 1.32 (0.98-1.78) for quartile 3 group (TTR 54.81%-77.63%), 1.40 (1.03-1.90) for quartile 2 group (TTR 32.59%-54.67%), and 1.53 (1.14-2.04) for quartile 1 group (TTR 0%-32.56%). Per 29.28% (1-SD) decrement in TTR significantly increased the risk of all-cause mortality (1.15 [1.04-1.26]). Similar results were observed in the cardiovascular (CV) mortality and the composite outcome of all-cause mortality plus CV rehospitalization, and in the subgroup analyses of either coronary artery bypass grafting or medical therapy, and different baseline SBP.<br /><b>Conclusions</b><br />In patients with ICM, the higher TTR was significantly associated with decreased risk of all-cause mortality, CV mortality and the composite outcome of all-cause mortality plus CV rehospitalization, regardless of whether the patient received coronary artery bypass grafting or medical therapy, and the level of baseline SBP. TTR may be a surrogate metric of long-term SBP control in patients with ICM.<br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 01 Apr 2023; 258:177-185</small></div>

<div><h4>Incidental detection of malignancy during pre-procedural workup for transcatheter aortic valve implantation: a longitudinal cohort study.</h4><i>Demirel C, Tomii D, Heg D, Okuno T, ... Windecker S, Pilgrim T</i><br /><AbstractText>The aim of this retrospective analysis was to investigate the prevalence and prognostic importance of incidental malignancy detected during pre-TAVI computed tomography. Among 579 patients, CT-work-up for TAVI exposed previously undetected malignancy in 4.5% of patients. TAVI patients with a new malignancy had a 2.9-fold increased risk of death at one year, and a 16 month shorter mean survival time compared to patients with no malignancy.</AbstractText><br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 01 Apr 2023; epub ahead of print</small></div>

<div><h4>Individual net clinical outcome with oral anticoagulation in atrial fibrillation using the ABC-AF risk scores.</h4><i>Hijazi Z, Lindbäck J, Oldgren J, Benz AP, ... Siegbahn A, Wallentin L</i><br /><b>Background</b><br />Decisions on stroke prevention strategies in patients with atrial fibrillation (AF) depend on the perceived risks of stroke and bleeding with different antithrombotic treatment strategies. The study objectives were to evaluate net clinical outcome with oral anticoagulation (OAC) for the individual patient with AF and to identify clinically relevant thresholds for OAC treatment.<br /><b>Methods</b><br />Patients with AF receiving OAC treatment in the randomized ARISTOTLE and RE-LY trials, with available biomarkers for calculation of ABC-AF scores at baseline, were included (n=23,121). Observed one-year risk on OAC was compared with predicted one-year risk if the same patients would not have received OAC using the ABC-AF scores calibrated for aspirin. Net clinical outcome was defined as the sum of stroke and major bleeding risks.<br /><b>Results</b><br />The ratio between the one-year incidence of major bleeding and stroke/systemic embolism events ranged from 1.4 to 10.6 according to different ABC-AF risk profiles. Net clinical outcome analyses showed that in patients with an ABC-AF-stroke risk >1% per year on OAC (>3% without OAC), treatment with OAC consistently provides larger net clinical benefit than no-OAC treatment. In patients with an ABC-AF-stroke risk <1.0% per year on OAC (<3% without OAC) an individualized balancing of risks regarding OAC or no-OAC treatment is needed.<br /><b>Conclusions</b><br />In patients with AF, the ABC-AF risk scores allow an individual and continuous estimate of the balance between benefits and risks with OAC treatment. This precision medicine tool therefore seems useful as decision support and visualize the net clinical benefit or harm with OAC treatment.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 27 Mar 2023; epub ahead of print</small></div>

<div><h4>Secondary Analysis of Electronic Opt-Out Consent in Pragmatic Research: A Study Design Method to Diversify Clinical Trials?</h4><i>Gupta P, Sandy LC, Glorioso TJ, Khanna A, ... Bull S, Ho PM</i><br /><AbstractText>We conducted a multi-center pragmatic trial of a low-risk intervention focused on medication adherence using an opt out consent approach, where patients could opt out by letter and then electronically. We focus on the cohort after opt-out by mail. Here, we describe that 8% of patients opted out electronically, resulting in a 92% participation rate. Patients who self-identify as Black or Hispanic were less likely to opt out in the study, and half the study cohort was female. This demographic data is useful for planning future trials employing this approach.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am Heart J: 24 Mar 2023; epub ahead of print</small></div>

<div><h4>Screening for Peripartum Cardiomyopathies using Artificial Intelligence in Nigeria (SPEC-AI Nigeria): Clinical Trial Rationale and Design.</h4><i>Adedinsewo DA, Morales-Lara AC, Dugan J, Garzon-Siatoya WT, ... Noseworthy PA, Carter RE</i><br /><b>Background</b><br />Artificial intelligence (AI), and more specifically deep learning, models have demonstrated the potential to augment physician diagnostic capabilities and improve cardiovascular health if incorporated into routine clinical practice. However, many of these tools are yet to be evaluated prospectively in the setting of a rigorous clinical trial - a critical step prior to implementing broadly in routine clinical practice.<br /><b>Objectives</b><br />To describe the rationale and design of a proposed clinical trial aimed at evaluating an AI-enabled electrocardiogram (AI-ECG) for cardiomyopathy detection in an obstetric population in Nigeria.<br /><b>Design</b><br />The protocol will enroll 1,000 pregnant and postpartum women who reside in Nigeria in a prospective randomized clinical trial. Nigeria has the highest reported incidence of peripartum cardiomyopathy worldwide. Women aged 18 and older, seen for routine obstetric care at 6 sites (2 Northern and 4 Southern) in Nigeria will be included. Participants will be randomized to the study intervention or control arm in a 1:1 fashion. This study aims to enroll participants representative of the general obstetric population at each site. The primary outcome is a new diagnosis of cardiomyopathy, defined as left ventricular ejection fraction (LVEF) < 50% during pregnancy or within 12 months postpartum. Secondary outcomes will include the detection of impaired left ventricular function (at different LVEF cut-offs), and exploratory outcomes will include the effectiveness of AI-ECG tools for cardiomyopathy detection, new diagnosis of cardiovascular disease, and the development of composite adverse maternal cardiovascular outcomes.<br /><b>Summary</b><br />This clinical trial focuses on the emerging field of cardio-obstetrics and will serve as foundational data for the use of AI-ECG tools in an obstetric population in Nigeria. This study will gather essential data regarding the utility of the AI-ECG for cardiomyopathy detection in a predominantly Black population of women and pave the way for clinical implementation of these models in routine practice.<br /><b>Clinicaltrials</b><br />gov: NCT05438576.<br /><br />Copyright © 2023 Elsevier Ltd. All rights reserved.<br /><br /><small>Am Heart J: 24 Mar 2023; epub ahead of print</small></div>

<div><h4>Contemporary laboratory assessment of acute cardiorenal syndrome for early diagnosis - a call for action.</h4><i>Jefferies JL, Kovesdy CP, Ronco C</i><br /><AbstractText>Acute cardiorenal syndrome (CRS), categorized as CRS type 1 and 3, is defined by the interplay of acute kidney injury or dysfunction and acute cardiac disease. For optimized diagnosis and management of CRS, strategies targeting multi-organ dysfunction must be adopted. Early diagnosis of acute CRS is important to enable timely initiation of appropriate treatment to prevent serious morbidity and mortality; however, traditional biomarkers are suboptimal. Over the past two decades, numerous biomarkers have been investigated for a better and more rapid diagnosis of CRS. Yet, the uptake of these contemporary biomarkers has been slow, possibly owing to the use of imperfect gold-standard reference tests. We believe that there is now scope for use of contemporary laboratory test panels to improve the diagnosis of acute CRS. In this review, we briefly discuss a proposed set of biomarkers for the diagnosis of type 1 and type 3 CRS.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>P-wave Terminal Force in Lead V1 and Outcomes in Patients with Persistent Atrial Fibrillation Undergoing Catheter Ablation.</h4><i>Sudo Y, Morimoto T, Tsushima R, Sogo M, ... Takahashi M, Okawa K</i><br /><b>Aims</b><br />The P-wave terminal force in electrocardiogram lead V1 (PTFV1) correlates with outcomes in patients with paroxysmal atrial fibrillation (AF). Nevertheless, the correlation between the PTFV1 and outcomes after AF ablation in patients with persistent AF remains unclear. This study aimed to determine whether the PTFV1 at 3 months after AF ablation could predict AF recurrence and cardiovascular events in patients with persistent AF.<br /><b>Methods</b><br />This historical cohort study examined 453 consecutive patients with persistent AF who underwent a first-time AF ablation. We measured the PTFV1 at 3 months after the ablation. An abnormal PTF was defined as a ≥4 mVms depression. The 3-year incidence of AF recurrence and composite cardiovascular events, including strokes, heart failure hospitalizations, and cardiovascular death, were compared between the abnormal and normal PTF groups.<br /><b>Results</b><br />Among 434 enrolled patients, 101 had an abnormal and 333 normal PTF at 3 months after AF ablation. Compared with the normal PTF group, the abnormal PTF group had a significantly higher incidence of AF recurrence (52.6% vs. 28.1%, log-rank P<0.001) and cardiovascular events (13.7% vs. 2.6%, log-rank P=0.005). After adjusting for the risk factors, an abnormal PTF was established as an independent predictor of AF recurrence (hazard ratio [HR] 2.12, 95% confidence interval [CI]: 1.44-3.13, P<0.001) and cardiovascular events (HR 3.26, 95% CI: 1.19-8.97, P=0.022).<br /><b>Conclusions</b><br />The PTFV1 at 3 months after AF ablation could be a valuable noninvasive predictor of both AF recurrence and cardiovascular events in patients with persistent AF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>Meta-analysis assessing the sensitivity and specificity of F-FDG PET/CT for the diagnosis of prosthetic valve endocarditis (PVE) using individual patient data (IPD).</h4><i>O\'Gorman P, Nair L, Kisiel N, Hughes I, ... Roque A, Singh K</i><br /><b>Importance</b><br />The use of <sup>18</sup>F-FDG PET/CT in diagnostic algorithms for PVE has increased since publication of studies and guidelines advocating its use. The assessment of test accuracy has been limited by small study sizes. We undertook a systematic review using individual patient data (IPD) meta-analysis techniques.<br /><b>Objective</b><br />To estimate the summary sensitivity and specificity of <sup>18</sup>F-FDG PET/CT in diagnosing PVE. We also assessed the effect of patient factors on test accuracy as defined by changes in the Odds Ratios associated with each factor. The effect of the PET/CT study on the final diagnosis was also assessed when compared to the preliminary Duke classification to determine in which patient group <sup>18</sup>F-FDG PET/CT had the greatest utility.<br /><b>Study selection</b><br />Studies were included if PET/CT was performed for suspicion of PVE and IPD of both the PET/CT result and final diagnosis defined by a gold-standard assessment was available. There were three possible final diagnoses (\"definite PVE\", \"possible PVE\" and \"rejected PVE\").<br /><b>Results</b><br />Seventeen studies were included with IPD available for 537 patients (from 538 scans). The summary sensitivity and specificity were 85.0 % (95% CI 74.2 - 91.8 %) and 86.5 % (95% CI 75.8 - 92.9%) respectively when patients with final diagnosis of \"possible PVE\" were classified as positive for PVE. When this group was classified as negative for PVE, sensitivity was 87.4% (95% CI 80.4 - 92.1%) and specificity was 84.9% (95% CI 71.5 - 92.6%). Patients with a known pathogen (especially coagulase negative staphylococcal species), elevated CRP, a biological or aortic valve infection appeared more likely to have an accurate PET/CT diagnosis. Those with a mechanical valve, prior antibiotic treatment or a TAVR valve were less likely to have an accurate test. Time since valve implantation and the presence of surgical adhesive did not appear to affect test accuracy. Of the patients with a preliminary Duke classification of \"possible PVE\", 84 % received a more conclusive final diagnosis of \"definite\" or \"rejected\" PVE after the PET/CT study.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br /><sup>18</sup>F-FDG PET/CT has high sensitivity and specificity in diagnosing PVE and the diagnostic utility is greatest in patients with a preliminary Duke classification of \"possible PVE\". Some patient factors appear to affect test accuracy, though these results should be interpreted with caution given low patient numbers for subgroup analyses.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>Postoperative pericardial effusion, pericardiotomy and atrial fibrillation: an explanatory analysis of the PALACS trial.</h4><i>Rong LQ, Franco AD, Rahouma M, Dimagli A, ... Girardi L, Gaudino M</i><br /><b>Background</b><br />In the Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery (PALACS) trial, posterior pericardiotomy was associated with a significant reduction in postoperative atrial fibrillation (POAF) after cardiac surgery. We aimed to investigate the mechanisms underlying this effect.<br /><b>Methods</b><br />We included PALACS patients with available echocardiographic data (n=387/420, 92%). We tested the hypotheses that the reduction in POAF with the intervention was associated with 1) a reduction in postoperative pericardial effusion and/or 2) an effect on left atrial size and function. Spline and multivariable logistic regression analyses were used.<br /><b>Results</b><br />Most patients (n=307, 79%) had postoperative pericardial effusions (anterior 68%, postero-lateral 51.9%). The incidence of postero-lateral effusion was significantly lower in patients undergoing pericardiotomy (37% vs 67%; p<0.001). The median size of anterior effusion was comparable between patients with and without POAF (5.0 [IQR 3.0-7.0] vs 5.0 [IQR 3.0-7.5] mm; p=0.42), but there was a non-significant trend towards larger postero-lateral effusion in the POAF group (5.0 [IQR 3.0-9.0] vs 4.0 [IQR 3.0-6.4] mm; p=0.06). There was a non-linear association between postero-lateral effusion and POAF at a cut-off at 10 mm (OR 2.70; 95%CI 1.13, 6.47; p=0.03) that was confirmed in multivariable analysis (OR 3.5, 95%CI 1.17, 10.58; p=0.02). Left atrial dimension and function did not change significantly after posterior pericardiotomy.<br /><b>Conclusions</b><br />Reduction in postero-lateral pericardial effusion is a plausible mechanism for the effect of posterior pericardiotomy in reducing POAF. Measures to reduce postoperative pericardial effusion are a promising approach to prevent POAF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>Effect of active vitamin-D on left ventricular mass index: results of a randomised controlled trial in type 2 diabetes and chronic kidney disease.</h4><i>Gnudi L, Fountoulakis N, Panagiotou A, Corcillo A, ... Ayis S, Karalliedde J</i><br /><b>Background</b><br />Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD).<br /><b>Methods</b><br />We performed a 48-week duration single centre randomised double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging (MRI). Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone (iPTH) were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac MRI. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n=19, placebo n=26).<br /><b>Results</b><br />Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the two treatment arms was 1.84 (-1.28, 4.96), similar between the two groups studied. iPTH fell only in the calcitriol group from 142 pg/ml [80-293] to 76 pg/ml [41-204](p=0.04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints.<br /><b>Conclusions</b><br />The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy (LVH) and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>Perioperative individualized hemodynamic optimization according to baseline mean arterial pressure in cardiac surgery patients: Rationale and design of the OPTIPAM randomized trial.</h4><i>Descamps R, Amour J, Besnier E, Bougle A, ... Fischer MO, OPTIPAM investigators</i><br /><b>Background</b><br />Postoperative morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB) remain high despite recent advances in both anesthesia and perioperative management. Among modifiable risk factors for postoperative complications, optimal arterial pressure during and after surgery has been under debate for years. Recent data suggest that optimizing arterial pressure to the baseline of the patient may improve outcomes. We hypothesize that optimizing the mean arterial pressure (MAP) to the baseline MAP of the patient during cardiac surgery with CPB and during the first 24 hours postoperatively may improve outcomes.<br /><b>Study design</b><br />The OPTIPAM trial (NCT05403697) will be a multicenter, randomized, open-label controlled trial testing the superiority of optimized MAP management as compared with a MAP of 65mmHg or more during both the intraoperative and postoperative periods in 1100 patients scheduled for cardiac surgery with CPB. The primary composite end point is the occurrence of acute kidney injury, neurological complications including stroke or postoperative delirium, and death. The secondary endpoints are hospital and intensive care unit lengths of stay, Day 7 and Day 90 mortality, postoperative cognitive dysfunction on Day 7 and Day 90, and quality of life at Day 7 and Day 90. An interim analysis will assess the safety of the intervention.<br /><b>Conclusion</b><br />The OPTIPAM trial will assess the effectiveness of an individualized target of mean arterial pressure in cardiac surgery with CPB in reducing postoperative morbidity.<br /><b>Clinical trial registration</b><br />NCT05403697.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>Effect of rosuvastatin 20mg versus rosuvastatin 5mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial.</h4><i>Cha JJ, Hong SJ, Kim JH, Lim S, ... Kim SY, Lim DS</i><br /><b>Background</b><br />Current guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients.<br /><b>Trial design</b><br />This investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months.<br /><b>Conclusion</b><br />The SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>Complementary evidence on the performance of coronary stents generated by a randomized controlled trial and a worldwide registry.</h4><i>Gautier A, Roffi M, Laanmets P, Munir S, ... Saito S, Chevalier B</i><br /><b>Background</b><br />Large-scale registries can provide valuable complementary data to randomized controlled trials (RCT) for the post-marketing evaluation of coronary stents, but their scientific relevance remains debated.<br /><b>Methods</b><br />We sought to compare the evidence on the performance of a single coronary stent platform generated by the RCT for its regulatory approval and a well-conducted international registry. Patients treated with the Ultimaster coronary stent in the CENTURY II (CII-UM) trial (n=551) were compared to patients in the real-world e-ULTIMASTER (e-UM) registry (n=35,389). All major events were adjudicated by an independent clinical event committee in both studies. Propensity weighted analysis was used to balance baseline and procedural differences between the two populations.<br /><b>Results</b><br />Coronary artery disease was more complex in e-UM compared to CII-UM, including more acute coronary syndromes, multivessel disease, left main, arterial or venous grafts and chronic total occlusions (p<0.005 for all). At one-year follow-up and after excluding periprocedural myocardial infarction (MI) there was no statistically significant difference between CII-UM and e-UM regarding all-cause death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.26-1.20, p=0.14), cardiac death (HR 0.71, 95% CI 0.29-1.72, p=0.45), target lesion failure (HR 1.18, 95% CI 0.78-1.78, p=0.44), and target vessel MI (HR 0.76, 95% CI 0.24-2.38, p=0.63). However, target vessel revascularization rate was significantly higher in CII-UM than in e-UM, HR 1.78, 95% CI 1.23-2.56, p=0.002.<br /><b>Conclusion</b><br />A well-conducted large-scale registry can provide valuable complementary evidence to RCTs on the post-market performance of new coronary stents, across a wider range of uses and various geographic areas.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 15 Mar 2023; epub ahead of print</small></div>

<div><h4>Identifying treatment heterogeneity in atrial fibrillation using a novel causal machine learning method.</h4><i>Ngufor C, Yao X, Inselman JW, Ross JS, ... Shah ND, Noseworthy PA</i><br /><b>Background</b><br />Lifelong oral anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent stroke. Over the last decade, multiple new oral anticoagulants (OACs) have expanded the number of treatment options for these patients. While population-level effectiveness of OACs has been compared, it is unclear if there is variability in benefit and risk across patient subgroups.<br /><b>Methods</b><br />We analyzed claims and medical data for 34,569 patients who initiated a non-vitamin K antagonist oral anticoagulant (NOAC; apixaban, dabigatran, and rivaroxaban) or warfarin for nonvalvular AF between 08/01/2010 and 11/29/2017 from the OptumLabs® Data Warehouse. A machine learning (ML) method was applied to match different OAC groups on several baseline variables including, age, sex, race, renal function, and CHA<sub>2</sub>DS<sub>2</sub> -VASC score. A causal ML method was then used to discover patient subgroups characterizing the head-to-head treatment effects of the OACs on a primary composite outcome of ischemic stroke, intracranial hemorrhage, and all-cause mortality.<br /><b>Results</b><br />The mean age, number of females and white race in the entire cohort of 34,569 patients were 71.2 (SD, 10.7) years, 14916 (43.1%), and 25051 (72.5%) respectively. During a mean follow up of 8.3 (SD, 9.0) months, 2110 (6.1%) of patients experienced the composite outcome, of whom 1675 (4.8%) died. The causal ML method identified 5 subgroups with variables favoring apixaban over dabigatran; 2 subgroups favoring apixaban over rivaroxaban; 1 subgroup favoring dabigatran over rivaroxaban; and 1 subgroup favoring rivaroxaban over dabigatran in terms of risk reduction of the primary endpoint. No subgroup favored warfarin and most dabigatran vs warfarin users favored neither drug. The variables that most influenced favoring one subgroup over another included Age, history of ischemic stroke, thromboembolism, estimated glomerular filtration rate, Race, and myocardial infarction.<br /><b>Conclusions</b><br />Among patients with AF treated with a NOAC or warfarin, a causal ML method identified patient subgroups with differences in outcomes associated with OAC use. The findings suggest that the effects of OACs are heterogeneous across subgroups of AF patients, which could help personalize the choice of OAC. Future prospective studies are needed to better understand the clinical impact of the subgroups with respect to OAC selection.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Am Heart J: 07 Mar 2023; epub ahead of print</small></div>