Journal: Am Heart J

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Abstract

Longer Term Benefits of Exercise and Escitalopram in the Treatment of Anxiety in Patients with Coronary Heart Disease: Six Month Follow-up of the UNWIND Randomized Clinical Trial.

Blumenthal JA, Smith PJ, Jiang W, Hinderliter A, ... Davidson J, Sherwood A
Background
Anxiety is a common comorbidity in patients with coronary heart disease (CHD) and is associated with worse prognosis. However, effective treatment for anxiety in CHD patients is uncertain. The UNWIND randomized clinical trial showed that 12-week treatment of escitalopram was better than exercise training or placebo in reducing anxiety in anxious CHD patients. The longer-term benefits of treatment for anxiety are not known.
Methods
Patients were randomized to 12 weeks of Escitalopram (up to 20 mg), Exercise (3 times/week), or placebo pill. At the conclusion of treatment, participants were followed for 6-months to determine the persistence of benefit on the primary anxiety endpoint assessed by the Hospital Anxiety and Depression Scale-Anxiety scale (HADS-A) and to assess the effects of treatment on major adverse cardiac events over a follow-up period of up to 6 years.
Results
Of the 128 participants initially randomized, 120 (94%) were available for follow-up. Participants randomized to the Escitalopram condition exhibited lower HADS-A scores (3.9 [3.1, 4.7]) compared to those randomized to Exercise (5.5 [4.6, 6.3]) (P = .007) and Placebo (5.3 [4.1, 6.5]) (P = .053). Over a median follow-up of 3.2 years (IQR: 2.3, 4.5), there were 29 adverse events but no significant between-group differences.
Conclusion
In the UNWIND trial, 12 weeks of escitalopram treatment was effective in reducing anxiety. These beneficial effects were sustained for 6 months post-treatment. Although moderate or vigorous physical activity has a number of health benefits, exercise was not an effective treatment for anxiety in patients with CHD.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 21 May 2022; epub ahead of print
Blumenthal JA, Smith PJ, Jiang W, Hinderliter A, ... Davidson J, Sherwood A
Am Heart J: 21 May 2022; epub ahead of print | PMID: 35609671
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Abstract

Associations of a Polygenic Risk Score with Coronary Artery Disease Phenotypes in The Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial.

Newman JD, Douglas PS, Zhbannikov I, Ferencik M, ... Lu MT, Voora D
A polygenic risk score (PGS) is associated with obstructive coronary artery disease (CAD) independent of traditional risk factors. Coronary computed tomography angiography (CTA) can characterize coronary plaques, including features of high-risk CAD. However, it is unknown if a PGS is associated with obstructive CAD and high-risk CAD phenotypes in patients with symptoms suggestive of CAD.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Am Heart J: 20 May 2022; epub ahead of print
Newman JD, Douglas PS, Zhbannikov I, Ferencik M, ... Lu MT, Voora D
Am Heart J: 20 May 2022; epub ahead of print | PMID: 35605652
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Abstract

The Trial to Assess Chelation Therapy 2 (TACT2): Rationale and Design.

Lamas GA, Anstrom KJ, Navas-Acien A, Boineau R, ... Mark DB, TACT2 Investigators
The Trial to Assess Chelation Therapy 2 (TACT2) is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or Na2EDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI). TACT2 completed enrollment of 1000 subjects in December 2020, and infusions in December 2021. Subjects are being followed for 2.5 to 5 years. The primary endpoint is a composite of the time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The trial is designed to have >85% power to detect a 30% relative reduction in the primary endpoint for each active treatment versus placebo comparison. TACT2 also includes a Trace Metals and Biorepository Core Lab, which will test the novel hypothesis that the prognostic benefits of chelation, if present, are due to removal of lead and cadmium from patients. Most of the design features of TACT2 were chosen to replicate selected features of the first TACT trial, which demonstrated a statistically significant reduction in cardiovascular outcomes in the EDTA chelation arm compared with placebo among patients with a prior MI, with the largest effect in patients with diabetes. Results from TACT2, if concordant with TACT, will provide definitive evidence of the benefit of edetate disodium-based chelation on cardiovascular outcomes, as well as the possible clinical importance of longitudinal changes in toxic metal levels of participants.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 19 May 2022; epub ahead of print
Lamas GA, Anstrom KJ, Navas-Acien A, Boineau R, ... Mark DB, TACT2 Investigators
Am Heart J: 19 May 2022; epub ahead of print | PMID: 35598636
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Abstract

Empagliflozin in Patients Post Myocardial Infarction Rationale and Design of the EMPACT-MI Trial.

Harrington J, Udell JA, Jones WS, Anker SD, ... Hernandez AF, Butler J
Background
Patients with acute myocardial infarction (MI) are at risk for developing heart failure (HF) and subsequently are at an increased risk of mortality. Sodium-glucose cotransporter-2 inhibitors have been proven to improve outcomes in patients with HF with reduced ejection fraction, and, in the case of empagliflozin, in HF with preserved ejection fraction even without diabetes, but their efficacy and safety in the post-MI population has not yet been evaluated.
Methods
The EMPACT-MI trial will evaluate the safety and efficacy of empagliflozin compared with placebo in patients hospitalized for MI with or at high risk of new onset HF, in addition to standard care. EMPACT-MI is a streamlined, multinational, randomized, double-blind, placebo-controlled trial randomizing 5,000 participants at approximately 480 centers in 22 countries. Eligible patients presenting with spontaneous MI must have new signs or symptoms of pulmonary congestion requiring treatment or new left ventricular dysfunction (LVEF<45%), and at least one additional risk factor for development of future HF. Eligible and consenting patients are randomized to empagliflozin 10mg or placebo daily in addition to standard of care within 14 days of hospital admission for MI. The primary composite endpoint is time to first hospitalization for HF or all-cause mortality.
Conclusions
EMPACT-MI will inform clinical practice regarding the role of empagliflozin in patients after an MI with high risk for the development of future HF and mortality.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 17 May 2022; epub ahead of print
Harrington J, Udell JA, Jones WS, Anker SD, ... Hernandez AF, Butler J
Am Heart J: 17 May 2022; epub ahead of print | PMID: 35595091
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Abstract

Ultrasound-facilitated, catheter-directed thrombolysis versus anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study.

Klok FA, Piazza G, Sharp ASP, Ainle FN, ... Rosenfield K, Konstantinides SV
Background
Due to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE).
Methods
The Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (i) confirmed acute PE; (ii) evidence of right ventricular (RV) dysfunction on imaging; (iii) a positive cardiac troponin test; and (iv) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis (USCDT) plus anticoagulation, versus anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11th 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium. No compensation was provided for authorship; employees of Boston Scientific are authors of the work and receive compensation through their employment.
Conclusions
Regardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 16 May 2022; epub ahead of print
Klok FA, Piazza G, Sharp ASP, Ainle FN, ... Rosenfield K, Konstantinides SV
Am Heart J: 16 May 2022; epub ahead of print | PMID: 35588898
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Abstract

Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multistate model.

Aulin J, Hijazi Z, Lindbäck J, Alexander JH, ... Wallentin L, ARISTOTLE Investigators
Background
Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.
Methods
The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n=2,048), (II) HF with preserved ejection fraction (HFpEF, n=2,520), and (III) No HF (n=7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.
Results
Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all p<0.0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.
Conclusions
In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 12 May 2022; epub ahead of print
Aulin J, Hijazi Z, Lindbäck J, Alexander JH, ... Wallentin L, ARISTOTLE Investigators
Am Heart J: 12 May 2022; epub ahead of print | PMID: 35569564
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Abstract

The efficacy of single-lead implantable cardioverter-defibrillator with atrial sensing dipole to detect atrial fibrillation and to reduce inappropriate therapy according to atrial sensing ON or OFF: Rationale and design of the SMART-CONTROL study, a prospective multicenter randomized trial: AF detection and inappropriate therapy in VDD-ICD.

Gwag HB, Kim HR, Park SJ, Kim J, ... On YK, Kim JS
Background
Few studies have compared the efficacy of single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (VDD-ICD) and conventional single-chamber ICD from the aspect of atrial fibrillation (AF) detection or inappropriate ICD therapy reduction. In the SMART-CONTROL trial (NCT03932604), we primarily aim to investigate whether the atrial sensing capability of VDD-ICD is useful in AF detection and inappropriate therapy reduction by randomly activating or deactivating the atrial sensing function.
Methods and design
This study was designed as a prospective, multicenter, open-label, randomized trial to enroll 640 patients with no history of clinical AF or rhythm control for AF within one year who were undergoing the implantation of VDD-ICD system. Patients are assigned randomly to atrial sensing \'ON\' or \'OFF\' group, with crossover allowed during follow-up. The co-primary outcomes are the incidence of AF detection and inappropriate ICD therapy over a 2-year follow-up period. The secondary outcomes include non-AF atrial tachyarrhythmia, ventricular tachyarrhythmia with or without ICD therapy, thromboembolic events, bleeding, heart failure hospitalization, mortality, a composite of adverse cardiovascular events, and long-term atrial sensing stability or variability.
Conclusion
We expect that this trial can evaluate the efficacy of a single-lead ICD system on various clinical outcomes including AF detection and inappropriate therapy reduction, and ultimately provide guidance to selection of ICD system.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 11 May 2022; epub ahead of print
Gwag HB, Kim HR, Park SJ, Kim J, ... On YK, Kim JS
Am Heart J: 11 May 2022; epub ahead of print | PMID: 35568193
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Impact:
Abstract

Prognosis of elderly non-valvular atrial fibrillation patients stratified by B-type natriuretic peptide: ELDERCARE-AF subanalysis.

Okazaki O, Higashino Y, Yokoya K, An Y, ... Okumura K, Yamashita T
Background
B-type natriuretic peptide (BNP) is a risk factor for stroke and cardiac death in patients with atrial fibrillation. We hypothesized the prognostic outcomes of very elderly non-valvular atrial fibrillation (NVAF) patients ineligible for standard anticoagulation treatment would vary according to BNP stratification.
Methods
In this subanalysis of the ELDERCARE-AF trial, patients were stratified by BNP levels at enrollment, and clinical outcomes compared among BNP subgroups. Hazard ratios were adjusted for age, atrial fibrillation type, body mass index, creatine clearance, congestive heart failure, and D-dimer. BNP levels were measured using chemiluminescence enzyme immunoassays.
Results
In total, 984 patients (average age: 86.6 years) not considered eligible for oral anticoagulant therapy at approved doses for stroke prevention were included. The BNP levels at enrollment were <200 (low), 200 to <400 (moderate), and ≥400 (high) pg/mL in 428, 300, and 256 patients, respectively. The number (%) of patients with stroke or systemic embolism (SSE) was 7 (1.2%), 24 (5.9%), and 28 (8.6%) in the low, moderate, and high BNP subgroups, respectively (adjusted hazard ratio 3.82, P=.0025 for low versus moderate BNP and 4.76, P=.0007 for low versus high BNP). There was no significant difference in major bleeding incidence between the BNP subgroups. Edoxaban 15 mg was associated with a consistent reduction in SSE versus placebo in all BNP subgroups.
Conclusions
Stratification by BNP level was associated with the incidence of SSE for very elderly NVAF patients ineligible for standard anticoagulation treatment, and the effect of edoxaban 15 mg was consistent across BNP levels.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 11 May 2022; epub ahead of print
Okazaki O, Higashino Y, Yokoya K, An Y, ... Okumura K, Yamashita T
Am Heart J: 11 May 2022; epub ahead of print | PMID: 35568194
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Impact:
Abstract

COMPARE LAAO: Rationale and design of the randomized controlled trial \'COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy\'.

Huijboom HFM, Maarse M, Aarnink E, van Dijk VF, ... Tijssen J, Boersma LVA
Background
Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking.
Study objectives
To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA) and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications.
Study design
This is a multicenter, investigator initiated, open label, blinded endpoint (PROBE), superiority driven RCT. Patients with AF, a CHA₂DS₂-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of one and a maximum of five years. Cost-effectiveness and budget impact analyses will be performed to allow decision making on reimbursement of LAAO for the target population in the Netherlands.
Summary
The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use.
Nct trial number
NCT04676880.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 07 May 2022; epub ahead of print
Huijboom HFM, Maarse M, Aarnink E, van Dijk VF, ... Tijssen J, Boersma LVA
Am Heart J: 07 May 2022; epub ahead of print | PMID: 35537503
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Abstract

Study Design and Rationale for the OCEAN(a)-DOSE (Olpasiran trials of Cardiovascular Events And LipoproteiN(a) reduction-DOSE Finding Study) Trial.

O\'Donoghue ML, López JAG, Knusel B, Gencer B, ... Kassahun H, Sabatine MS
Background
Data support lipoprotein(a) [Lp(a)] being a risk factor for atherogenesis. Olpasiran is a small interfering RNA molecule that markedly reduces Lp(a) production in hepatocytes.
Study design
The OCEAN(a)-DOSE trial is a multicenter, randomized, double-blind, placebo-controlled dose-finding study in 281 subjects with established atherosclerotic disease and Lp(a) >150 nmol/L. Patients were randomly allocated to one of 4 active subcutaneous doses of olpasiran (10mg q12 weeks, 75mg q12 weeks, 225mg q12 weeks or 225mg q24 weeks) or matched placebo. The primary objective is to evaluate the effects of olpasiran dosed every 12 weeks compared with placebo on the mean percent change in Lp(a) from baseline at 36 weeks. Enrollment is now complete and follow-up is ongoing.
Conclusions
The OCEAN(a)-DOSE trial is assessing the Lp(a)-lowering efficacy and safety of olpasiran. These data will be used to determine optimal dosing and design for a cardiovascular outcomes trial. This study was funded by Amgen. (ClinicalTrials.gov NCT04270760).

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 06 May 2022; epub ahead of print
O'Donoghue ML, López JAG, Knusel B, Gencer B, ... Kassahun H, Sabatine MS
Am Heart J: 06 May 2022; epub ahead of print | PMID: 35588897
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Abstract

Prognostic value of brain natriuretic peptides in patients with pulmonary arterial hypertension: a systematic review and meta-analysis.

Hendriks PM, van de Groep LD, Veen KM, van Thor MCJ, ... Post MC, van den Bosch AE
Background
Multiple biomarkers have been investigated in the risk stratification of patients with pulmonary arterial hypertension (PAH). This systematic review and meta-analysis is the first to investigate the prognostic value of (NT-pro)BNP in patients with PAH.
Methods
A systematic literature search was performed using MEDLINE, Embase, Web of Science, the Cochrane Library and Google scholar to identify studies on the prognostic value of baseline (NT-pro)BNP levels in PAH. Studies reporting hazard ratios (HR) for the endpoints mortality or lung transplantation were included. A random effects meta-analysis was performed to calculate the pooled HR of (NT-pro)BNP levels at the time of diagnosis. To account for different transformations applied to (NT-pro)BNP, the HR was calculated for a twofold difference of the weighted mean (NT-pro)BNP level of 247 pmol/L, for studies reporting a HR based on a continuous (NT-pro)BNP measurement.
Results
Sixteen studies were included, representing 6999 patients (mean age 45.2-65.0 years, 97.3% PAH). Overall, 1460 patients reached the endpoint during a mean follow-up period between 1-10 years. Nine studies reported HRs based on cut-off values. The risk of mortality was increased for both elevated NT-proBNP and BNP with a pooled HR based on unadjusted HRs of 2.75 (95%-CI: 1.86-4.07) and 3.87 (95% CI 2.69-5.57) respectively. Six studies reported HRs for (NT-pro)BNP on a continues scale. A twofold difference of the weighted mean NT-proBNP resulted in an increased risk of mortality with a pooled HR of 1.17 (95%-CI: 1.03-1.32).
Conclusion
Increased levels of (NT-pro)BNP are associated with a significantly increased risk of mortality in PAH patients.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 06 May 2022; epub ahead of print
Hendriks PM, van de Groep LD, Veen KM, van Thor MCJ, ... Post MC, van den Bosch AE
Am Heart J: 06 May 2022; epub ahead of print | PMID: 35533723
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Abstract

Morphine and Clinical Outcomes in Patients with ST segment elevation Myocardial Infarction Treated with Fibrinolytic and Antiplatelet Therapy: Insights from the TREAT Trial.

Cantor WJ, Tan M, Berwanger O, Lavi S, ... Granger CB, Goodman SG
Background
Morphine is commonly used to relieve pain, anxiety and dyspnea in STEMI but it lowers blood pressure and delays the activity of oral antiplatelet agents. The impact of morphine on clinical outcomes remains unknown. This analysis was performed to determine if morphine use was associated with increased risk of adverse clinical events among STEMI patients treated with fibrinolytic therapy and clopidogrel or ticagrelor.
Methods
In the Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis (TREAT) study, 3,799 STEMI patients treated with fibrinolysis were randomized to receive clopidogrel or ticagrelor. Morphine use was left to the discretion of the treating physicians. In this pre-specified analysis, we evaluated clinical outcomes based on the use and timing of morphine administration. Outcomes were stratified by randomized treatment group. Multivariable analysis was performed using Inverse Probability Treatment Weighting (IPTW) weighting.
Results
Morphine was used in 53% of patients. After adjustment using IPTW weighting, morphine use was associated with higher hazard of reinfarction at 7 days (HR 4.9, p=0.0006) and 30 days (HR 1.7, p=0.04), and lower hazard of major bleeding (HR 0.37, p=0.006). There was no significant difference in mortality at any time point.
Conclusions
Among patients with STEMI treated with fibrinolytic therapy, morphine use was associated with a higher risk of early reinfarction and a lower risk of major bleeding but no difference in mortality.
Clinical trial registration
clinicaltrials.gov Identifier: NCT02298088.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 06 May 2022; epub ahead of print
Cantor WJ, Tan M, Berwanger O, Lavi S, ... Granger CB, Goodman SG
Am Heart J: 06 May 2022; epub ahead of print | PMID: 35533724
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Abstract

Comparison of severe maternal morbidity in pregnancy by modified World Health Organization Classification of maternal cardiovascular risk.

Denoble AE, Goldstein SA, Wein MLE, Grotegut CA, Federspiel JJ
Objective
To compare rates of severe maternal morbidity (SMM) for pregnant patients with a cardiac diagnosis classified by the modified World Health Organization (mWHO) classification to those without a cardiac diagnosis.
Study design
This retrospective study using the 2015-2019 Nationwide Readmissions Database identified hospitalizations, comorbidities, and outcomes using diagnosis and procedure codes. The primary exposure was cardiac diagnosis, classified into low-risk (mWHO class I and II) and moderate-to-high-risk (mWHO class II/III, III, or IV). The primary outcome was SMM or death during the delivery hospitalization; secondary outcomes included cardiac-specific SMM during delivery hospitalizations and readmissions after the delivery hospitalization.
Results
A weighted national estimate of 14,995,122 delivery admissions was identified, including 46,541 (0.31%) with mWHO I-II diagnoses and 37,330 (0.25%) with mWHO II/III-IV diagnoses. Patients with mWHO II/III-IV diagnoses experienced SMM at the highest rates (22.8% vs 1.6% for no diagnosis; with adjusted relative risk (aRR) of 5.67 [95% CI: 5.36 to 6.00]). The risk of death was also highest for patients with mWHO II/III-IV diagnoses (0.3% vs. <0.1% for no diagnosis; aRR 18.07 [95% CI: 12.25-26.66]). Elevated risk of SMM and death persisted to 11 months postpartum for those patients with mWHO II/III-IV diagnoses.
Conclusions
In this nationwide database, SMM is highest among individuals with moderate-to-severe cardiac disease based on mWHO classification. This risk persists in the year postpartum. These results can be used to enhance pregnancy counseling.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 05 May 2022; epub ahead of print
Denoble AE, Goldstein SA, Wein MLE, Grotegut CA, Federspiel JJ
Am Heart J: 05 May 2022; epub ahead of print | PMID: 35526569
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Impact:
Abstract

Comparison of Anticoagulation with Left Atrial Appendage Closure after AF Ablation: Rationale and Design of the OPTION randomized trial.

Wazni O, Boersma L, Healey JS, Mansour M, ... Allocco DJ, Reddy VY
Background
For patients with symptomatic atrial fibrillation (AF), physicians typically offer AF ablation for symptom relief; however, patients often anticipate/expect a life free from anticoagulation. This belief puts patients at increased risk of stroke due to the potential for asymptomatic AF post-ablation if anticoagulation is ceased contrary to clinical guidelines. Although the WATCHMAN device has been FDA-approved to decrease the risk of thromboembolism from the left atrial appendage (LAA) in patients with an appropriate rationale to avoid oral anticoagulation, it has not been well-studied following AF ablation. Additionally, there are limited data comparing the WATCHMAN device to direct oral anticoagulants. The OPTION study will investigate whether LAA closure with the WATCHMAN FLX device is a reasonable alternative to oral anticoagulation following percutaneous catheter ablation for nonvalvular AF.
Trial design
OPTION is a multinational, multicenter, prospective randomized clinical trial. Patients with a CHA2DS2-VASc of ≥2 in men or ≥3 in women and who underwent a AF catheter ablation procedure between 90 and 180 days prior to randomization (sequential) or are planning to have catheter ablation within 10 days of randomization (concomitant) will be randomized in a 1:1 allocation of WATCHMAN FLX versus control. Control patients will start or continue market-approved oral anticoagulation for the duration of the trial. A total of 1600 patients were randomized from 130 global investigational sites. Follow-up for both device and control patients will occur at 3, 12, 24, and 36 months. The primary effectiveness non-inferiority endpoint is stroke (ischemic or hemorrhagic), all-cause death, or systemic embolism at 36 months. The primary safety superiority endpoint is non-procedural bleeding through 36 months (International Society on Thrombosis and Haemostasis [ISTH] major bleeding or clinically relevant non-major bleeding). The secondary non-inferiority endpoint is ISTH major bleeding through 36 months (including procedural bleeding).
Conclusions
This trial will assess the safety and efficacy of WATCHMAN FLX in a post-ablation contemporary clinical AF patient population at risk of stroke.
Clinicaltrials
gov Identifier: NCT03795298.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 05 May 2022; epub ahead of print
Wazni O, Boersma L, Healey JS, Mansour M, ... Allocco DJ, Reddy VY
Am Heart J: 05 May 2022; epub ahead of print | PMID: 35526570
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Impact:
Abstract

Genome-First Recall of Healthy Individuals by Polygenic Risk Score Reveals Differences in Coronary Artery Calcium.

Forrest IS, Chan L, Chaudhary K, Saha A, ... Nadkarni GN, Do R
Genetic risk for coronary artery disease (CAD) is commonly measured with polygenic risk scores (PRS); yet, the relationship of atherosclerotic burden with PRS in healthy individuals not at high clinical risk for CAD (i.e., without a high pooled cohort equations [PCE] score) is unknown. Here, we implemented a novel recall-by-PRS strategy to measure coronary artery calcium (CAC) scores prospectively in 53 healthy individuals with extreme high PRS (median [IQR] PRS=94% [83-98]) and low PRS (median [IQR] PRS=3.6% [1.2-10]). The high PRS group was associated with a 2.8-fold greater CAC than the low PRS group, adjusted for age, sex, BMI, smoking, and statin use, and had a 6.7-fold greater proportion of individuals with CAC exceeding 300 HU. These findings reveal that extreme PRS tracks with CAD risk even in those without high clinical risk and demonstrate proof of principle for recall-by-PRS approaches that should be assessed prospectively in larger trials.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Am Heart J: 05 May 2022; epub ahead of print
Forrest IS, Chan L, Chaudhary K, Saha A, ... Nadkarni GN, Do R
Am Heart J: 05 May 2022; epub ahead of print | PMID: 35526571
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Impact:
Abstract

Sacubitril/Valsartan vs. ACEi/ARB at Hospital Discharge and 5-Year Survival in Older Patients with Heart Failure with Reduced Ejection Fraction: A Decision Analysis Approach.

Gilstrap L, Zipkin RJ, Barnes JA, King A, ... Gaziano TA, Tosteson ANA
Background
In clinical trials, sacubitril/valsartan has demonstrated significant survival benefits compared to angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Whether older patients with heart failure with reduced ejection fraction (HFrEF) benefit as much, due to higher rates of comorbidities, frailty and drug discontinuation, is unknown.
Methods and results
Using a cohort of Medicare beneficiaries hospitalized with HFrEF between 2016 and 2018, we determined all-cause mortality and HF-readmission rates among patients not given ACEi/ARB or sacubitril/valsartan at hospital discharge, by age. We then used risk reductions from the SOLVD, PARADIGM-HF and PIONEER-HF trials to estimate the benefits of ACEi/ARB and sacubitril/valsartan. We then incorporated age-specific estimates of drug discontinuation from Medicare. A Markov decision process model was used to simulate 5-year survival and estimate number needed to treat (NNT), comparing discharge on ACEi/ARB vs. sacubitril/valsartan by age. After accounting for drug discontinuation rates, which were surprisingly slightly higher among those discharged on ACEi/ARB (2.3%/month vs. 1.9%/month), there was a small but significant survival advantage to discharge on sacubitril/valsartan over 5 years (+0.81 months [95% CI 0.80, 0.81]). The benefit of sacubitril/valsartan over ACEi/ARB did not decrease with increasing age - the NNT among 66-74-year-old patients was 84 and among 85+ year-old patients was 67.
Conclusions
Even after accounting for \"real world\" rates of drug discontinuation, discharge on sacubitril/valsartan after conferred a small, but significant, survival advantage which does not appear to wane with increasing age.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Am Heart J: 04 May 2022; epub ahead of print
Gilstrap L, Zipkin RJ, Barnes JA, King A, ... Gaziano TA, Tosteson ANA
Am Heart J: 04 May 2022; epub ahead of print | PMID: 35525261
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Impact:
Abstract

A Randomized Multicenter Trial to Evaluate Early Invasive Strategy for Patients with Acute ST-segment Elevation Myocardial Infarction Presenting 24-48 Hours from Symptom Onset: protocol of the RESCUE-MI study.

Gao W, Zhong X, Ma Y, Huang D, ... Qian J, Ge J
Background
For ST-segment elevation myocardial infarction (STEMI) patients presenting 24-48 hours from symptom onset, whether early invasive strategy should be performed still remains controversial.
Methods
This is a prospective, open-label, multicenter, investigator initiated, randomised controlled trial (NCT04962178) to evaluate the efficacy of early invasive strategy for STEMI patients within 24-48h of symptom onset. A total of 366 patients will be included from 10 hospitals in mainland China. They will be randomly (1:1) divided into 2 groups: the early invasive strategy group (primary percutaneous coronary intervention, PPCI) and conservative strategy group (optimal medical therapy with primary PCI not performed).All patients will be followed for 1 month. The primary endpoint is myocardial infarction size on cardiac magnetic resonance (CMR). The secondary endpoints are as follows: 1, major adverse cardiovascular events (MACE), which is defined as a composite of cardiac death, recurrent myocardial infarction, ischemic driven target vessel revascularization and stroke; 2, other CMR endpoints, including microvascular obstruction, intramyocardial hemorrhage, myocardial area at risk, left ventricular ejection fraction, left ventricular end diastolic volume and left ventricular end systolic volume.
Discussion
This study is designed to evaluate the efficacy of early invasive strategy for STEMI patients within 24-48h of symptom onset and will add more evidence for clinical practice.
Trial registration
ClinicalTrials.gov Identifier: NCT04962178. Registered on 14July 2021.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 04 May 2022; epub ahead of print
Gao W, Zhong X, Ma Y, Huang D, ... Qian J, Ge J
Am Heart J: 04 May 2022; epub ahead of print | PMID: 35525262
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Impact:
Abstract

The Effect of Empagliflozin on Contractile Reserve in Heart Failure: Prespecified Sub-Study of a Randomized, Double-Blind, and Placebo-Controlled Trial.

Jensen J, Omar M, Ali M, Frederiksen PH, ... Eifer Møller J, Schou M
Background
Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve cardiac structure but most studies suggest no change in left ventricular (LV) systolic function at rest. Whether SGLT2 inhibitors improve LV contractile reserve is unknown. We investigated the effect of empagliflozin on LV contractile reserve in patients with heart failure (HF) and reduced ejection fraction (HFrEF).
Methods
Prespecified sub-study of the Empire HF trial, a double-blind, placebo-controlled, and randomized trial. Patients with LV ejection fraction (LVEF) ≤40% on guideline-directed HF therapy were randomized (1:1) to empagliflozin 10 mg or placebo for 12 weeks. The treatment effect on contractile reserve was assessed by low dose dobutamine stress echocardiography.
Results
In total, 120 patients were included. The mean age was 68 (SD 10) years, 83% were male, and the mean LVEF was 38 (SD 10) %. Respectively 60 (100%) and 59 (98%) patients in the empagliflozin and placebo groups completed stress echocardiography. No statistically significant effect of empagliflozin was observed for the contractile reserve assessed by LV-GLS [adjusted mean absolute change, empagliflozin versus placebo, 0.7% (95% CI -0.5 to 2.0, P=0.25)] or LVEF [adjusted mean absolute change, empagliflozin versus placebo, 2.2% (95% CI -1.4 to 5.8, P=0.22)] from baseline to 12 weeks. LV-GLS contractile reserve was associated with accelerometer-measured daily activity level [coefficient -24 accelerometer counts (95% CI -46 to -1.8, P=0.03)].
Conclusions
Empagliflozin for 12 weeks added to guideline-directed HF therapy did not improve LV contractile reserve in patients with HFrEF.
Registration
NCT03198585. https://www.
Clinicaltrials
gov/ct2/show/NCT03198585?term=Empire±HF&draw=2&rank=1.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 02 May 2022; epub ahead of print
Jensen J, Omar M, Ali M, Frederiksen PH, ... Eifer Møller J, Schou M
Am Heart J: 02 May 2022; epub ahead of print | PMID: 35513022
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Impact:
Abstract

ReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals (GUARD-AF): Rationale and Design of the GUARD-AF Randomized Trial of Screening for Atrial Fibrillation with a 14-day Patch-Based Continuous ECG Monitor.

Singer DE, Atlas SJ, Go AS, Lopes RD, ... Lenane JC, Aronson RS
Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF. The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic (ECG) patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial\'s efficacy endpoint is hospitalization for stroke (either ischemic or hemorrhagic) and the trial\'s safety endpoint is hospitalization for a bleeding event. Endpoints will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care. Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained. GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous ECG monitor. The results will contribute important information on the yield of patch-based AF screening, the \"burden\" of AF detected (percent time in AF, longest episode), and physicians\' OAC decisions as a function of AF burden. GUARD-AF\'s stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Am Heart J: 23 Apr 2022; epub ahead of print
Singer DE, Atlas SJ, Go AS, Lopes RD, ... Lenane JC, Aronson RS
Am Heart J: 23 Apr 2022; epub ahead of print | PMID: 35472303
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Impact:
Abstract

Dual Antiplatelet Therapy Duration after Percutaneous Coronary Intervention using Drug Eluting Stents in High Bleeding Risk Patients: A Systematic Review and Meta-analysis.

Garg A, Rout A, Farhan S, Waxman S, ... Angiolillo DJ, Rao SV
Background
Optimal dual antiplatelet therapy (DAPT) duration in patients at high bleeding risk (HBR) is not fully defined. We aimed to compare the safety and effectiveness of short-term DAPT (S-DAPT) with longer duration DAPT (L-DAPT) after percutaneous coronary intervention (PCI) with drug eluting stents (DES) in patients at HBR.
Methods
We searched for studies comparing S-DAPT (≤3 months) followed by aspirin or P2Y 12 inhibitor monotherapy against L-DAPT (6-12 months) after PCI in HBR patients. Primary end-points of interest were major bleeding and myocardial infarction (MI). Random-effects meta-analyses were performed to calculate odds ratios with 95% CIs.
Results
Six randomized trials and three propensity-matched studies (n= 16,848) were included in the primary analysis. Compared with L-DAPT (n=8,422), major bleeding was lower with S-DAPT (n=8,426) [OR 0.68; 95% CI 0.51-0.89] whereas MI did not differ significantly between the two groups [1.16; 0.94-1.44]. There were no significant differences in risks of death, stroke or stent thrombosis (ST) between S-DAPT and L-DAPT groups. These findings were consistent when propensity-matched studies were analysed separately. Finally, there was a numerically higher, albeit statistically non-significant, ST in the S-DAPT arm of patients without an indication for OAC [1.98; 0.86-4.58].
Conclusion
Among HBR patients undergoing current generation DES implantation, S-DAPT reduces bleeding without an increased risk of death or MI compared with L-DAPT.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 15 Apr 2022; epub ahead of print
Garg A, Rout A, Farhan S, Waxman S, ... Angiolillo DJ, Rao SV
Am Heart J: 15 Apr 2022; epub ahead of print | PMID: 35436504
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Impact:
Abstract

Computed tomography follow-up after elective proximal aortic surgery: less is more?

de Oliveira Marreiros DJ, Tomšič A, van Brakel TJ, Hamming JF, ... Hjortnaes J, Klautz RJM
Study objective
The added value of computed tomography (CT) follow-up after elective proximal aortic surgery is unclear. We evaluated the benefit of CT follow-up by assessing the incidence of aorta-related complications and reinterventions detected during routine CT follow-up.
Methods
Data on 314 patients undergoing first time elective proximal aortic surgery between 2000 and 2015 were collected. The primary study endpoints were aorta-related complications and reinterventions, detected during routine CT follow-up. Secondary study endpoints included all aorta-related complications and reinterventions, irrespective of the mode of detection and survival.
Results
Median CT follow-up time was 6.8 (IQR 4.1-9.8) years, during which a total of 1303 routine follow-up CT-scans (median 4, IQR 3-5) were performed. During CT follow-up, aorta-related complications were detected in 18 (5.7%) patients, of which 6 (1.6%) underwent reintervention. In total, 28 aorta-related complications were observed in 23 (7.3%) patients, of which 9 led to reintervention. In order to detect one aorta-related complication leading to reintervention, 218 routine follow-up CT-scans were required. The unadjusted and EuroSCORE II adjusted hazard ratios of not undergoing CT follow-up on mortality were 1.260 (95% CI 0.705-2.251) and 0.830 (95% CI 0.430-1.605), respectively.
Conclusions
Following first time elective proximal aortic surgery, aorta-related complications are uncommon, are not always detected during CT follow-up and, if detected, often do not result in reintervention. Therefore, a more conservative CT follow-up protocol could be considered in selected patients to reduce lifetime radiation burden and healthcare costs.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 15 Apr 2022; epub ahead of print
de Oliveira Marreiros DJ, Tomšič A, van Brakel TJ, Hamming JF, ... Hjortnaes J, Klautz RJM
Am Heart J: 15 Apr 2022; epub ahead of print | PMID: 35436505
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Impact:
Abstract

Discontinuing vs. Continuing ACEIs and ARBs in Hospitalized Patients with COVID-19 According to Disease Severity: Insights from the BRACE CORONA Trial.

Macedo AVS, de Barros E Silva PGM, de Paula TC, Moll-Bernardes RJ, ... Alexander JH, Lopes RD
Background
We explored the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with COVID-19 according to baseline disease severity.
Methods
We randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity.
Results
At presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 [SD 6.3] days) and continuation (mean 23.8 [SD 6.5] days), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 [SD 9.5] days) than continuation (mean 21.6 [SD 7.6] days), with a mean ratio of 0.90 (95% CI 0.81-1.00; p-interaction=0.01). The impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity.
Conclusions
Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity.
Clinical trial registration
ClinicalTrials.gov (NCT04364893).

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 08 Apr 2022; epub ahead of print
Macedo AVS, de Barros E Silva PGM, de Paula TC, Moll-Bernardes RJ, ... Alexander JH, Lopes RD
Am Heart J: 08 Apr 2022; epub ahead of print | PMID: 35405099
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Impact:
Abstract

Compression stockings for treating vasovagal syncope (COMFORTS-II) trial: rationale and design of a triple-blind, multi-center, randomized controlled trial.

Tavolinejad H, Poopak A, Sadeghian S, Bozorgi A, ... Aminorroaya A, Tajdini M
Background
Reduced venous return is an important trigger of vasovagal syncope (VVS). Elastic compression stockings (ECS) can modify venous return and be of therapeutic interest; however, evidence for ECS efficacy in VVS is scarce. This randomized controlled trial was designed to address the issue.
Methods
COMFORTS-II is a multicenter, triple-blind, parallel design, randomized controlled trial aimed to assess the efficacy of ECS in preventing VVS recurrences. Using central online randomization, 268 participants will be allocated to two arms (1:1 ratio), wearing intervention ECS (25-30 mmHg pressure) or sham ECS (≤10 mmHg pressure). All participants will receive standard VVS treatment in the form of education, and lifestyle modification recommendations (drinking 2-3 liters/day of fluids and consuming 10 grams/day-roughly half a tablespoon-of table salt). Adherence to ECS treatment will be evaluated through diary sheets, and compared between study arms. Follow-up continues for one year, and is conducted via a 24/7 phone line available to patients and trimonthly visits. The co-primary outcomes are proportion of participants with any syncopal recurrence and time to first syncopal episode. Secondary outcomes include frequency of VVS spells, time intervals between recurrences, and incidence of any patient-reported adverse effects.
Conclusion
To the best of our knowledge, COMFORTS-II is the first clinical trial to assess ECS efficacy among patients with VVS, addressing an important gap in evidence for VVS treatments.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 08 Apr 2022; epub ahead of print
Tavolinejad H, Poopak A, Sadeghian S, Bozorgi A, ... Aminorroaya A, Tajdini M
Am Heart J: 08 Apr 2022; epub ahead of print | PMID: 35405100
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Impact:
Abstract

Association of readmission penalty amount with subsequent 30-day risk standardized readmission and mortality rates among patients hospitalized with heart failure: An analysis of get with the guidelines - heart failure participating centers.

Patel KV, Keshvani N, Pandey A, Vaduganathan M, ... Yancy CW, Fonarow GC
Background
The Hospital Readmissions Reduction Program penalizes hospitals with excess 30-day risk-standardized readmission rates (RSRR) for heart failure (HF). The association of financial penalty amount with subsequent short-term clinical outcomes is unknown.
Methods
Patients admitted to American Heart Association Get With The Guidelines-HF registry participating centers from October 1, 2012 through December 1, 2015 who had Medicare-linked data were included. October 2012 hospital-specific penalty amounts were calculated based on diagnosis-related group payments and excess readmission ratios. Adjusted Cox models were created to evaluate the association of penalty amount categories (non-penalized: 0%; low-penalized: >0%-<0.50%; mid-penalized ≥0.50%-<0.99%; high-penalized ≥0.99%) with subsequent 30-day RSRR and risk-standardized mortality rates (RSMR). Trends in post-discharge 30-day RSRR and RSMR from 2012 to 2015 were analyzed across hospitals stratified by penalty amount categories.
Results
The present study included 61,329 patients who were admitted across 262 hospitals. Compared with patients admitted to non-penalized hospitals (36.3%), those admitted to increasingly penalized hospitals were more likely to have higher 30-day RSRR (low-penalized [43.9%]: HR, 1.10 [95% CI, 1.04-1.16]; mid-penalized [12.0%]: HR, 1.07 [95% CI, 0.99-1.16]; high-penalized [7.9%]: HR, 1.23 [95% CI, 1.12-1.35]) but not 30-day RSMR. Over time, 30-day RSRR and RSMR did not meaningfully change across penalized versus non-penalized hospitals.
Conclusions
Financial penalties based on 30-day RSRR are not associated with declines in 30-day RSRR or RSMR from 2012 to 2015 among patients hospitalized with HF. Financially penalizing hospitals based on current Hospital Readmissions Reduction Program metrics may not incentivize improvements in short-term clinical outcomes for HF.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 30 Mar 2022; 246:1-11
Patel KV, Keshvani N, Pandey A, Vaduganathan M, ... Yancy CW, Fonarow GC
Am Heart J: 30 Mar 2022; 246:1-11 | PMID: 34973189
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Impact:
Abstract

Challenges of long-term dual antiplatelet therapy use following acute coronary syndromes.

Sidhu MS, Lyubarova R, Bangalore S, Bonaca MP
An acute coronary syndrome (ACS) event is associated with a high risk of recurrent ACS, stroke, and death. To ameliorate the risk of subsequent events, current guidelines for ST-segment elevation myocardial infarction and non-ST-segment elevation ACS recommend long-term management strategies for secondary prevention including risk factor modification and anti-ischemic and antiplatelet therapies. Dual antiplatelet therapy (DAPT), comprising aspirin plus a P2Y12 inhibitor, is a critical component of secondary prevention therapy following ACS. However, despite the importance of DAPT for secondary prevention after ACS, questions remain over the optimal duration of therapy. Clinical evidence is emerging that maintenance DAPT >12 months lowers the risk of recurrent ACS events; however, this benefit must be considered against any potential risks of prolonged DAPT such as bleeding. Several tools for bleeding risk assessment have shown promise; however, their limited accuracy and discriminative power necessitates further development. Assessment of patient ischemic risk should consider the complexity of the percutaneous coronary intervention (PCI) procedure, anatomic burden of coronary artery disease, and additional underlying risk factors. Consequently, identifying patients in whom the risk:benefit ratio favors prolonged DAPT may prove invaluable for clinicians in deciding which patients should continue or stop taking DAPT at 12 months after PCI, or consider P2Y12 inhibitor monotherapy as an option. This article reviews the most recent information about the risks and benefits of DAPT continued for >12 months after ACS and provides critical guidance to assist physicians in identifying patients most likely to benefit from a secondary prevention strategy with DAPT.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:44-64
Sidhu MS, Lyubarova R, Bangalore S, Bonaca MP
Am Heart J: 30 Mar 2022; 246:44-64 | PMID: 34933000
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Impact:
Abstract

Out-of-pocket payments for part d covered medications by medicare fee-for-service beneficiaries with heart failure with reduced ejection fraction.

Fendrick AM, Djatche L, Pulungan Z, Teigland C, ... Hilkert R, Mentz R
Background
Out-of-pocket (OOP) drug costs for Medicare Fee-for-Service (FFS) beneficiaries with heart failure with reduced ejection fraction (HFrEF) are not well characterized. This study evaluated Part D OOP spending by Medicare beneficiaries with chronic HFrEF, stratified by those with and without a worsening HF event (WHFE).
Methods
Medicare FFS 100% Part D claims were used to identify HFrEF patients with 12 months of continuous Part D enrollment in 2018. HFrEF was defined as 1 inpatient or 2 outpatient claims of systolic HF or 1 systolic HF plus 1 HF outpatient claim. WHFE was defined as having a HF hospitalization or intravenous diuretic use within 12 months of HFrEF index date. OOP costs by Medicare Part D coverage phase for all covered drugs were calculated for HFrEF patients, and those with and without WHFE.
Results
Of 305,373 Medicare patients with HFrEF, 26% had a WHFE. Total mean (SD) OOP drug costs among all HFrEF patients was $1,166 (1,205)/year. Patients with WHFE and patients without WHFE had respectively a mean (SD) annual OOP costs of $1,302 (1,273) and $1,117 (1,176). Over 39% of HFrEF patients entered the \"donut hole\" (44% and 37% of patients with WHFE and without WHFE, respectively), while 11% of HFrEF patients entered the catastrophic phase (13% and 10% of patients with and without WHFE, respectively).
Conclusions
More than 1 in 10 patients with heart failure entered the catastrophic phase within Medicare-Fee-For-Service, whereas in 2018 only 10% of costs were attributable to heart failure medication and 90% to comorbidities.

Copyright © 2021 Merck Sharp & Dohme Corp,, The Author(s). Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:74-81
Fendrick AM, Djatche L, Pulungan Z, Teigland C, ... Hilkert R, Mentz R
Am Heart J: 30 Mar 2022; 246:74-81 | PMID: 34774543
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Impact:
Abstract

Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts.

Bagiella E, Puskas JD, Moskowitz AJ, Gelijns AC, ... Mack MJ, Goldstein DJ
Background
Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery.
Methods
The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization.
Conclusions
The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:12-20
Bagiella E, Puskas JD, Moskowitz AJ, Gelijns AC, ... Mack MJ, Goldstein DJ
Am Heart J: 30 Mar 2022; 246:12-20 | PMID: 34936861
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Impact:
Abstract

Socioeconomic disparities in healthcare utilization for atherosclerotic cardiovascular disease.

Jain B, Bajaj SS, Paguio JA, Yao JS, ... Dee EC, Bhatt DL
Background
The impact of the social determinants of health on healthcare utilization for patients with atherosclerotic cardiovascular disease (ASCVD) remains incompletely characterized.
Methods
We queried the National Health Interview Survey from 2000-2018 to examine disparities in healthcare utilization metrics by education, income-to-poverty ratio, and health insurance coverage for adults with self-reported ASCVD.
Results
We show that, while education and income-to-poverty ratios demonstrated significant disparities for provider visits and preventive screenings, the largest disparities were noted for health insurance coverage.
Conclusions
These trends suggest that efforts to expand private or government insurance to improve coverage for patients with ASCVD may address healthcare utilization-based disparities.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:161-165
Jain B, Bajaj SS, Paguio JA, Yao JS, ... Dee EC, Bhatt DL
Am Heart J: 30 Mar 2022; 246:161-165 | PMID: 35093303
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Impact:
Abstract

Risk and predictors of mortality after implantable cardioverter-defibrillator implantation in patients with sarcoid cardiomyopathy.

Higgins AY, Annapureddy AR, Wang Y, Minges KE, ... Miller EJ, Freeman JV
Background
Implantable cardioverter-defibrillators (ICDs) are recommended for patients with cardiac sarcoidosis (CS) with an indication for pacing, prior ventricular arrhythmias, cardiac arrest, or left ventricular ejection fraction <35%, but data on outcomes are limited.
Methods
Using data from the National Cardiovascular Data Registry ICD Registry between April 1, 2010 and December 31, 2015, we evaluated a propensity matched cohort of CS patients implanted with ICDs versus non-ischemic cardiomyopathies (NICM). We compared mortality using Kaplan-Meier survival curves and Cox proportional hazards models.
Results
We identified 1,638 patients with CS and 8,190 propensity matched patients with NICM. The rate of death at 1 and 2 years was similar in patients with CS and patients with NICM (5.2% vs 5.4%, P = 0.75 and 9.0% vs 9.3%, P = 0.72, respectively). After adjusting for other covariates, patients with CS had similar mortality at 2 years after ICD implantations compared with NICM patients (RR 1.03, 95% CI 0.87-1.23). Among patients with CS, multivariable logistic regression identified 6 factors significantly associated with increased 2-year mortality: presence of heart failure (HR 1.92, 95% CI 1.44-3.22), New York Heart Association (NYHA) Class III heart failure (HR 1.68, 95% CI 1.16-2.45), NYHA Class IV heart failure (HR 3.08, 95% CI 1.49-6.39), atrial fibrillation/flutter (HR 1.66, 95% CI 1.17-2.35), chronic lung disease (HR 1.64, 95% CI 1.17-2.29), creatinine >2.0 mg/dL (HR 4.07, 95% CI 2.63-6.30), and paced rhythm (HR 2.66, 95% CI 1.07-6.59).
Conclusion
Mortality following ICD implantation was similar in CS patients compared with propensity matched NICM patients. Presence of heart failure, NYHA class, atrial fibrillation/flutter, chronic lung disease, renal dysfunction, and paced rhythm at time of implantation were all predictors of increased 2-year mortality among CS patients with ICDs.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Mar 2022; 246:21-31
Higgins AY, Annapureddy AR, Wang Y, Minges KE, ... Miller EJ, Freeman JV
Am Heart J: 30 Mar 2022; 246:21-31 | PMID: 34968442
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Impact:
Abstract

One-year outcome after percutaneous coronary intervention in nonagenarians: Insights from the J-PCI OUTCOME registry.

Otowa K, Kohsaka S, Sawano M, Matsuura S, ... Nakamura M, Ikari Y
Background
Nonagenarian patients who undergo percutaneous coronary intervention (PCI) are increasing, and a few previous studies have reported their long-term outcomes. However, differences in their long-term outcomes between generations remain unclear. This study aimed to investigate 1-year all-cause and cardiovascular (CV) mortality, and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke) of nonagenarian patients who underwent PCI compared with the other elder patients, using a nationwide registration system.
Methods
The patient-level data registered between January 2017 and December 2017 was extracted from the J-PCI OUTCOME Registry endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT). The one-year all-cause and cardiovascular (CV) mortality, MACE, and major bleeding events were identified.
Results
Out of 40,722 patients over 60 years of age, 880 (2.1%) were nonagenarians. For nonagenarians, the 1-year mortality rate was substantial (13.5%). The MACE and CV death rates were also high (8.1%, and 6.8%, respectively) for nonagenarians, and these event rates were approximately 1.5 times higher in nonagenarians than octogenarians. Multivariate regression analysis showed that presentation with cardiogenic shock [hazard ratio (HR) 2.32; 95 confidence intervals (CI): 1.22-4.41], or cardiac arrest (HR 2.91; 90% CI: 1.28-6.62), and use of oral anticoagulants (HR 2.10; 90% CI: 1.07-4.12) were the predictors of 1-year MACE.
Conclusions
Even in the contemporary era, nonagenarians who have undergone PCI still face a considerably increased risk for adverse cardiovascular events that reduces long-term survival. In addition to having poorer lesion characteristics, adverse events, including death, MACEs, and major bleeding, occurred 1.5 times more frequently in nonagenarians than in octogenarians.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:105-116
Otowa K, Kohsaka S, Sawano M, Matsuura S, ... Nakamura M, Ikari Y
Am Heart J: 30 Mar 2022; 246:105-116 | PMID: 35016854
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Impact:
Abstract

Association of plasma endothelin-1 with blood pressure progression among Blacks: The Jackson Heart Study.

Kaze AD, Gao X, Musani SK, Bidulescu A, ... Abdalla M, Echouffo-Tcheugui JB
Background
Despite pathophysiological links between endothelin (ET)-1 and hypertension in Black adults, there is no population-based data appraising the association of plasma ET-1 with longitudinal blood pressure (BP) changes in Blacks.
Methods
We analyzed data from 1197 Jackson Heart Study participants without hypertension (mean age 47.8 years [SD: 12.0]; 64.2% women), with plasma ET-1 available at the baseline examination (2000-2004). Poisson regression with robust variance was used to generate risk ratios (RRs) and 95% confidence intervals (CIs) of BP progression (an increase by ≥1 BP category based on the 2017 American College of Cardiology/American Heart Association classification) and incident hypertension (BP ≥ 130/80 mm Hg or use of antihypertensive medication) at follow-up (2005-2008 or 2009-2013).
Results
Over a median follow-up of 7 years (range: 4-11), 71.2% (n = 854) progressed to a higher BP stage and 64.6% (n = 773) developed hypertension. After adjusting for possible confounders, each unit increment in baseline log (ET-1) was associated with higher risks of BP progression (RR 1.15 [95% CI 1.03-1.29], P = .016) and incident hypertension (RR 1.15 [95% CI 1.01-1.31], P = .032). Compared to those in the lowest ET-1 quartile, participants in the highest quartile had significantly higher risks of BP progression (RR 1.20 [95% CI 1.05-1.37], P = .007) and incident hypertension (RR 1.16 [95% CI 1.00-1.36], P = .052).
Conclusions
In a large, community-based sample of African Americans, higher plasma ET-1 concentrations were associated with higher risks of BP progression and incident hypertension.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:144-151
Kaze AD, Gao X, Musani SK, Bidulescu A, ... Abdalla M, Echouffo-Tcheugui JB
Am Heart J: 30 Mar 2022; 246:144-151 | PMID: 34986393
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Impact:
Abstract

Rationale and design of a study to assess the safety and efficacy of rNAPc2 in COVID-19: the Phase 2b ASPEN-COVID-19 trial.

Hess CN, Capell WH, Bristow MR, Ruf W, ... Hsia J, Bonaca MP
Background
The interaction between thrombosis and inflammation appears central to COVID-19-associated coagulopathy and likely contributes to poor outcomes. Tissue factor is a driver of disordered coagulation and inflammatory signaling in viral infections and is important for viral replication; therefore, tissue factor may be an important therapeutic target in COVID-19.
Study design
ASPEN-COVID-19 (NCT04655586) is a randomized, prospective open-label blinded endpoint (PROBE), active comparator Phase 2b trial to evaluate the safety and efficacy of recombinant Nematode Anticoagulant Protein c2 (rNAPc2), a potent tissue factor inhibitor, in patients hospitalized with COVID-19 with elevated D-dimer levels. This report describes the design of the Phase 2b dose ranging and proof of concept study. Participants are randomly assigned, in a 1:1:2 ratio, to lower or higher dose rNAPc2 by subcutaneous injection on days 1, 3, and 5 or to heparin according to local standard of care; randomization is stratified by baseline D-dimer level (at 2X upper limit of normal). The primary efficacy endpoint for Phase 2b is proportional change in D-dimer concentration from baseline to Day 8 or day of discharge, whichever is earlier. The primary safety endpoint is major or non-major clinically relevant bleeding through Day 8. Phase 2b enrollment began in December 2020 and is projected to complete ∼160 participants by Q4 2021.
Conclusions
ASPEN-COVID-19 will provide important data on a novel therapeutic approach that may improve outcomes in hospitalized COVID-19 patients beyond available anticoagulants by targeting tissue factor, with potential effects on not only thrombosis but also inflammation and viral propagation.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:136-143
Hess CN, Capell WH, Bristow MR, Ruf W, ... Hsia J, Bonaca MP
Am Heart J: 30 Mar 2022; 246:136-143 | PMID: 34986394
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Impact:
Abstract

The influence of heart failure on clinical and economic outcomes among older adults ≥75 years of age with acute myocardial infarction.

Pasala S, Cooper LB, Psotka MA, Sinha SS, ... Batchelor W, Damluji AA
Background
We aimed to evaluate the influence of heart failure (HF) on clinical and economic outcomes among older adults ≥75 years of age during their acute myocardial infarction (AMI) admission in large population-based study from the United States. We also evaluated the clinical characteristics associated with the presence of HF and the predictors of mortality, healthcare utilization, and cost among older adults with AMI.
Methods
From January 1, 2000, to December 31, 2016, AMI admission was identified using the primary diagnosis and concomitant HF was identified using any non-primary diagnoses in the Premier Healthcare Database.
Results
Of the 468,654 patients examined, 42,946 (9%) had concomitant HF during their AMI admission. These patients were older, more often female, and were more likely to be White. Patients with concomitant HF were more likely to be frail than non-HF patients (59% vs 15%, P < .001). The mean (SD) Elixhauser comorbidity index was 2.6 (2.5) vs 0.4 (1.1), P < .001 in the AMI with HF vs AMI only group. The use of percutaneous coronary intervention in those with AMI and HF was lower than those with AMI only (15% vs 31%, P < .001). The overall mortality rate for those with HF was 12%, the median [IQR] hospital length of stay was 5 [3,9] days, and only 25% of patients were discharged home. A higher proportion of patients were discharged to rehabilitation or hospice if they had AMI and HF (Rehabilitation: 33% vs 20%, P < .001; Hospice: 5% vs 3%, P < .001). The mean unadjusted cost of an AMI hospitalization in patients with concomitant HF was lower ($12,411 ± $14,860) than in those without HF ($15,828 ± $19,330). After adjusting for age, gender, race, hypertension, frailty, revascularization strategy, and death, the average cost of hospitalization attributed to concomitant HF was +$1,075 (95% CI +876 to $1,274) when compared to AMI patients without HF.
Conclusion
In patients ≥75 years of age, AMI with concomitant HF carries higher risk of death, but at ages ≥85 years, the risk difference diminishes due to other competing risks. HF was also associated with longer hospital length of stay and higher likelihood of referral to hospice and rehabilitation facilities when compared to older patients without HF. Care for these older adults is associated with increased hospitalization costs. Measures to identify HF in older adults during their AMI admission are necessary to optimize health outcomes, care delivery, and costs.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:65-73
Pasala S, Cooper LB, Psotka MA, Sinha SS, ... Batchelor W, Damluji AA
Am Heart J: 30 Mar 2022; 246:65-73 | PMID: 34922928
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Impact:
Abstract

Same day discharge following non-elective PCI for non-ST elevation acute coronary syndromes.

Hariri E, Kassas I, Hammoud MA, Hansra B, ... Smith CS, Barringhaus KG
Background:
and aim
Timing of discharge after percutaneous coronary intervention (PCI) is a crucial aspect of procedural safety and patient turnover. We examined predictors and outcomes of same-day discharge (SDD) after non-elective PCI for non-ST elevation acute coronary syndromes (NSTE-ACS) in comparison with next-day discharge (NDD).
Methods
Baseline demographic, clinical, and procedural data were collected as were in-hospital outcomes and post-PCI length of stay (LOS) for all patients undergoing non-elective PCI for NSTE-ACS between 2011 and 2014 at a central tertiary care center. Thirty day and 1-year mortality and bleeding as well as 30-day readmission rates were determined from social security record and medical chart review. Logistic regression was performed to identify predictors of SDD, and propensity-matched analysis was done to examine the differences in outcomes between NDD and SDD.
Results
Out of 2,529 patients who underwent non-elective PCI for NSTE-ACS from 2011 to 2014, 1,385 met the inclusion criteria (mean age = 63 years; 26% women) and were discharged either the same day of (N = 300) or the day after (N = 1,085) PCI. Thirty-day and one-year mortality and major bleeding rates were similar between the 2 groups. Logistic regression identified male sex, radial access, negative troponin biomarker status, and procedure start time as predictors of SDD. In propensity-matched analyses, there was no difference in 30-day mortality and readmission between SDD and NDD groups.
Conclusions
SDD after non-elective PCI for NSTE-ACS may be a reasonable alternative to NDD for selected low-risk patients with comparable mortality, bleeding, and readmission rates.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:125-135
Hariri E, Kassas I, Hammoud MA, Hansra B, ... Smith CS, Barringhaus KG
Am Heart J: 30 Mar 2022; 246:125-135 | PMID: 34998967
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Impact:
Abstract

Association between race/ethnicity and income on the likelihood of coronary revascularization among postmenopausal women with acute myocardial infarction: Women\'s health initiative study.

Tertulien T, Roberts MB, Eaton CB, Cene CW, ... Nassir R, Breathett K
Background
Historically, race, income, and gender were associated with likelihood of receipt of coronary revascularization for acute myocardial infarction (AMI). Given public health initiatives such as Healthy People 2010, it is unclear whether race and income remain associated with the likelihood of coronary revascularization among women with AMI.
Methods
Using the Women\'s Health Initiative Study, hazards ratio (HR) of revascularization for AMI was compared for Black and Hispanic women vs White women and among women with annual income <$20,000/year vs ≥$20,000/year over median 9.5 years follow-up(1993-2019). Proportional hazards models were adjusted for demographics, comorbidities, and AMI type. Results were stratified by revascularization type: percutaneous coronary intervention and coronary artery bypass grafting(CABG). Trends by race and income were compared pre- and post-2010 using time-varying analysis.
Results
Among 5,284 individuals with AMI (9.5% Black, 2.8% Hispanic, and 87.7% White; 23.2% <$20,000/year), Black race was associated with lower likelihood of receiving revascularization for AMI compared to White race in fully adjusted analyses [HR:0.79(95% Confidence Interval:[CI]0.66,0.95)]. When further stratified by type of revascularization, Black race was associated with lower likelihood of percutaneous coronary intervention for AMI compared to White race [HR:0.72(95% CI:0.59,0.90)] but not for CABG [HR:0.97(95%CI:0.72,1.32)]. Income was associated with lower likelihood of revascularization [HR:0.90(95%CI:0.82,0.99)] for AMI. No differences were observed for other racial/ethnic groups. Time periods (pre/post-2010) were not associated with change in revascularization rates.
Conclusion
Black race and income remain associated with lower likelihood of revascularization among patients presenting with AMI. There is a substantial need to disrupt the mechanisms contributing to race, sex, and income disparities in AMI management.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:82-92
Tertulien T, Roberts MB, Eaton CB, Cene CW, ... Nassir R, Breathett K
Am Heart J: 30 Mar 2022; 246:82-92 | PMID: 34998968
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Impact:
Abstract

Early detection of obstructive coronary artery disease in the asymptomatic high-risk population: objectives and study design of the EARLY-SYNERGY trial.

Ties D, van Dorp P, Pundziute G, van der Aalst CM, ... Oudkerk M, van der Harst P
Background
Coronary artery disease (CAD) burden for society is expected to steeply increase over the next decade. Improved feasibility and efficiency of preventive strategies is necessary to flatten the curve. Acute myocardial infarction (AMI) is the main determinant of CAD-related mortality and morbidity, and predominantly occurs in individuals with more advanced stages of CAD causing subclinical myocardial ischemia (obstructive CAD; OCAD). Unfortunately, OCAD can remain subclinical until its destructive presentation with AMI or sudden death. Current primary preventive strategies are not designed to differentiate between non-OCAD and OCAD and the opportunity is missed to treat individuals with OCAD more aggressively.
Methods
EARLY-SYNERGY is a multicenter, randomized-controlled clinical trial in individuals with coronary artery calcium (CAC) presence to study (1.) the yield of cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) for early OCAD diagnosis and (2) whether early OCAD diagnosis improves outcomes. Individuals with CAC score ≥300 objectified in 2 population-based trials (ROBINSCA; ImaLife) are recruited for study participation. Eligible candidates are randomized 1:1 to cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) or no additional functional imaging. In the CMR-MPI arm, feedback on imaging results is provided to primary care provider and participant in case of guideline-based actionable findings. Participants are followed-up for clinical events, healthcare utilization and quality of life.
Conclusions
EARLY-SYNERGY is the first randomized-controlled clinical trial designed to test the hypothesis that subclinical OCAD is widely present in the general at-risk population and that early differentiation of OCAD from non-OCAD followed by guideline-recommended treatment improves outcomes.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:166-177
Ties D, van Dorp P, Pundziute G, van der Aalst CM, ... Oudkerk M, van der Harst P
Am Heart J: 30 Mar 2022; 246:166-177 | PMID: 35038412
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Impact:
Abstract

Prevalence and prognostic significance of ischemic late gadolinium enhancement pattern in non-ischemic dilated cardiomyopathy.

De Angelis G, De Luca A, Merlo M, Nucifora G, ... Muser D, Sinagra G
Background
Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM.
Methods
A total of 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation.
Results
Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, P = .006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055-4.015], P = .034 with respect to non-ischemic LGE).
Conclusions
The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 30 Mar 2022; 246:117-124
De Angelis G, De Luca A, Merlo M, Nucifora G, ... Muser D, Sinagra G
Am Heart J: 30 Mar 2022; 246:117-124 | PMID: 35045326
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Impact:
Abstract

Ertugliflozin to reduce arrhythmic burden in ICD/CRT patients (ERASe-trial) - A phase III study.

von Lewinski D, Tripolt NJ, Sourij H, Pferschy PN, ... Scherr D, ERASe study group
Sodium glucose cotransporter 2 (SGLT2) have proven profound positive effects in heart failure with reduced ejection fraction (HFrEF). These effects are independent from the presence of diabetes. Metabolic effects, antiinflammatory, and antifibrotic properties are discussed as underlying mechanisms. Despite a strong correlation of ventricular arrhythmias with HFrEF, the impact of ertugliflozin on the ventricular arrhythmic burden has not been investigated, yet. Therefore, the Ertugliflozin to Reduce Arrhythmic burden in ICD ± CRT patientS (ERASe) trial was designed to investigate the efficacy and safety of ertugliflozin in patients with reduced and midrange ejection fraction (EF) with or without diabetes.
Methods:
Within a multicentre, national, randomized, double-blind, placebo-controlled, phase 3b trial we aim to enrol a total of 402 patients across Austria. Patients with reduced or midrange EF and ICD ± CRT therapy >3 months and previous ventricular tachycardia (at least 10 documented VT episodes within the last 12 months) are randomized in a 1:1 ratio to ertugliflozin (5 mg once daily orally administered) or matching placebo. The primary endpoint of the ERASe trial is to investigate the impact of ertugliflozin on total burden of ventricular arrhythmias. Further objectives will include number of therapeutic interventions of implanted devices, atrial fibrillation and heart failure biomarkers.
Conclusion:
The ERASe trial will be the first trial to test ertugliflozin in heart failure patients with nonpreserved ejection fraction and ongoing ICD ± CRT therapy regardless of their diabetic status. The ERASe trial may therefore extend the concept of SGLT2 inhibition to improve cardiac remodelling, including reduced arrhythmic burden. Trial registration Identifier EudraCT Nr. 2020-002581-14 / ClinicalTrials.gov Identifier: NCT04600921.


Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:152-160
von Lewinski D, Tripolt NJ, Sourij H, Pferschy PN, ... Scherr D, ERASe study group
Am Heart J: 30 Mar 2022; 246:152-160 | PMID: 35045327
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Impact:
Abstract

Angiography-derived physiology guidance vs usual care in an All-comers PCI population treated with the healing-targeted supreme stent and Ticagrelor monotherapy: PIONEER IV trial design.

Hara H, Serruys PW, O\'Leary N, Gao C, ... Onuma Y, PIONEER IV trial investigator
Background
Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI).
Methods/design
The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent\'s fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR<0.91 distal to the stent, or if the delta QFR (across the stent) is >0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non-inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non-inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years.
Summary
The PIONEER IV trial aims to demonstrate non-inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy.
Clinical trial registration
ClinicalTrials.gov UNIQUE IDENTIFIER: NCT04923191 CLASSIFICATIONS: Interventional Cardiology.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 30 Mar 2022; 246:32-43
Hara H, Serruys PW, O'Leary N, Gao C, ... Onuma Y, PIONEER IV trial investigator
Am Heart J: 30 Mar 2022; 246:32-43 | PMID: 34990582
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Impact:
Abstract

Clinical events classification (CEC) in clinical trials: Report on the current landscape and future directions - proceedings from the CEC Summit 2018.

Sharma A, Mahaffey KW, Gibson CM, Hicks KA, ... Wilson M, Lopes RD
Importance
Clinical events adjudication is pivotal for generating consistent and comparable evidence in clinical trials. The methodology of event adjudication is evolving, but research is needed to develop best practices and spur innovation.
Observations
A meeting of stakeholders from regulatory agencies, academic and contract research organizations, pharmaceutical and device companies, and clinical trialists convened in Chicago, IL, for Clinical Events Classification (CEC) Summit 2018 to discuss key topics and future directions. Formal studies are lacking on strategies to optimize CEC conduct, improve efficiency, minimize cost, and generally increase the speed and accuracy of the event adjudication process. Major challenges to CEC discussed included ensuring rigorous quality of the process, identifying safety events, standardizing event definitions, using uniform strategies for missing information, facilitating interactions between CEC members and other trial leadership, and determining the CEC\'s role in pragmatic trials or trials using real-world data. Consensus recommendations from the meeting include the following: (1) ensure an adequate adjudication infrastructure; (2) use negatively adjudicated events to identify important safety events reported only outside the scope of the primary endpoint; (3) conduct further research in the use of artificial intelligence and digital/mobile technologies to streamline adjudication processes; and (4) emphasize the importance of standardizing event definitions and quality metrics of CEC programs.

Conclusions:
and relevance
As novel strategies for clinical trials emerge to generate evidence for regulatory approval and to guide clinical practice, a greater understanding of the role of the CEC process will be critical to optimize trial conduct and increase confidence in the data generated.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2022; 246:93-104
Sharma A, Mahaffey KW, Gibson CM, Hicks KA, ... Wilson M, Lopes RD
Am Heart J: 30 Mar 2022; 246:93-104 | PMID: 34973948
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Impact:
Abstract

Preexisting frailty and outcomes in older patients with acute myocardial infarction.

Udell JA, Lu D, Bagai A, Dodson JA, ... Roe MT, Alexander KP
Background
Little is known about the prevalence and prognostic impact of preexisting frailty on acute care and in-hospital outcomes in older adults in the setting of acute myocardial infarction (AMI).
Methods
Preexisting frailty was assessed at baseline in consecutive AMI patients ≥65 years of age treated at 778 hospitals participating in the NCDR ACTION Registry between January 1, 2015 to December 31, 2016. Three domains of preexisting frailty (cognition, ambulation, and functional independence) were abstracted from chart review and summed in 2 ways: an ACTION Frailty Scale based on responses to 6 groups adapted from the Canadian Study of Health and Aging Clinical Frailty Scale and an ACTION Frailty Score derived by summing a rank score of 0-2 assigned for each grade (total ranged between 0 to 6). Multivariable logistic regression examined the association between assigned frailty by score or scale and in-hospital mortality.
Results
Among 143,722 older AMI patients, 108,059 (75.2%) were fit and/or well and 6,484 (4.5%) were vulnerable to frailty, while 7,527 (5.2%) had mild, 3,913 (2.7%) had moderate, 2,715 had (1.9%) severe, and 632 (0.4%) had very severe frailty according to the ACTION Frailty Scale, while 14,392 (10.0%) could not be categorized due to incomplete ascertainment. Frail patients were older, more frequently female, of non-white race and/or ethnicity, and less likely to be treated with guideline-recommended therapies. Increasing severity of frailty by this scale was associated with a step-wise higher risk for in-hospital mortality (P-trend < .001). Patient categories of the ACTION Frailty Score provided similar results. After adjustment, each 1-unit increase in Frailty Score was associated with a 12% higher mortality risk (OR 1.12, 95% CI 1.10-1.15).
Conclusions
Among older patients with acute myocardial infarction, frailty is common and independently associated with in-hospital mortality. These findings show the importance of pragmatic evaluation of frailty in hospital-level quality scores, guideline recommendations, and incorporation into other registry data collection efforts.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 24 Mar 2022; 249:34-44
Udell JA, Lu D, Bagai A, Dodson JA, ... Roe MT, Alexander KP
Am Heart J: 24 Mar 2022; 249:34-44 | PMID: 35339451
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Impact:
Abstract

Balance of benefit and risk of ticagrelor in patients with diabetes and stable coronary artery disease according to bleeding risk assessment with the CRUSADE score: Data from THEMIS and THEMIS PCI.

Ducrocq G, Bhatt DL, Lee JJ, Kui N, ... Simon T, Steg PG
Background
The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population.
Methods
The population was divided into tertiles: score ≤22, 23 to 33, and ≥34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted.
Results
Patients in the lower risk tertile experienced fewer ischemic events with ticagrelor than placebo, whereas there was no significant benefit from ticagrelor in the other tertiles (Pinteraction = .008). Bleeding rates were consistently increased with ticagrelor across all tertiles (Pinteraction = .79). Ticagrelor reduced NACE in the first tertile (HR = 0.74, 95% CI = 0.61-0.90) but not in the others (HR = 1.03, 95% CI = 0.86-1.23 and HR = 1.05, 95% CI = 0.91-1.22, respectively; Pinteraction = .012).
Conclusions
In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 20 Mar 2022; 249:23-33
Ducrocq G, Bhatt DL, Lee JJ, Kui N, ... Simon T, Steg PG
Am Heart J: 20 Mar 2022; 249:23-33 | PMID: 35321823
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Impact:
Abstract

Variation in statin prescription among veterans with HIV and known atherosclerotic cardiovascular disease.

Erqou S, Papaila A, Halladay C, Ge A, ... Wu WC, Rudolph JL
Background
People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population.
Objective
Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD.
Methods
We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription.
Results
Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use.
Conclusion
In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 19 Mar 2022; 249:12-22
Erqou S, Papaila A, Halladay C, Ge A, ... Wu WC, Rudolph JL
Am Heart J: 19 Mar 2022; 249:12-22 | PMID: 35318028
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Impact:
Abstract

Double-Blind, Placebo-Controlled Evaluation of Biorest Liposomal Alendronate in Diabetic Patients Undergoing PCI: The BLADE-PCI Trial: The BLADE-PCI Trial.

Généreux P, Chernin G, Assali AR, Peruga JZ, ... Stone GW, Jonas M
Background
Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the BLADE-PCI trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI with drug-eluting stents (DES) in reducing NIH as measured by optical coherence tomography (OCT) post-procedure in patients with DM.
Methods
Patients with DM were randomized to a bolus infusion of LABR-312 versus placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by OCT.
Results
From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3%±9.2 versus 14.6%±8.5, p=0.35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups.
Conclusions
Among patients with DM undergoing PCI with DES, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Am Heart J: 16 Mar 2022; epub ahead of print
Généreux P, Chernin G, Assali AR, Peruga JZ, ... Stone GW, Jonas M
Am Heart J: 16 Mar 2022; epub ahead of print | PMID: 35305955
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Impact:
Abstract

Independence of Clinical Events Committees: A Consensus Statement from Clinical Research Organizations.

Spitzer E, Fanaroff AC, Gibson CM, Seltzer J, ... Mahaffey KW, Lopes RD
Randomized clinical trials (RCTs) are the gold standard to assess the causal relationship between an intervention and subsequent outcomes, also known as clinical endpoints. In order to limit bias, central clinical events committees (CEC) are established to ensure consistent event reporting across participating centers, as well as complete and accurate ascertainment of all endpoints. The adjudicators are clinicians with expertise in research methodology within the trial-specific therapeutic area, who are charged with determining whether each potential event conforms to the trial endpoint definition. RCTs employing standardized definitions are powerful tools for reducing bias, but they are not infallible. In fact, the vulnerability of clinical research to a myriad of biases has encouraged scientists, clinical research organizations, and regulatory agencies to design strategies for bias mitigation that are central to ensuring the credibility of findings. Given these considerations, assessment of the independence of adjudicators has become a priority among organizations coordinating CECs; however, no standard definition of CEC member independence has been developed. The current consensus statement leverages from previous consensus regarding the definition of DSMB independence to create a standardized definition of independent CEC (ICEC). In addition, it provides guidance on best practices and implementation of ICECs.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 12 Mar 2022; epub ahead of print
Spitzer E, Fanaroff AC, Gibson CM, Seltzer J, ... Mahaffey KW, Lopes RD
Am Heart J: 12 Mar 2022; epub ahead of print | PMID: 35296411
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Impact:
Abstract

Randomized Evaluation of Vessel Preparation With Orbital Atherectomy Prior to Drug-Eluting Stent Implantation in Severely Calcified Coronary Artery Lesions: Design and Rationale of the ECLIPSE Trial.

Généreux P, Kirtane AJ, Kandzari DE, Armstrong EJ, ... O\'Neill WW, Stone GW
Background
Severe coronary artery calcification has been associated with stent underexpansion, procedural complications, and increased rates of early and late adverse clinical events in patients undergoing percutaneous coronary intervention (PCI). To date, no lesion preparation strategy has been shown to definitively improve outcomes of PCI for calcified coronary artery lesions.
Study design and objectives
ECLIPSE (NCT03108456) is a prospective, randomized, multicenter trial designed to evaluate two different vessel preparation strategies in severely calcified coronary artery lesions. The routine use of the Diamondback 360® Coronary Orbital Atherectomy System (OAS) is compared with conventional balloon angioplasty prior to drug-eluting stent implantation. The trial aims to enroll approximately 2000 subjects with a primary clinical endpoint of target vessel failure, defined as the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization assessed at 1 year. The co-primary endpoint is the acute post-procedural in-stent minimal cross-sectional area as assessed by optical coherence tomography in a 500-subject cohort. Enrollment is anticipated to complete in 2022 with total clinical follow-up planned for 2 years.
Conclusions
ECLIPSE is a large-scale, prospective randomized trial powered to demonstrate whether a vessel preparation strategy of routine OAS is superior to conventional balloon angioplasty prior to implantation of drug-eluting stents in severely calcified coronary artery lesions.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 10 Mar 2022; epub ahead of print
Généreux P, Kirtane AJ, Kandzari DE, Armstrong EJ, ... O'Neill WW, Stone GW
Am Heart J: 10 Mar 2022; epub ahead of print | PMID: 35288105
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Impact:
Abstract

Surrogate markers of gut dysfunction are related to heart failure severity and outcome - from the BIOSTAT-CHF consortium.

Israr MZ, Zhan H, Salzano A, Voors AA, ... Suzuki T, BIOSTAT-CHF investigators (full author list as appendix)
Background
The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would be useful in assessment of HF (e.g., severity, adverse outcomes) and risk stratification.
Methods
A panel of gut-related biomarkers including metabolites of the choline/carnitine- pathway [acetyl-L-carnitine, betaine, choline, γ-butyrobetaine, L-carnitine and trimethylamine-N-oxide (TMAO)] and the gut peptide, Trefoil Factor-3 (TFF-3), were investigated in 1,783 patients with worsening HF enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and associations with HF severity and outcomes, and use in risk stratification were assessed.
Results
Metabolites of the carnitine-TMAO pathway (acetyl-L-carnitine, γ-butyrobetaine, L-carnitine and TMAO) and TFF-3 were associated with the composite outcome of HF hospitalisation or all-cause mortality at 3 years [HR 2.04-2.93 (95% CI 1.30-4.71) p≤0.002]. Combining the carnitine-TMAO metabolites with TFF-3, as a gut dysfunction panel, showed a graded association; a greater number of elevated markers was associated with higher New York Heart Association class (p<0.001), higher plasma concentrations of B-type natriuretic peptide (p<0.001), and worse outcome [HR 1.90-4.58 (95% CI 1.19-6.74) p≤0.008]. Addition of gut dysfunction biomarkers to the contemporary BIOSTAT HF risk model also improved prediction for the aforementioned composite outcome [C-statistics p≤0.011, NRI 13.5-21.1 (95% CI 2.7-31.9) p≤0.014].
Conclusions
A panel of biomarkers of gut dysfunction showed graded association with severity of HF and adverse outcomes. Biomarkers as surrogate markers are potentially useful for assessment of gut dysfunction to HF pathophysiology and in risk stratification.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 08 Mar 2022; epub ahead of print
Israr MZ, Zhan H, Salzano A, Voors AA, ... Suzuki T, BIOSTAT-CHF investigators (full author list as appendix)
Am Heart J: 08 Mar 2022; epub ahead of print | PMID: 35278373
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Impact:
Abstract

Prognostic Value of Echocardiography for Heart Failure and Death in Adults with Chronic Kidney Disease.

Fitzpatrick JK, Ambrosy AP, Parikh RV, Tan TC, ... Go AS, CRIC Study Investigators
Background
Adults with chronic kidney disease (CKD) are at increased risk of heart failure (HF) morbidity and mortality. Despite well-characterized abnormalities in cardiac structure in CKD, it remains unclear how to optimally leverage echocardiography to risk stratify CKD patients.
Methods
We evaluated associations between echocardiographic parameters and risk of HF hospitalization and death using Cox proportional hazard models and forward selection with integrated discrimination improvement (IDI).
Results
The study included 3,505 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Mean age was 59±11 years, HF prevalence was 10%, and mean left ventricular (LV) ejection fraction (LVEF) was 54±9%. During mean 11 (interquartile range: 8 to 12) years of follow-up, event rates per 100-person years for HF hospitalizations and death, respectively, were 9.4 (95% Confidence Interval [CI]: 7.9-11.3) and 8.9 (95% CI: 7.6-10.5) for participants with LVEF <40%, 3.5 (95% CI: 3.0-4.2) and 4.6 (95% CI: 4.0-5.2) for patients with LVEF 40-49%, and 1.9 (95% CI: 1.7-2.1) and 3.1 (95% CI: 2.9-3.3) for patients with LVEF >50%. The rate of HF hospitalizations and deaths increased with lower eGFR across all LVEF categories. LV mass index, LVEF, and LV geometry had the strongest association with outcomes but provided modest incremental prognostic value to a baseline clinical model (IDI =0.14 and ΔAUC=0.017 for HF hospitalization, IDI =0.12 and ΔAUC=0.008 for death).
Conclusions
Baseline echocardiographic parameters are independently associated with increased risk of subsequent HF morbidity and mortality but provide only marginal incremental prognostic utility beyond clinical characteristics in the setting of CKD.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 08 Mar 2022; epub ahead of print
Fitzpatrick JK, Ambrosy AP, Parikh RV, Tan TC, ... Go AS, CRIC Study Investigators
Am Heart J: 08 Mar 2022; epub ahead of print | PMID: 35278374
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Impact:
Abstract

Short-term PM exposure and early-readmission risk: a retrospective cohort study in North Carolina heart failure patients.

Wyatt LH, Weaver AM, Moyer J, Schwartz JD, ... Cascio WE, Ward-Caviness C
Background
Short-term changes in ambient fine particulate matter (PM2.5) increase the risk for unplanned hospital readmissions. However, this association has not been fully evaluated for high-risk patients or examined to determine if the readmission risk differs based on time since discharge. Here we investigate the relation between ambient PM2.5 and 30-day readmission risk in heart failure (HF) patients using daily time windows and examine how this risk varies with respect to time following discharge.
Methods
We performed a retrospective cohort study of 17,674 patients with a recorded HF diagnosis between 2004 and 2016. The cohort was identified using the EPA CARES electronic health record resource. The association between ambient daily PM2.5 (μg/m3) concentration and 30-day readmissions was evaluated using time-dependent Cox proportional hazard models. PM2.5 associated readmission risk was examined throughout the 30-day readmission period and for early readmissions (1-3 days post-discharge). Models for 30-day readmissions included a parametric continuous function to estimate the daily PM2.5 associated readmission hazard. Fine-resolution ambient PM2.5 data were assigned to patient residential address and hazard ratios are expressed per 10 μg/m3 of PM2.5. Secondary analyses examined potential effect modification based on the time after a HF diagnosis, urbanicity, medication prescription, comorbidities, and type of HF.
Results
The hazard of a PM2.5-related readmission within three days of discharge was 1.33 (95% CI 1.18-1.51). This PM2.5 readmission hazard was slightly elevated in patients residing in non-urban areas (1.43, 95%CI 1.22-1.67) and for HF patients without a beta-blocker prescription prior to the readmission (1.35; 95% CI 1.19-1.53).
Conclusion
Our findings add to the evidence indicating substantial air quality-related health risks in individuals with underlying cardiovascular disease. Hospital readmissions are key metrics for patients and providers alike. As a potentially modifiable risk factor, air pollution-related interventions may be enacted that might assist in reducing costly and burdensome unplanned readmissions.

Published by Elsevier Inc.

Am Heart J: 05 Mar 2022; epub ahead of print
Wyatt LH, Weaver AM, Moyer J, Schwartz JD, ... Cascio WE, Ward-Caviness C
Am Heart J: 05 Mar 2022; epub ahead of print | PMID: 35263652
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Impact:
Abstract

Associated Factors and Clinical Outcomes in Mechanical Circulatory Support use in Patients Undergoing High Risk On-Pump Cardiac Surgery: Insights from the LEVO-CTS trial.

Verma S, Rathwell S, Fremes S, Zheng Y, ... Goodman SG, Diepen SV
Background
We describe variables and outcomes associated with peri-operative mechanical circulatory support (MCS) utilization among patients enrolled in the Levosimendan in patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial.
Methods
In the LEVO-CTS trial, MCS utilization (defined as intra-aortic balloon pump [IABP], extracorporeal membrane oxygenation [ECMO], or surgical ventricular assist devise [VAD]) within 5 days of surgery was examined. The association between MCS use and outcomes including 90-day mortality, 30-day renal-replacement therapy, and hospital and critical stay length of stay (LOS) were determined.
Results
Among the 849 patients from 70 centers randomized to levosimendan or placebo, 85 (10.0%) patients were treated with MCS (71 IABP, 7 ECMO, 7 VAD); with 89.4% started on post-operative day zero. Inter-institutional use ranged from 0 to 100%. Variables independently associated with MCS utilization included combined coronary artery bypass grafting and valve surgery (adjusted odds ratio [OR] 2.73, 95% confidence interval [CI] 1.70-4.37, p<0.001), history of lung disease (OR 1.70, 95% CI 1.06-2.70, p=0.029), and history of heart failure (OR 2.44, 95% CI 1.10-5.45, p=0.027). Adjusted 90-day mortality (22.4% vs 4.1%, hazard ratio [HR] 6.11, 95% CI 3.95-9.44, p<0.001) was higher, and median critical care LOS (8.0 vs 4.0 days, p<0.001) was longer in patients managed with MCS.
Conclusion
In a randomized controlled trial of high-risk cardiac surgical patients in North America, we observed patient, and surgical variables associated with MCS utilization. MCS use was associated with a higher risk of post-operative mortality.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Am Heart J: 05 Mar 2022; epub ahead of print
Verma S, Rathwell S, Fremes S, Zheng Y, ... Goodman SG, Diepen SV
Am Heart J: 05 Mar 2022; epub ahead of print | PMID: 35263653
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Impact:
Abstract

Distinct triglyceride-glucose trajectories are associated with different risks of incident cardiovascular disease in normal-weight adults.

Tian X, Zuo Y, Chen S, Meng X, ... Luo Y, Wang A
Background
Long-term patterns of the triglyceride-glucose index (TyG index) and their effects on CVD among normal-weight adults are poorly characterized. This study aimed to identify TyG index trajectories in normal-weight adults and to determine their association with the risk of incident CVD.
Methods
This study included 40,473 normal-weight participants who were free of stroke and myocardial infarction prior to or in 2012. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], and the TyG index trajectories during 2006-2012 were identified by latent mixture modeling.
Results
We identified five distinct TyG index trajectories according to TyG index range and changing pattern over time: low-stable (n=9,806; mean TyG index 7.84-7.93), moderate-stable (n=22,066; mean TyG index 8.43-8.52), high-decreasing (n=1,469; mean TyG index 9.83-8.75), moderate-increasing (n=5,842; mean TyG index 8.98-9.26), and high-stable (n=1,290; mean TyG index 9.91-10.07). During 6.74 years of follow-up, we documented 1,577 incident CVD events. Compared with the low-stable pattern, the highest risk of CVD was observed in the high-stable pattern (hazard ratio [HR], 2.24; 95% confidence interval [CI]: 1.73-2.90), followed by the moderate-increasing pattern (HR, 1.70; 95% CI, 1.43-2.04), the high-decreasing pattern (HR, 1.45; 95% CI, 1.11-1.89), and the moderate-stable pattern (HR, 1.25; 95% CI, 1.08-1.44). Similar results were also observed for stroke and myocardial infarction.
Conclusions
Distinct TyG index trajectories were significantly associated differently subsequent risk of CVD in normal-weight individuals. These observations suggested that long-term trajectories of TyG index may be useful for predicting CVD among normal-weight adults.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 02 Mar 2022; epub ahead of print
Tian X, Zuo Y, Chen S, Meng X, ... Luo Y, Wang A
Am Heart J: 02 Mar 2022; epub ahead of print | PMID: 35248535
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Impact:
Abstract

Clinical trajectory of patients with a worsening heart failure event and reduced ventricular ejection fraction.

Carnicelli AP, Clare RM, Hofmann P, Chiswell K, ... Sarocco P, Mentz RJ
Background
Recent data suggest that patients with heart failure with reduced ejection fraction (HFrEF) and worsening heart failure (WHF) have potential for greater benefit from newer HF therapies. We investigated characteristics and outcomes of patients with HFrEF and WHF by severity of left ventricular dysfunction.
Methods
We identified patients with chronic symptomatic HFrEF (left ventricular ejection fraction [LVEF] ≤35%) and evidence of WHF (emergency department visit or hospitalization for acute HF within 12 months of index echocardiogram) treated at Duke University between 1/2009 and 12/2018. Patients were stratified by LVEF≤25% or 26% to35%. Cox models were used to estimate cause-specific hazard ratios and 5-year event incidence of death and hospitalization across the range of LVEF.
Results
Of 2823 patients with HFrEF and WHF, 1620 (57.4%) had an LVEF≤25% and 1203 (42.6%) had an LVEF 26% to35%. Compared to patients with LVEF 26% to35%, those with LVEF≤25% were younger and more commonly men with a lower cardiovascular comorbidity burden. Patients with LVEF≤25% were less commonly on beta blockers (85.9% vs 90.5%) but more commonly treated with mineralocorticoid receptor antagonists (49.3% vs 41.1%) and implantable defibrillators (41.3% vs 28.2%). Patients with LVEF≤25% had significantly higher hazards for death (HR 1.24 [95% CI 1.11 - 1.38]), all-cause hospitalization (HR 1.21 [95% CI 1.10 - 1.33]), and HF hospitalization (HR 1.25 [95% CI 1.1 - 1.38]) through 5-years.
Conclusions
More than half of patients with chronic HFrEF and WHF have severe LV dysfunction. Important differences in comorbidities, HF therapies, and outcomes exist between those with LVEF≤25% and those with LVEF 26% to35%.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:110-116
Carnicelli AP, Clare RM, Hofmann P, Chiswell K, ... Sarocco P, Mentz RJ
Am Heart J: 27 Feb 2022; 245:110-116 | PMID: 34932997
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Impact:
Abstract

Achievement and quality measure attainment in patients hospitalized with atrial fibrillation: Results from The Get With The Guidelines - Atrial Fibrillation (GWTG-AFIB) registry.

Ullal AJ, Holmes DN, Lytle BL, Matsouaka RA, ... Turakhia MP, Perino AC
Background
The Get With The Guidelines - Atrial Fibrillation (GWTG-AFIB) Registry uses achievement and quality measures to improve the care of patients with atrial fibrillation (AF). We sought to evaluate overall and site-level variation in attainment of these measures among sites participating in the GWTG-AFIB Registry.
Methods
From the GWTG-AFIB registry, we included patients with AF admitted between 1/3/2013 and 6/30/2019. We described patient-level attainment and variation in attainment across sites of 6 achievement measures with 1) defect-free scores (percent of patients with all eligible measures attained), and 2) composite opportunity scores (percent of all eligible patient measures attained). We also described attainment of 11 quality measures at the patient-level.
Results
Among 80,951 patients hospitalized for AF (age 70±13 years, 47.0% female; CHA2DS2-VASc 3.6±1.8) at 132 sites. Site-level defect-free scores ranged from 4.7% to 85.8% (25th, 50th, 75th percentile: 32.7%, 52.1%, 64.4%). Composite opportunity scores ranged from 39.4% to 97.5% (25th, 50th, 75th: 68.1%, 80.3%, 87.1%). Attainment was notably low for the following quality measures: 1) aldosterone antagonist prescription when ejection fraction ≤35% (29% of those eligible); and 2) avoidance of antiplatelet therapy with OAC in patients without coronary/peripheral artery disease (81% of those eligible).
Conclusions
Despite high overall attainment of care measures across GWTG-AFIB registry sites, large site variation was present with meaningful opportunities to improve AF care beyond OAC prescription, including but not limited to prescription of aldosterone antagonists in those with AF and systolic dysfunction and avoidance of non-indicated adjunctive antiplatelet therapy.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:90-99
Ullal AJ, Holmes DN, Lytle BL, Matsouaka RA, ... Turakhia MP, Perino AC
Am Heart J: 27 Feb 2022; 245:90-99 | PMID: 34932998
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Impact:
Abstract

Tricuspid valve disease prevalence and the impact of tricuspid valve surgery on cardiovascular events and hospital resource use in medicare beneficiaries.

Vemulapalli S, Kerr MSD, Roberts GJ, Prillinger JB, Meduri CU, McCarthy P
Background
Tricuspid valve disease (TVD) is presumed common, however, little is known about its prevalence or the impact of tricuspid valve surgery (TVS) on healthcare resource use.
Methods
To describe the prevalence of TVD and assess the impact of TVS on resource utilization, Medicare Fee-For-Service beneficiaries from 2011 -2019 were assessed for the prevalence of non-rheumatic TVD. Hospital costs and rates of all-cause, cardiovascular (CV), and heart failure (HF) hospitalizations were compared in the 3 months pre TVS to acute (0-3 months) and chronic (3 -12 months) post TVS periods.
Results
Among 80.3 million beneficiaries from 2011 - 2019 Q1, over 700,000 (0.9%) had non-rheumatic TVD with 1.4% undergoing TVS. Thirty-day and 1 year mortality after TVS was 5.5% to15.5%. Compared with pre-surgery, CV and HF hospitalizations decreased from 0.12 to 0.08 per patient-month (P <.001), and 0.06 to 0.04 (P <.001) acutely. All-cause hospitalizations increased from 0.18 per patient-month to 0.23 per patient-month acutely post-surgery (P <.001), before decreasing to 0.09 per patient-month chronically (P <.001). Hospital costs increased from $2,174 per patient-month to $4,171 per patient-month acutely (P < .001), before falling to $1,441 per patient-month (P < .001) chronically. Lower costs for HF and CV hospitalization in both acute (P = .028 and P < .001, respectively) and chronic (P < .001 for both) periods were observed.
Conclusions
TVS is associated with reduced CV and HF hospitalizations and associated hospital costs. Future work should determine whether transcatheter tricuspid valve repair offers similar or additional benefits.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:100-109
Vemulapalli S, Kerr MSD, Roberts GJ, Prillinger JB, Meduri CU, McCarthy P
Am Heart J: 27 Feb 2022; 245:100-109 | PMID: 34932999
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Impact:
Abstract

Effects of long-term testosterone treatment on cardiovascular outcomes in men with hypogonadism: Rationale and design of the TRAVERSE study.

Bhasin S, Lincoff AM, Basaria S, Bauer DC, ... Nissen SE, TRAVERSE Study Investigators
Background
Testosterone exerts some effects on the cardiovascular system that could be considered beneficial; some other effects may potentially increase the risk of cardiovascular (CV) events. Neither the long-term efficacy nor safety of testosterone treatment has been studied in an adequately-powered randomized trial.
Methods
The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study is a randomized, double-blind, placebo-controlled, parallel group, non-inferiority, multicenter study. Eligible participants are men, 45 to 80 years, with serum testosterone concentration <300 ng/dL and hypogonadal symptoms, who have evidence pre-existing CV disease or increased risk of CV disease. Approximately 6,000 subjects will be randomized to either 1.62% transdermal testosterone gel or a matching placebo gel daily for an anticipated duration of up to 5 years. The primary outcome is CV safety defined by the major adverse CV event composite of nonfatal myocardial infarction, nonfatal stroke, or death due to CV causes. The trial will continue until at least 256 adjudicated major adverse CV event endpoints have occurred to assess whether the 95% (2-sided) upper confidence limit for a hazard ratio of 1.5 can be ruled out. Secondary endpoints include prostate safety defined as the incidence of adjudicated high grade prostate cancer and efficacy in domains of sexual function, bone fractures, depression, anemia, and diabetes.
Results
As of July 1, 2021, 5,076 subjects had been randomized.
Conclusions
The TRAVERSE study will determine the CV safety and long-term efficacy of testosterone treatment in middle-aged and older men with hypogonadism with or at increased risk of CV disease.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:41-50
Bhasin S, Lincoff AM, Basaria S, Bauer DC, ... Nissen SE, TRAVERSE Study Investigators
Am Heart J: 27 Feb 2022; 245:41-50 | PMID: 34871580
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Impact:
Abstract

Harmonization of the definition of sudden cardiac death in longitudinal cohorts of the European Sudden Cardiac Arrest network - towards Prevention, Education, and New Effective Treatments (ESCAPE-NET) consortium.

Warming PE, Ågesen FN, Lynge TH, Jabbari R, ... Tfelt-Hansen J, ESCAPE-NET Investigators
Background
The burden of sudden cardiac death (SCD) in the general population is substantial and SCD frequently occurs among people with few or no known risk factors for cardiac disease. Reported incidences of SCD vary due to differences in definitions and methodology between cohorts. This study aimed to develop a method for adjudicating SCD cases in research settings and to describe uniform case definitions of SCD in an international consortium harmonizing multiple longitudinal study cohorts.
Methods
The harmonized SCD definitions include both case definitions using data from multiple sources (eg, autopsy reports, medical history, eyewitnesses) as well as a method using only information from registers (eg, cause of death registers, ICD-10 codes). Validation of the register-based method was done within the consortium using the multiple sources definition as gold standard and presenting sensitivity, specificity, accuracy and positive predictive value.
Results
Consensus definitions of \"definite,\" \"possible\" and \"probable\" SCD for longitudinal study cohorts were reached. The definitions are based on a stratified approach to reflect the level of certainty of diagnosis and degree of information. The definitions can be applied to both multisource and register-based methods. Validation of the method using register-information in a cohort comprising 1335 cases yielded a sensitivity of 74%, specificity of 88%, accuracy of 86%, and positive predictive value of 54%.
Conclusions
This study demonstrated that a harmonization of SCD classification across different methodological approaches is feasible. The developed classification can be used to study SCD in longitudinal cohorts and to merge cohorts with different levels of information.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:117-125
Warming PE, Ågesen FN, Lynge TH, Jabbari R, ... Tfelt-Hansen J, ESCAPE-NET Investigators
Am Heart J: 27 Feb 2022; 245:117-125 | PMID: 34936862
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Impact:
Abstract

Dysglycemia and incident heart failure among blacks: The jackson heart study.

Echouffo-Tcheugui JB, Mwasongwe SE, Musani SK, Hall ME, ... Mentz RJ, Bertoni AG
Background
We aimed to investigate the associations of glycemic markers (hemoglobin A1C [HbA1C], fasting plasma glucose [FPG] and glycemic status [normoglycemia, prediabetes and diabetes]) with incident heart failure (HF) and its subtypes, among Blacks.
Methods
We included 2,290 community-dwelling Blacks (64% women, mean age 58 years) without prevalent HF from the Jackson Heart Study who attended the second exam (2005 - 2008). The associations between glycemic markers and incident HF (and subtypes including HF with preserved ejection fraction [HFpEF] and reduced ejection fraction [HFrEF]) were evaluated using Cox proportional hazards regression models, adjusting for risk factors and coronary heart disease.
Results
There were 119 incident HF events (48 HFpEF, 58 HFrEF, and 13 unclassified HF events) over a median follow-up of 10.5 years. Higher levels of HbA1C (HR per SD increment, 1.30; 95% CI 1.12, 1.51) and FPG (HR per SD increment FPG: 1.32; 95% CI: 1.17, 1.48) were associated with a higher risk of incident HF. Compared to normal glycemia, diabetes status was associated with a higher risk of incident HF (HR: 1.24; 95%CI: 1.02, 2.05). HbA1C was significantly associated with higher risks of HFpEF (HR per SD increment: 1.41, 95% CI: 1.18, 1.69) and HFrEF (HR per SD increment: 1.32; 95% CI: 1.12, 1.56). FPG was significantly associated with higher risk of HFpEF (HR per SD increment: 1.35, 95% CI: 1.14, 1.62) but not HFrEF (HR per SD increment: 1.12; 95% CI: 0.53, 2.35).
Conclusions
Among community-dwelling Blacks, higher levels of glycemic markers were associated with higher risk of HF subtypes.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:1-9
Echouffo-Tcheugui JB, Mwasongwe SE, Musani SK, Hall ME, ... Mentz RJ, Bertoni AG
Am Heart J: 27 Feb 2022; 245:1-9 | PMID: 34808103
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Impact:
Abstract

Outcomes of prolonged dual anti-platelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A nationwide registry-based study.

Christensen DM, Schjerning AM, Sindet-Pedersen C, Lamberts M, ... Gislason G, Strange JE
Background
Randomized controlled trials have shown a reduced risk of ischemic events and an increased risk of bleeding in patients treated with prolonged dual anti-platelet therapy (DAPT) beyond 12 months following acute coronary syndrome (ACS). We aimed to investigate outcomes of prolonged DAPT vs aspirin monotherapy (ASA) in a real-world population.
Methods and results
Using nationwide registries, we identified all patients with ACS who underwent percutaneous coronary intervention and received 12-month DAPT between January 2013 and October 2016. Patients still on DAPT were compared to patients on ASA at index date (15 months after ACS-date) and followed for up to 2 years. Cox regression models were employed to calculate standardized risks of all-cause mortality, major adverse cardiovascular event (MACE), and major bleeding. The study included 7,449 patients, 1,901 on DAPT (median age 66, 72.1% male) and 5,548 on ASA (median age 65, 75.1% male). Standardized absolute 2-year risk of all-cause mortality, MACE, and major bleeding was 2.7%, 3.7%, and 5.4% for DAPT vs 2.2%, 3.8%, and 1.3% for ASA. DAPT was not associated with a significant standardized 2-year risk difference (SRD) of all-cause mortality (SRD: 0.5%, 95% confidence interval [CI]: -0.9 to 1.7) or MACE (SRD: -0.1%, 95% CI -1.8 to 1.6), but a significantly higher risk of major bleeding (SRD: 4.1%, 95% CI 1.8-6.6).
Conclusions
In a nationwide cohort of ACS patients undergoing percutaneous coronary intervention, prolonged DAPT was not significantly associated with a reduced risk of all-cause mortality or MACE, but an increased risk of major bleeding. Future randomized controlled trials should investigate the optimal anti-platelet regimen in this patient group.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 27 Feb 2022; 245:81-89
Christensen DM, Schjerning AM, Sindet-Pedersen C, Lamberts M, ... Gislason G, Strange JE
Am Heart J: 27 Feb 2022; 245:81-89 | PMID: 34902311
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Impact:
Abstract

The prospective randomized trial of the optimal evaluation of cardiac symptoms and revascularization: Rationale and design of the PRECISE trial.

Nanna MG, Vemulapalli S, Fordyce CB, Mark DB, ... Rogers C, Douglas PS
Background
Clinicians vary widely in their preferred diagnostic approach to patients with non-acute chest pain. Such variation exposes patients to potentially avoidable risks, as well as inefficient care with increased costs and unresolved patient concerns.
Methods
The Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization (PRECISE) trial (NCT03702244) compares an investigational \"precision\" diagnostic strategy to a usual care diagnostic strategy in participants with stable chest pain and suspected coronary artery disease (CAD).
Results
PRECISE randomized 2103 participants with stable chest pain and a clinical recommendation for testing for suspected CAD at 68 outpatient international sites. The investigational precision evaluation strategy started with a pre-test risk assessment using the PROMISE Minimal Risk Tool. Those at lowest risk were assigned to deferred testing (no immediate testing), and the remainder received coronary computed tomographic angiography (cCTA) with selective fractional flow reserve (FFRCT) for any stenosis meeting a threshold of ≥30% and <90%. For participants randomized to usual care, the clinical care team selected the initial noninvasive or invasive test (diagnostic angiography) according to customary practice. The use of cCTA as the initial diagnostic strategy was proscribed by protocol for the usual care strategy. The primary endpoint is time to a composite of major adverse cardiac events (MACE: all-cause death or non-fatal myocardial infarction) or invasive cardiac catheterization without obstructive CAD at 1 year. Secondary endpoints include health care costs and quality of life.
Conclusions
PRECISE will determine whether a precision approach comprising a strategically deployed combination of risk-based deferred testing and cCTA with selective FFRCT improves the clinical outcomes and efficiency of the diagnostic evaluation of stable chest pain over usual care.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 27 Feb 2022; 245:136-148
Nanna MG, Vemulapalli S, Fordyce CB, Mark DB, ... Rogers C, Douglas PS
Am Heart J: 27 Feb 2022; 245:136-148 | PMID: 34953768
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Impact:
Abstract

Delayed medical care due to transportation barriers among adults with atherosclerotic cardiovascular disease.

Acquah I, Hagan K, Valero-Elizondo J, Javed Z, ... Cainzos-Achirica M, Nasir K
Background
In patients with atherosclerotic cardiovascular disease (ASCVD), barriers related to transportation may impair access to care, with potential implications for prognosis. Although few studies have explored transportation barriers among patients with ASCVD, the correlates of delayed care due to transportation barriers have not been examined in this population. We aimed to examine this in U.S. patients with ASCVD using nationally representative data.
Methods
Using data from the 2009-2018 National Health Interview Survey, we estimated the self-reported prevalence of delayed medical care due to transportation barriers among adults with ASCVD, overall and by sociodemographic characteristics. Logistic regression was used to examine the association between various sociodemographic characteristics and delayed care due to transportation barriers.
Results
Among adults with ASCVD, 4.5% (95% CI; 4.2, 4.8) or ∼876,000 annually reported delayed care due to transportation barriers. Income (low-income: odds ratio [OR] 4.43, 95% CI [3.04, 6.46]; lowest-income: OR 6.35, 95% CI [4.36, 9.23]) and Medicaid insurance (OR 4.53; 95% CI [3.27, 6.29]) were strongly associated with delayed care due to transportation barriers. Additionally, younger individuals, women, non-Hispanic Black adults, and those from the U.S. South or Midwest, had higher odds of reporting delayed care due to transportation barriers.
Conclusions
Approximately 5% of adults with ASCVD experience delayed care due to transportation barriers. Vulnerable groups include young adults, women, low-income people, and those with public/no insurance. Future studies should analyze the feasibility and potential benefits of interventions such as use of telehealth, mobile clinics, and provision of transportation among patients with ASCVD in the U.S.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:60-69
Acquah I, Hagan K, Valero-Elizondo J, Javed Z, ... Cainzos-Achirica M, Nasir K
Am Heart J: 27 Feb 2022; 245:60-69 | PMID: 34902312
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Impact:
Abstract

Electronic alerts to initiate anticoagulation dialogue in patients with atrial fibrillation.

Gutierrez JA, Christian RT, Aday AW, Gu L, ... Banerjee S, Rao SV
Importance
The benefit of an electronic support system for the prescription and adherence to oral anticoagulation therapy among patients with atrial fibrillation (AF) and atrial flutter at heightened risk for of stroke and systemic thromboembolism is unclear.
Objective
To evaluate the effect of a combined alert intervention and shared decision-making tool to improve prescription rates of oral anticoagulation therapy and adherence.
Design, setting, and participants
A prospective single arm study of 939 consecutive patients treated at a large tertiary healthcare system.
Exposures
An electronic support system comprising 1) an electronic alert to identify patients with AF or atrial flutter, a CHA2DS2-VASc score ≥ 2, and not on oral anticoagulation and 2) electronic shared decision-making tool to promote discussions between providers and patients regarding therapy.
Main outcomes and measures
The primary endpoint was prescription rate of anticoagulation therapy. The secondary endpoint was adherence to anticoagulation therapy defined as medication possession ratio ≥ 80% during the 12 months of follow-up.
Results
Between June 13, 2018 and August 31, 2018, the automated intervention identified and triggered a unique alert for 939 consecutive patients with AF or atrial flutter, a CHA2DS2-VASc score ≥2 who were not on oral anticoagulation. The median CHA2DS2-VASc score among all patients identified by the alert was 2 and the median untreated duration prior to the alert was 495 days (interquartile range 123 - 1,831 days). Of the patients identified by the alert, 345 (36.7%) initiated anticoagulation therapy and 594 (63.3%) did not: 68.7% were treated with a non-Vitamin K antagonist oral anticoagulant (NOAC), 22.0% with warfarin, and 9.3 % combination of NOAC and warfarin. Compared with historical anticoagulation rates, the electronic alert was associated with a 23.6% increase in anticoagulation prescriptions. The overall 1-year rate of adherence to anticoagulant therapy was 75.4% (260/345).

Conclusion:
and relevance
An electronic automated alert can successfully identify patients with AF and atrial flutter at high risk for stroke, increase oral anticoagulation prescription, and support high rates of adherence.

Published by Elsevier Inc.

Am Heart J: 27 Feb 2022; 245:29-40
Gutierrez JA, Christian RT, Aday AW, Gu L, ... Banerjee S, Rao SV
Am Heart J: 27 Feb 2022; 245:29-40 | PMID: 34808105
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Impact:
Abstract

Noninvasive echocardiographic cardiac power output predicts mortality in cardiac intensive care unit patients.

Burstein B, Anand V, Ternus B, Tabi M, ... Oh JK, Jentzer JC
Background
Low cardiac power output (CPO), measured invasively, can identify critically ill patients at increased risk of adverse outcomes, including mortality. We sought to determine whether non-invasive, echocardiographic CPO measurement was associated with mortality in cardiac intensive care unit (CICU) patients.
Methods
Patients admitted to CICU between 2007 and 2018 with echocardiography performed within one day (before or after) admission and who had available data necessary for calculation of CPO were evaluated. Multivariable logistic regression determined the relationship between CPO and adjusted hospital mortality.
Results
A total of 5,585 patients (age of 68.3 ± 14.8 years, 36.7% female) were evaluated with admission diagnoses including acute coronary syndrome (ACS) in 56.7%, heart failure (HF) in 50.1%, cardiac arrest (CA) in 12.2%, shock in 15.5%, and cardiogenic shock (CS) in 12.8%. The mean left ventricular ejection fraction (LVEF) was 47.3 ± 16.2%, and the mean CPO was 1.04 ± 0.37 W. There were 419 in-hospital deaths (7.5%). CPO was inversely associated with the risk of hospital mortality, an association that was consistent among patients with ACS, HF, and CS. On multivariable analysis, higher CPO was associated with reduced hospital mortality (OR 0.960 per 0.1 W, 95CI 0.0.926-0.996, P = .03). Hospital mortality was particularly high in patients with low CPO coupled with reduced LVEF, increased vasopressor requirements, or higher admission lactate.
Conclusions
Echocardiographic CPO was inversely associated with hospital mortality in unselected CICU patients, particularly among patients with increased lactate and vasopressor requirements. Routine calculation and reporting of CPO should be considered for echocardiograms performed in CICU patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:149-159
Burstein B, Anand V, Ternus B, Tabi M, ... Oh JK, Jentzer JC
Am Heart J: 27 Feb 2022; 245:149-159 | PMID: 34953769
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Impact:
Abstract

Cardiovascular determinants of impaired placental function in women with cardiac dysfunction.

Siegmund AS, Pieper PG, Bilardo CM, Gordijn SJ, ... van Veldhuisen DJ, Dickinson MG
Female heart disease has for a long time been an underrecognized problem in the field of cardiology. With an ever-growing number of these patients getting pregnant, cardiac dysfunction during pregnancy is an increasingly large medical problem. Previous work has shown that maternal heart disease may have an adverse effect on pregnancy outcome in both mother and child. The placenta forms the connection and it is postulated that cardiac dysfunction negatively affects the placenta, and consequently, neonatal outcome. Given the paucity of data in this field, more research on the influence of cardiac (mal)function on placental (mal)function is needed. The present review describes placental function in women with various types of cardiac dysfunction, thereby aiming to provide more insight into possible underlying mechanisms of placental malfunction. Organ dysfunction in patients with heart failure is for an important part based on reduced perfusion and venous congestion. This has been shown in other organs such as kidneys, liver and brain. In pregnant women with cardiac dysfunction, placental dysfunction may follow similar patterns. Moreover, other factors, such as pre-existing hypertension and chronic hypoxia may lead to further impairment of placental function, through abnormal vascular remodeling of the uterine spiral arteries. The pathophysiology of placental dysfunction in pregnant women with cardiac dysfunction may thus be multifactorial. It is therefore important to monitor closely cardiac and placental function in such high-risk pregnancies. Gaining a better understanding of the underlying pathophysiological mechanisms may have important clinical implications in terms of pregnancy counseling, monitoring and outcome.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:126-135
Siegmund AS, Pieper PG, Bilardo CM, Gordijn SJ, ... van Veldhuisen DJ, Dickinson MG
Am Heart J: 27 Feb 2022; 245:126-135 | PMID: 34902313
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Impact:
Abstract

Cardiac MRI predictors of good long-term outcomes in patients with repaired TOF.

Majeed A, Geva T, Sleeper LA, Graf JA, ... Mulder BJM, Valente AM
Background
Risk stratification in patients with repaired tetralogy of Fallot (rTOF) have focused on poor clinical outcomes while predictors of a benign clinical course have not been characterized.
Objective
The goal of this study was to Identify cardiac magnetic resonance (CMR) markers of a good clinical course late after TOF repair.
Methods
Clinical and CMR data from the International Multicenter TOF Registry (INDICATOR) were analyzed. The primary outcome was time to the earliest occurrence of a composite of death, aborted sudden death, and sustained ventricular tachycardia (VT). The secondary outcome was time to the earliest occurrence of atrial arrhythmia, nonsustained VT, and NYHA class >II. Multinomial regression was used to identify predictors of the 3-category outcome: (a) good outcome, defined as freedom from the primary AND secondary outcomes at age 50 years; (b) poor outcome, defined as presence of the primary outcome before age 50 years; and (c) intermediate outcome, defined as not fulfilling criteria for good or poor outcomes.
Results
Among 1088 eligible patients, 96 had good outcome, 60 experienced poor outcome, and 932 had intermediate outcome. Patients were age 25.8±10.8 years at the time of the index CMR. Median follow-up was 5.8 years (IQR 3.0, 9.9) after CMR in event-free patients. By univariate analysis, smaller right ventricular (RV) end-systolic and end-diastolic volume index, smaller left ventricular end-systolic volume index, higher right and left ventricular ejection fraction, lower right and left ventricular mass index, and lower left ventricular mass/volume ratio were associated with good outcome. Multivariable modeling identified higher RV ejection fraction (OR 2.38 per 10% increase, P = .002) and lower RV mass index (OR 1.72, per 10 g/m2 decrease, P = .002) as independently associated with good outcome after adjusting for age at CMR. Classification and regression tree analysis identified important thresholds associated with good outcome that were specific to patients age ≥37 years at the time of CMR; these were RV ejection fraction ≥42% and RV mass index <39 g/m2.
Conclusions
Adults with rTOF and no more than mild RV dysfunction combined with no significant RV hypertrophy are likely to be free from serious adverse clinical events into their sixth decade of life and may require less frequent cardiac testing.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:70-77
Majeed A, Geva T, Sleeper LA, Graf JA, ... Mulder BJM, Valente AM
Am Heart J: 27 Feb 2022; 245:70-77 | PMID: 34875276
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Impact:
Abstract

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

Piccini JP, Ahlsson A, Dorian P, Gillinov MA, ... Ferguson WG, Benussi S
Background
Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations.
Methods
The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety.
Conclusions
The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:51-59
Piccini JP, Ahlsson A, Dorian P, Gillinov MA, ... Ferguson WG, Benussi S
Am Heart J: 27 Feb 2022; 245:51-59 | PMID: 34687654
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Impact:
Abstract

Fibroblast growth factor-23 and subclinical markers of cardiac dysfunction: The coronary artery risk development in young adults (CARDIA) study.

Akhabue E, Wong M, Mehta R, Isakova T, ... Gutierrez OM, Carnethon M
Background
Elevated Fibroblast Growth Factor-23 (FGF23) levels have been associated with greater left ventricular mass (LVM) and heart failure. Whether higher FGF23 is associated with higher LVH prevalence and longitudinal changes in LVM and myocardial strain in middle-aged adults without cardiovascular disease (CVD) or chronic kidney disease (CKD) is unknown.
Methods
We studied 3,113 adults without CVD at baseline participating in the Year 25 (2010-2011) follow-up exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We studied the association of Year 25 c-terminal FGF23 concentrations with indexed LVM (LVMI=LVM/height2.7), LVH and myocardial strain as assessed by speckle tracking strain echocardiography. Among the 2,758 (88.6%) participants who returned for the Year 30 examination, we also investigated the association of Year 25 FGF23 with 5 Year change in LVMI, strain parameters and incident LVH.
Results
The mean age was 50.0 (±3.6) years, 56.8% were female, 45.7% were Black and 6.4% had CKD. There was 6.0% LVH prevalence at Year 25. Mean 5 Year change in LVMI was 5.3 (±7.7) grams/meter. In multivariable models, FGF23 in the highest quartile was associated with greater odds of LVH at Year 25 compared to lower quartiles. [Odds Ratio 95% CI: 1.81 (1.28, 2.58)] with similar findings after exclusion of participants with CKD. There was no interaction between FGF23 and race (P = .18) or sex (P = .80). There was no association between FGF23 and global longitudinal strain. There was no association between FGF23 and 5 Year change in LVMI. There was no association between higher FGF23 and 5 year incident LVH.
Conclusions
In a middle-aged adult population without known CVD or CKD, higher FGF23 was associated with greater odds of LVH, but not with greater increases in LVM over time. Further study is needed to elucidate whether FGF23 is a risk marker for underlying LVH or a mechanism for increased LVM over time in younger and middle-aged adult populations without CKD.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:10-18
Akhabue E, Wong M, Mehta R, Isakova T, ... Gutierrez OM, Carnethon M
Am Heart J: 27 Feb 2022; 245:10-18 | PMID: 34861237
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Impact:
Abstract

Rationale and design of the safe and timely antithrombotic removal - ticagrelor (STAR-T) trial: A prospective, multi-center, double-blind, randomized controlled trial evaluating reductions in postoperative bleeding with intraoperative removal of ticagrelor by the drugsorb™-ATR device in patients undergoing cardiothoracic surgery within 48 hours from last ticagrelor dose.

Gibson CM, Mack MJ, Lee VT, Schneider DJ, ... Cutlip DE, Deliargyris EN
Background
Ticagrelor is often administered to patients with acute coronary syndromes. However, when these patients require urgent or emergent cardiothoracic (CT) surgery the presence of ticagrelor significantly increases surgical bleeding. The goal of the current trial is to evaluate the effectiveness and safety of the DrugSorb-ATR hemoadsorption device for the intraoperative removal of ticagrelor to reduce postoperative bleeding in the above patient population. The Safe and Timely Antithrombotic Removal - Ticagrelor (STAR-T) Trial is a multi-center, double-blind, randomized, controlled trial enrolling patients who require cardiothoracic surgery on cardiopulmonary bypass (CPB) within 48 hours of last ticagrelor dose.
Methods
Subjects will be randomized 1:1 to receive either the DrugSorb-ATR device or an identical sham device during CPB. The study will enroll up to 120 subjects at 20 U.S centers, and the primary outcome is the composite of fatal perioperative bleeding, moderate/severe/massive bleeding according to the Universal Definition of Perioperative Bleeding in Cardiac Surgery (UDPB), and 24 hours chest tube drainage. The components of the composite are hierarchically ranked according to clinical significance and the primary analysis will utilize the Win Ratio method. Percent change in ticagrelor levels before and after CPB (drug removal) will be the key secondary endpoint. An independent Clinical Events Committee will adjudicate all clinical endpoints including safety endpoints relating to postoperative thrombotic events. Subjects will be followed through 30 days after the index operation.
Conclusions
The results from STAR-T, if positive, will potentially support FDA market approval for DrugSorb-ATR, and provide a solution to an important unmet clinical need.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2022; 245:19-28
Gibson CM, Mack MJ, Lee VT, Schneider DJ, ... Cutlip DE, Deliargyris EN
Am Heart J: 27 Feb 2022; 245:19-28 | PMID: 34736855
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Impact:
Abstract

Virtual AppLication-Supported Environment to INcrease Exercise During Cardiac Rehabilitation Study (VALENTINE) Study: Rationale and Design.

Jeganathan VS, Golbus JR, Gupta K, Luff E, ... Kheterpal S, Nallamothu BK
Background
In-person, exercise-based cardiac rehabilitation improves physical activity and reduces morbidity and mortality for patients with cardiovascular disease. However, activity levels may not be optimized and decline over time after patients graduate from cardiac rehabilitation. Scalable interventions through mobile health (mHealth) technologies have the potential to augment activity levels and extend the benefits of cardiac rehabilitation.
Methods
The VALENTINE Study is a prospective, randomized-controlled, remotely-administered trial designed to evaluate an mHealth intervention to supplement cardiac rehabilitation for low- and moderate-risk patients (ClinicalTrials.gov NCT04587882). Participants are randomized to the control or intervention arms of the study. Both groups receive a compatible smartwatch (Fitbit Versa 2 or Apple Watch 4) and usual care. Participants in the intervention arm of the study additionally receive a just-in-time adaptive intervention (JITAI) delivered as contextually tailored notifications promoting low-level physical activity and exercise throughout the day. In addition, they have access to activity tracking and goal setting through the mobile study application and receive weekly activity summaries via email. The primary outcome is change in 6-minute walk distance at 6-months and, secondarily, change in average daily step count. Exploratory analyses will examine the impact of notifications on immediate short-term smartwatch-measured step counts and exercise minutes.
Conclusions
The VALENTINE study leverages innovative techniques in behavioral and cardiovascular disease research and will make a significant contribution to our understanding of how to support patients using mHealth technologies to promote and sustain physical activity.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Am Heart J: 26 Feb 2022; epub ahead of print
Jeganathan VS, Golbus JR, Gupta K, Luff E, ... Kheterpal S, Nallamothu BK
Am Heart J: 26 Feb 2022; epub ahead of print | PMID: 35235834
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Impact:
Abstract

Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence (AWARE) Trial: Design and Rationale.

Nair GM, Birnie DH, Wells GA, Nery PB, ... Angaran P, Essebag V
Background
Recurrence of atrial fibrillation (AF) after a pulmonary vein isolation procedure is often due to electrical reconnection of the pulmonary veins. Repeat ablation procedures may improve freedom from AF but are associated with increased risks and health care costs. A novel ablation strategy in which patients receive \"augmented\" ablation lesions has the potential to reduce the risk of AF recurrence.
Methods
The Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence (AWARE) Trial was designed to evaluate whether an augmented wide-area circumferential antral (WACA) ablation strategy will result in fewer atrial arrhythmia recurrences in patients with symptomatic paroxysmal AF, compared with a conventional WACA strategy.
Results
The AWARE trial was a multicenter, prospective, randomized, open, blinded endpoint trial that has completed recruitment (ClinicalTrials.gov NCT02150902). Patients were randomly assigned (1:1) to either the control arm (single WACAlesion set) or the interventional arm (augmented- double WACA lesion set performed after the initial WACA). The primary outcome was atrial tachyarrhythmia (AA; atrial tachycardia [AT], atrial flutter [AFl] or AF) recurrence between days 91 and 365 post catheter ablation. Patient follow-up included 14-day continuous ambulatory ECG monitoring at 3, 6 and 12 months after catheter ablation. Three questionnaires were administered during the trial- the EuroQuol-5D (EQ-5D) quality of life scale, the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale and a patient satisfaction scale.
Conclusions
The AWARE trial was designed to evaluate whether a novel approach to catheter ablation reduced the risk of AA recurrence in patients with symptomatic paroxysmal AF.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 23 Feb 2022; epub ahead of print
Nair GM, Birnie DH, Wells GA, Nery PB, ... Angaran P, Essebag V
Am Heart J: 23 Feb 2022; epub ahead of print | PMID: 35219715
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Impact:
Abstract

Design and Rationale for the Supermarket and Web-Based Intervention Targeting Nutrition (SuperWIN) for Cardiovascular Risk Reduction Trial.

Couch SC, Helsley RN, Siegel FU, Saelens BE, ... Bhatt DL, Steen DL
Purpose
The prevalence of chronic diseases is increasing largely due to suboptimal dietary habits. It is not known whether individualized, supermarket-based, nutrition education delivered by registered dietitians, utilizing the advantages of the in-store and online environments, and electronically collected purchasing data, can increase dietary quality.
Methods and results
The Supermarket and Web-based Intervention targeting Nutrition (SuperWIN) for Cardiovascular Risk Reduction Trial is a randomized, controlled dietary intervention study. Adults identified from a primary care network with one or more risk factors were randomized at their preferred store to: 1) standard of care plus individualized, point- of-purchase (POP) nutrition education; 2) standard of care plus individualized, POP nutrition education enhanced with online shopping technologies and training; or 3) standard of care alone. Educational sessions within each store\'s clinic and aisles, emphasized the Dietary Approaches to Stop Hypertension (DASH) diet. The primary assessment was an intention-to-treat comparison on the effects of the dietary interventions on mean change in DASH score (90-point range) from baseline to 3 months (post-intervention). Additional outcomes included blood pressure, lipids, weight, purchasing behavior, food literacy, and intervention feedback. Between April 2019 through February 2021, 267 participants were randomized (20 excluded due to COVID pandemic). Median age was 58 years, 69% were female, 64% had a college degree, 53% worked full-time, 64% were obese, 73% were treated with blood pressure and 42% with cholesterol medications, and most had low-to-moderate diet quality.
Conclusion
The SuperWIN Trial was designed to provide a rigorous evaluation of the efficacy of two novel, comprehensive, supermarket-based dietary intervention programs.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 22 Feb 2022; epub ahead of print
Couch SC, Helsley RN, Siegel FU, Saelens BE, ... Bhatt DL, Steen DL
Am Heart J: 22 Feb 2022; epub ahead of print | PMID: 35218725
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Impact:
Abstract

Use of Coronary Computed Tomography or Polygenic Risk Scores to Prompt Action to Reduce Coronary Artery Disease Risk: The CAPAR-CAD Trial.

Verma KP, Marwick T, Duarte C, Meikle P, Inouye M, Carrington MJ
Background
The traditional primary prevention paradigm for coronary artery disease (CAD) centers on population-based algorithms to classify individual risk. However, this approach often misclassifies individuals and leaves many in the \'intermediate\' category, for whom there is no clear preferred prevention strategy. Coronary artery calcium (CAC) and polygenic risk scoring (PRS) are two contemporary tools for risk prediction to enhance the impact of effective management.
Aims
To determine how these CAC and PRS impact upon adherence to pharmacotherapy and lifestyle measures in asymptomatic individuals with subclinical atherosclerosis.
Methods
The CAPAR-CAD study is a multi-centre, open, randomised controlled trial in Victoria, Australia. Participants are self-selected individuals aged 40 to 70 years with no prior history of cardiovascular disease (CVD), intermediate 10-year risk for CAD as determined by the pooled cohort equation (PCE), and CAC score >0. All participants will have a health assessment, a full CT coronary angiogram (CTCA), and PRS calculation. They will then be randomised to receive their risk presented either as PCE and CAC, or PCE and PRS. The intervention includes e-Health coaching focused on risk factor management, health education and pharmacotherapy, and follow-up to augment adherence to statin medication. The primary endpoint is change in low density lipoprotein cholesterol (LDL-C) from baseline to 12 months. The secondary endpoint is between-group differences in behaviour modification and adherence to statin pharmacotherapy.
Results
As at 31st July 2021 we have screened 1903 individuals. We present the results of the 574 participants deemed eligible after baseline assessment.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 22 Feb 2022; epub ahead of print
Verma KP, Marwick T, Duarte C, Meikle P, Inouye M, Carrington MJ
Am Heart J: 22 Feb 2022; epub ahead of print | PMID: 35218726
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Impact:
Abstract

Randomized Evaluation of Decision Support Interventions for Atrial Fibrillation: Rationale and Design of the RED-AF study.

Jones AE, McCarty MM, Brito JP, Noseworthy PA, ... Ozanne EM, STEP-UP AFIB Writing Group
Shared decision making (SDM) improves the likelihood that patients will receive care in a manner consistent with their priorities. To facilitate SDM, decision aids (DA) are commonly used, both to prepare a patient before their clinician visit, as well as to facilitate discussion during the visit. However, the relative efficacy of patient-focused or encounter-based DAs on SDM and patient outcomes remains largely unknown. We aim to directly estimate the comparative effectiveness of two DA\'s on SDM observed in encounters to discuss stroke prevention strategies in patients with atrial fibrillation (AF). The study aims to recruit 1200 adult patients with non-valvular AF who qualify for anticoagulation therapy, and their clinicians who manage stroke prevention strategies, in a 2 × 2 cluster randomized multi-center trial at six sites. Two DA\'s were developed as interactive, online, non-linear tools: a patient decision aid (PDA) to be used by patients before the encounter, and an encounter decision aid (EDA) to be used by clinicians with their patients during the encounter. Patients will be randomized to PDA or usual care; clinicians will be randomized to EDA or usual care. Primary outcomes are quality of SDM, patient decision making, and patient knowledge. Secondary outcomes include anticoagulation choice, adherence, and clinical events. This trial is the first randomized, head-to-head comparison of the effects of an EDA versus a PDA on SDM. Our results will help to inform future SDM interventions to improve patients\' AF outcomes and experiences with stroke prevention strategies.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 22 Feb 2022; epub ahead of print
Jones AE, McCarty MM, Brito JP, Noseworthy PA, ... Ozanne EM, STEP-UP AFIB Writing Group
Am Heart J: 22 Feb 2022; epub ahead of print | PMID: 35218727
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This program is still in alpha version.