Journal: Am Heart J

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Abstract

Rationale and Design of a Large Population Study to Validate Software for the Assessment of Atrial Fibrillation from Data Acquired by a Consumer Tracker or Smartwatch: The Fitbit Heart Study.

Lubitz SA, Faranesh AZ, Atlas SJ, McManus DD, ... Pantelopoulos A, Foulkes AS
Background
Early detection of atrial fibrillation or flutter (AF) may enable prevention of downstream morbidity. Consumer wrist-worn wearable technology is capable of detecting AF by identifying irregular pulse waveforms using photoplethysmography (PPG). The validity of PPG-based software algorithms for AF detection requires prospective assessment.
Methods
The Fitbit Heart Study (NCT04380415) is a single-arm remote clinical trial examining the validity of a novel PPG-based software algorithm for detecting AF. The proprietary Fitbit algorithm examines pulse waveform intervals during analyzable periods in which participants are sufficiently stationary. Fitbit consumers with compatible wrist-worn trackers or smartwatches were invited to participate. Enrollment began May 6, 2020 and as of October 1, 2020, 455,699 participants enrolled. Participants in whom an irregular heart rhythm was detected were invited to attend a telehealth visit and eligible participants were then mailed a one-week single lead electrocardiographic (ECG) patch monitor. The primary study objective is to assess the positive predictive value of an irregular heart rhythm detection for AF during the ECG patch monitor period. Additional objectives will examine the validity of irregular pulse tachograms during subsequent heart rhythm detections, self-reported AF diagnoses and treatments, and relations between irregular heart rhythm detections and AF episode duration and time spent in AF.
Conclusions
The Fitbit Heart Study is a large-scale remote clinical trial comprising a unique software algorithm for detection of AF. The study results will provide critical insights into the use of consumer wearable technology for AF detection, and for characterizing the nature of AF episodes detected using consumer-based PPG technology.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 14 Apr 2021; epub ahead of print
Lubitz SA, Faranesh AZ, Atlas SJ, McManus DD, ... Pantelopoulos A, Foulkes AS
Am Heart J: 14 Apr 2021; epub ahead of print | PMID: 33865810
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Abstract

Neighborhood education status drives racial disparities in clinical outcomes in PPCM.

Getz KD, Lewey J, Tam V, Irizarry OC, ... Aplenc R, Arany Z
Importance
Peripartum cardiomyopathy (PPCM) disproportionately affects women of African ancestry. Additionally, clinical outcomes are worse in this subpopulation compared to White women with PPCM. The extent to which socioeconomic parameters contribute to these racial disparities is not known.
Objective
To quantify the association between area-based proxies of socioeconomic status (SES) and clinical outcomes in PPCM, and to determine the potential contribution of these factors to racial disparities in outcomes.
Design, setting, and participants
A retrospective cohort study was performed at the University of Pennsylvania Health System, a tertiary referral center serving a population with a high proportion of Black individuals. The cohort included 220 women with PPCM, 55% of whom were Black or African American. Available data included clinical and demographic characteristics as well as residential address georeferenced to US Census-derived block group measures of SES.
Main outcomes and measures
Rates of sustained cardiac dysfunction (defined as persistent LVEF <50%, LVAD placement, transplant, or death) were compared by race and block group-level measures of SES, and a composite neighborhood concentrated disadvantage index (NDI). The contributions of area-based socioeconomic parameters to the association between race and sustained cardiac dysfunction were quantified.
Results
Black race and higher NDI were both independently associated with sustained cardiac dysfunction (relative risk [RR] 1.63, confidence interval [CI] 1.13-2.36; and RR 1.29, CI 1.08-1.53, respectively). Following multivariable adjustment, effect size for NDI remained statistically significant, but effect size for Black race did not. The impact of low neighborhood education on racial disparities in outcomes was stronger than that of low neighborhood income (explaining 45% and 0% of the association with black race, respectively). After multivariate adjustment, only low area-based education persisted as significantly correlating with sustained cardiac dysfunction (RR 1.49; CI 1.02-2.17).
Conclusions
Both Black race and NDI independently associate with adverse outcomes in women with PPCM in a single center study. Of the specific components of NDI, neighborhood low education was most strongly associated with clinical outcome and partially explained differences in race. These results suggest interventions targeting social determinants of health in disadvantaged communities may help to mitigate outcome disparities.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 11 Apr 2021; epub ahead of print
Getz KD, Lewey J, Tam V, Irizarry OC, ... Aplenc R, Arany Z
Am Heart J: 11 Apr 2021; epub ahead of print | PMID: 33857409
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Abstract

Clinical Features and Outcomes in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction: Early versus Recent Experience with Impella.

Singh H, Mehta RH, O\'Neill W, Kapur NK, ... Rosman H, Kaki A
Objectives
To compare clinical features and outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) treated in the early experience with Impella percutaneous ventricular assist device and patients treated recently.
Background
Since pre-market approval (PMA) of Impella device as treatment for AMICS, use of the device has grown considerably.
Methods
We retrospectively analyzed 649 AMICS patients treated with perioperative Impella, with 291 patients treated from 2008 to 2014 comprising the early experience cohort and 358 patients treated from 2017 to 2019 comprising the recent experience cohort. The primary end point was risk adjusted in-hospital mortality.
Results
Mean age and gender distribution of patients was similar in the two cohorts. The recent cohort had more invasive hemodynamic monitoring (64% vs 46%; p<0.001) and less use of an intra-aortic balloon pump prior to Impella (15% vs 41%; p<0.001). Recently treated patients were significantly more likely to receive Impella support prior to PCI (58% vs 44%; p=0.005). In-hospital mortality was lower in the recent cohort (48% versus 56%; p=0.043). This difference was however no longer significant after risk adjustment (adjusted OR 0.89, 95% CI 0.59-1.34, p=0.59). Rates of acute kidney injury, major bleeding, and vascular complications requiring surgery were also significantly lower in the recent cohort.
Conclusions
Use of Impella for AMICS during recent years is associated with lower unadjusted in-hospital mortality, which may reflect better patient selection, earlier device implantation, and improved management algorithms. In-depth understanding of these factors may inform the development of future treatment protocols.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 09 Apr 2021; epub ahead of print
Singh H, Mehta RH, O'Neill W, Kapur NK, ... Rosman H, Kaki A
Am Heart J: 09 Apr 2021; epub ahead of print | PMID: 33848505
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Abstract

Renin-Angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) Registry.

Núñez-Gil IJ, Olier I, Feltes G, Viana-Llamas MC, ... Macaya C, HOPE COVID-19 investigators (Cols appendix)
Background
The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site.
Methods
HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications.
Results
We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure.
Conclusion
RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 08 Apr 2021; epub ahead of print
Núñez-Gil IJ, Olier I, Feltes G, Viana-Llamas MC, ... Macaya C, HOPE COVID-19 investigators (Cols appendix)
Am Heart J: 08 Apr 2021; epub ahead of print | PMID: 33845032
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Impact:
Abstract

Patient-centered contrast thresholds to reduce acute kidney injury in high-risk patients undergoing percutaneous coronary intervention.

Malik AO, Amin A, Kennedy K, Qintar M, ... Mehran R, Spertus JA
Background
Contrast volume used during percutaneous coronary intervention has a direct relationship with contrast-associated acute kidney injury. While several models estimate the risk of contrast-associated acute kidney injury, only the strategy of limiting contrast volume to 3 × estimated glomerular filtration rate (eGFR) gives actionable estimates of safe contrast volume doses. However, this method does not consider other patient characteristics associated with risk, such as age, diabetes or heart failure.
Methods
Using the National Cardiovascular Data Registry acute kidney injury risk model, we developed a novel strategy to define safe contrast limits by entering a contrast term into the model and using it to meet specific (eg, 10%) relative risk reductions. We then estimated acute kidney injury rates when our patient-centered model-derived thresholds were and were not exceeded using data from CathPCI version 5 between April 2018 and June 2019. We repeated the same analysis in a sub-set of patients who received ≤3 × eGFR contrast.
Results
After excluding patients on hemodialysis, below average risk (<7%), missing data and multiple percutaneous coronary interventions, our final analytical cohort included 141,133 patients at high risk for acute kidney injury. The rate of acute kidney injury was 10.0% when the contrast thresholds derived from our patient-centered model were met and 18.2% when they were exceeded (P < .001). In patients who received contrast ≤3 × eGFR (n = 82,318), contrast-associated acute kidney injury rate was 9.8% when the contrast thresholds derived from our patient centered model were met and 14.5% when they were exceeded (P < .001).
Conclusions
A novel strategy for developing personalized contrast volume thresholds, provides actionable information for providers that could decrease rates of contrast-associated acute kidney injury. This strategy needs further prospective testing to assess efficacy in improving patient outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:51-59
Malik AO, Amin A, Kennedy K, Qintar M, ... Mehran R, Spertus JA
Am Heart J: 30 Mar 2021; 234:51-59 | PMID: 33359778
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Impact:
Abstract

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

Fagel ND, Amoroso G, Vink MA, Slagboom T, ... de Winter RJ, Riezebos RK
Background
In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor.
Methods
In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated.
Results
In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49).
Conclusions
In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:42-50
Fagel ND, Amoroso G, Vink MA, Slagboom T, ... de Winter RJ, Riezebos RK
Am Heart J: 30 Mar 2021; 234:42-50 | PMID: 33422517
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Abstract

Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

Ge Z, Kan J, Gao XF, Kong XQ, ... Zhang JJ, Chen SL
Background
Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion.
Trial design
DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure.
Conclusions
DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:101-110
Ge Z, Kan J, Gao XF, Kong XQ, ... Zhang JJ, Chen SL
Am Heart J: 30 Mar 2021; 234:101-110 | PMID: 33465369
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Impact:
Abstract

Late kidney injury after transcatheter aortic valve replacement.

Adachi Y, Yamamoto M, Shimura T, Yamaguchi R, ... Hayashida K, OCEAN-TAVI Investigators
Background
Information on early to late-phase kidney damage in patients who underwent transcatheter aortic valve replacement (TAVR) is scarce. We aimed to identify the predictive factors for late kidney injury (LKI) at 1-year and patient prognosis beyond 1-year after TAVR.
Methods
We retrospectively reviewed 1,705 patients\' data from the Japanese TAVR multicenter registry. Acute kidney injury (AKI) and LKI, defined as an increase of at least 0.3 mg/dL in creatinine level, a relative 50% decrease in kidney function from baseline to 48 hours and 1-year, were evaluated. The patients were categorized into the 4 groups as AKI-/LKI- (n = 1.362), AKI+/LKI- (n = 95), AKI-/LKI+ (n = 199), and AKI+/LKI+ (n = 46).
Results
The cumulative 3-year mortality rates were significantly increased across the four groups (12.5%, 15.8%, 24.6%, 25.8%, P < .001). Multivariate analysis revealed that chronic kidney disease, coronary artery disease, periprocedural AKI, and heart failure-related re-admission within 1-year were significantly associated with LKI. The Cox regression analysis revealed that AKI-/LKI+ and AKI+/LKI+ were independent predictors of increased late mortality beyond 1-year after TAVR (P = .001 and P = .01).
Conclusions
LKI was influenced by adverse cardio-renal events and was associated with increased risks of late mortality beyond 1-year after TAVR.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Mar 2021; 234:122-130
Adachi Y, Yamamoto M, Shimura T, Yamaguchi R, ... Hayashida K, OCEAN-TAVI Investigators
Am Heart J: 30 Mar 2021; 234:122-130 | PMID: 33454371
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Impact:
Abstract

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery - LAA-CLOSURE trial protocol.

Kiviniemi T, Bustamante-Munguira J, Olsson C, Jeppsson A, ... van Putte B, LAA-CLOSURE Investigators
Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Pre-specified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 29 Mar 2021; epub ahead of print
Kiviniemi T, Bustamante-Munguira J, Olsson C, Jeppsson A, ... van Putte B, LAA-CLOSURE Investigators
Am Heart J: 29 Mar 2021; epub ahead of print | PMID: 33798494
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Impact:
Abstract

Design and Rationale of The Randomized Trial of Comprehensive LifEstyle ModificatioN, Optimal Pharmacological Treatment and Utilizing PET Imaging for Quantifying and Managing Stable CoronaRy ArterY Disease (The CENTURY Study).

Kitkungvan D, Johnson NP, Kirkeeide R, Haynie M, ... Sdringola S, Gould KL
Background
The literature reports no randomized trial in chronic coronary artery disease (CAD) of a comprehensive management strategy integrating intense lifestyle management, maximal medical treatment to specific goals and high precision quantitative cardiac positron emission tomography (PET) for identifying high mortality risk patients needing essential invasive procedures. We hypothesize that this comprehensive strategy achieves greater risk factor reduction, lower major adverse cardiovascular events and fewer invasive procedures than standard practice.
Methods
The CENTURY Study (NCT00756379) is a randomized-controlled-trial study in patients with stable or at high risk for CAD. Patients are randomized to standard of care (Standard group) or intense comprehensive lifestyle-medical treatment to targets and PET guided interventions (Comprehensive group). Comprehensive Group patients are regularly consulted by the CENTURY team implementing diet/lifestyle/exercise program and medical treatment to target risk modification. Cardiac PET at baseline, 24-, and 60-months quantify the physiologic severity of CAD and guide interventions in the Comprehensive group while patients and referring physicians of the Standard group are blinded to PET results. The primary end-point is the CENTURY risk score reduction during 5 years follow-up. The secondary endpoint is a composite of death, non-fatal myocardial infarction, stroke, and coronary revascularization.
Conclusions
The CENTURY Study is the first study in stable CAD to test the incremental benefit of a comprehensive strategy integrating intense lifestyle modification, medical treatment to specific goals, and high-precision quantitative myocardial perfusion imaging to guide revascularization. A total of 1028 patients have been randomized, and the 5 years follow-up will conclude in 2022.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 20 Mar 2021; epub ahead of print
Kitkungvan D, Johnson NP, Kirkeeide R, Haynie M, ... Sdringola S, Gould KL
Am Heart J: 20 Mar 2021; epub ahead of print | PMID: 33762179
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Impact:
Abstract

Validity of different dose reduction criteria for apixaban.

Hawkins NM, Er L, Sandhu RK, Kaul P, ... Levin A, Andrade JG
Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 20 Mar 2021; epub ahead of print
Hawkins NM, Er L, Sandhu RK, Kaul P, ... Levin A, Andrade JG
Am Heart J: 20 Mar 2021; epub ahead of print | PMID: 33762178
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Impact:
Abstract

Comparison of 1-month Versus 12-month Dual Antiplatelet Therapy after Implantation of Drug-eluting Stents Guided by either Intravascular Ultrasound or Angiography in Patients with Acute Coronary Syndrome: Rationale and Design of Prospective, Multicenter, Randomized, Controlled IVUS-ACS & ULTIMATE-DAPT trial.

Ge Z, Gao XF, Kan J, Kong XQ, ... Zhang JJ, Chen SL
Background
Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor.
Methods
The IVUS-ACS & ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine 1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and 2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (1st randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥ Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (2nd randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3 or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the 2nd randomized population.
Conclusion
The IVUS-ACS & ULTIMATE-DAPT trial is designed to test the efficacy and safety of two different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 19 Mar 2021; epub ahead of print
Ge Z, Gao XF, Kan J, Kong XQ, ... Zhang JJ, Chen SL
Am Heart J: 19 Mar 2021; epub ahead of print | PMID: 33621541
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Impact:
Abstract

Venous thromboembolism among patients hospitalized with COVID-19 at Veterans Health Administration Hospitals.

Gutierrez JA, Samsky MD, Schulteis RD, Gu L, ... Aday AW, Rao SV
Patients with coronavirus disease 2019 (COVID-19) are at heightened risk of venous thromboembolic events (VTE), though there is no data examining when these events occur following a COVID-19 diagnosis. We therefore sought to characterize the incidence, timecourse of events, and outcomes of VTE during the COVID-19 pandemic in a national healthcare system using data from Veterans Affairs Administration.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 17 Mar 2021; 237:1-4
Gutierrez JA, Samsky MD, Schulteis RD, Gu L, ... Aday AW, Rao SV
Am Heart J: 17 Mar 2021; 237:1-4 | PMID: 33745899
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Impact:
Abstract

Rationale and Design of the Women\'s IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) Trial.

Handberg EM, Merz CNB, Cooper-Dehoff R, Wei J, ... Rogatko A, Pepine CJ
Background
Approximately half of all women with anginal symptoms and/or signs of ischemia and no obstructive coronary artery disease (INOCA) referred for coronary angiography have elevated risk for major adverse cardiac events (MACE), poor quality of life (QoL) and resource consumption. Yet, guidelines focus on symptom management while clinical practice typically advocates only reassurance. Pilot studies of INOCA subjects suggest benefit with intensive medical therapy (IMT) that includes high-intensity statins and angiotensin converting enzyme inhibitors (ACE-I) or receptor blockers (ARB) to provide the rationale for a randomized pragmatic trial to limit MACE.
Methods
The Women\'s IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) of a pragmatic strategy of IMT vs. usual care (UC) in 4,422 symptomatic women with INOCA (NCT03417388) in ∼70 US sites. The hypothesis is that IMT will reduce the primary outcome of first occurrence of MACE by 20% vs. UC at ∼2.5 year followup. Secondary outcomes include QoL, time to return to \"duty\"/work, healthcare utilization, angina, cardiovascular death and individual primary outcome components over 3 years follow-up. The study utilizes web-based data capture, e-consents, single IRB and centralized pharmacy distribution of strategy medications directly to patients\' homes to reduce site and patient burden. A biorepository will collect blood samples to assess potential mechanisms.
Conclusions
The results of this trial will provide important data necessary to inform guidelines regarding how best to manage this growing and challenging population of women with INOCA.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 17 Mar 2021; epub ahead of print
Handberg EM, Merz CNB, Cooper-Dehoff R, Wei J, ... Rogatko A, Pepine CJ
Am Heart J: 17 Mar 2021; epub ahead of print | PMID: 33745898
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Impact:
Abstract

Potent P2Y12 Inhibitors versus Clopidogrel in Elderly Patients with Acute Coronary Syndrome: Systematic Review and Meta-Analysis: P2Y12 inhibitors and elderly patients with ACS.

Fujisaki T, Kuno T, Ando T, Briasoulis A, Takagi H, Bangalore S
Background
Potent P2Y12 inhibitors reduce cardiovascular events but increase bleeding in patients presenting with acute coronary syndrome (ACS). Elderly patients are at increased risk of bleeding and whether the benefit-risk ratio of potent P2Y12 inhibitors remains favorable is not known.
Objectives
To investigate the efficacy and safety of potent P2Y12 inhibitors versus clopidogrel in elderly patients with ACS.
Methods
PUBMED and EMBASE were searched through July 2020 for randomized control trials (RCTs) or subgroup analyses of RCTs investigating potent P2Y12 inhibitors (prasugrel or ticagrelor) or clopidogrel in elderly (age ≥ 65 years) patients with ACS. The primary outcome was major adverse cardiovascular events (MACE).
Results
Our search identified 9 RCTs with a total of 10,792 elderly patients. When compared with clopidogrel, potent P2Y12 inhibitors had similar risk of MACE (hazard ratio (HR): 0.94; 95%; confidence interval (CI) [0.85-1.06], P=0.31, I2=9%), all-cause mortality (HR: 0.89; 95% CI [0.74-1.07], P=0.22, I2=29%), reduced the risk of cardiovascular death (HR: 0.82; 95% CI [0.68-0.98], P=0.03, I2=16%) but increased the risk of major bleeding (HR: 1.27; 95% CI [1.04-1.56], P=0.02, I2=0%). In a subgroup analysis, ticagrelor reduced all-cause mortality (HR: 0.73; 95% CI [0.55-0.98]) and cardiovascular death (HR: 0.70; 95% CI [0.54-0.90]) compared with clopidogrel.
Conclusions
Among elderly patients with ACS, potent P2Y12 inhibitors reduce cardiovascular death but increase bleeding with no difference in MACE or all-cause death when compared with clopidogrel. Further RCTs are needed to refine P2Y12 inhibitor selection for elderly patients with ACS.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 14 Mar 2021; epub ahead of print
Fujisaki T, Kuno T, Ando T, Briasoulis A, Takagi H, Bangalore S
Am Heart J: 14 Mar 2021; epub ahead of print | PMID: 33737060
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Impact:
Abstract

Effectiveness of the quadrivalent high-dose influenza vaccine for prevention of cardiovascular and respiratory events in people aged 65 years and above: Rationale and design of a real-world pragmatic randomized clinical trial.

Hollingsworth R, Palmu A, Pepin S, Dupuy M, ... Samson S, De Bruijn I
Background
Influenza has been an acknowledged cause of respiratory disease for decades. However, considerable related, and often unappreciated, disease burden stems from cardiovascular complications, exacerbations of underlying medical conditions and secondary respiratory complications, with the highest burden in the elderly. This novel study combines the gold standard method of a randomized controlled trial with real-world data collection through national registries, to assess the relative effectiveness of high-dose (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing cardio-respiratory hospitalizations in a large cohort of adults aged ≥65 years.
Methods and results
This trial (NCT04137887) is a Phase III/IV, modified double-blinded, randomized, registry-based trial, conducted by the Finnish Institute for Health and Welfare (THL). Participants (n>120 000) are being enrolled over multiple influenza seasons and randomized (1:1) to receive QIV-HD or QIV-SD. Participant follow-up is based on data collection up to 11 months post-vaccination using Finnish national health registries. The primary objective is to demonstrate the relative superior effectiveness of QIV-HD over QIV-SD in preventing cardio-respiratory hospitalizations up to 6 months post-vaccination. Safety will be assessed using automated online tools throughout the study, with causality assessed using statistical and probabilistic methods; serious adverse reactions and adverse events of special interest will be investigated individually.
Conclusion
This large, real-world, randomized study will provide valuable insight into the contribution of influenza in causing severe cardio-respiratory events, and the role of vaccination with QIV-HD in reducing these outcomes compared to the current standard of care.
Funding
Sanofi Pasteur.

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

Am Heart J: 12 Mar 2021; 237:54-61
Hollingsworth R, Palmu A, Pepin S, Dupuy M, ... Samson S, De Bruijn I
Am Heart J: 12 Mar 2021; 237:54-61 | PMID: 33722585
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Impact:
Abstract

Curriculum in Cardiology To Adjust or Not to Adjust: The Role of Different Covariates in Cardiovascular Observational Studies.

Etminan M, Brophy JM, Collins G, Nazemipour M, Mansournia MA
Covariate adjustment is integral to the validity of observational studies assessing causal effects. It is common practice to adjust for as many variables as possible in observational studies in the hopes of reducing confounding by other variables. However, indiscriminate adjustment for variables using standard regression models may actually lead to biased estimates. In this paper, we differentiate between confounders, mediators, colliders, and effect modifiers. We will discuss that while confounders should be adjusted for in the analysis, one should be wary of adjusting for colliders. Mediators should not be adjusted for when examining the total effect of an exposure on an outcome. Automated statistical programs should not be used to decide which variables to include in causal models. Using a case scenario in cardiology, we will demonstrate how to identify confounders, colliders, mediators and effect modifiers and the implications of adjustment or non-adjustment for each of them.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 11 Mar 2021; epub ahead of print
Etminan M, Brophy JM, Collins G, Nazemipour M, Mansournia MA
Am Heart J: 11 Mar 2021; epub ahead of print | PMID: 33722586
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Impact:
Abstract

Sex Disparities in Patients with Symptomatic Severe Aortic Stenosis.

Lowenstern A, Sheridan P, Wang TY, Boero I, ... Peterson ED, Brennan JM
Background
We evaluated whether there is equitable distribution across sexes of treatment and outcomes for aortic valve replacement (AVR), via surgical (SAVR) or transcatheter (TAVR) methods, in symptomatic severe aortic stenosis (ssAS) patients.
Methods
Using de-identified data, we identified 43,822 patients with ssAS (2008-2016). Multivariate competing risk models were used to determine the likelihood of any AVR, while accounting for the competing risk of death. Association between sex and one-year mortality, stratified by AVR status, was evaluated using multivariate Cox regression models with AVR as a time-dependent variable.
Results
Among patients with ssAS, 20,986 (47.9%) were female. Females were older (median age 81 vs. 78, p<0.001), more likely to have body mass index <20 (8.5% vs. 3.5%), and home oxygen use (4.4% vs. 3.4%, p<0001 for all). Overall, 12,129 (27.7%) patients underwent AVR for ssAS. Females were less likely to undergo AVR compared with males (24.1% vs. 31.0%, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.77-0.83), but when treated, were more likely to undergo TAVR (37.9% vs. 30.9%, adjusted HR 1.21, 95% CI 1.15-1.27). Untreated females and males had similarly high rates of mortality at one year (31.1% vs. 31.3%, adjusted HR 0.98, 95% CI 0.94-1.03). Among those undergoing AVR, females had significantly higher mortality (10.2% vs. 9.4%, adjusted HR 1.24, 95% CI 1.10-1.41), driven by increased SAVR-associated mortality (9.0% vs. 7.6%, adjusted HR 1.43, 95% CI 1.21-1.69).
Conclusions
Treatment rates for ssAS patients remain suboptimal with disparities in female treatment.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 11 Mar 2021; epub ahead of print
Lowenstern A, Sheridan P, Wang TY, Boero I, ... Peterson ED, Brennan JM
Am Heart J: 11 Mar 2021; epub ahead of print | PMID: 33722584
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Impact:
Abstract

Transcatheter aortic valve replacement in low-risk patients: 2-year results from the LRT trial.

Waksman R, Torguson R, Medranda GA, Shea C, ... Satler LF, Rogers T
Background
Previous studies from the Low Risk TAVR (LRT) trial demonstrated that transcatheter aortic valve replacement (TAVR) is safe and feasible in low-risk patients, with excellent 30-day and 1-year outcomes. The objective of this study was to report clinical outcomes and the impact of 30-day hypoattenuated leaflet thickening (HALT) on structural valve deterioration (SVD) 2 years after TAVR.
Methods
The LRT trial was the first Food and Drug Administration-approved Investigational Device Exemption trial in the United States to evaluate the safety and feasibility of TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis (AS). Valve hemodynamics and SVD by echo were recorded 30 days, 1 year, and 2 years post-TAVR.
Results
The LRT trial enrolled 200 low-risk patients to receive TAVR. Their mean age was 73.6 years and 61.5% were men. At 2-year follow-up, the mortality rate was 4.2%; the cardiovascular death rate was 1.6%. The disabling stroke rate was 1.1%, permanent pacemaker implantation rate was 8.6%, and 4 patients (2.2%) presented with endocarditis (2 between years 1 and 2). Of the 14% of TAVR subjects who had evidence of HALT at 30 days, there was no impact on valve hemodynamics, endocarditis or stroke at 2 years.
Conclusions
TAVR for low-risk patients with symptomatic severe tricuspid AS is safe at 2 years. The presence of HALT at 30 days did not impact the early hemodynamic improvements nor the durability of the valve structure.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 09 Mar 2021; 237:25-33
Waksman R, Torguson R, Medranda GA, Shea C, ... Satler LF, Rogers T
Am Heart J: 09 Mar 2021; 237:25-33 | PMID: 33713618
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Impact:
Abstract

Effect of a Smartphone-Based Intervention on Secondary Prevention Medication Prescriptions After Coronary Artery Bypass Graft Surgery: The MISSION-1 Randomized Controlled Trial.

Qu J, Du J, Rao C, Chen S, ... Zheng Z, MISSION-1 Collaborative Group
Background
Studies found that patients who underwent coronary artery bypass grafting (CABG) often fail to receive optimal evidence-based secondary prevention medications. We evaluated the effectiveness of a smartphone-based quality improvement effort on improving prescription of medical therapies.
Methods
In this cluster-randomized controlled trial, 60 hospitals were randomized to a control arm (n=30) or to an intervention arm using smartphone-based multifaceted quality improvement interventions (n=30). The primary outcome was prescription of statin. The secondary outcomes were prescription of beta-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACE inhibitor or ARB), and optimal medical therapy for eligible patients.
Results
Between June 1, 2015 and September 15, 2016, a total of 10006 CABG patients were enrolled (5653 in 26 intervention and 4353 in 29 control hospitals, five hospitals withdrew). Statin prescribing rate was 87.8% in the intervention arm and 84.4% in the control arm. We saw no evidence of an effect of intervention on statin prescribing in the intention-to-treat analysis (odds ratio, 1.31; 95% confidence interval, 0.68 to 2.54; P=0.43) or in key patient subsets. The prescription rates of ACE inhibitor or ARB and optimal medical therapy were comparable between study groups, while beta-blocker was more often prescribed in the intervention arm. Post hoc analysis demonstrated a greater increase in statin prescribing rate over time in the intervention arm.
Conclusions
A smartphone-based quality improvement intervention compared with usual care did not increase statin prescribing for patients who received CABG. New studies focusing on the best practice of this technique may be warranted.
Clinical trial registration
https://www.clinicaltrials.gov (NCT02430012).

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 05 Mar 2021; epub ahead of print
Qu J, Du J, Rao C, Chen S, ... Zheng Z, MISSION-1 Collaborative Group
Am Heart J: 05 Mar 2021; epub ahead of print | PMID: 33689732
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Impact:
Abstract

Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial.

Aminorroaya A, Tavolinejad H, Sadeghian S, Jalali A, ... Ngarmukos T, Tajdini M
Background
The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions.
Methods
In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization.
Conclusion
The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 05 Mar 2021; 237:5-12
Aminorroaya A, Tavolinejad H, Sadeghian S, Jalali A, ... Ngarmukos T, Tajdini M
Am Heart J: 05 Mar 2021; 237:5-12 | PMID: 33689731
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Impact:
Abstract

Randomized comparison of early supplemental oxygen versus ambient air in patients with confirmed myocardial infarction: Sex-related outcomes from DETO2X-AMI.

Alfredsson J, James SK, Erlinge D, Herlitz J, ... Hofmann R, DETO2X-SWEDEHEART Investigators
Background
The purpose of this study is to investigate the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI).
Methods
The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis including 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure at long-term follow-up, stratified according to sex.
Results
Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found (P= .16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone, there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment.
Conclusion
Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or heart failure in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age.

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

Am Heart J: 05 Mar 2021; 237:13-24
Alfredsson J, James SK, Erlinge D, Herlitz J, ... Hofmann R, DETO2X-SWEDEHEART Investigators
Am Heart J: 05 Mar 2021; 237:13-24 | PMID: 33689730
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Impact:
Abstract

Efficacy of a Centralized, Blended Electronic and Human Intervention to Improve Direct Oral Anticoagulant Adherence: Smartphones to improve rivaroxaban ADHEREnce in Atrial Fibrillation (SmartADHERE) A Randomized Clinical Trial: SmartADHERE rivaroxaban adherence trial.

Turakhia M, Sundaram V, Smith SN, Ding V, ... Mahaffey KW, smartADHERE Investigators
Background
Improving adherence to direct oral anticoagulants (DOAC) is challenging, and simple text messaging reminders have not been effective.
Methods
SmartADHERE was a randomized trial that tested a personalized digital and human direct oral anticoagulant adherence intervention compared to usual care. Eligibility required age ≥ 18, newly-prescribed (≤ 90 days) rivaroxaban for atrial fibrillation (AF), 1 of 4 at-risk criteria for nonadherence, and a smartphone. The intervention consisted of combination of a medication management smartphone app, daily app-based reminders, adaptive text messaging, and phone-based counseling for severe nonadherence. The primary outcome was the proportion of days covered by rivaroxaban (PDC) at 6 months. There were 25 U.S. sites, all cardiology and electrophysiology outpatient practices, activated for a target sample size of 378, but the study was terminated by the sponsor prior to reaching target enrollment.
Results
There were 139 participants (age 65±9.6 years, 30% female, median CHA2DS2-VASc score 3 with IQR 2-4, mean total medication burden 7.7±4.4). DOAC adherence was high in both arms with no difference in the primary outcome (PDC 0.86±0.25 intervention vs 0.88±0.25 control, p=0.62) or in secondary outcomes including PDC ≥ 0.80 and medication persistence. Per protocol analyses had similar results. Because of the high overall PDC, the likelihood to answer the primary hypothesis was only 51% even if target enrollment were achieved. There were no study-related adverse events.
Conclusions
The use of a centralized digital and human adherence intervention was feasible across multiple sites. Overall adherence was much higher than expected despite pre-screening for at-risk individuals. SmartADHERE illustrates the challenges of trials of behavioral and technology interventions, where enrollment itself may lead to selection bias or treatment effects. Pragmatic study designs, such as cluster randomization or stepped-wedge implementation, should be considered to improve enrollment and generalizability.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 03 Mar 2021; epub ahead of print
Turakhia M, Sundaram V, Smith SN, Ding V, ... Mahaffey KW, smartADHERE Investigators
Am Heart J: 03 Mar 2021; epub ahead of print | PMID: 33676886
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Impact:
Abstract

Rivaroxaban monotherapy versus combination therapy according to patient risk of stroke and bleeding in atrial fibrillation and stable coronary disease: AFIRE trial subanalysis.

Akao M, Yasuda S, Kaikita K, Ako J, ... Matsui K, Ogawa H
Background
In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy.
Methods
In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy end point was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding defined by the International Society on Thrombosis and Haemostasis.
Results
Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS2, p for interaction = 0.727 for efficacy, 0.395 for safety; CHA2DS2-VASc, p for interaction = 0.740 for efficacy, 0.265 for safety) or bleeding risk (HAS-BLED, p for interaction = 0.581 for efficacy, 0.225 for safety). There was also no evidence of statistical heterogeneity across patient risk categories for other end points; stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, MI, MI or unstable angina, death from any cause, any bleeding, or net adverse clinical events.
Conclusions
The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding.
Clinical trial registration
UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Feb 2021; 236:59-68
Akao M, Yasuda S, Kaikita K, Ako J, ... Matsui K, Ogawa H
Am Heart J: 27 Feb 2021; 236:59-68 | PMID: 33657403
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Impact:
Abstract

Sociodemographic differences in utilization and outcomes for temporary cardiovascular mechanical support in the setting of cardiogenic shock.

Thangam M, Luke AA, Johnson DY, Amin AP, ... Huang K, Joynt Maddox KE
Background
Temporary mechanical circulatory support (MCS) devices are increasingly used in cardiogenic shock, but whether sociodemographic differences by sex, race and/or ethnicity, insurance status, and neighborhood poverty exist in the utilization of these devices is unknown.
Methods
Retrospective cross-sectional study using the National Inpatient Sample for 2012-2017. Logistic regression models were used to examine predictors of use of temporary MCS devices and for in-hospital mortality, clustering by hospital-year.
Results
Our study population included 109,327 admissions for cardiogenic shock. Overall, 14.3% of admissions received an intra-aortic balloon pump, 4.2% a percutaneous ventricular assist device, and 1.8% extracorporeal membranous oxygenation (ECMO). After adjusting for age, comorbidities, and hospital characteristics, use of temporary MCS was lower in women compared to men (adjusted odds ratio [aOR] = 0.76, P < .001), Black patients compared to white ones (aOR = 0.73, P < .001), those insured by Medicare (aOR = 0.75, P < .001), Medicaid (aOR = 0.74, P < .001), or uninsured (aOR = 0.90, P = .015) compared to privately insured, and those in the lowest income neighborhoods (aOR = 0.94, P = .003) versus other neighborhoods. Women, admissions covered by Medicare, Medicaid, or uninsured, and those from low-income neighborhoods also had higher mortality rates even after adjustment for MCS implantation.
Conclusions
There are differences in the use of temporary MCS in the setting of cardiogenic shock among specific populations within the United States. The growing use of MCS for treating cardiogenic shock highlights the need to better understand its impact on outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 24 Feb 2021; epub ahead of print
Thangam M, Luke AA, Johnson DY, Amin AP, ... Huang K, Joynt Maddox KE
Am Heart J: 24 Feb 2021; epub ahead of print | PMID: 33359779
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Impact:
Abstract

Total vascular resistance increases during volume-unloading in asymptomatic single ventricle patients.

Vaiyani D, Matsuo K, Kanaan U, Patel B, ... Sachdeva R, Petit CJ
Objective
While the surgical stages of single ventricle (SV) palliation serve to separate pulmonary venous and systemic venous return, and to volume-unload the SV, staged palliation also results in transition from parallel to series circulation, increasing total vascular resistance. How this transition affects pressure loading of the SV is as yet unreported.
Methods
We performed a retrospective chart review of Stage I, II, and III cardiac catheterization (CC) and echocardiographic data from 2001-2017 in all SV pts, with focus on systemic, pulmonary, and total vascular resistance (SVR, PVR, TVR respectively). Longitudinal analyses were performed with log-transformed variables. Effects of SVR-lowering medications were analyzed using Wilcoxon rank-sum testing.
Results
There were 372 total patients who underwent CC at a Stage I (median age of 4.4 months, n=310), Stage II (median age 2.7 years, n = 244), and Stage III (median age 7.3 years, n = 113). Total volume loading decreases with progression to Stage III (P< 0.001). While PVR gradually increases from Stage II to Stage III, and SVR increases from Stage I to Stage III, TVR dramatically increases with progress towards series circulation. TVR was not affected by use of systemic vasodilator therapy. TVR, PVR, SVR, and CI did not correlate with indices of SV function at Stage III.
Conclusions
TVR steadily increases with an increasing contribution from SVR over progressive stages. TVR was not affected by systemic vasodilator agents. TVR did not correlate with echo-based indices of SV function. Further studies are needed to see if modulating TVR can improve exercise tolerance and outcomes.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 24 Feb 2021; 236:69-79
Vaiyani D, Matsuo K, Kanaan U, Patel B, ... Sachdeva R, Petit CJ
Am Heart J: 24 Feb 2021; 236:69-79 | PMID: 33640333
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Impact:
Abstract

Does study subject diversity influence cardiology research site performance?: Insights from 2 U.S. National Coronary Stent Registries.

Batchelor WB, Damluji AA, Yong C, Fiuzat M, ... O\'Connor CM, Mehran R
Background
Minorities and women are underrepresented in cardiovascular research. Whether their higher enrollment can be predicted or influences research site performance is unclear.
Methods
We evaluated 104 sites that enrolled 4,184 patients in the U.S. Platinum Diversity (PD) and Promus Element Plus (PE Plus) studies (2012 to 2016). Research sites were ranked from lowest to highest minority and female enrollment, respectively. United States Census Bureau division and core-based statistical area (CBSA) populations were determined for each site and the following study performance metrics compared across quartiles of minority and female enrollment, respectively: (1) study subject enrollment rate (SER), (2) time to first patient enrolled, (3) rate of follow-up visits not done, (4) rate of follow-up visits out of window, and (5) protocol deviation rate (PDR). Multivariable regression was used to predict SER and PDR.
Results
Minority enrollment varied by region (P = .025) and population (P = .024) with highest recruitment noted in the Pacific, West South Central, South Atlantic, Mid-Atlantic and East North Central divisions. Female enrollment bore no relationship to region (P = .67) or population (P = .40). Median SER was similar in sites withi the highest vs lowest quartile of minority enrollment (SER of 4 vs 5 patients per month, respectively, P =0.78) and highest vs. lowest female enrollment (SER of 4 vs 4, respectively, P = .21). Median PDR was lower in sites within the highest vs lowest minority enrollment (0.23 vs 0.50 PDs per patient per month, respectively, P = .01) and highest vs. lowest female enrollment (0.28 vs. 0.37 PDs per patient per month, respectively, P = .04). However, this relationship did not persist after multivariable adjustment. All other site performance metrics were comparable across quartiles of minority and female enrollment.
Conclusions
Minority, but not female enrollment, correlated with research site geographic region and surrounding population. High enrollment of minorities and women did not influence study performance metrics. These findings help inform future strategies aimed at increasing clinical trial diversity.
Trial registration
The PD and PE Plus studies are registered at www.clinicaltrials.gov under identifiers NCT02240810 and NCT01589978, respectively.
Key points
Question: Does the enrollment of more Blacks, Hispanics and women in US cardiovascular research studies influence the overall rate of study subject enrollment and/or other key study site performance metrics and can diverse enrollment be predicted?
Findings
In this pooled analysis of 104 sites that enrolled 4,184 patients in the Platinum Diversity and Promus Element Plus Post-Approval Studies, we found that the enrollment of higher proportions of underrepresented minorities and women was univariately associated with lower protocol deviation rates while having no effect on other site performance metrics. A site\'s geographic location and surrounding population predicted minority, but not female enrollment. Meaning: These findings suggest that cardiovascular research subject diversity may be predicted from site characteristics and enhanced without compromising key study performance metrics. These insights help inform future strategies aimed at improving clinical trial diversity.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 23 Feb 2021; 236:37-48
Batchelor WB, Damluji AA, Yong C, Fiuzat M, ... O'Connor CM, Mehran R
Am Heart J: 23 Feb 2021; 236:37-48 | PMID: 33636137
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Impact:
Abstract

Access to cardiac surgery centers for cardiac and non-cardiac hospitalizations in adolescents and adults with congenital heart defects- a descriptive case series study.

Insaf TZ, Sommerhalter KM, Jaff TA, Farr SL, ... Lui GK, Van Zutphen AR
Background
Individuals with congenital heart defects (CHDs) are recommended to receive all inpatient cardiac and noncardiac care at facilities that can offer specialized care. We describe geographic accessibility to such centers in New York State and determine several factors associated with receiving care there.
Methods
We used inpatient hospitalization data from the Statewide Planning and Research Cooperative System (SPARCS) in New York State 2008-2013. In the absence of specific adult CHD care center designations during our study period, we identified pediatric/adult and adult-only cardiac surgery centers through the Cardiac Surgery Reporting System to estimate age-based specialized care. We calculated one-way drive and public transit time (in minutes) from residential address to centers using R gmapsdistance package and the Google Maps Distance Application Programming Interface (API). We calculated prevalence ratios using modified Poisson regression with model-based standard errors, fit with generalized estimating equations clustered at the hospital level and subclustered at the individual level.
Results
Individuals with CHDs were more likely to seek care at pediatric/adult or adult-only cardiac surgery centers if they had severe CHDs, private health insurance, higher severity of illness at encounter, a surgical procedure, cardiac encounter, and shorter drive time. These findings can be used to increase care receipt (especially for noncardiac care) at pediatric/adult or adult-only cardiac surgery centers, identify areas with limited access, and reduce disparities in access to specialized care among this high-risk population.

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

Am Heart J: 22 Feb 2021; 236:22-36
Insaf TZ, Sommerhalter KM, Jaff TA, Farr SL, ... Lui GK, Van Zutphen AR
Am Heart J: 22 Feb 2021; 236:22-36 | PMID: 33636136
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Impact:
Abstract

Plasma trimethylamine N-oxide (TMAO) levels predict future risk of coronary artery disease in apparently healthy individuals in the EPIC-Norfolk prospective population study.

Tang WHW, Li XS, Wu Y, Wang Z, ... Boekholdt SM, Hazen SL
Background
Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear.
Methods and results
In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P < .001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; P = .001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], P < .001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], P < .05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile).
Conclusion
In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 20 Feb 2021; epub ahead of print
Tang WHW, Li XS, Wu Y, Wang Z, ... Boekholdt SM, Hazen SL
Am Heart J: 20 Feb 2021; epub ahead of print | PMID: 33626384
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Impact:
Abstract

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy.

Ohiomoba RO, Youmans QR, Ezema A, Akanyirige P, ... Yancy CW, Okwuosa IS
Objective
Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM.
Methods
We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models.
Results
Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30).
Conclusions
In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 19 Feb 2021; 236:13-21
Ohiomoba RO, Youmans QR, Ezema A, Akanyirige P, ... Yancy CW, Okwuosa IS
Am Heart J: 19 Feb 2021; 236:13-21 | PMID: 33621542
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Impact:
Abstract

Natriuretic peptide plasma concentrations and risk of cardiovascular versus non-cardiovascular events in heart failure with reduced ejection fraction: Insights from the PARADIGM-HF and ATMOSPHERE trials.

Khan MS, Kristensen SL, Vaduganathan M, Kober L, ... McMurray JJ, Butler J
Background
N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations are independent prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF). Whether a differential risk association between NT-proBNP plasma concentrations and risk of cardiovascular (CV) vs non-CV adverse events exists is not well known.
Objective
To assess if there is a differential proportional risk of CV vs non-CV adverse events by NT-proBNP plasma concentrations.
Methods
In this post hoc combined analysis of PARADIGM-HF and ATMOSPHERE trials, proportion of CV vs non-CV mortality and hospitalizations were assessed by NT-proBNP levels (<400, 400-999, 1000-1999, 2000-2999, and >3000 pg/mL) at baseline using Cox regression adjusting for traditional risk factors.
Results
A total of 14,737 patients with mean age of 62 ± 8 years (24% history of atrial fibrillation [AF]) were studied. For CV deaths, the event rates per 1000 patient-years steeply increased from 33.8 in the ≤400 pg/mL group to 142.3 in the ≥3000 pg/mL group, while the non-CV death event rates modestly increased from 9.0 to 22.7, respectively. Proportion of non-CV deaths decreased across the 5 NT-proBNP groups (21.1%, 18.4%, 17.9%, 17.4%, and 13.7% respectively). Similar trend was observed for non-CV hospitalizations (46.4%, 42.6%, 42.9%, 42.0%, and 36.9% respectively). These results remained similar when stratified according to the presence of AF at baseline and prior HF hospitalization within last 12 months.
Conclusions
The absolute CV event rates per patient years of follow-up were greater and had higher stepwise increases than non-CV event rates across a broad range of NT-proBNP plasma concentrations indicating a differential risk of CV events at varying baseline NT-proBNP values. These results have implications for future design of clinical trials.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 19 Feb 2021; 237:45-53
Khan MS, Kristensen SL, Vaduganathan M, Kober L, ... McMurray JJ, Butler J
Am Heart J: 19 Feb 2021; 237:45-53 | PMID: 33621540
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Impact:
Abstract

Biodegradable polymer sirolimus-eluting stents vs durable polymer everolimus-eluting stents in patients undergoing percutaneous coronary intervention: A meta-analysis of individual patient data from 5 randomized trials.

Pilgrim T, Rothenbühler M, Siontis GC, Kandzari DE, ... Waksman R, Windecker S
Background
Newest generation drug-eluting stents combine biodegradable polymers with ultrathin stent platforms in order to minimize vessel injury and inflammatory response. Evidence from randomized controlled trials suggested that differences in stent design translate into differences in clinical outcome. The aim of the present study was to evaluate the safety and efficacy of ultrathin strut, biodegradable polymer sirolimus eluting stents (BP SES) compared with thin strut, durable polymer everolimus-eluting stents (DP EES) among patients undergoing percutaneous coronary intervention (PCI).
Methods
We pooled individual participant data from 5 randomized trials (NCT01356888, NCT01939249, NCT02389946, NCT01443104, NCT02579031) including a total of 5,780 patients, and performed a one-stage meta-analysis using a mixed effects Cox regression model.
Results
At a median duration of follow-up of 739 days (interquartile range 365-1,806 days), target-lesion failure occurred in 337 (10.3%) and 304 (12.2%) patients treated with BP SES and DP EES (HR 0.86, 95%CI 0.71-1.06, P = .16). There were no significant differences between BP SES and DP EES with regards to cardiac death (111 (3.4%) vs 102 (4.1%); HR 1.05, 95%CI 0.80-1.37, P = .73), target-vessel myocardial infarction (136 (4.1%) vs 126 (5.0%), HR 0.79, 95%CI 0.62-1.01, P = .061), and clinically-driven target-lesion revascularization (163 (5.0%) vs 147 (5.9%); HR 0.94, 95%CI 0.75-1.18, P = .61). The effect was consistent across major subgroups. In a landmark analysis, there was no significant interaction between treatment effect and timing of events.
Conclusions
In this patient-level meta-analysis of 5 randomized controlled trials, BP SES were associated with a similar risk of target-lesion failure compared with DP EES among patients undergoing PCI.
Study registration
PROSPERO registry (CRD42018109098).

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 16 Feb 2021; 235:140-148
Pilgrim T, Rothenbühler M, Siontis GC, Kandzari DE, ... Waksman R, Windecker S
Am Heart J: 16 Feb 2021; 235:140-148 | PMID: 33609498
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Impact:
Abstract

Modified design of stimulation of the left ventricular endocardium for cardiac resynchronization therapy in nonresponders, previously untreatable and high-risk upgrade patients (SOLVE-CRT) trial.

Singh JP, Walsh MN, Kubo SH, Auricchio A, ... Rinaldi CA, Ullery S
The WiSE system is a novel, leadless endocardial system that can provide cardiac resynchronization therapy in patients who cannot be treated with a conventional epicardial left ventricular lead. Safety and efficacy were being evaluated in the pivotal, randomized, double-blind SOLVE-CRT Trial (Stimulation of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy.) The trial was initiated in 2018; however, patient enrollment was significantly impacted by the COVID-19 pandemic necessitating a change in design. This article describes the revised trial and the scientific rationale for the specific changes in the protocol.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 14 Feb 2021; 235:158-162
Singh JP, Walsh MN, Kubo SH, Auricchio A, ... Rinaldi CA, Ullery S
Am Heart J: 14 Feb 2021; 235:158-162 | PMID: 33596412
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Impact:
Abstract

Association between ambient air pollution and county-level cardiovascular mortality in the United States by social deprivation index.

Bevan GH, Freedman DA, Lee EK, Rajagopalan S, Al-Kindi SG
Background
Air pollution and socioeconomic status have both been strongly associated with cardiovascular (CV) outcomes. We sought to determine if socioeconomic status modifies the risk association between fine particulate matter air pollution (PM2.5) and CV mortality.
Methods
We linked county-level age-adjusted CV mortality data from Multiple Cause of Death files (2000-2016, ICD10: I00-I99) with 2015 Social Deprivation Index (SDI), a validated estimate of socioeconomic status, and modelled spatial and temporal mean annual PM2.5 exposures (2012-2018). Higher SDI suggests greater deprivation and lower socioeconomic status. Associations between PM2.5 and age adjusted CV mortality were estimated using linear models.
Results
A total of 5,769,315 cardiovascular deaths from 2012-2018 across 3106 United States counties were analyzed. Both PM2.5 (β (SE) 7.584 (0.938), P < .001) and SDI scores (β (SE) 0.591 (0.140), P < .001) were independently associated with age-adjusted CV mortality (R2 = 0.341). The association between PM2.5 and CV mortality were stronger among counties with highest SDI, P value for interaction = .012.
Conclusion
Social deprivation and PM2.5 exposures were independently associated with county level age-adjusted CV mortality. The associations between PM2.5 and CV mortality were stronger in counties with high vs low social deprivation. SDI and PM2.5 represent potential targets to reduce CV mortality disparities and interventions to reduce PM2.5 exposure may be most impactful in communities of low socioeconomic status.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 12 Feb 2021; 235:125-131
Bevan GH, Freedman DA, Lee EK, Rajagopalan S, Al-Kindi SG
Am Heart J: 12 Feb 2021; 235:125-131 | PMID: 33592167
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Impact:
Abstract

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study.

Capell WH, Barnathan ES, Piazza G, Spyropoulos AC, ... Hiatt WR, Bonaca MP
Background
COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established.
Study design
PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events.
Conclusions
PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 08 Feb 2021; 235:12-23
Capell WH, Barnathan ES, Piazza G, Spyropoulos AC, ... Hiatt WR, Bonaca MP
Am Heart J: 08 Feb 2021; 235:12-23 | PMID: 33577800
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Impact:
Abstract

Rivaroxaban versus warfarin in patients with atrial fibrillation enrolled in Latin America: Insights from ROCKET AF.

Blumer V, Rivera M, Corbalán R, Becker RC, ... Fox KAA, Patel MR
Background
ROCKET AF demonstrated the efficacy and safety of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). We examined baseline characteristics and outcomes in patients enrolled in Latin America compared with the rest of the world (ROW).
Methods
ROCKET AF enrolled 14,264 patients from 45 countries. Of these, 1,878 (13.2%) were from 7 Latin American countries. The clinical characteristics and outcomes (adjusted by baseline characteristics) of these patients were compared with 12,293 patients from the ROW. Treatment outcomes of rivaroxaban compared with warfarin were also stratified by region.
Results
The annual rate of stroke/SE was similar in those from Latin American and ROW (P= .63), but all-cause and vascular death were significantly higher than in ROW (HR 1.40, 95% CI 1.20-1.64; HR 1.38, 95% CI 1.14-1.68; P< .001). Rates of major or nonmajor clinically relevant bleeding tended to be lower in Latin America (HR 0.89, 95% CI 0.80-1.0; P= .05). Rates of stroke and/or SE were similar with rivaroxaban and warfarin in patients from Latin America and ROW (HR 0.83, 95% CI 0.54-1.29 vs HR 0.89, 95% CI 0.75-1.07; interaction P= .77).
Conclusions
Patients with AF in Latin America had similar rates of stroke and/or SE, higher rates of vascular death, and lower rates of bleeding compared with patients in the ROW. The effect of rivaroxaban compared with warfarin in Latin America was similar to the ROW. Further studies analyzing patient- and country-specific determinants of these regional differences in Latin America are warranted.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 07 Feb 2021; 236:4-12
Blumer V, Rivera M, Corbalán R, Becker RC, ... Fox KAA, Patel MR
Am Heart J: 07 Feb 2021; 236:4-12 | PMID: 33571477
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Impact:
Abstract

Interventional cardiologists\' perceptions of percutaneous coronary intervention quality measurement and feedback.

Prabhu KM, Don C, Sayre GG, Kearney KE, ... Au DH, Doll JA
Background
Interventional cardiologists receive feedback on their clinical care from a variety of sources including registry-based quality measures, case conferences, and informal peer interactions. However, the impact of this feedback on clinical care is unclear.
Methods
We interviewed interventional cardiologists regarding the use of feedback to improve their care of percutaneous coronary intervention (PCI) patients. Interviews were assessed with template analysis using deductive and inductive techniques.
Results
Among 20 interventional cardiologists from private, academic, and Department of Veterans Affairs practice, 85% were male, 75% performed at least 100 PCIs annually, and 55% were in practice for 5 years or more. All reported receiving feedback on their practice, including formal quality measures and peer learning activities. Many respondents were critical of quality measure reporting, citing lack of trust in outcomes measures and poor applicability to clinical care. Some respondents reported the use of process measures such as contrast volume and fluoroscopy time for benchmarking their performance. Case conferences and informal peer feedback were perceived as timelier and more impactful on clinical care. Respondents identified facilitators of successful feedback interventions including transparent processes, respectful and reciprocal peer relationships, and integration of feedback into collective goals. Hierarchy and competitive environments inhibited useful feedback.
Conclusions
Despite substantial resources dedicated to performance measurement and feedback for PCI, interventional cardiologists perceive existing quality measures to be of only modest value for improving clinical care. Catherization laboratories should seek to integrate quality measures into a holistic quality program that emphasizes peer learning, collective goals and mutual respect.

Published by Elsevier Inc.

Am Heart J: 06 Feb 2021; 235:97-103
Prabhu KM, Don C, Sayre GG, Kearney KE, ... Au DH, Doll JA
Am Heart J: 06 Feb 2021; 235:97-103 | PMID: 33567319
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Impact:
Abstract

Percutaneous coronary intervention in patients with stable coronary artery disease and left ventricular systolic dysfunction: insights from the VA CART program.

Brophy TJ, Warsavage TJ, Hebbe AL, Plomondon ME, ... Gutierrez JA, Swaminathan RV
Background
Revascularization of ischemic cardiomyopathy by coronary artery bypass grafting has been shown to improve survival among patients with left ventricular ejection fraction (LVEF) ≤35%, but the role of percutaneous coronary intervention (PCI) in this context is incompletely described. This study sought to evaluate the effect of PCI on mortality and hospitalization among patients with stable coronary artery disease and reduced left ventricular ejection fraction.
Methods
We performed a retrospective analysis comparing PCI with medical therapy among patients with ischemic cardiomyopathy in the Veterans Affairs Health Administration. Patients with angiographic evidence of 1 or more epicardial stenoses amenable to PCI and LVEF ≤35% were included in the analysis. Outcome data were determined by VA and non-VA data sources on mortality and hospital admission.
Results
From 2008 through 2015, a study sample of 4,628 patients was identified, of which 1,322 patients underwent ad hoc PCI. Patients were followed to a maximum of 3 years. Propensity score weighted landmark analysis was used to evaluate the primary and secondary outcomes. The primary outcome of all-cause mortality was significantly lower in the PCI cohort compared with medical therapy (21.6% vs 30.0%, P <.001). The secondary outcome of all-cause rehospitalization or death was also lower in the PCI cohort (76.5% vs 83.8%, P <.001).
Conclusions
In this retrospective analysis of patients with ischemic cardiomyopathy with coronary artery disease amenable to PCI and LVEF ≤35%, revascularization by PCI was associated with decreased all-cause mortality and decreased all-cause death or rehospitalization.

Published by Elsevier Inc.

Am Heart J: 06 Feb 2021; 235:149-157
Brophy TJ, Warsavage TJ, Hebbe AL, Plomondon ME, ... Gutierrez JA, Swaminathan RV
Am Heart J: 06 Feb 2021; 235:149-157 | PMID: 33567318
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Impact:
Abstract

Rationale and design of the pragmatic randomized trial of icosapent ethyl for high cardiovascular risk adults (MITIGATE).

Ambrosy AP, Malik UI, Thomas RC, Parikh RV, ... Bhatt DL, Go AS
Objective
The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD).
Background
IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs.
Methods
MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time.
Conclusion
The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 Jan 2021; 235:54-64
Ambrosy AP, Malik UI, Thomas RC, Parikh RV, ... Bhatt DL, Go AS
Am Heart J: 27 Jan 2021; 235:54-64 | PMID: 33516752
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Impact:
Abstract

Prevalence of ideal cardiovascular health in young adults: A birth cohort from southern Brazil.

Oliveira RS, Schneider BC, Callo-Quinte G, Oliveira IO, ... Wehrmeister FC, Menezes AMB
Background
Ideal cardiovascular health (ICH) aims at primordial prevention of cardiovascular diseases in the population. However, there is a lack of research describing ICH in youth from middle-income countries. The aims of this study were to describe the prevalence of ICH at 18- and 22-year-old and to investigate the influence of socioeconomic status.
Methods
The sample consisted of participants from the Pelotas 1993 birth-cohort followed-up at 18- (n = 4,106) and 22-year-old (n = 3,810). Ideal metrics were created for diet, smoking, body mass index, physical activity, blood pressure, total cholesterol, and blood glucose. The presence of 4 or more ideal metrics was defined as ICH. Socioeconomic status was obtained using wealth quintiles calculated with factor analysis based on analysis based on the ownership of household and education. The impact of socioeconomic status on ICH metrics was statistically measured using the slope index of inequality.
Results
The prevalence of ICH was 84.5% (95% confidence interval [CI] = 82.7-86.2%) and 84.1% (82.3-85.8%) at 18-year-old and decreased to 61.1% (58.4-63.7%) and 68.7% (66.2-71.2%) at 22-years old, for male and female, respectively. Socioeconomic status influenced ICH and its components differently in males and females. Wealthiest females had ICH prevalence 19 percentage points (pp) (11-27 pp) higher compared to the poorest, whereas poorest males had ICH prevalence 12 pp (1-21 pp) higher compared to the wealthiest. Longitudinal decreases in ICH components were mostly present in the poorest females.
Conclusions
In middle-income countries, the prevalence of ICH is high at 18-year-old and decreases in a 4-year follow-up. Socioeconomic status influences differently individuals\' ICH between sexes. Efforts are needed to maintain ICH in youth and different strategies may be required between the social status.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 26 Jan 2021; 235:65-73
Oliveira RS, Schneider BC, Callo-Quinte G, Oliveira IO, ... Wehrmeister FC, Menezes AMB
Am Heart J: 26 Jan 2021; 235:65-73 | PMID: 33508220
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Impact:
Abstract

Periodontal Disease, Atrial Fibrillation and Stroke.

Sen S, Redd K, Trivedi T, Moss K, ... Beck J, Offenbacher S
Background
We recently described the association between periodontal disease (PD) and stroke risk.
Purpose
The purpose of this study was to test the association between PD, dental care utilization and incident atrial fibrillation (AF), as well as AF as a mediator to PD- stroke association.
Methods
In dental cohort of the Atherosclerosis Risk in Communities Study (ARIC), participants without prior AF underwent full-mouth periodontal measurements. PD was defined on an ordinal scale as healthy (referent), mild, moderate and severe. In ARIC main cohort, participants were classified as regular or episodic dental care users. These patients were followed for AF, over 17 years. Cox proportional hazards models adjusted for AF risk factors were used to study relationships between PD severity, dental care utilization and AF. Mediation analysis was used to test if AF mediated the PD- stroke association.
Results
In dental ARIC cohort, 5,958 were assessed without prior AF, 754 were found to have AF. Severe PD was associated with AF on both univariable (crude HR, 1.54; 95% CI, 1.26-1.87) and multivariable (adjusted HR, 1.31, 95% CI, 1.06-1.62) analyses. Mediation analysis suggested AF mediates the association between PD and stroke. In the main ARIC cohort, 9,666 participants without prior AF were assessed for dental care use, 1558 were found to have AF. Compared with episodic users, regular users had a lower risk for AF on univariable (crude HR, 0.82, 95% CI, 0.74-0.90) and multivariable (adjusted HR, 0.88, 95% CI, 0.78-0.99) analyses.
Conclusions
PD is associated with AF. The association may explain the PD-stroke risk. Regular users had a lower risk of incident AF compared with episodic users.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 23 Jan 2021; 235:36-43
Sen S, Redd K, Trivedi T, Moss K, ... Beck J, Offenbacher S
Am Heart J: 23 Jan 2021; 235:36-43 | PMID: 33503409
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Impact:
Abstract

Impact of insurance status on ICD implantation practice patterns: Insights from the NCDR ICD registry.

Ahmed I, Merchant FM, Curtis JP, Parzynski CS, Lampert R
Background
Whether insurance status influences practice patterns in implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) defibrillators, when indicated, is not known.
Methods and results
We analyzed the NCDR ICD Registry to evaluate associations of insurance status with guidelines-based receipt of CRT, as well as device-type, complication rates, and use of optimal medical therapy defined by guidelines. Among 798,028 patients with de novo ICD implants, we included only patients < 65 years (those older have Medicare) and excluded those admitted before 2006 (n=1,835) or with insurance coverage other than Medicare, Medicaid or private insurance (n=25,695) leaving 286,556 for analysis. Inverse probability of treatment weighting was used to control for imbalances between groups. Mean age was 53 years, 29% were female. Patients with private insurance and Medicare were more likely to receive CRT-D when indicated (79.6%, OR 1.19 95% CI 1.09-1.28, P <.001 and 78.5%, OR 1.11 95% CI 1.01-1.21 P = .03, respectively) compared to the uninsured (76.7%). The uninsured were also more likely than other groups to receive a single-chamber device. Complication rates did not differ. Uninsured patients were, however, more likely to receive optimal medical therapy, particularly in the subgroup receiving the implant for primary prevention.
Conclusions
In propensity-weighted analysis, uninsured patients are less likely to receive CRT when indicated but more likely to be receiving optimal medical therapy at discharge. Reasons for differences in device implantation practices based on insurance status require further study.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 23 Jan 2021; 235:44-53
Ahmed I, Merchant FM, Curtis JP, Parzynski CS, Lampert R
Am Heart J: 23 Jan 2021; 235:44-53 | PMID: 33503408
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Impact:
Abstract

Red blood cell transfusion threshold and mortality in cardiac intensive care unit patients.

Jentzer JC, Lawler PR, Katz JN, Wiley BM, ... Barsness GW, Kor DJ
Background
The benefit of red blood cell (RBC) transfusion in anemic critically-ill patients with cardiovascular disease is uncertain, as is the optimal threshold at which RBC transfusion should be considered. We sought to examine the association between RBC transfusion and mortality stratified by nadir Hgb level and admission diagnosis among cardiac intensive care unit (CICU) patients.
Methods
Retrospective single-center cohort of 11,754 CICU patients admitted between 2007 and 2018. The association between RBC transfusion and hospital mortality at each nadir Hgb (<8 g/dL, 8-9.9 g/dL, ≥10 g/dL) was assessed using multivariable logistic regression adjusted for the propensity to receive RBC transfusion.
Results
The study population had a mean age of 68±15 years, including 38% females; 1,134 (11.4%) received RBC transfusion. Admission diagnoses included: acute coronary syndrome , 42%; heart failure, 50%; cardiac arrest , 12%; and cardiogenic shock , 12%. Patients who received RBC transfusion had higher crude hospital mortality (19% vs. 8%, P<.001). RBC transfusion was associated with lower adjusted hospital mortality in patients with nadir Hgb <8 g/dL after propensity adjustment, including subgroups with acute coronary syndrome, cardiac arrest, or cardiogenic shock (all P <.01). RBC transfusion was not associated with lower adjusted hospital mortality in any subgroup of patients with nadir Hgb ≥8 g/dL.
Conclusions
These observational data suggest the use of a Hgb threshold <8 g/dL for RBC transfusion in most CICU patients, although we could not exclude a potential benefit of RBC transfusion at a nadir Hgb of 8 to 9.9 g/dL; we did not observe any benefit from RBC transfusion at a nadir Hgb ≥10 g/dL.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 22 Jan 2021; 235:24-35
Jentzer JC, Lawler PR, Katz JN, Wiley BM, ... Barsness GW, Kor DJ
Am Heart J: 22 Jan 2021; 235:24-35 | PMID: 33497698
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Impact:
Abstract

Variation in use and dosing escalation of renin angiotensin system, mineralocorticoid receptor antagonist, angiotensin receptor neprilysin inhibitor and beta-blocker therapies in heart failure and reduced ejection fraction: Association of comorbidities.

Albert NM, Tyson RJ, Hill CL, DeVore AD, ... Thomas L, Fonarow GC
Background
In patients with heart failure and reduced ejection fraction (HFrEF), angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), or angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists (MRA), and beta-blockers (βB) are underutilized. It is unknown if patients with and without comorbidities have similar ACEi/ARB/ARNI, MRA, and βB prescription patterns.
Methods
Baseline data from the CHAMP-HF (Change the Management of Patients with Heart Failure) registry were categorized by history of atrial fibrillation, asthma/chronic lung disease, obstructive sleep apnea, and depression. Using multivariate hierarchical logistic models, associations of ACEi/ARB/ARNI, MRA and βB medication use and dose by comorbidities were assessed after adjusting for patient characteristics.
Results
Of 4,815 HFrEF patients from 152 CHAMP-HF sites, ACEi/ARB/ARNI use was lower in patients with more comorbidities, and generally, MRA use was low and βB use was high. In adjusted analyses, patients with HFrEF and comorbid obstructive sleep apnea, vs. without, were more likely to be prescribed ARNI (OR [95% CI]: 1.25 [1.00, 1.55]); P = .047 and MRA (1.31 [1.11, 1.55]); P = .002 and less likely to be prescribed ACEi (0.74 [0.63, 0.88]); P < .001. Patients with atrial fibrillation, vs. without, were less likely to receive ACEi/ARB (0.82 [0.71, 0.95]); P = .006 and any study medication (0.81 [0.67, 0.97]); P = .020. Comorbid lung disease and history of depression were not associated with HFrEF prescriptions.
Conclusions
Renin-angiotensin-aldosterone blockade therapy prescription and dose varied by comorbidity status, but βB therapy did not. In quality efforts, leaders need to consider use and dosing of prescriptions in light of prevalent comorbidities.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 22 Jan 2021; 235:82-96
Albert NM, Tyson RJ, Hill CL, DeVore AD, ... Thomas L, Fonarow GC
Am Heart J: 22 Jan 2021; 235:82-96 | PMID: 33497697
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Impact:
Abstract

Edoxaban versus warfarin in patients with atrial fibrillation in relation to the risk of stroke: A secondary analysis of the ENGAGE AF-TIMI 48 study.

de Groot JR, Ruff CT, Murphy SA, Hamershock RA, ... Antman EM, Giugliano RP
Introduction
The efficacy and safety of the oral factor Xa inhibitor edoxaban compared to warfarin stratified by CHA2DS2VASc scores have not been described.
Methods
The ENGAGE AF-TIMI 48 trial randomized patients with atrial fibrillation to once-daily edoxaban or warfarin. We classified patients based on CHA2DS2VASc score and compared pharmacokinetics (edoxaban concentration), pharmacodynamics (anti-factor Xa [FXa] with edoxaban, time-in-therapeutic range for warfarin), efficacy (stroke or systemic embolism [SSE]), safety (major bleeding [MB], intracranial hemorrhage), and cardiovascular mortality, for the approved edoxaban regimen vs warfarin.
Results
The distribution CHA2DS2VASc score were:≤3, N = 4159 (29.6%); 4, N = 4066 (28.9%); 5, N = 3165 (22.5%); and ≥6, N = 2681 (19.1%). Increasing rates of SSE (1.05 to 2.99%/year) and MB (2.27 to 4.66%/year) were observed in the warfarin arm as the CHA2DS2VASc score increased. The hazard ratios per unit increase of CHA2DS2VASc score were 1.29 (1.21-1.38) and 1.26 (1.17-1.36) for SSE, and 1.20 (1.13-1.27) and 1.19 (1.12-1.27) for MB, with warfarin and edoxaban, respectively. Time-in-therapeutic range in warfarin-treated patients was similar and high (median 68%-69%) across CHA2DS2VASc scores, whereas edoxaban trough concentration, exogenous anti-FXa activity and %inhibition of endogenous FXa were higher at increasing CHA2DS2VASc scores. Edoxaban reduced SSE, MB, intracranial hemorrhage, and cardiovascular mortality vs warfarin to a similar degree across the range of CHA2DS2VASc scores (P-int = 0.90, 0.96, 0.21, and 0.37, respectively). Because of higher event rates the number of events prevented with edoxaban tended to be greater in patients with higher CHA2DS2VASc scores.
Conclusion
The benefit and safety of edoxaban versus warfarin is maintained across CHA2DS2VASc scores. While the relative risk reductions remain similar, edoxaban provides incrementally larger absolute reductions in outcomes over warfarin in patients with higher CHA2DS2VASc scores.

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

Am Heart J: 21 Jan 2021; 235:132-139
de Groot JR, Ruff CT, Murphy SA, Hamershock RA, ... Antman EM, Giugliano RP
Am Heart J: 21 Jan 2021; 235:132-139 | PMID: 33493453
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This program is still in alpha version.