Journal: Am Heart J

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Abstract

African American-Caucasian American Differences in Aortic Valve Replacement in Patients with Severe Aortic Stenosis: Racial Differences in AVR.

Yankey GS, Jackson LR, Marts C, Chiswell K, ... Samad Z, Thomas KL
Background
Among patients with severe aortic stenosis (AS), there are limited data on aortic valve replacement (AVR), reasons for non-receipt and mortality by race.
Methods
Utilizing the Duke Echocardiography Laboratory Database, we analyzed data from 110,711 patients who underwent echocardiography at Duke University Medical Center between 1999-2013. We identified 1,111 patients with severe AS who met ≥1 of 3 criteria for AVR: ejection fraction ≤50%, diagnosis of heart failure, or need for coronary artery bypass surgery. Logistic regression models were used to assess the association between race, AVR and 1-year mortality. Chi-squared testing was used to assess potential racial differences in reasons for AVR non-receipt.
Results
Among the 1,111 patients (143 AA and 968 CA) eligible for AVR, AA were more often women, had more diabetes, renal insufficiency, aortic regurgitation and left ventricular hypertrophy. CA were more often smokers, had more ischemic heart disease, hyperlipidemia and higher median income levels. There were no racial differences in surgical risk utilizing logistic euroSCORES. Relative to CA, AA had lower rates of AVR (aOR 0.46, 95% CI 0.3-0.71, p<0.001) yet similar 1-year mortality (aHR 0.81, 95% CI 0.57-1.17, p=0.262). There were no significant differences in reasons for AVR non-receipt.
Conclusion
Among patients with severe AS eligible for AVR, AA patients were less likely to undergo AVR. Despite racial differences in AVR, there were no significant differences in mortality within 1-year or reasons for AVR non-receipt.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 12 Jan 2021; epub ahead of print
Yankey GS, Jackson LR, Marts C, Chiswell K, ... Samad Z, Thomas KL
Am Heart J: 12 Jan 2021; epub ahead of print | PMID: 33453161
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Abstract

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

Thiele H, Freund A, Gimenez MR, de Waha-Thiele S, ... Zeymer U,
Background
In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted.
Study design
The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke.
Conclusions
The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 07 Jan 2021; epub ahead of print
Thiele H, Freund A, Gimenez MR, de Waha-Thiele S, ... Zeymer U,
Am Heart J: 07 Jan 2021; epub ahead of print | PMID: 33428901
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Impact:
Abstract

IMPACT OF TARGETED PULMONARY ARTERIAL HYPERTENSION THERAPY IN PATIENTS WITH COMBINED POST- AND PRE-CAPILLARY PULMONARY HYPERTENSION.

Moghaddam N, Swiston JR, Tsang MY, Levy R, Lee L, Brunner NW
Background
Combined post- and pre-capillary pulmonary hypertension (CpcPH) portends poor outcomes in pulmonary hypertension related to left heart disease (PH-LHD). While recent evidence does not support the use of targeted pulmonary arterial hypertension (PAH) therapy in PH-LHD, there is a lack of clinical data on their use in CpcPH. We evaluated the outcomes in patients with CpcPH treated with PAH therapies.
Methods
Retrospectively, 50 patients meeting hemodynamic criteria of CpcPH and started on PAH-targeted drugs were identified. Fifty age- and gender-matched PAH patients were chosen as controls. We evaluated the change in 6-minute walk distance (6MWD), WHO functional class (FC), tricuspid annular plane systolic excursion (TAPSE), BNP or NT-proBNP, and pulmonary artery systolic pressure (PASP) at 3, 6, 12, and 24 months of follow-up.
Results
After adjusting for age and gender, there was no improvement in WHO FC in CpcPH over 2 year (odds ratio of change to FC I/II 1.01, 95% CI 0.98 to 1.04). There was no significant improvement in 6MWD (ß coefficient 0.21, 95% CI -0.98 to 1.4), reduction in BNP/NT-proBNP (ß coefficient -12.16, 95% CI -30.68 to 6.37), increase in TAPSE (ß coefficient 0.074, 95% CI 0.010 to 0.139), or decrease in PASP (0.996, 95% CI 0.991 to 1.011) in CpcPH with therapy. There was higher mortality in CpcPH compared to PAH on treatment (24% vs 4%, p=0.003).
Conclusion
There were no improvements in symptoms, exercise capacity, or echocardiographic parameters with PAH-targeted therapy in CpcPH. Further studies into potential treatments benefiting this population are needed.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 06 Jan 2021; epub ahead of print
Moghaddam N, Swiston JR, Tsang MY, Levy R, Lee L, Brunner NW
Am Heart J: 06 Jan 2021; epub ahead of print | PMID: 33422519
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Abstract

Acute Kidney Injury after Radial or Femoral Artery Access in ST-Segment Elevation Myocardial Infarction: AKI-SAFARI.

Marbach JA, Wells G, Santo PD, So D, ... Bernick J, May ML
Background
Acute kidney injury complicating primary percutaneous coronary intervention is an independent predictor of short- and long-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). Prior studies suggest a lower incidence of acute kidney injury (AKI) in patients undergoing percutaneous coronary intervention through radial artery compared to femoral artery access; however, no randomized clinical trials have specifically investigated this question in patients presenting with STEMI.
Methods
To determine whether radial access is associated with a reduced frequency of AKI following primary percutaneous coronary intervention we performed a substudy of the SAFARI-STEMI trial. The SAFARI-STEMI trial was an open-label, multicenter trial, which randomized patients presenting with STEMI to radial access (RA) or femoral access (FA), between July 2011 and December 2018. The primary outcome of this post-hoc analysis was the incidence of AKI, defined as an absolute (>0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline.
Results
In total 2,285 (99.3%) of the patients enrolled in SAFARI-STEMI were included in the analysis - 1,132 RA and 1,153 FA. AKI occurred in 243 (21.5%) RA patients and 226 (19.6%) FA patients (RR 0.91, 95% CI 0.78-1.07; p=0.27). An absolute increase in serum creatinine >0.5 mg/dL was seen in 49 (4.3%) radial and 52 (4.5%) femoral patients (RR 1.04, 95% CI 0.71-1.53; p=0.83). AKI was lower in both groups when the KDIGO definition was applied (RA 11.9% vs. FA 10.8%; RR 0.90, 95% CI 0.72-1.13; p=0.38).
Conclusions
Among STEMI patients enrolled in the SAFARI-STEMI trial there was no association between catheterization access site and AKI, irrespective of the definition applied. These results challenge the independent association between catheterization access site and acute kidney injury noted in prior investigations.
Trial registration
ClinicalTrials.gov identifier: NCT01398254.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 06 Jan 2021; epub ahead of print
Marbach JA, Wells G, Santo PD, So D, ... Bernick J, May ML
Am Heart J: 06 Jan 2021; epub ahead of print | PMID: 33422518
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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. Published by Elsevier Inc.

Am Heart J: 06 Jan 2021; epub ahead of print
Fagel ND, Amoroso G, Vink MA, Slagboom T, ... de Winter RJ, Riezebos RK
Am Heart J: 06 Jan 2021; epub ahead of print | PMID: 33422517
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Impact:
Abstract

Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes: a prospective study: Abbreviated title: GDF-15, all-cause mortality and CVD.

Bao X, Borné Y, Xu B, Orho-Melander M, ... Melander O, Engström G
Background
Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for death as a competing risk, and if GDF-15 provides superior prediction performance than other biomarkers.
Methods
Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n =4,143, aged 57.4 ± 5.96 years, 38.6 % men) from Malmö Diet and Cancer-Cardiovascular Cohort and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality and all-cause mortality was studied in relation to GDF-15 using Cox proportional hazards regression, with adjustment for potential confounders. Confounding from death as competing risk was carefully checked using the Fine and Gray subdistribution hazard model. Predictive capabilities were further evaluated using C-statistics, continuous net reclassification improvement, and integrated discrimination improvement.
Results
During follow-up, 424 coronary events, 327 ischemic stroke, 368 cardiovascular deaths, and 1,308 all-cause deaths occurred. After controlling for death from other causes as competing events, only all-cause mortality remained significantly related to GDF-15. The addition of GDF-15 significantly improved prediction for all-cause mortality in addition to the traditional risk factors, high-sensitive C-reactive protein and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Only NT-proBNP improved prediction for CVD mortality.
Conclusions
GDF-15 is a robust biomarker for all-cause mortality but less reliable for coronary event, ischemic stroke or cardiovascular mortality. Competing risk from death is an important consideration when interpreting the results.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 05 Jan 2021; epub ahead of print
Bao X, Borné Y, Xu B, Orho-Melander M, ... Melander O, Engström G
Am Heart J: 05 Jan 2021; epub ahead of print | PMID: 33421373
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Impact:
Abstract

Risk Markers of Incident Atrial Fibrillation in Patients with Coronary Heart Disease.

Tomasdottir M, Held C, Hadziosmanovic N, Westerbergh J, ... Wallentin L, Hijazi Z
Background
In patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD.
Methods and results
13,153 patients with optimally treated CHD included in the STABILITY trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial. The median (min-max) age was 64 years (range 26-92) and 2514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (p≤0.05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios.
Conclusions
In patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.

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

Am Heart J: 01 Jan 2021; epub ahead of print
Tomasdottir M, Held C, Hadziosmanovic N, Westerbergh J, ... Wallentin L, Hijazi Z
Am Heart J: 01 Jan 2021; epub ahead of print | PMID: 33400910
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Impact:
Abstract

Internet search volume for chest pain during the COVID-19 pandemic.

Ciofani JL, Han D, Allahwala UK, Asrress KN, Bhindi R

During the COVID-19 pandemic there has been a reduction in hospital admissions for acute myocardial infarction. This manuscript presents the analysis of Google Trends meta-data and shows a marked spike in search volume for chest pain that is strongly correlated with COVID-19 case numbers in the United States. This raises a concern that fear of contracting COVID-19 may be leading patients to self-triage using internet searches.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:157-159
Ciofani JL, Han D, Allahwala UK, Asrress KN, Bhindi R
Am Heart J: 30 Dec 2020; 231:157-159 | PMID: 33010246
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Impact:
Abstract

Cost-effectiveness of combined catheter ablation and left atrial appendage closure for symptomatic atrial fibrillation in patients with high stroke and bleeding risk.

Kawakami H, Nolan MT, Phillips K, Scuffham PA, Marwick TH
Background
Combined catheter ablation (CA) and left atrial appendage closure (LAAC) have been proposed for management of symptomatic atrial fibrillation (AF) in patients with high stroke and bleeding risk. We assessed the cost-effectiveness of combined CA and LAAC compared with CA and standard oral anticoagulation (OAC) in symptomatic AF.
Methods
A Markov model was developed to assess total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio among 2 post-CA strategies: (1) standard OAC and (2) LAAC (combined CA and LAAC procedure). The base-case used a 10-year time horizon and consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with high thrombotic (CHADS-VASc = 3) and bleeding risk (HAS-BLED = 3), and planned for AF ablation. Values for transition probabilities, utilities, and costs were derived from the literature. Costs were converted to 2020 US dollars. Half-cycle correction was applied, and costs and QALYs were discounted at 3% annually. Sensitivity analyses were performed for significant variables and scenario analyses for higher embolic risk.
Results
In the base-case cohort of 10,000 patients followed for 10 years, total costs for the LAAC strategy were $29,027 and for OAC strategy were $27,896. The LAAC strategy was associated with 122 fewer disabling strokes and 203 fewer intracranial hemorrhages per 10,000 patients compared with the OAC strategy. The LAAC strategy had an incremental cost-effectiveness ratio of $11,072/QALY. In sensitivity analyses, although cost-effectiveness was highly dependent on the risk of intracranial hemorrhage in the LAAC strategy and the cost of the combined procedure, LAAC was superior to OAC under the most circumstances. Scenario analyses demonstrated that the combined procedure was more cost-effective in patients with higher stroke risk.
Conclusions
In symptomatic AF patients with high stroke and bleeding risk who are planned for CA, the combined CA and LAAC procedure may be a cost-effective therapeutic option and be more beneficial to patients with CHADS-VASc risk score ≥3.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:110-120
Kawakami H, Nolan MT, Phillips K, Scuffham PA, Marwick TH
Am Heart J: 30 Dec 2020; 231:110-120 | PMID: 32822655
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Impact:
Abstract

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT).

Wiggers H, Køber L, Gislason G, Schou M, ... Mellemkjær S, Gustafsson F
Objectives
The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT).
Methods
Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years.
Results
As of May 2020, 296 patients have been randomized at 20 centers in Denmark.
Conclusion
The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:137-146
Wiggers H, Køber L, Gislason G, Schou M, ... Mellemkjær S, Gustafsson F
Am Heart J: 30 Dec 2020; 231:137-146 | PMID: 33039340
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Impact:
Abstract

Ultra-low-dose quadruple combination blood pressure-lowering therapy in patients with hypertension: The QUARTET randomized controlled trial protocol.

Chow CK, Atkins ER, Billot L, Chalmers J, ... Webster R, Rodgers A

High blood pressure is the leading cause of preventable morbidity and mortality globally. Many patients remain on single-drug treatment with poor control, although guidelines recognize that most require combination therapy for blood pressure control. Our hypothesis is that a single-pill combination of 4 blood pressure-lowering agents each at a quarter dose may provide a simple, safe, and effective blood pressure-lowering solution which may also improve long-term adherence. The Quadruple UltrA-low-dose tReaTment for hypErTension (QUARTET) double-blind, active-controlled, randomized clinical trial will examine whether ultra-low-dose quadruple combination therapy is more effective than guideline-recommended standard care in lowering blood pressure. QUARTET will enroll 650 participants with high blood pressure either on no treatment or on monotherapy. Participants will be randomized 1:1 and allocated to intervention therapy of a single pill (quadpill) containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or to control therapy of a single identical-appearing pill containing irbesartan 150 mg. In both arms, step-up therapy of open-label amlodipine 5 mg will be provided if blood pressure is >140/90 at 6 weeks. The primary outcome is the difference between groups in the change from baseline in mean unattended automated office systolic blood pressure at 12-week follow-up. The primary outcome and some secondary outcomes will be assessed at 12 weeks; there is an optional 12-month extension phase to assess longer-term efficacy and tolerability. Our secondary aims are to assess if this approach is safe, has fewer adverse effects, and has better tolerability compared to standard care control. QUARTET will therefore provide evidence for the effectiveness and safety of a new paradigm in the management of high blood pressure.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 30 Dec 2020; 231:56-67
Chow CK, Atkins ER, Billot L, Chalmers J, ... Webster R, Rodgers A
Am Heart J: 30 Dec 2020; 231:56-67 | PMID: 33017580
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Impact:
Abstract

Design and rationale of the XIENCE short DAPT clinical program: An assessment of the safety of 3-month and 1-month DAPT in patients at high bleeding risk undergoing PCI with an everolimus-eluting stent.

Valgimigli M, Cao D, Makkar RR, Bangalore S, ... Wang J, Mehran R

Dual antiplatelet therapy (DAPT) is key for the prevention of recurrent ischemic events after percutaneous coronary intervention (PCI); however, it increases the risk of bleeding complications. While new generation drug-eluting stents have been shown superior to bare-metal stents after a short DAPT course, the optimal DAPT duration in patients at high bleeding risk (HBR) remains to be determined. TRIAL
Design:
The XIENCE Short DAPT program consists of three prospective, single-arm studies (XIENCE 90, XIENCE 28 Global and XIENCE 28 USA) investigating 3- or 1-month DAPT durations in HBR patients undergoing PCI with the XIENCE stent. The XIENCE 90 study is being conducted in the US and enrolled 2047 subjects who discontinued DAPT at 3 months if they were free from myocardial infarction (MI), repeat coronary revascularization, stroke, or stent thrombosis. The XIENCE 28 program includes the USA study, enrolling 642 patients in US and Canada, and the Global study, enrolling 963 patients in Europe and Asia. In XIENCE 28, patients were to discontinue DAPT at 1 month post-PCI if event-free. The primary hypothesis for both XIENCE 90 and XIENCE 28 is that a short DAPT regimen will be non-inferior to a conventional DAPT duration with respect to the composite of all-cause death or MI. Patients enrolled in the prospective multicenter post-market XIENCE V USA study will be used as historical control group in a stratified propensity-adjusted analysis.
Conclusions:
The XIENCE Short DAPT Program will provide insights into the safety and efficacy of 2 abbreviated DAPT regimens of 3- and 1-month duration in a large cohort of HBR patients undergoing PCI with the XIENCE stent.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:147-156
Valgimigli M, Cao D, Makkar RR, Bangalore S, ... Wang J, Mehran R
Am Heart J: 30 Dec 2020; 231:147-156 | PMID: 33031789
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Impact:
Abstract

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

Guimarães HP, de Barros E Silva PGM, Liporace IL, Sampaio RO, ... Berwanger O,

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain.
Design:
RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:128-136
Guimarães HP, de Barros E Silva PGM, Liporace IL, Sampaio RO, ... Berwanger O,
Am Heart J: 30 Dec 2020; 231:128-136 | PMID: 33045224
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Impact:
Abstract

Association between intensive care unit utilization for patients with non-ST-segment elevation myocardial infarction and patient experience.

Fanaroff AC, Chen AY, van Diepen S, Mylod D, Peterson ED, Wang TY

Routine intensive care unit (ICU) utilization for patients with initially stable non-ST segment elevation myocardial infarction is not associated with improved short- or long-term patient outcomes; however, the association with patient experience has not been reported. Using Hospital Consumer Assessment of Healthcare Providers and Systems patient survey data linked to ICU use data from the National Cardiovascular Data Registry, we found no association between hospital-level ICU utilization and metrics of patient experience, including communication, staff responsiveness, and overall satisfaction.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:32-35
Fanaroff AC, Chen AY, van Diepen S, Mylod D, Peterson ED, Wang TY
Am Heart J: 30 Dec 2020; 231:32-35 | PMID: 33045223
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Impact:
Abstract

Rationale and design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction.

Gibson CM, Kastelein JJP, Phillips AT, Aylward PE, ... Ridker P, Mehran R

Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age ≥ 18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or ≥2 of the following: age ≥ 65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365 days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:121-127
Gibson CM, Kastelein JJP, Phillips AT, Aylward PE, ... Ridker P, Mehran R
Am Heart J: 30 Dec 2020; 231:121-127 | PMID: 33065120
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Impact:
Abstract

National trends and 30-day readmission rates for next-day-discharge transcatheter aortic valve replacement: An analysis from the Nationwide Readmissions Database, 2012-2016.

Yerasi C, Tripathi B, Wang Y, Forrestal BJ, ... Rogers T, Waksman R

Transcatheter aortic valve replacement (TAVR) has evolved toward a minimalist approach, resulting in shorter hospital stays. Real-world trends of next-day discharge (NDD) TAVR are unknown. This study aimed to evaluate underlying trends and readmissions of NDD TAVR.
Methods
This study was derived from the Nationwide Readmissions Database from 2012 to 2016. International Classification of Diseases, Ninth and Tenth Revisions, codes were used to identify patients. Any discharge within 1 day of admission was identified as NDD. NDD TAVR trends over the years were analyzed, and any admissions within 30 days were considered readmissions. A hierarchical logistic regression model was used to identify predictors of readmission.
Results
Of 49,742 TAVR procedures, 3,104 were NDD. The percentage of NDD TAVR increased from 1.5% (46/3,051) in 2012 to 12.2% (2,393/19,613) in 2016. However, the 30-day readmission rate remained the same over the years (8.6%). The patients\' mean age was 80.3 ± 8.4 years. Major readmission causes were heart-failure exacerbation (16%), infections (9%), and procedural complications (8%). In 2016, there were significantly higher late conduction disorder and gastrointestinal bleeding readmission rates than in 2012-2015. Significant predictors of readmission were anemia, baseline conduction disease, cardiac arrhythmias, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, neoplastic disorders, and discharge to facility.
Conclusions
The percentage of NDD TAVR increased over the years; however, readmission rates remained the same, with a higher rate of conduction abnormality-related hospitalizations in 2016. Careful discharge planning that includes identification of baseline factors that predict readmission and knowledge of etiologies may further prevent 30-day readmissions.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:25-31
Yerasi C, Tripathi B, Wang Y, Forrestal BJ, ... Rogers T, Waksman R
Am Heart J: 30 Dec 2020; 231:25-31 | PMID: 33091365
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Impact:
Abstract

Lipid temporal trends in normal-weight youth.

Zachariah JP, Shittu T, Wang Y

Atherosclerosis begins in youth, partly driven by excess weight (EW) and abnormal lipids. Despite pediatric obesity worsening, lipids improved. Given the relation between EW and abnormal lipids, changes in normal-weight (NW) youth may be relevant. We examined the proportions and temporal trends of youth with abnormal lipids who were NW versus EW.
Methods
Analysis was done from National Health and Nutrition Examination Surveys 1988-2016. Data were extracted for 10- to 20-year-olds measured with anthropometrics and laboratory testing to determine proportions of NW versus EW with total cholesterol >190 mg/dL, high-density lipoprotein cholesterol (HDL-C) <40 mg/dL, and calculated non-HDL-C >145 mg/dL (N = 14,785). In survey-weighted regression analysis, a weight-status interaction term was used to examine effect modification in the lipid temporal trend.
Results
Over time, EW prevalence increased, whereas dyslipidemia decreased (trend P value < .001 for both). For the pooled sample, EW more than doubled the risk of each lipid disorder (P < .0001 for each). However, for each abnormal lipid, 26%-63% were NW. As the temporal trend in abnormal lipids declined, the proportion with abnormal lipids who were NW also declined. On regression analysis, temporal declines in NW and EW differed for HDL-C.
Conclusions
NW constituted more than a quarter to half of youth with abnormal lipids. Over time, youth with abnormal lipids were less often NW. The novel observation that a high proportion of youth with abnormal lipids are NW is relevant to debates on universal lipid screening, the focus on weight reduction in youth lipid management, and conventional wisdom in cardiometabolic health.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:68-72
Zachariah JP, Shittu T, Wang Y
Am Heart J: 30 Dec 2020; 231:68-72 | PMID: 33096104
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Impact:
Abstract

Statins and atherosclerotic cardiovascular outcomes in patients on incident dialysis and with atherosclerotic heart disease.

Shavadia JS, Wilson J, Edmonston D, Platt A, ... Pendergast J, Scialla JJ

Statins failed to reduce cardiovascular (CV) events in trials of patients on dialysis. However, trial populations used criteria that often excluded those with atherosclerotic heart disease (ASHD), in whom statins have the greatest benefit, and included outcome composites with high rates of nonatherosclerotic CV events that may not be modified by statins. Here, we study whether statin use associates with lower atherosclerotic CV risk among patients with known ASHD on dialysis, including in those likely to receive a kidney transplant, a group excluded within trials but with lower competing mortality risks.
Methods
Using data from the United States Renal Data System including Medicare claims, we identified adults initiating dialysis with ASHD. We matched statin users 1:1 to statin nonusers with propensity scores incorporating hard matches for age and kidney transplant listing status. Using Cox models, we evaluated associations of statin use with the primary composite of fatal/nonfatal myocardial infarction and stroke (including within prespecified subgroups of younger age [<50 years] and waitlisting status); secondary outcomes included all-cause mortality and the composite of all-cause mortality, nonfatal myocardial infarction, or stroke.
Results
Of 197,716 patients with ASHD, 47,562 (24%) were consistent statin users from which we created 46,186 matched pairs. Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]). Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01).
Conclusions
Our large observational analyses are consistent with trials in more selected populations and suggest that statins may not meaningfully reduce atherosclerotic CV events even among incident dialysis patients with established ASHD and those likely to receive kidney transplants.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:36-44
Shavadia JS, Wilson J, Edmonston D, Platt A, ... Pendergast J, Scialla JJ
Am Heart J: 30 Dec 2020; 231:36-44 | PMID: 33096103
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Impact:
Abstract

Left bundle-branch block is associated with asimilar dyssynchronous phenotype in heart failure patients with normal and reduced ejection fractions.

Friedman DJ, Emerek K, Kisslo J, Søgaard P, Atwater BD
Background
Few therapies improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF). If left bundle-branch block (LBBB) is associated with left ventricular dyssynchrony and impaired cardiac performance in HFpEF, cardiac resynchronization therapy could be a promising treatment.
Methods
We performed a cross-sectional analysis of selected patients with HFpEF (ejection fraction ≥50%) with and without LBBB (normal conduction, NC) and patients with HFrEF and LBBB who were suitable cardiac resynchronization therapy candidates to describe and contextualize the mechanical phenotype of LBBB in HFpEF. Systolic and diastolic isovolumic times, ejection time(ET), and diastolic filling time(DFT) were measured on spectral tissue Doppler echocardiographic images and indexed to the heart rate. Dyssynchrony pattern was assessed using speckle-tracked longitudinal strain patterns. Comparisons were performed using analysis of variance and χ test with posthoc pairwise comparisons as indicated.
Results
Eighty-two HFpEF (50 with NC, 32 with LBBB) and 149 HFrEF (all with LBBB) patients met criteria. Overall, 84.4% with HFpEF/LBBB and 91.3% with HFrEF/LBBB had demonstrable mechanical dyssynchrony compared to 0% with HFpEF/NC. Compared to HFpEF/NC, HFpEF/LBBB had significantly prolonged isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and total isovolumetric time and significantly shorter ET (all indexed). LBBB/HFrEF patients, compared to LBBB/HFpEF patients, had increased ICT and IRT with decreased DFT but similar ET.
Conclusions
Patients with HFpEF and LBBB frequently have an LBBB dyssynchrony phenotype, prolonged ICT and IRT, and reduced ET compared to HFpEF patients with NC. The electromechanical dyssynchrony and disordered cardiac timing of HFpEF with LBBB are similar to HFrEF with LBBB.

Published by Elsevier Inc.

Am Heart J: 30 Dec 2020; 231:45-55
Friedman DJ, Emerek K, Kisslo J, Søgaard P, Atwater BD
Am Heart J: 30 Dec 2020; 231:45-55 | PMID: 33098811
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Impact:
Abstract

Long-term outcomes of arrhythmia and distinct electrophysiological features in congenitally corrected transposition of the great arteries in an Asian cohort.

Tseng WC, Huang CN, Chiu SN, Lu CW, ... Chen CA, Wu MH

Congenitally corrected transposition of the great arteries (ccTGA) is associated with various types of arrhythmia, including supraventricular tachycardia (SVT) and complete atrioventricular block (cAVB). Our study aims to characterize the arrhythmia burden, associated risk factors, arrhythmia mechanisms, and the long-term follow-up results in patients with ccTGA in a large Asian cohort.
Methods
We enrolled 104 patients (43 women and 61 men) diagnosed with ccTGA at our institution. The mean age at last follow-up was 20.8 years.
Results
For 40 patients (38%) with tachyarrhythmia, paroxysmal SVT (PSVT) and atrial arrhythmia were observed in 17 (16%) and 27 (26%) patients, respectively, with 4 patients (4%) having both types of SVT. The 20-year and 30-year SVT-free survival rates were 68% and 54%, respectively. Seven patients (7%) developed cAVB: 2 (2%) developed spontaneously, and the other 5 (5%) was surgically complicated (surgical risk of cAVB: 7%, all associated with ventricular septal defect repair surgery). PSVT was mostly associated with accessory pathways (5/9) but also related to twin atrioventricular nodal reentry tachycardia (3/9) and atrioventricular nodal reentry tachycardia (1/9). Most of the accessory pathways were located at tricuspid valve (9/10). Catheter ablation successfully eliminated all PSVT substrates (10/10) and most of the atrial arrhythmia substrates (3/5), with low recurrence rate.
Conclusions
The arrhythmia burden in patients with ccTGA is high and increases over time. However, cAVB incidence was relatively low and kept stationary in this Asian cohort. The mechanisms of SVT are complicated and can be controlled through catheter ablation.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:73-81
Tseng WC, Huang CN, Chiu SN, Lu CW, ... Chen CA, Wu MH
Am Heart J: 30 Dec 2020; 231:73-81 | PMID: 33098810
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Impact:
Abstract

The impact of left atrium size on selection of the pulmonary vein isolation method for atrial fibrillation: Cryoballoon or radiofrequency catheter ablation.

Ikenouchi T, Inaba O, Takamiya T, Inamura Y, ... Sasano T, Nitta J
Background
Pulmonary vein isolation (PVI) is the cornerstone of ablation strategies for atrial fibrillation (AF), and noninferiority of cryoballoon (CB) over radiofrequency (RF) ablation has been previously reported. One of the risk factors of recurrence is left atrium (LA) enlargement. This study aimed to analyze the impact of LA enlargement on the selection of CB or RF ablation for AF patients.
Methods
A total of 2,224 AF patients (64.4 ± 10.7 years, 65.5% male) who underwent PVI were analyzed retrospectively. Left atrial diameter (LAD) and volume (LAV) were measured using echocardiography before the procedures. LA enlargement was defined as LAD ≥40 mm and LAV index (LAVI) ≥35 mL/m. Patients undergoing CB and RF ablation were propensity score matched, and 376 matched pairs were evaluated.
Results
Cox proportional hazard analysis revealed that LAD (95% CI, 1.01-1.05), LAV (95% CI, 1.01-1.02), and LAVI (95% CI, 1.01-1.03) were independent predictors of recurrence. CB showed equivalent clinical outcomes to those of RF with shorter procedure time required for patients without LA enlargement. CB was inferior to RF in patients with LA enlargement (LAD, 74.5% vs 84.6%, P = .028; LAVI, 74.7% vs 83.4%, P = .015), and large LAVI was associated with a higher prevalence of non-PV foci (35% vs 29%, P = .008).
Conclusions
CB ablation may be recommended for patients without enlarged LA based on the short procedure time and efficacy, whereas RF would be more appropriate in large LAs. LAVI may be a valuable reference to predict PVI outcomes and in selecting the ablation method.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:82-92
Ikenouchi T, Inaba O, Takamiya T, Inamura Y, ... Sasano T, Nitta J
Am Heart J: 30 Dec 2020; 231:82-92 | PMID: 33098808
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Impact:
Abstract

Outpatient versus observation/inpatient management of emergency department patients rapidly ruled-out for acute myocardial infarction: Findings from the HIGH-US study.

Nowak RM, Jacobsen G, Limkakeng A, Peacock WF, ... Singer AJ, deFilippi CR
Background
The actual Emergency Department (ED) dispositions of patients enrolled in observational studies and meeting criteria for rapid acute myocardial infarction (AMI) rule-out are unknown. Additionally, their presenting clinical profiles, cardiac testing/treatments received, and outcomes have not been reported.
Methods
Patients in the HIGH-US study (29 sites) that ruled-out for AMI using a high-sensitivity cardiac troponin I 0/1-hour algorithm were evaluated. Clinical characteristics of patients having ED discharge were compared to patients placed in observation or hospital admitted (OBS/ADM). Reports of any OBS/ADM cardiac stress test (CST), cardiac catheterization (Cath) and coronary revascularization were reviewed. One year AMI/death and major adverse cardiovascular event rates were determined.
Results
Of the 1,020 ruled-out AMI patients 584 (57.3%) had ED discharge. The remaining 436 (42.7%) were placed in OBS/ADM. Patients with risk factors for AMI, including personal or family history of coronary artery disease, hypertension, previous stroke or abnormal ECG were more often placed in OBS/ADM. 175 (40.1%) had a CST. Of these 32 (18.3%) were abnormal and 143 (81.7%) normal. Cath was done in 11 (34.3%) of those with abnormal and 13 (9.1%) with normal CST. Of those without an initial CST 85 (32.6%) had Cath. Overall, revascularizations were performed in 26 (6.0%) patients. One-year AMI/death rates were low/similar (P = .553) for the groups studied.
Conclusions
Rapidly ruled-out for AMI ED patients having a higher clinician perceived risk for new or worsening coronary artery disease and placed in OBS/ADM underwent many diagnostic tests, were infrequently revascularized and had excellent outcomes. Alternate efficient strategies for these patients are needed.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:6-17
Nowak RM, Jacobsen G, Limkakeng A, Peacock WF, ... Singer AJ, deFilippi CR
Am Heart J: 30 Dec 2020; 231:6-17 | PMID: 33127532
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Impact:
Abstract

Association between levosimendan, postoperative AKI, and mortality in cardiac surgery: Insights from the LEVO-CTS trial.

Jawitz OK, Stebbins AS, Raman V, Alhanti B, ... Alexander JH, Lopes RD
Objectives
We aimed to evaluate the association between levosimendan treatment and acute kidney injury (AKI) as well as assess the clinical sequelae of AKI in cardiac surgery patients with depressed left ventricular function (ejection fraction <35%).
Methods
Patients in the LEVO-CTS trial undergoing on-pump coronary artery bypass grafting (CABG), valve, or CABG/valve surgery were stratified by occurrence and severity of postoperative AKI using the AKIN classification. The association between levosimendan infusion and AKI was modeled using multivariable regression.
Results
Among 854 LEVO-CTS patients, 231 (27.0%) experienced postoperative AKI, including 182 (21.3%) with stage 1, 35 (4.1%) with stage 2, and 14 (1.6%) with stage 3 AKI. The rate of AKI was similar between patients receiving levosimendan or placebo. The odds of 30-day mortality significantly increased by AKI stage compared to those without AKI (stage 1: adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI] 0.8-4.9; stage 2: aOR 9.1, 95% CI 3.2-25.7; stage 3: aOR 12.4, 95% CI 3.0-50.4). No association was observed between levosimendan, AKI stage, and odds of 30-day mortality (interaction P = .69). Factors independently associated with AKI included increasing age, body mass index, diabetes, and increasing baseline systolic blood pressure. Increasing baseline eGFR and aldosterone antagonist use were associated with a lower risk of AKI.
Conclusions
Postoperative AKI is common among high-risk patients undergoing cardiac surgery and associated with significantly increased risk of 30-day death or dialysis. Levosimendan was not associated with the risk of AKI.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:18-24
Jawitz OK, Stebbins AS, Raman V, Alhanti B, ... Alexander JH, Lopes RD
Am Heart J: 30 Dec 2020; 231:18-24 | PMID: 33127531
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Impact:
Abstract

Impact of the COVID-19 pandemic on patterns of outpatient cardiovascular care.

Wosik J, Clowse MEB, Overton R, Adagarla B, ... Pencina MJ, Pagidipati NJ
Background
The coronavirus disease 2019 (COVID-19) pandemic brought about abrupt changes in the way health care is delivered, and the impact of transitioning outpatient clinic visits to telehealth visits on processes of care and outcomes is unclear.
Methods
We evaluated ordering patterns during cardiovascular telehealth clinic visits in the Duke University Health System between March 15 and June 30, 2020 and 30-day outcomes compared with in-person visits in the same time frame in 2020 and in 2019.
Results
Within the Duke University Health System, there was a 33.1% decrease in the number of outpatient cardiovascular visits conducted in the first 15 weeks of the COVID-19 pandemic, compared with the same time period in 2019. As a proportion of total visits initially booked, 53% of visits were cancelled in 2020 compared to 35% in 2019. However, patients with cancelled visits had similar demographics and comorbidities in 2019 and 2020. Telehealth visits comprised 9.3% of total visits initially booked in 2020, with younger and healthier patients utilizing telehealth compared with those utilizing in-person visits. Compared with in-person visits in 2020, telehealth visits were associated with fewer new (31.6% for telehealth vs 44.6% for in person) or refill (12.9% vs 15.6%, respectively) medication prescriptions, electrocardiograms (4.3% vs 31.4%), laboratory orders (5.9% vs 21.8%), echocardiograms (7.3% vs 98%), and stress tests (4.4% vs 6.6%). When adjusted for age, race, and insurance status, those who had a telehealth visit or cancelled their visit were less likely to have an emergency department or hospital encounter within 30 days compared with those who had in-person visits (adjusted rate ratios (aRR) 0.76 [95% 0.65, 0.89] and aRR 0.71 [95% 0.65, 0.78], respectively).
Conclusions
In response to the perceived risks of routine medical care affected by the COVID-19 pandemic, different phenotypes of patients chose different types of outpatient cardiology care. A better understanding of these differences could help define necessary and appropriate mode of care for cardiology patients.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:1-5
Wosik J, Clowse MEB, Overton R, Adagarla B, ... Pencina MJ, Pagidipati NJ
Am Heart J: 30 Dec 2020; 231:1-5 | PMID: 33137309
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Impact:
Abstract

Thrombosis in hospitalized patients with viral respiratory infections versus COVID-19.

Smilowitz NR, Subashchandran V, Yuriditsky E, Horowitz JM, ... Hochman JS, Berger JS

We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses nationwide from 2012 to 2014 and compared this to the incidence among patients hospitalized with COVID-19 at a large health system in New York. Non-COVID-19 viral respiratory illness was complicated by acute MI in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (5% vs 16%; P< .001).
Background
Thrombosis is a prominent feature of the novel Coronavirus disease 2019 (COVID-19). The incidence of thrombosis during hospitalization for non-COVID-19 viral respiratory infections is uncertain. We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses compared to COVID-19.
Methods
Adults age >18 years hospitalized with a non-COVID-19 viral respiratory illness between 2002 and 2014 were identified. The primary study outcome was a composite of venous and arterial thrombotic events, including myocardial infarction (MI), acute ischemic stroke, and venous thromboembolism (VTE), as defined by ICD-9 codes. The incidence of thrombosis in non-COVID-19 viral respiratory illnesses was compared to the recently published incidence of thrombosis in COVID-19 from 3,334 patients hospitalized in New York in 2020.
Results
Among 954,521 hospitalizations with viral pneumonia from 2002 to 2014 (mean age 62.3 years, 57.1% female), the combined incidence of arterial and venous thrombosis was 5.0%. Acute MI occurred in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. Patients with thrombosis had higher in-hospital mortality (14.9% vs 3.3%, P< .001) than those without thrombosis. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (median age 64; 39.6% female) in 2020 (5% vs 16%; P< .001)
Conclusion:
In a nationwide analysis of hospitalizations for viral pneumonias, thrombosis risk was lower than that observed in patients with COVID-19. Investigations into mechanisms of thrombosis and risk reduction strategies in COVID-19 and other viral respiratory infections are necessary.

Published by Elsevier Inc.

Am Heart J: 30 Dec 2020; 231:93-95
Smilowitz NR, Subashchandran V, Yuriditsky E, Horowitz JM, ... Hochman JS, Berger JS
Am Heart J: 30 Dec 2020; 231:93-95 | PMID: 33181067
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Impact:
Abstract

Helicobacter pylori screening in clinical routine during hospitalization for acute myocardial infarction.

Wärme J, Sundqvist M, Mars K, Aladellie L, ... Hofmann R, Bäck M
Background
Potent antithrombotic therapy has significantly improved prognosis for patients with acute myocardial infarction (AMI), however, at a price of increased bleeding risk. Chronic gastric infection with Helicobacter pylori (Hp) commonly causes upper gastrointestinal bleeding and is proposed as a risk factor for subsequent bleeding post AMI. The prevalence of active Hp in a current AMI population and the feasibility of Hp screening as part of routine clinical care are unclear.
Objective
To determine the prevalence of active Hp infection in a contemporary AMI cohort and to establish the feasibility of Hp diagnosis as part of routine clinical MI care.
Design
Multicenter, prospective cohort study.
Setting
Two university hospitals in Stockholm, Sweden.
Participants
Patients admitted for AMI between November 6, 2019 and April 4, 2020. After written informed consent, Hp diagnostics was performed with a bedside urea breath test (Diabact, Mayoly Spindler) incorporated into routine care during the hospitalization period.
Exposure
Positive test for Hp infection.
Main outcomes and measures
The primary outcome was the prevalence of Hp infection. Secondary aims included predictive factors in patient characteristics and outcomes which were obtained from linkage with national registries. Predefined subgroup analyses included stratification for proton pump inhibitor use and infarct type.
Results
Three hundred and ten consecutive AMI patients (median age 67; 23% female; 41% ST-elevation MI [STEMI]) were enrolled. Overall, the Hp prevalence was 20% (95%CI, 15.5-24.7). Hp positive status was significantly more common in smokers compared with nonsmokers (36% vs 21%, respectively; P < .05) and in patients presenting with STEMI compared with Non-STEMI (26% vs 15%, respectively; P = .02). The latter observation remained significant after multivariable adjustment. After exclusion of 97 subjects with current proton pump inhibitor use, the Hp prevalence was 24% (95%CI, 18.9-31.0).
Conclusions
Active Hp infection is common in a contemporary AMI population and may represent a modifiable risk factor for upper gastrointestinal bleeding, which has been hitherto disregarded. Hp screening as part of clinical routine during AMI hospitalization was feasible. A future randomized trial is needed to determine whether routine Hp screening and subsequent eradication therapy reduces bleeding complications and improves prognosis.
Key points
Question: Is Helicobacter pylori (Hp) infection sufficiently common in patients with acute myocardial infarction (AMI) to consider systematic screening, and can Hp diagnostics be performed during AMI hospitalization?
Findings
In this multicenter prospective cohort study of 310 consecutive AMI patients, Hp infection was established in at least 20% of patients. Infected patients were significantly more likely to be active smokers and to present with ST-elevation MI. Meaning: Hp screening as part of clinical routine during AMI hospitalization was feasible. Given the high Hp prevalence detected, Hp diagnostics and eradication to reduce bleeding complications and to improve prognosis after AMI should be further investigated.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:105-109
Wärme J, Sundqvist M, Mars K, Aladellie L, ... Hofmann R, Bäck M
Am Heart J: 30 Dec 2020; 231:105-109 | PMID: 33144087
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Impact:
Abstract

Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design.

Nordenskjöld AM, Agewall S, Atar D, Baron T, ... Tornvall P, Lindahl B

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6-8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial \'Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients\' (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients.
Methods:
MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. SUMMARY: While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Dec 2020; 231:96-104
Nordenskjöld AM, Agewall S, Atar D, Baron T, ... Tornvall P, Lindahl B
Am Heart J: 30 Dec 2020; 231:96-104 | PMID: 33203618
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Impact:
Abstract

NT-proBNP level before primary PCI and risk of poor myocardial reperfusion: insight from the On-Time II trial.

Fabris E, Ten Berg JM, Hermanides RS, Dambrink JPOE, ... Hamm C, van \'t Hof AWJ
Background
N-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP), a marker for neurohumoral activation, have been associated with adverse outcome in patients with myocardial infarction. NT-proBNP levels may reflect extensive ischemia and microvascular damage, therefore we investigated the potential association between baseline NT-proBNP level and ST-resolution (STR), a marker of myocardial reperfusion, after primary percutaneous coronary intervention (pPCI).
Methods
we performed a post-hoc analysis of the On-TIME II trial (which randomized ST-elevation myocardial infarction (STEMI) patients to pre-hospital tirofiban administration vs placebo). Patients with measured NT-proBNP before angiography were included. Multivariate logistic-regression analyses was performed to investigate the association between baseline NTproBNP level and STR one hour after pPCI.
Results
Out of 984 STEMI patients, 918 (93.3%) had NT-proBNP values at baseline. Patients with STR <70% had higher NT-proBNP values compared to patients with complete STR (>70%) [Mean ±SD 375.2 ±1021.7 vs 1007.4 ±2842.3, Median (IQR) 111.7 (58.4-280.0) vs 168.0 (62.3-601.3), p<0.001]. At multivariate logistic regression analysis, independent predictors associated with higher risk of poor myocardial reperfusion (STR <70%) were: NT-proBNP (OR 1.17, 95%CI 1.04-1.31, p= 0.009), diabetes mellitus (OR 1.87, 95%CI 1.14-3.07, p=0.013), anterior infarct location (OR 2.74, 95% CI 2.00-3.77, p<0.001), time to intervention (OR 1.06, 95%CI 1.01-1.11, p=0.021), randomisation to placebo (OR 1.45, 95%CI 1.05-1.99, p= 0.022).
Conclusions
In STEMI patients, higher baseline NT-proBNP level was independently associate with higher risk of poor myocardial reperfusion, supporting the potential use of NT-proBNP as an early marker for risk stratification of myocardial reperfusion after pPCI in STEMI patients.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 30 Dec 2020; epub ahead of print
Fabris E, Ten Berg JM, Hermanides RS, Dambrink JPOE, ... Hamm C, van 't Hof AWJ
Am Heart J: 30 Dec 2020; epub ahead of print | PMID: 33388289
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Impact:
Abstract

Expansion of Transcatheter Aortic Valve Replacement in the United States: Expansion of TAVR in US.

Mentias A, Sarrazin MV, Desai M, Kapadia S, Cram P, Girotra S
Background
Patterns of diffusion of TAVR in the US and its relation to racial disparities in TAVR utilization remain unknown.
Methods
We identified TAVR hospitals in the continental US from 2012-2017 using Medicare database and mapped them to Hospital Referral Regions (HRR). We calculated driving distance from each residential ZIP code to the nearest TAVR hospital and calculated the proportion of the U.S. population, in general and by race, that lived <100 miles driving distance from the nearest TAVR center. Using a discrete time hazard logistic regression model, we examined the association of hospital and HRR variables with the opening of a TAVR program.
Results
The number of TAVR hospitals increased from 230 in 2012 to 540 in 2017. The proportion of the U.S. population living <100 miles from nearest TAVR hospital increased from 89.3% in 2012 to 94.5% in 2017. Geographic access improved for all racial and ethnic subgroups: Whites (84.1% to 93.6%), Blacks (90.0% to 97.4%), and Hispanics (84.9% to 93.7%). Within a HRR, the odds of opening a new TAVR program were higher among teaching hospitals (OR 1.48, 95% CI 1.16-1.88) and hospital bed size (OR 1.44, 95% CI 1.37-1.52). Market-level factors associated with new TAVR programs were proportion of Black (per 1%, OR 0.78, 95% CI 0.69-0.89) and Hispanic (per 1%, OR 0.82, 95% CI 0.75-0.90) residents, the proportion of hospitals within the HRR that already had a TAVR program (per 10%, OR 1.07, 95% CI 1.03-1.11), P<0.01 for all.
Conclusion
The expansion of TAVR programs in the U.S. has been accompanied by an increase in geographic coverage for all racial subgroups. Further study is needed to determine reasons for TAVR underutilization in Blacks and Hispanics.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 30 Dec 2020; epub ahead of print
Mentias A, Sarrazin MV, Desai M, Kapadia S, Cram P, Girotra S
Am Heart J: 30 Dec 2020; epub ahead of print | PMID: 33388288
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Impact:
Abstract

Out-of-hospital Cardiac Arrest: A Systematic Review of Current Risk Scores to Predict Survival.

Gue YX, Adatia K, Kanji R, Potpara T, Yh G, Gorog DA
Importance
The arrest and the post-arrest period are an incredibly emotionally traumatic time for family and friends of the affected individual. There is a need to assess prognosis early in the patient pathway to offer objective, realistic and non-emotive information to the next-of-kin regarding the likelihood of survival.
Objective
To present a systematic review of the clinical risk scores available to assess patients on admission following out-of-hospital cardiac arrest (OHCA) which can predict in-hospital mortality.
Evidence review
A systematic search of online databases Embase, MEDLINE and Cochrane Central Register of Controlled Trials was conducted up until 20th November 2020.
Findings
Out of 1,817 initial articles, we identified a total of 28 scoring systems, with 11 of the scores predicting mortality following OHCA included in this review. The majority of the scores included arrest characteristics (initial rhythm and time to return of spontaneous circulation) as prognostic indicators. Out of these, the three most clinically-useful scores, namely those which are easy-to-use, comprise of commonly available parameters and measurements, and which have high predictive value are the OHCA, NULL-PLEASE and rCAST scores, which appear to perform similarly. Of these, the NULL-PLEASE score is the easiest to calculate and has also been externally validated.
Conclusion
Clinicians should be aware of these risk scores, which can be used to provide objective, non-emotive and reproducible information to the next-of-kin on the likely prognosis following OHCA. However, in isolation, these scores should not form the basis for clinical decision-making.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Am Heart J: 29 Dec 2020; epub ahead of print
Gue YX, Adatia K, Kanji R, Potpara T, Yh G, Gorog DA
Am Heart J: 29 Dec 2020; epub ahead of print | PMID: 33387469
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Impact:
Abstract

Effects of Sodium-Glucose Cotransporter 1 and 2 Inhibitors on Cardiovascular and Kidney Outcomes in Type 2 Diabetes: A Meta-analysis Update.

Salah HM, Al\'Aref SJ, Khan MS, Al-Hawwas M, ... Lopes RD, Fudim M

In this report, we aim to provide an updated meta-analysis of the sodium-glucose cotransporter 2 (SGLT2) inhibitors trial data with the new trial data on sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor. We searched Medline, Cochrane library, and Embase databases for randomized clinical trials comparing cardiovascular and kidney outcomes between SGLT2 and dual SGLT1/2 inhibitors and placebo. Nine randomized clinical trials with a total of 60,914 patients with type 2 diabetes were included. In patients with type 2 diabetes, the use of SGLT2 and dual SGLT1/2 inhibitors improves the cardiovascular and kidney outcome.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Am Heart J: 28 Dec 2020; epub ahead of print
Salah HM, Al'Aref SJ, Khan MS, Al-Hawwas M, ... Lopes RD, Fudim M
Am Heart J: 28 Dec 2020; epub ahead of print | PMID: 33385359
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Impact:
Abstract

The Role of Cardiac Testing with the 0/1-Hour High-Sensitivity Cardiac Troponin Algorithm Evaluating for Acute Myocardial Infarction.

McCord J, Hana A, Cook B, Hudson MP, ... Jacobsen G, Nowak R
Background
The role of cardiac testing in the 3 zones (rule-out, observation, and rule-in) of the 0/1-hour algorithm to evaluate for acute myocardial infarction (AMI) has not been well-studied. This study evaluated the 0/1-hour algorithm with a high-sensitivity cardiac troponin (hs-cTnI) assay and investigated cardiac testing in the 3 zones.
Methods
Patients (n = 552) at a single urban center were enrolled if they were evaluated for AMI. Blood samples were obtained at presentation, 1 hour, and 3 hours for hs-cTnI. Follow-up at 30-45 days for death/AMI was done. The results of echocardiograms, stress testing, and coronary angiography were recorded.
Results
In total, 45 (8.2%) had AMI (27 Type 1 and 18 Type 2) during the index hospitalization while at follow-up death/AMI occurred in 11 (2.0%) of patients. The rule-out algorithm had a negative predictive value for AMI of 99.6% while the rule-in zone had a positive predictive value of 56.6%. The MACE rate at follow-up was 0.4% for those in the rule-out group. There were 6/95 (6.3%) abnormal stress tests in the rule-out zone and 4 of these were false positives.
Conclusions
The 0/1-hour algorithm had high diagnostic sensitivity and negative predictive value for AMI, and adverse events were very low in patients in the rule-out zone. Noninvasive testing in rule-out zone patients had low diagnostic yield.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 25 Dec 2020; epub ahead of print
McCord J, Hana A, Cook B, Hudson MP, ... Jacobsen G, Nowak R
Am Heart J: 25 Dec 2020; epub ahead of print | PMID: 33373603
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Impact:
Abstract

Trends in Healthcare Resource Use and Expenditures in Patients with Newly Diagnosed Paroxysmal Supraventricular Tachycardia in the United States.

Chew DS, Sacks NC, Emden MR, Preib MT, ... Wood D, Pokorney SD
Background
Few data are available on the temporal patterns of health resource utilization (HRU) and expenditures around paroxysmal supraventricular tachycardia (PSVT) diagnosis. This study assessed the longitudinal trends in HRU and expenditures in the 3-years preceding and subsequent to PSVT diagnosis.
Methods
Adult patients (age 18 to 65 years) with newly diagnosed PSVT were identified using administrative claims from the IBM MarketScan® Research Database between January 1, 2008 and December 31, 2016 and propensity-score matched (1:1) with non-PSVT controls.
Results
Among the 12,305 PSVT patients compared with matched controls, PSVT was associated with statistically significant higher annual rates of emergency department visits, physician office visits, inpatient hospitalizations, and diagnostic testing. HRU increased in the years preceding PSVT diagnosis, reaching its peak in the year following PSVT diagnosis. Over the six-year follow-up period, PSVT was associated with higher mean annual per patient expenditures ($12,665) compared to matched controls ($6,004; p<0.001). Upon diagnosis of PSVT, the mean expenditures per PSVT patient doubled from $11,714 in the year immediately preceding index diagnosis to $23,335 in the first post-diagnosis year. Inpatient services, diagnostic testing, and ablation procedures were the principle drivers of higher mean expenditures in the first year post-PSVT diagnosis versus the year prior to PSVT diagnosis.
Conclusions
PSVT presents a substantial economic burden to health care systems. The annual expenditure per PSVT patient is within the range previously reported for atrial fibrillation. The increased HRU and expenditures in the year following diagnosis, which do not return to baseline, suggest a potential gap in non-interventional, long-term PSVT management.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Am Heart J: 22 Dec 2020; epub ahead of print
Chew DS, Sacks NC, Emden MR, Preib MT, ... Wood D, Pokorney SD
Am Heart J: 22 Dec 2020; epub ahead of print | PMID: 33359780
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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, Amin AP, Lasala J, 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/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 (IABP), 4.2% a percutaneous ventricular assist devices (pVAD), 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<0.001), Black patients compared to white ones (aOR=0.73, p<0.001), those insured by Medicare (aOR=0.75, p<0.001), Medicaid (aOR=0.74, p<0.001), or uninsured (aOR=0.90, p=0.015) compared to privately insured, and those in the lowest income neighborhoods (aOR=0.94, p=0.003) 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. Published by Elsevier Inc.

Am Heart J: 22 Dec 2020; epub ahead of print
Thangam M, Luke AA, Amin AP, Lasala J, Huang K, Joynt Maddox KE
Am Heart J: 22 Dec 2020; epub ahead of print | PMID: 33359779
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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 (e.g. 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<0.001). 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 <0.001).
Conclusion
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 Ltd. All rights reserved.

Am Heart J: 22 Dec 2020; epub ahead of print
Malik AO, Amin A, Kennedy K, Qintar M, ... Mehran R, Spertus JA
Am Heart J: 22 Dec 2020; epub ahead of print | PMID: 33359778
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Impact:
Abstract

Non-Warfarin Oral Anticoagulant Copayments and Adherence in Atrial Fibrillation:A Population-Based Cohort Study.

Rome BN, Gagne JJ, Avorn J, Kesselheim AS
Background
In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence.
Methods
Using a national claims database of commercially-insured patients, we performed a cohort study of patients with atrial fibrillation who newly initiated a NOAC from 2012-2018. Patients were stratified into low (<$35), medium ($35-$59), or high (≥$60) copayments and propensity-score weighted based on demographics, insurance characteristics, comorbidities, prior health care utilization, calendar year, and the NOAC received. Follow-up was 1 year, with censoring for switching to a different anticoagulant, undergoing an ablation procedure, disenrolling from the insurance plan, or death. The primary outcome was adherence, measured by proportion of days covered (PDC). Secondary outcomes included NOAC discontinuation (no refill for 30 days after the end of NOAC supply) and switching anticoagulants. We compared PDC using a Kruskal-Wallis test and rates of discontinuation and switching using Cox proportional hazards models.
Results
After weighting patients across the 3 copayment groups, the effective sample size was 15,659 patients, with balance across 50 clinical and demographic covariates (standardized differences <0.1). Mean age was 62 years, 29% of patients were female, and apixaban (43%) and rivaroxaban (38%) were the most common NOACs. Higher copayments were associated with lower adherence (p<0.001), with a PDC of 0.82 (Interquartile range [IQR] 0.36-0.98) among those with high copayments, 0.85 (IQR 0.41-0.98) among those with medium copayments, and 0.88 (IQR 0.41-0.99) among those with low copayments. Compared to patients with low copayments, patients with high copayments had higher rates of discontinuation (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.08-1.19; p<0.001).
Conclusions
Among atrial fibrillation patients newly initiating NOACs, higher copayments in commercial insurance were associated with lower adherence and higher rates of discontinuation in the first year. Policies to lower or limit cost-sharing of important medications may lead to improved adherence and better outcomes among patients receiving NOACs.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 20 Dec 2020; epub ahead of print
Rome BN, Gagne JJ, Avorn J, Kesselheim AS
Am Heart J: 20 Dec 2020; epub ahead of print | PMID: 33358690
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Impact:
Abstract

Effects of Canagliflozin on Cardiovascular, Renal, and Safety Outcomes in Participants With Type 2 Diabetes and Chronic Kidney Disease According to History of Heart Failure: Results From the CREDENCE Trial.

Sarraju A, Li J, Cannon CP, Chang TI, ... Jardine M, Mahaffey KW

We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P<0.001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >0.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Am Heart J: 19 Dec 2020; epub ahead of print
Sarraju A, Li J, Cannon CP, Chang TI, ... Jardine M, Mahaffey KW
Am Heart J: 19 Dec 2020; epub ahead of print | PMID: 33358942
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Impact:
Abstract

Management of Heart Failure in Cardiac Amyloidosis Using an Ambulatory Diuresis Clinic.

Vaishnav J, Hubbard A, Chasler JE, Lepley D, ... Russell SD, Gilotra NA
Background
Recurrent congestion in cardiac amyloidosis (CA) remains a management challenge, often requiring high dose diuretics and frequent hospitalizations. Innovative outpatient strategies are needed to effectively manage HF in patients with CA. Ambulatory diuresis has not been well studied in restrictive cardiomyopathy. Therefore, we aimed to examine the outcomes of an ambulatory diuresis clinic in the management of congestion related to CA.
Methods and results
We retrospectively studied patients with CA seen in an outpatient HF disease management clinic for 1) safety outcomes of ambulatory intravenous (IV) diuresis and 2) health care utilization. Forty-four patients with CA were seen in the clinic a total of 203 times over 6 months. Oral diuretics were titrated at 96 (47%) visits. IV diuretics were administered at 56 (28%) visits to 17 patients. There were no episodes of severe acute kidney injury or symptomatic hypotension. There was a significant decrease in emergency department and inpatient visits and associated charges after index visit to the clinic. The proportion of days hospitalized per 1000 patient days of follow-up decreased as early as 30 days (147.3 vs 18.1/1000 patient days of follow-up, p<0.001) and persisted through 180 days (33.6 vs 22.9/1000 patient days of follow-up, p<0.001) pre- vs. post-index visit to the clinic.
Conclusions
We demonstrate the feasibility of ambulatory IV diuresis in patients with CA. Our findings also suggest that use of a HF disease management clinic may reduce acute care utilization in patients with CA. Leveraging multidisciplinary outpatient HF clinics may be an effective alternative to hospitalization in patients with HF due to CA, a population who otherwise carries a poor prognosis and contributes to high health care burden.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 18 Dec 2020; epub ahead of print
Vaishnav J, Hubbard A, Chasler JE, Lepley D, ... Russell SD, Gilotra NA
Am Heart J: 18 Dec 2020; epub ahead of print | PMID: 33352187
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Impact:
Abstract

Prevalence of Control Groups in Cardiovascular Clinical Trials: An Analysis of ClinicalTrials.gov from 2009 through 2019.

Zheutlin AR, Caldwell DJ, Al Danaf J, Shah RU

Clinical trials provide the foundational evidence that guide many patient-facing decisions however, the therapeutic effect and safety of an intervention is best evaluated when compared to a control group. We used ClinicalTrials.gov to describe the proportion of registered Phase III and IV cardiovascular clinical trials that contain a control group from 2009 through 2019. Of 1,677 registered Phase III and IV cardiovascular clinical trials, 81.2% contain a control group, and the annual prevalence remained unchanged between 2009 and 2019.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Am Heart J: 17 Dec 2020; epub ahead of print
Zheutlin AR, Caldwell DJ, Al Danaf J, Shah RU
Am Heart J: 17 Dec 2020; epub ahead of print | PMID: 33347871
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Impact:
Abstract

Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: rationale and design of the randomized Altshock- 2 trial.

Nuccia M, Claudia M, Alice S, Guido T, ... Federico P,
Background
Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in in this setting. We present the design of a study aimed at addressing this research gap.
Methods and design
The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary endpoint will be 60 days patients\' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy and maximum sequential organ failure assessment score. Safety endpoints will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (non-cerebral) embolism. The sample size for the study is 200 patients.
Implications
The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 14 Dec 2020; epub ahead of print
Nuccia M, Claudia M, Alice S, Guido T, ... Federico P,
Am Heart J: 14 Dec 2020; epub ahead of print | PMID: 33338464
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Impact:
Abstract

Paclitaxel-Coated Devices in the Treatment of Femoropopliteal Stenosis among patients ≥65 years old: An ACC PVI Registry Analysis.

Weissler EH, Annapureddy A, Wang Y, Secemsky EA, ... Curtis JP, Jones WS
Background
The connection between paclitaxel-coated devices (PCD) use during peripheral vascular interventions (PVI) and mortality is debated. We aimed to analyze patterns of PCD use and the safety and effectiveness of PCD use in the superficial femoral and/or popliteal arteries.
Methods
Patients undergoing PVI of femoropopliteal lesions with and without PCD between 01/01/2015 and 06/30/2017 were compared using the American College of Cardiology\'s National Cardiovascular Data Registry PVI Registry. Outcomes were derived from Centers for Medicare & Medicaid claims data. The primary outcome was all-cause mortality at 6-, 12-, and 24-months following PVI. Inverse probability weighting and frailty models were used to assess the differences between groups. The analysis was IRB-approved.
Results
In the overall cohort consisting of 6,302 femoropopliteal PVIs, PCD-PVI patients were more likely to be treated for claudication (63.5% versus 51.3%, p<0.001), less likely to have a chronic total occlusion (24.6% versus 34.7%, p<0.001), and more likely to be treated in certain geographic and practice settings. In the analytic cohort consisting of 1,666 femoropopliteal PVIs with linked claims outcomes (888 PCD-PVI, 53.3%), unadjusted rates of all outcomes were lower in PCD-PVI patients. After adjustment, there were no significant differences in mortality following PCD-PVI versus non-PCD PVI at one year (adjusted RR 0.78, 95%CI 0.60-1.01, p=0.055) or two years (aRR 0.98, 95%CI 0.77-1.24, p=0.844).
Conclusions
There were significant differences between the patients in whom and settings in which PCD-PVI was versus was not used. PCD-PVI was not associated with an increased risk of two-year mortality in real-world use.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 11 Dec 2020; epub ahead of print
Weissler EH, Annapureddy A, Wang Y, Secemsky EA, ... Curtis JP, Jones WS
Am Heart J: 11 Dec 2020; epub ahead of print | PMID: 33321119
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Impact:
Abstract

iPhone App compared with standard blood pressure measurement -The iPARR trial: The iPARR trial.

Dörr M, Weber S, Birkemeyer R, Leonardi L, ... Burkard T, Eckstein J
Background
The possibility to use built-in smartphone-cameras for photoplethysmographic (PPG) recording of pulse waves lead to the release of numerous health apps, claiming to measure blood pressure (BP) based on PPG signals. Even though these apps are highly popular, not a single one is clinically validated. Aim of the current study was to test systolic BP (sBP) estimation by a promising new algorithm in a large clinical setting.
Methods
The study was designed based on the European Society of Hypertension International Protocol Revision 2010 (ESH-IP2010). Each individual received seven sequential BP measurements, starting with the reference device - an automated oscillometric cuff device -  followed by the PPG recording at the patients\' index finger.
Results
A total 1036 subjects were recruited of which 965 could be included for final analysis leading to 2895 pairs of comparison. Mean (±SD) error between test and reference device was -0.41 (±16.52) mmHg. Only 38.1% of all 2895 BP comparisons reached a delta within ±5 mmHg, while 29.3% reached a delta larger than 15 mmHg. Bland-Altman plot showed an overestimation of smartphone sBP in comparison to reference sBP in low range and an underestimation in high sBP range.
Conclusions
According to the ESH-IP2010 specifications the algorithm failed validation criteria for sBP measurement and was not commercialized. These findings emphasize that health apps should be rigorously validated according to common guidelines before market release as under- and/or overestimation of BP is potentially exposing persons at health risks in short and long term.
Trial registration
ClinicalTrials.gov, number NCT02552030.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 11 Dec 2020; epub ahead of print
Dörr M, Weber S, Birkemeyer R, Leonardi L, ... Burkard T, Eckstein J
Am Heart J: 11 Dec 2020; epub ahead of print | PMID: 33321118
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Impact:
Abstract

Differences between patients with cardiovascular disease and cancer referred for palliative care.

Warraich HJ, Wolf SP, Troy J, Swetz KM, ... Desai AS, Kamal AH

Our analysis from a national registry shows that compared to cancer, cardiovascular disease patients referred to palliative care are a decade older, have worse functional status and clinician-estimated prognosis. Both groups have very high symptom burden, with cardiovascular disease patients experiencing more dyspnea while pain, nausea, and fatigue are more common in cancer.

Published by Elsevier Inc.

Am Heart J: 07 Dec 2020; 233:5-9
Warraich HJ, Wolf SP, Troy J, Swetz KM, ... Desai AS, Kamal AH
Am Heart J: 07 Dec 2020; 233:5-9 | PMID: 33306993
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Impact:
Abstract

Individual Patient Data from the Pivotal Randomized Controlled Trials of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (COMBINE AF): Design and Rationale: From the COMBINE AF (A COllaboration between Multiple institutions to Better Investigate Non-vitamin K antagonist oral anticoagulant usE in Atrial Fibrillation) Investigators.

Carnicelli AP, Hong H, Giugliano RP, Connolly SJ, ... Granger CB, On Behalf Of The Combine Af Investigators
Background
Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date.
Design
COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771).
Conclusions
In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 05 Dec 2020; epub ahead of print
Carnicelli AP, Hong H, Giugliano RP, Connolly SJ, ... Granger CB, On Behalf Of The Combine Af Investigators
Am Heart J: 05 Dec 2020; epub ahead of print | PMID: 33296688
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Impact:
Abstract

Cardiac resynchronization therapy improves the ventricular function of patients with Fontan physiology.

Joyce J, O\'Leary ET, Mah DY, Harrild DM, Rhodes J

Past studies have not detected consistent improvement in ventricular function (VFxn) following initiation of cardiac resynchronization therapy (CRT) in Fontan patients. However, these studies used qualitative assessments of VFxn and/or quantitative assessments of VFxn that rely upon anatomic and/or geometric assumptions that may not be valid in patients with single ventricles. To address this, we used quantitative indices of global VFxn (dP/dt and the Tei index) that are not encumbered by the limitations associated with the indices used in previous studies of CRT in Fontan patients.
Methods
Patients with Fontan physiology who had received CRT therapy from 2004 to 2019 were included in the study. They were compared to a concurrent group of Fontan patients who had received standard dual-chamber pacemakers (DCPMs).
Results
VFxn was assessed at 3 time points: prior to, shortly after, and late after initiation of pacemaker therapy. Prior to initiation of pacemaker therapy, VFxn of the CRT patients tended to be worse than that of the DCPM patients. For both groups, VFxn appeared to be stable or slightly improved shortly after initiation of pacemaker therapy. In the CRT group, VFxn improved significantly between early and late follow-up. In contrast, VFxn in DCPM patients tended to decline during this period. Changes in VFxn correlated with concurrent changes in New York Heart Association classification.
Conclusions
Quantitative assessments of VFxn using indices not confounded by complex cardiac anatomy, segmental wall motions abnormalities, or inappropriate geometric assumptions revealed that CRT in Fontan patients is associated with preservation or improvement VFxn compared to standard DCPM. Changes in VFxn correlate with concurrent changes in New York Heart Association classification.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 29 Nov 2020; 230:82-92
Joyce J, O'Leary ET, Mah DY, Harrild DM, Rhodes J
Am Heart J: 29 Nov 2020; 230:82-92 | PMID: 33017579
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Impact:
Abstract

Temporal trends in risk profiles among patients hospitalized for heart failure.

Hamo CE, Fonarow GC, Greene SJ, Vaduganathan M, ... DeVore AD, Butler J
Background
Postdischarge mortality following hospitalization for heart failure with reduced ejection fraction (HFrEF) has remained high and unchanged over the past 2 decades, despite effective therapies for HFrEF. We aimed to explore whether these patterns could in part be explained by changes in longitudinal risk profile and HF severity over time.
Methods
Among patients hospitalized for HF in the GWTG-HF registry from January 2005 to December 2018 with available data, we evaluated GWTG-HF and ADHERE risk scores, observing in-hospital mortality per-year. The risk profiles and outcomes were described overall and by subgroups based on ejection fraction (EF), diabetes mellitus (DM), sex, and age.
Results
Overall, 335,735 patients were included (50% HFrEF, 46% DM, 48% female, mean age 74 years). In-hospital mortality increased by 2.0% per year from 2005 to 2018. There was no significant change in mean GWTG-HF risk score overall or when stratified by EF groups (P = 0.46 HFrEF, p = 0.26 HF mid-range EF [HFmrEF], and P = 0.72 HF preserved EF [HFpEF]), age, sex, or presence of DM. The observed/expected ratio based on the GWTG-HF risk score was 0.93 (0.91-0.96), 0.83 (0.77-0.90), 0.92 (0.89-95) for HFrEF, HFmrEF, and HFpEF, respectively. Similar findings were seen when risk was assessed using ADHERE risk score.
Conclusions
There were no significant changes in average risk profiles among hospitalized HF patients over the study duration. These data do not support the notion that worsening risk profile explains the lack of improved outcomes despite therapeutic advances, underscoring the importance of aggressive implementation of guideline-recommended therapies and investigation of novel treatments.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 28 Nov 2020; 232:154-163
Hamo CE, Fonarow GC, Greene SJ, Vaduganathan M, ... DeVore AD, Butler J
Am Heart J: 28 Nov 2020; 232:154-163 | PMID: 33264607
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Impact:
Abstract

Diagnosis, prevention, and management of delirium in the intensive cardiac care unit.

Cortés-Beringola A, Vicent L, Martín-Asenjo R, Puerto E, ... Fernando Arribas , Bueno H

Delirium is a frequent complication in patients admitted to intensive cardiac care units (ICCU) with potentially severe consequences including increased risks of mortality, cognitive impairment and dependence at discharge, and longer times on mechanical ventilation and hospital stay. Delirium has been widely documented and studied in general intensive care units and in patients after cardiac surgery, but it has barely been studied in acute nonsurgical cardiac patients. Moreover, delirium (especially in its hypoactive form) is commonly misdiagnosed. We propose a protocol for delirium prevention and management in ICCUs. A daily comprehensive assessment to improve detection should be done using validated scales (ie, confusion assessment method). Preventive measures are particularly relevance and constitute the basis of treatment as well, acting on reversible risk factors, including environmental interventions, such as quiet time, sleep promotion, family support, communication, and adequate treatment of pain and dyspnea. Pharmacological prophylaxis is not indicated with the exception of patients at risk of withdrawal syndrome but should only be used in patients with confirmed delirium. Dexmedetomidine is the drug of choice in patients with severe agitation, and those weaning from invasive mechanical ventilation. As the complexity of ICCUs increases, clinical scenarios posing challenges for the management of delirium become more frequent. Efforts should be done to improve the identification of patients at risk during admission in order to establish preventive interventions to avoid this complication. Patient-centered protocols will increase the awareness of the healthcare professionals for better prevention and earlier diagnosis and will positively impact on prognosis.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 27 Nov 2020; 232:164-176
Cortés-Beringola A, Vicent L, Martín-Asenjo R, Puerto E, ... Fernando Arribas , Bueno H
Am Heart J: 27 Nov 2020; 232:164-176 | PMID: 33253676
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Impact:
Abstract

Impact of chronic total occlusion and revascularization strategy in patients with infarct-related cardiogenic shock: A subanalysis of the culprit-shock trial.

Braik N, Guedeney P, Behnes M, Desch S, ... Montalescot G, Akin I
Background
The impact of coronary artery chronic total occlusion (CTO) and its management with percutaneous coronary intervention (PCI) in the setting of myocardial infarction (MI) related cardiogenic shock (CS) remains unclear.
Methods
This is a pre-specified analysis from the culprit-lesion-only PCI vs multivessel PCI in CS (CULPRIT-SHOCK) trial which randomized patients presenting with MI and multivessel disease complicated by CS to a culprit-lesion-only or immediate multivessel PCI strategy. CTO was defined by central core-laboratory evaluation. The independent associations between the presence of CTO and adverse outcomes at 30 days and 1 year were assessed using multivariate logistics models.
Results
A noninfarct related CTO was present in 157 of 667 (23.5%) analyzed patients. Patients presenting with CTO had more frequent diabetes mellitus or prior PCI but less frequently presented with ST segment elevation MI as index event. The presence of CTO was associated with higher rate of death at 30 days (adjusted Odds ratio 1.63; 95% confidence interval [CI] 1.01-2.60). Rate of death at 1 year was also increased but did not reach statistical significance (adjusted Odds ratio 1.62; 95%CI 0.99-2.66). Compare to immediate multivessel PCI, a strategy of culprit-lesion-only PCI was associated with lower rates of death or renal replacement therapy at 30 days in patients with and without CTO (Odds ratio 0.79 95%CI 0.42-1.49 and Odds ratio 0.67 95%CI 0.48-0.96, respectively), without significant interaction (P = .68).
Conclusions
In patients with MI-related CS and multivessel disease, the presence of CTO is associated with adverse outcomes while a strategy of culprit-lesion-only PCI seems beneficial regardless of the presence of CTO.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 26 Nov 2020; 232:185-193
Braik N, Guedeney P, Behnes M, Desch S, ... Montalescot G, Akin I
Am Heart J: 26 Nov 2020; 232:185-193 | PMID: 33253678
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Impact:
Abstract

Defect-free care trends in the Paul Coverdell National Acute Stroke Program, Program, 2008-2018.

Overwyk KJ, Yin X, Tong X, King SMC, Wiltz JL
Background
In an effort to improve stroke quality of care and patient outcomes, quality of care metrics are monitored to assess utilization of evidence-based stroke care processes as part of the Paul Coverdell National Acute Stroke Program (PCNASP). We aimed to assess temporal trends in defect-free care (DFC) received by stroke patients in the PCNASP between 2008 and 2018.
Methods
Quality of care data for 10 performance measures were available for 849,793 patients aged ≥18 years who were admitted to a participating hospital with a clinical diagnosis of stroke between 2008 and 2018. A patient who receives care according to all performance measures for which they are eligible, receives \"defect-free care\" (DFC) (eg, appropriate medications, assessments, and education). Generalized estimating equations were used to examine the factors associated with receipt of DFC.
Results
DFC among ischemic stroke patients increased from 38.0% in 2008 to 80.8% in 2018 (P < .0001), with the largest improvement seen in receipt of stroke education (relative percent change, RPC = 64%). Similarly, DFC for hemorrhagic stroke and transient ischemic attack patients increased from 46.7% to 82.6% (RPC = 76.9%) and 39.9% to 85.0% (RPC = 113.0%) (P < .001), respectively. Among ischemic stroke patients, the adjusted odds for receiving DFC were lower for women, patients aged 18 to 54 years, Medicaid or Medicare participants, and patients with atrial fibrillation (P < .05).
Conclusions
From 2008 to 2018, receipt of DFC by ischemic stroke patients significantly increased in the PCNASP; however certain subgroups were less likely to receive this level of care. Targeted quality improvement initiatives could result in even further improvements among all stroke patients and help reduce disparities in care.

Published by Elsevier Inc.

Am Heart J: 26 Nov 2020; 232:177-184
Overwyk KJ, Yin X, Tong X, King SMC, Wiltz JL
Am Heart J: 26 Nov 2020; 232:177-184 | PMID: 33253677
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Impact:
Abstract

Beta-blocker and ACE-inhibitor dosing as a function of body surface area: From the HF-ACTION trial.

Brooksbank JA, Greene SJ, Harris HM, Stebbins A, ... O\'Connor CM, Mentz RJ

Recognizing that body surface area (BSA) is a commonly used metric to inform medication dosing across fields of medicine, it is possible that patients with heart failure with reduced ejection fraction (HFrEF) with higher BSA may be more likely to tolerate higher doses of GDMT. Using the HF-ACTION trial, we examined (1) the relationship between BSA and achievement of target dosing of evidence-based beta-blocker and angiotensin-converting enzyme inhibitor (ACEI) therapy, and (2) the associations and interactions between target dosing, clinical outcomes, and BSA.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 23 Nov 2020; 233:1-4
Brooksbank JA, Greene SJ, Harris HM, Stebbins A, ... O'Connor CM, Mentz RJ
Am Heart J: 23 Nov 2020; 233:1-4 | PMID: 33245905
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Impact:
Abstract

A multi-modal diagnostic model improves detection of cardiac amyloidosis among patients with diagnostic confirmation by cardiac biopsy.

Zhang KW, Zhang R, Deych E, Stockerl-Goldstein KE, Gorcsan J, Lenihan DJ
Background
Timely recognition of cardiac amyloidosis is clinically important, but the diagnosis is frequently delayed.
Objectives
We sought to identify a multi-modality approach with the highest diagnostic accuracy in patients evaluated by cardiac biopsy, the diagnostic gold standard.
Methods
Consecutive patients (N = 242) who underwent cardiac biopsy for suspected amyloidosis within an 18-year period were retrospectively identified. Cardiac biomarker, ECG, and echocardiography results were examined for correlation with biopsy-proven disease. A prediction model for cardiac amyloidosis was derived using multivariable logistic regression.
Results
The overall cohort was characterized by elevated BNP (median 727 ng/mL), increased left ventricular wall thickness (IWT; median 1.7 cm), and reduced voltage-to-mass ratio (median 0.06 mm/[g/m]). One hundred and thirteen patients (46%) had either light chain (n = 53) or transthyretin (n = 60) amyloidosis by cardiac biopsy. A prediction model including age, relative wall thickness, left atrial pressure by E/e\', and low limb lead voltage (<0.5 mV) showed good discrimination for cardiac amyloidosis with an optimism-corrected c-index of 0.87 (95% CI 0.83-0.92). The diagnostic accuracy of this model (79% sensitivity, 84% specificity) surpassed that of traditional screening parameters, such as IWT in the absence of left ventricular hypertrophy on ECG (98% sensitivity, 20% specificity) and IWT with low limb lead voltage (49% sensitivity, 91% specificity).
Conclusion
Among patients with an advanced infiltrative cardiomyopathy phenotype, traditional biomarker, ECG, and echocardiography-based screening tests have limited individual diagnostic utility for cardiac amyloidosis. A prediction algorithm including age, relative wall thickness, E/e\', and low limb lead voltage improves the detection of cardiac biopsy-proven disease.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 16 Nov 2020; 232:137-145
Zhang KW, Zhang R, Deych E, Stockerl-Goldstein KE, Gorcsan J, Lenihan DJ
Am Heart J: 16 Nov 2020; 232:137-145 | PMID: 33212046
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Impact:
Abstract

The associations between direct and delayed critical care unit admission with mortality and readmissions among patients with heart failure.

Raslan IR, Ross HJ, Fowler RA, Scales DC, ... Austin PC, Lee DS
Background
Although greater than 20% of patients hospitalized with heart failure (HF) are admitted to a critical care unit, associated outcomes, and costs have not been delineated. We determined 30-day mortality, 30-day readmissions, and hospital costs associated with direct or delayed critical care unit admission.
Methods
In a population-based analysis, we compared HF patients who were admitted to critical care directly from the emergency department (direct), after initial ward admission (delayed), or never admitted to critical care during their hospital stay (ward-only).
Results
Among 178,997 HF patients (median age 80 [IQR 71-86] years, 49.6% men) 36,175 (20.2%) were admitted to critical care during their hospitalization (April 2003 to March 2018). Critical care patients were admitted directly from the emergency department (direct, 81.9%) or after initial ward admission (delayed, 18.1%). Multivariable-adjusted hazard ratios (HR) for all-cause 30-day mortality were: 1.69 for direct (95% confidence interval [CI]; 1.55, 1.84) and 4.92 for delayed (95% CI; 4.26, 5.68) critical care-admitted compared to ward-only patients. Multivariable-adjusted repeated events analysis demonstrated increased risk for all-cause 30-day readmission with both direct (HR 1.04, 95% CI; 1.01, 1.08, P = .013) and delayed critical care unit admissions (HR 1.20, 95% CI; 1.13, 1.28, P < .001). Median 30-day costs were $12,163 for direct admissions, $20,173 for delayed admissions, and $9,575 for ward-only patients (P < .001).
Conclusions
While critical care unit admission indicates increased risk of mortality and readmission at 30 days, those who experienced delayed critical care unit admission exhibited the highest risk of death and highest costs of care.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 05 Nov 2020; 233:20-38
Raslan IR, Ross HJ, Fowler RA, Scales DC, ... Austin PC, Lee DS
Am Heart J: 05 Nov 2020; 233:20-38 | PMID: 33166518
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Impact:
Abstract

Incidence of acute coronary syndrome during national lock-down: Insights from nationwide data during the Coronavirus disease 2019 (COVID-19) pandemic.

Østergaard L, Butt JH, Kragholm K, Schou M, ... Køber L, Fosbøl EL
Background
Urgent recognition and treatment are needed in patients with acute coronary syndrome (ACS), however this may be difficult during the Coronavirus disease 2019 (COVID-19) pandemic with a national lock-down. We aimed to examine the incidence of ACS after national lock-down.
Methods
The Danish government announced national lock-down on March 11, 2020 and first phase of reopening was announced on April 6. Using Danish nationwide registries, we identified first-time ACS admissions in (1) January 1 to May 7, 2017-2019, and (2) January 1, 2020 to May 6, 2020. Incidence rates of ACS admissions per week for the 2017 to 2019 period and the 2020 period were computed and incidence rate ratios (IRR) were computed using Poisson regression analysis.
Results
The number of ACS admissions were 8,204 (34.6% female, median age 68.3 years) and 2,577 (34.0% female, median age 68.5 years) for the 2017 to 2019- and 2020 period, respectively. No significant differences in IRRs were identified for weeks 1 to 9 (January 1 to March 4) for 2020 compared with week 1 to 9 for 2017 to 2019. In 2020, significant lower IRRs were identified for week 10 (March 5 to 11) IRR = 0.71 (95% confidence intervals [CI]: 0.58 to 0.87), week 11 (12 to 18 March) IRR = 0.68 (0.56 to 0.84), and week 14 (April 2 to April 8) IRR = 0.79 (0.65 to 0.97). No significant differences in IRRs were identified for week 15 to 18 (April 9 to May 6). In subgroup analysis, we identified that the main result was driven by male patients, and patients ≥60 years.
Conclusions
During the COVID-19 pandemic with an established national lock-down we identified a significant decline around 30% in the incidence of ACS admissions. Along with the reopening of society, ACS admissions were stabilized at levels equal to previous years.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 05 Nov 2020; 232:146-153
Østergaard L, Butt JH, Kragholm K, Schou M, ... Køber L, Fosbøl EL
Am Heart J: 05 Nov 2020; 232:146-153 | PMID: 33160947
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Impact:
Abstract

Rationale and design of a randomized clinical trial comparing safety and efficacy of myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: The LANDMARK trial.

Kawashima H, Soliman O, Wang R, Ono M, ... Baumbach A, Serruys PW
Background
The recent approval of transcatheter aortic valve replacement (TAVR) in patients with low operative risk has paved the way for the introduction of novel and potentially improved technologies. The safety and efficacy of these novel technologies should be investigated in randomized control trials against the contemporary TAVR devices. The objective of the LANDMARK trial is to compare the balloon-expandable Myval transcatheter heart valve (THV) series with contemporary THV (SAPIEN THV and Evolut THV series) series in patients with severe symptomatic native aortic stenosis.
Methods/design
The LANDMARK trial (ClinicalTrials.govNCT04275726, EudraCT number 2020-000,137-40) is a prospective, randomized, multinational, multicenter, open-label, and noninferiority trial of approximately 768 patients treated with TAVR via the transfemoral approach. Patients will be allocated in a 1:1 randomization to Myval THV series (n = 384) or to contemporary THV (n = 384) (either of SAPIEN THV or Evolut THV series). The primary combined safety and efficacy endpoint is a composite of all-cause mortality, all stroke (disabling and nondisabling), bleeding (life-threatening or disabling), acute kidney injury (stage 2 or 3), major vascular complications, prosthetic valve regurgitation (moderate or severe), and conduction system disturbances (requiring new permanent pacemaker implantation), according to the Valve Academic Research Consortium-2 criteria at 30-day follow-up. All patients will have follow-up to 10 years following TAVR.
Summary
The LANDMARK trial is the first randomized head-to-head trial comparing Myval THV series to commercially available THVs in patients indicated for TAVR. We review prior data on head-to-head comparisons of TAVR devices and describe the rationale and design of the LANDMARK trial.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 05 Nov 2020; 232:23-38
Kawashima H, Soliman O, Wang R, Ono M, ... Baumbach A, Serruys PW
Am Heart J: 05 Nov 2020; 232:23-38 | PMID: 33160946
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Impact:
Abstract

Sex and race differences in safety and effectiveness of the HEART pathway accelerated diagnostic protocol for acute chest pain.

Snavely AC, Hendley N, Stopyra JP, Lenoir KM, ... Miller CD, Mahler SA
Background
The HEART Pathway is an accelerated diagnostic protocol for Emergency Department patients with possible acute coronary syndrome. The objective was to compare the safety and effectiveness of the HEART Pathway among women vs men and whites vs non-whites.
Methods
A subgroup analysis of the HEART Pathway Implementation Study was conducted. Adults with chest pain were accrued from November 2013 to January 2016 from 3 Emergency Departments in North Carolina. The primary outcomes were death and myocardial infarction (MI) and hospitalization rates at 30 days. Logistic regression evaluated for interactions of accelerated diagnostic protocol implementation with sex or race and changes in outcomes within subgroups.
Results
A total of 8,474 patients were accrued, of which 53.6% were female and 34.0% were non-white. The HEART Pathway identified 32.6% of females as low-risk vs 28.5% of males (P = 002) and 35.6% of non-whites as low-risk vs 28.0% of whites (P < .0001). Among low-risk patients, death or MI at 30 days occurred in 0.4% of females vs 0.5% of males (P = .70) and 0.5% of non-whites vs 0.3% of whites (P = .69). Hospitalization at 30 days was reduced by 6.6% in females (aOR: 0.74, 95% CI: 0.64-0.85), 5.1% in males (aOR: 0.87, 95% CI: 0.75-1.02), 8.6% in non-whites (aOR: 0.72, 95% CI: 0.60-0.86), and 4.5% in whites (aOR: 0.83, 95% CI: 0.73-0.94). Interactions were not significant.
Conclusion
Women and non-whites are more likely to be classified as low-risk by the HEART Pathway. HEART Pathway implementation is associated with decreased hospitalizations and a very low death and MI rate among low-risk patients regardless of sex or race.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 05 Nov 2020; 232:125-136
Snavely AC, Hendley N, Stopyra JP, Lenoir KM, ... Miller CD, Mahler SA
Am Heart J: 05 Nov 2020; 232:125-136 | PMID: 33160945
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Impact:
Abstract

Important considerations for trials for peripheral arterial disease: Lessons learned from the paclitaxel mortality signal: A report on behalf of the registry assessment for peripheral interventional Devices (RAPID) Paclitaxel Pathways Program.

Lottes AE, Whatley EM, Royce SM, Bertges DJ, ... Rosenfield K, Krucoff MW

The Registry Assessment of Peripheral Devices (RAPID) convened a multidisciplinary group of stakeholders including clinicians, academicians, regulators and industry representatives to conduct an in-depth review of limitations associated with the data available to assess the paclitaxel mortality signal. Available studies were evaluated to identify strengths and limitations in the study design and data quality, which were translated to lessons learned to help guide the design, execution, and analyses of future studies. We suggest numerous actionable responses, such as the development and use of harmonized data points and outcomes in a consensus lean case report form. We advocate for reduction in missing data and efficient means for accrual of larger sample sizes in Peripheral arterial disease studies or use of supplemental datasets. Efforts to share lessons learned and working collaboratively to address such issues may improve future data in this device area and ultimately benefit patients. Condensed Abstract: Data sources evaluating paclitaxel-coated devices were evaluated to identify strengths and limitations in the study design and data quality, which were translated to lessons learned to help guide the design, execution, and analyses of future studies. We suggest numerous actionable responses, which we believe may improve future data in this device area and ultimately benefit patients.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 03 Nov 2020; 232:71-83
Lottes AE, Whatley EM, Royce SM, Bertges DJ, ... Rosenfield K, Krucoff MW
Am Heart J: 03 Nov 2020; 232:71-83 | PMID: 33157067
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Impact:
Abstract

Efficacy and safety of dapagliflozin in acute heart failure: Rationale and design of the DICTATE-AHF trial.

Cox ZL, Collins SP, Aaron M, Hernandez GA, ... Stubblefield WB, Lindenfeld J
Background
Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure.
Objective
The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care.
Methods
DICTATE-AHF is a prospective, multicenter, open-label, randomized trial enrolling a planned 240 patients in the United States. Patients with type 2 diabetes hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 mL/min/1.73m are eligible for participation. Patients are randomly assigned 1:1 to dapagliflozin 10 mg once daily or structured usual care until day 5 or hospital discharge. Both treatment arms receive protocolized diuretic and insulin therapies. The primary endpoint is diuretic response expressed as the cumulative change in weight per cumulative loop diuretic dose in 40 mg intravenous furosemide equivalents. Secondary and exploratory endpoints include inpatient worsening AHF, 30-day hospital readmission for AHF or diabetic reasons, change in NT-proBNP, and measures of natriuresis. Safety endpoints include the incidence of hyper/hypoglycemia, ketoacidosis, worsening kidney function, hypovolemic hypotension, and inpatient mortality.
Conclusions
The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 01 Nov 2020; 232:116-124
Cox ZL, Collins SP, Aaron M, Hernandez GA, ... Stubblefield WB, Lindenfeld J
Am Heart J: 01 Nov 2020; 232:116-124 | PMID: 33144086
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Impact:
Abstract

Atrial fibrillation is a marker of increased mortality risk in nonischemic heart failure-Results from the DANISH trial.

Boas R, Thune JJ, Pehrson S, Køber L, ... Svendsen JH, Dixen U
Background
Atrial fibrillation (AF) in heart failure (HF) patients has been associated with a worse outcome. Similarly, excessive supraventricular ectopic activity (ESVEA) has been linked to development of AF, stroke, and death. This study aimed to investigate AF and ESVEA\'s association with outcomes and effect of prophylactic implantable cardioverter defibrillator (ICD) implantation in nonischemic HF patients.
Methods
A total of 850 patients with nonischemic HF, left ventricle ejection fraction ≤35%, and elevated N-terminal pro-brain natriuretic peptides underwent 24 hours Holter recording. The presence of AF (≥30 seconds) and ESVEA (≥30 supraventricular ectopic complexes (SVEC) per hour or run of SVEC ≥20 beats) were registered. Outcomes were all-cause mortality, cardiovascular death (CVD), and sudden cardiac death (SCD).
Results
AF was identified in 188 patients (22%) and ESVEA in 84 patients (10%). After 4 years and 11 months of follow-up, a total of 193 patients (23%) had died. AF was associated with all-cause mortality (hazard ratio [HR] 1.44; confidence interval [CI] 1.04-1.99; P = .03) and CVD (HR 1.59; CI 1.07-2.36; P = .02). ESVEA was associated with all-cause mortality (HR 1.73; CI 1.16-2.57; P = .0073) and CVD (HR 1.76; CI 1.06-2.92; P = .03). Neither AF nor ESVEA was associated with SCD. ICD implantation was not associated with an improved prognosis for neither AF (P value for interaction = .17), nor ESVEA (P value for interaction = .68).
Conclusions
Both AF and ESVEA were associated with worsened prognosis in nonischemic HF. However, ICD implantation was not associated with an improved prognosis for either group.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 01 Nov 2020; 232:61-70
Boas R, Thune JJ, Pehrson S, Køber L, ... Svendsen JH, Dixen U
Am Heart J: 01 Nov 2020; 232:61-70 | PMID: 33144085
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Impact:
Abstract

Rationale and design of the TAILOR-PCI digital study: Transitioning a randomized controlled trial to a digital registry.

Pereira NL, Avram R, So DY, Iturriaga E, ... Farkouh ME, Olgin JE
Background
Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) is the largest cardiovascular genotype-based randomized pragmatic trial (NCT#01742117) to evaluate the role of genotype-guided selection of oral P2Y inhibitor therapy in improving ischemic outcomes after PCI. The trial has been extended from the original 12- to 24-month follow-up, using study coordinator-initiated telephone visits. TAILOR-PCI Digital Study tests the feasibility of extending the trial follow-up in a subset of patients for up to 24 months using state-of-the-art digital solutions. The rationale, design, and approach of extended digital study of patients recruited into a large, international, multi-center clinical trial has not been previously described.
Methods
A total of 930 patients from U.S. and Canadian sites previously enrolled in the 5,302 patient TAILOR-PCI trial within 23 months of randomization are invited by mail to the Digital Study website (http://tailorpci.eurekaplatform.org) and by up to 2 recruiting telephone calls. Eureka, a direct-to-participant digital research platform, is used to consent and collect prospective data on patients for the digital study. Patients are asked to answer health-related surveys at fixed intervals using the Eureka mobile app and or desktop platform. The likelihood of patients enrolled in a randomized clinical trial transitioning to a registry using digital technology, the reasons for nonparticipation and engagement rates are evaluated. To capture hospitalizations, patients may optionally enable geofencing, a process that allows background location tracking and triggering of surveys if a hospital visit greater than 4 hours is detected. In addition, patients answer digital hospitalization surveys every month. Hospitalization data received from the Digital Study will be compared to data collected from study coordinator telephone visits during the same time frame.
Conclusions
The TAILOR-PCI Digital Study evaluates the feasibility of transitioning a large multicenter randomized clinical trial to a digital registry. The study could provide evidence for the ability of digital technology to follow clinical trial patients and to ascertain trial-related events thus also building the foundation for conducting digital clinical trials. Such a digital approach may be especially pertinent in the era of COVID-19.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 30 Oct 2020; 232:84-93
Pereira NL, Avram R, So DY, Iturriaga E, ... Farkouh ME, Olgin JE
Am Heart J: 30 Oct 2020; 232:84-93 | PMID: 33129990
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Impact:
Abstract

Cardiovascular Safety and Efficacy of Vadadust for the Treatment of Anemia in Non-Dialysis Dependent CKD:  Design and Baseline Characteristics.

Chertow GM, Pergola PE, Agarwal R, Block GA, ... Winkelmayer WC, Eckardt KU

Current clinical practice guidelines for anemia management in non-dialysis dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises two global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N=1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N=1725) had hemoglobin between 8-11 g/dL (US) or 9-12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include 1) correction/conversion (weeks 0-23); 2) maintenance (weeks 24-52); 3) long-term treatment (week 53 to end of treatment); and 4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics were similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 28 Oct 2020; epub ahead of print
Chertow GM, Pergola PE, Agarwal R, Block GA, ... Winkelmayer WC, Eckardt KU
Am Heart J: 28 Oct 2020; epub ahead of print | PMID: 33129989
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Impact:
Abstract

Characteristics of clinical trials evaluating cardiovascular therapies for Coronavirus Disease 2019 Registered on ClinicalTrials.gov: a cross sectional analysis.

Varshney AS, Wang DE, Bhatt AS, Blood A, ... Bhatt DL, Kochar A

Morbidity and mortality associated with COVID-19 has increased exponentially, and patients with cardiovascular (CV) disease are at risk for poor outcomes. Several lines of evidence suggest a potential role for CV therapies in COVID-19 treatment. Characteristics of clinical trials of CV therapies related to COVID-19 registered on ClinicalTrials.gov have not been described.
Methods
ClinicalTrials.gov was queried on August 7, 2020 for COVID-19 related trials. Studies evaluating established CV drugs, other fibrinolytics (defibrotide), and extracorporeal membrane oxygenation were included. Studies evaluating anti-microbial, convalescent plasma, non-colchicine anti-inflammatory, and other therapies were excluded. Trial characteristics were tabulated from study-specific entries.
Results
A total of 2,935 studies related to COVID-19 were registered as of August 7, 2020. Of these, 1,645 were interventional studies, and the final analytic cohort consisted of 114 studies evaluating 10 CV therapeutic categories. Antithrombotics (32.5%; n = 37) were most commonly evaluated, followed by pulmonary vasodilators (14.0%; n = 16), renin-angiotensin-aldosterone system-related therapies (12.3%; n = 14), and colchicine (8.8%; n = 10). Trials evaluating multiple CV therapy categories and CV therapies in combination with non-CV therapies encompassed 4.4% (n = 5) and 9.6% (n = 11) of studies, respectively. Most studies were designed for randomized allocation (87.7%; n = 100), enrollment of less than 1000 participants (86.8%; n = 99), single site implementation (55.3%; n = 63), and had a primary outcome of mortality or a composite including mortality (56.1%; n = 64). Most study populations consisted of patients hospitalized with COVID-19 (81.6%; n = 93). At the time of database query, 28.9% (n = 33) of studies were not yet recruiting and the majority were estimated to be completed after December 2020 (67.8%; n = 78). Most lead sponsors were located in North America (43.9%; n = 50) or Europe (36.0%; n = 41).
Conclusions
A minority (7%) of clinical trials related to COVID-19 registered on ClinicalTrials.gov plan to evaluate CV therapies. Of CV therapy studies, most were planned to be single center, enroll less than 1000 inpatients, sponsored by European or North American academic institutions, and estimated to complete after December 2020. Collectively, these findings underscore the need for a network of sites with a platform protocol for rapid evaluation of multiple therapies and generalizability to inform clinical care and health policy for COVID-19 moving forward.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 25 Oct 2020; 232:105-115
Varshney AS, Wang DE, Bhatt AS, Blood A, ... Bhatt DL, Kochar A
Am Heart J: 25 Oct 2020; 232:105-115 | PMID: 33121978
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Abstract

Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes-Systematic review and meta-analysis of randomized placebo-controlled trials.

Salah HM, Al\'Aref SJ, Khan MS, Al-Hawwas M, ... Lopes RD, Fudim M

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved cardiovascular and kidney outcomes. However, the magnitude and potential heterogeneity of effect across patients with varying types of cardiometabolic and kidney disease is unclear. To examine the effect of SGLT2i on cardiovascular and kidney outcomes among patients with type 2 diabetes mellitus (T2DM), and independent of T2DM status, among patients with heart failure (HF), and chronic kidney disease.
Method
Medline, Embase, Cochrane library and scientific conferences were searched from inception till September 24, 2020 for randomized controlled trials comparing cardiovascular and kidney outcomes between SGLT2i and placebo. Random effects hazard ratios (HR) with 95% confidence intervals (CIs) were calculated.
Results
Eight trials with a combined 59,747 patients were included. In the overall population, SGLT2i reduced the risk of all-cause mortality (HR 0.84; 95% CI [0.78-0.91]), cardiovascular mortality (HR 0.84; 95% CI [0.76-0.93]) hospitalization for HF (HR 0.69; 95% CI [0.64-0.74]), myocardial infarction (HR 0.91; 95% CI [0.84-0.99]), and composite kidney outcome (HR 0.62; 95% CI [0.56-0.70]). There was no significant effect on the risk of stroke (HR 0.98; 95% CI [0.86-1.11]). Results were consistent across subgroups stratified by diabetes and HF status. SGLT2i use was not associated with a greater risk of hypoglycemia (OR 0.92; 95% CI [0.84-1.01]) or amputation (OR 1.25; 95% CI [0.97-1.62]). There were 64 diabetic ketoacidosis events with SGLT2i use and 18 with placebo (OR 2.86; 95% CI [1.39-5.86]).
Conclusions
In patients with cardiometabolic and kidney disease, SGLT2i improved cardiovascular and kidney outcomes, regardless of T2DM, HF, and/or CKD status. The magnitude of risk reduction was largest for hospitalization for HF and progression of kidney disease, more modest for mortality and MI and absent for stroke.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 23 Oct 2020; 232:10-22
Salah HM, Al'Aref SJ, Khan MS, Al-Hawwas M, ... Lopes RD, Fudim M
Am Heart J: 23 Oct 2020; 232:10-22 | PMID: 33214130
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Abstract

Oral anticoagulant use in patients with atrial fibrillation and mitral valve repair.

Nathan AS, Yang L, Geng Z, Dayoub EJ, ... Giri J, Groeneveld PW
Background
Patients with atrial fibrillation (AF) who have undergone mitral valve repair are at risk for thromboembolic strokes. Prior to 2019, only vitamin K antagonists were recommended for patients with AF who had undergone mitral valve repair despite the introduction of direct oral anticoagulants (DOAC) in 2010.
Objective
To characterize the use of anticoagulants in patients with AF who underwent surgical mitral valve repair (sMVR) or transcatheter mitral valve repair (tMVR).
Methods
We performed a retrospective cohort analysis of patients with AF undergoing sMVR or tMVR between 04/2014 and 12/2018 using Optum\'s de-identified Clinformatics® Data Mart Database. We identified anticoagulants prescribed within 90 days of discharge from hospitalization.
Results
Overall, 1997 patients with AF underwent valve repair: 1560 underwent sMVR, and 437 underwent tMVR. The mean CHADS-VASc score among all patients was 4.1 (SD 1.9). The overall use of anticoagulation was unchanged between 2014 (72.2%) and 2018 (70.0%) (P = .49). Among patients who underwent sMVR or tMVR between April 2014 and December 2018, the use of VKA therapy decreased from 62.9% to 32.1% (P < .01 for trend) and the use of DOACs increased from 12.4% to 37.3% (P < .01 for trend).
Conclusions
Among patients with AF who underwent sMVR or tMVR between 2014 and 2018, roughly 30% of patients were not treated with any anticoagulant within 90 days of discharge, despite an elevated stroke risk in the cohort. The rate of DOAC use increased steadily over the study period but did not significantly increase the rate of overall anticoagulant use in this high-risk cohort.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 23 Oct 2020; 232:1-9
Nathan AS, Yang L, Geng Z, Dayoub EJ, ... Giri J, Groeneveld PW
Am Heart J: 23 Oct 2020; 232:1-9 | PMID: 33214129
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Abstract

Adherence with lipid screening guidelines in standard- and high-risk children and adolescents.

Berger JH, Chen F, Faerber JA, O\'Byrne ML, Brothers JA

Because atherosclerosis begins in childhood, universal lipid screening is recommended with special attention to conditions predisposing to early atherosclerosis. Data about real-world penetration of these guidelines is not available.
Methods
Retrospective cohort study using MarketScan® commercial and Medicaid insurance claims databases, a geographically representative sample of U.S. children. Subjects who passed through the 9- to 11-year window and had continuous insurance coverage between 1/1/2013 and 12/31/2016 were studied. Multivariable models were calculated, evaluating the association between other patient factors and the likelihood of screening. The primary hypothesis was that screening rates would be low, but that high-risk conditions would be associated with a higher likelihood of screening.
Results
In total, 572,522 children (51% male, 33% black, 11% Hispanic, 51% Medicaid) were studied. The prevalence of high-risk conditions was 2.2%. In unadjusted and adjusted analyses, these subjects were more likely to be screened than standard-risk subjects (47% vs. 20%, OR: 3.7, 95% CI 3.5-3.8, P < .001). Within this group, the diagnosis-specific likelihood of screening varied (26-69%). Endocrinopathies (OR 5.4, 95% CI 5.2-5.7), solid organ transplants (OR 5.0, 95% CI 3.8-6.6), and metabolic disease (OR 3.9, 95% CI 3.1-5.0, all P < .001) were associated with the highest likelihood of undergoing screening.
Conclusions
Despite national recommendations, lipid screening was performed in a minority of children. Though subjects with high-risk conditions had a higher likelihood of screening, rates remained low. This study highlights the need for research and advocacy regarding obstacles to lipid screening of children in the United States.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 23 Oct 2020; 232:39-46
Berger JH, Chen F, Faerber JA, O'Byrne ML, Brothers JA
Am Heart J: 23 Oct 2020; 232:39-46 | PMID: 33229294
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Abstract

Shock in the cardiac intensive care unit: Changes in epidemiology and prognosis over time.

Jentzer JC, Ahmed AM, Vallabhajosyula S, Burstein B, ... Best PJ, Bell MR

There are few studies documenting the changing epidemiology and outcomes of shock in cardiac intensive care unit (CICU) patients. We sought to describe the changes in shock epidemiology and outcomes over time in a CICU population.
Methods
We included 1859 unique patients admitted to the Mayo Clinic Rochester CICU from 2007 through 2018 with an admission diagnosis of shock. Temporal trends, including mortality, were assessed across 3-year periods.
Results
Shock comprised 15.1% of CICU admissions during the study period, increasing from 8.8% of CICU admissions in 2007 to 21.6% in 2018 (P < .01 for trend). Mean age was 68 ± 14 years (38% females). Shock was cardiogenic in 65%, septic in 10% and mixed cardiogenic-septic in 15%. Concomitant diagnoses in patients with cardiogenic shock (CS) included acute coronary syndrome (ACS) in 17%, heart failure (HF) in 35% and both in 40%. There was no significant change in the prevalence of individual shock subtypes over time (P > .1). Among patients with CS, the prevalence of ACS decreased and the prevalence of HF increased over time (P < .01). Hospital mortality was highest among patients with mixed shock (39%; P = .05). Among patients with CS, hospital mortality was lower among those with HF compared to those without HF (31% vs. 40%, P < .01). Hospital mortality decreased over time among patients with shock (P < .01) and CS (P = .02).
Conclusions
The prevalence of shock in the CICU has increased over time, with a substantial prevalence of mixed CS. The etiology of CS has changed over the last decade with HF overtaking ACS as the most common cause of CS in the CICU.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 23 Oct 2020; 232:94-104
Jentzer JC, Ahmed AM, Vallabhajosyula S, Burstein B, ... Best PJ, Bell MR
Am Heart J: 23 Oct 2020; 232:94-104 | PMID: 33257304
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Abstract

Synthesis of systematic reviews of percutaneous device closure of patent foramen ovale (PFO) for prevention of recurrent cryptogenic stroke: Redundant publications and methodological deficiencies.

Husaini M, Esmaeeli A, Thangam M, Doering M, Brown DL

Critical assessments of systemic reviews and meta-analyses have found them to often be redundant, lacking in novel perspectives, of poor methodological quality, and written by authors with potential conflicts of interest. We sought to investigate these issues as they relate to systemic reviews and meta-analyses of percutaneous patent foramen ovale closure for the prevention of recurrent cryptogenic stroke.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 21 Oct 2020; 232:57-60
Husaini M, Esmaeeli A, Thangam M, Doering M, Brown DL
Am Heart J: 21 Oct 2020; 232:57-60 | PMID: 33098809
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This program is still in alpha version.