Journal: J Am Coll Cardiol

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Abstract

Cardiovascular Complications of Opioid Use: JACC State-of-the-Art Review.

Krantz MJ, Palmer RB, Haigney MCP

Opioids are the most potent of all analgesics. Although traditionally used solely for acute self-limited conditions and palliation of severe cancer-associated pain, a movement to promote subjective pain (scale, 0 to 10) to the status of a \"fifth vital sign\" bolstered widespread prescribing for chronic, noncancer pain. This, coupled with rising misuse, initiated a surge in unintentional deaths, increased drug-associated acute coronary syndrome, and endocarditis. In response, the American College of Cardiology issued a call to action for cardiovascular care teams. Opioid toxicity is primarily mediated via potent μ-receptor agonism resulting in ventilatory depression. However, both overdose and opioid withdrawal can trigger major adverse cardiovascular events resulting from hemodynamic, vascular, and proarrhythmic/electrophysiological consequences. Although natural opioid analogues are devoid of repolarization effects, synthetic agents may be proarrhythmic. This perspective explores cardiovascular consequences of opioids, the contributions of off-target electrophysiologic properties to mortality, and provides practical safety recommendations.

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

J Am Coll Cardiol: 18 Jan 2021; 77:205-223
Krantz MJ, Palmer RB, Haigney MCP
J Am Coll Cardiol: 18 Jan 2021; 77:205-223 | PMID: 33446314
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Abstract

Cardiovascular Aging and Longevity: JACC State-of-the-Art Review.

Pietri P, Stefanadis C

Cardiovascular aging and longevity are interrelated through many pathophysiological mechanisms. Many factors that promote atherosclerotic cardiovascular disease are also implicated in the aging process and vice versa. Indeed, cardiometabolic disorders such as hyperglycemia, insulin resistance, dyslipidemia, and arterial hypertension share common pathophysiological mechanisms with aging and longevity. Moreover, genetic modulators of longevity have a significant impact on cardiovascular aging. The current knowledge of genetic, molecular, and biochemical pathways of aging may serve as a substrate to introduce interventions that might delay cardiovascular aging, thus approaching the goal of longevity. In the present review, the authors describe pathophysiological links between cardiovascular aging and longevity and translate these mechanisms into clinical data by reporting genetic, dietary, and environmental characteristics from long-living populations.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Jan 2021; 77:189-204
Pietri P, Stefanadis C
J Am Coll Cardiol: 18 Jan 2021; 77:189-204 | PMID: 33446313
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Abstract

International Impact of COVID-19 on the Diagnosis of Heart Disease.

Einstein AJ, Shaw LJ, Hirschfeld C, Williams MC, ... Paez D, INCAPS COVID Investigators Group
Background
The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.
Objectives
The study sought to assess COVID-19\'s impact on global cardiovascular diagnostic procedural volumes and safety practices.
Methods
The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.
Results
Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth.
Conclusions
COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world\'s economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted.

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

J Am Coll Cardiol: 18 Jan 2021; 77:173-185
Einstein AJ, Shaw LJ, Hirschfeld C, Williams MC, ... Paez D, INCAPS COVID Investigators Group
J Am Coll Cardiol: 18 Jan 2021; 77:173-185 | PMID: 33446311
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Abstract

Cardiovascular Deaths During the COVID-19 Pandemic in the United States.

Wadhera RK, Shen C, Gondi S, Chen S, Kazi DS, Yeh RW
Background
Although the direct toll of COVID-19 in the United States has been substantial, concerns have also arisen about the indirect effects of the pandemic. Hospitalizations for acute cardiovascular conditions have declined, raising concern that patients may be avoiding hospitals because of fear of contracting severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2). Other factors, including strain on health care systems, may also have had an indirect toll.
Objectives
This investigation aimed to evaluate whether population-level deaths due to cardiovascular causes increased during the COVID-19 pandemic.
Methods
The authors conducted an observational cohort study using data from the National Center for Health Statistics to evaluate the rate of deaths due to cardiovascular causes after the onset of the pandemic in the United States, from March 18, 2020, to June 2, 2020, relative to the period immediately preceding the pandemic (January 1, 2020 to March 17, 2020). Changes in deaths were compared with the same periods in the previous year.
Results
There were 397,042 cardiovascular deaths from January 1, 2020, to June 2, 2020. Deaths caused by ischemic heart disease increased nationally after the onset of the pandemic in 2020, compared with changes over the same period in 2019 (ratio of the relative change in deaths per 100,000 in 2020 vs. 2019: 1.11, 95% confidence interval: 1.04 to 1.18). An increase was also observed for deaths caused by hypertensive disease (1.17, 95% confidence interval: 1.09 to 1.26), but not for heart failure, cerebrovascular disease, or other diseases of the circulatory system. New York City experienced a large relative increase in deaths caused by ischemic heart disease (2.39, 95% confidence interval: 1.39 to 4.09) and hypertensive diseases (2.64, 95% confidence interval: 1.52 to 4.56) during the pandemic. More modest increases in deaths caused by these conditions occurred in the remainder of New York State, New Jersey, Michigan, and Illinois but not in Massachusetts or Louisiana.
Conclusions
There was an increase in deaths caused by ischemic heart disease and hypertensive diseases in some regions of the United States during the initial phase of the COVID-19 pandemic. These findings suggest that the pandemic may have had an indirect toll on patients with cardiovascular disease.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Jan 2021; 77:159-169
Wadhera RK, Shen C, Gondi S, Chen S, Kazi DS, Yeh RW
J Am Coll Cardiol: 18 Jan 2021; 77:159-169 | PMID: 33446309
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Abstract

Predictive Value of the Residual SYNTAX Score in Patients With Cardiogenic Shock.

Barthélémy O, Rouanet S, Brugier D, Vignolles N, ... Thiele H, Montalescot G
Background
In hemodynamically stable patients, complete revascularization (CR) following percutaneous coronary intervention (PCI) is associated with a better prognosis in chronic and acute coronary syndromes.
Objectives
This study sought to assess the extent, severity, and prognostic value of remaining coronary stenoses following PCI, by using the residual SYNTAX score (rSS), in patients with cardiogenic shock (CS) related to myocardial infarction (MI).
Methods
The CULPRIT-SHOCK (Culprit Lesion Only Percutaneous Coronary Intervention [PCI] Versus Multivessel PCI in Cardiogenic Shock) trial compared a multivessel PCI (MV-PCI) strategy with a culprit lesion-only PCI (CLO-PCI) strategy in patients with multivessel coronary artery disease who presented with MI-related CS. The rSS was assessed by a central core laboratory. The study group was divided in 4 subgroups according to tertiles of rSS of the participants, thereby isolating patients with an rSS of 0 (CR). The predictive value of rSS for the 30-day primary endpoint (mortality or severe renal failure) and for 30-day and 1-year mortality was assessed using multivariate logistic regression.
Results
Among the 587 patients with an rSS available, the median rSS was 9.0 (interquartile range: 3.0 to 17.0); 102 (17.4%), 100 (17.0%), 196 (33.4%), and 189 (32.2%) patients had rSS = 0, 0 < rSS ≤5, 5 < rSS ≤14, and rSS >14, respectively. CR was achieved in 75 (25.2%; 95% confidence interval [CI]: 20.3% to 30.5%) and 27 (9.3%; 95% CI: 6.2% to 13.3%) of patients treated using the MV-PCI and CLO-PCI strategies, respectively. After multiple adjustments, rSS was independently associated with 30-day mortality (adjusted odds ratio per 10 units: 1.49; 95% CI: 1.11 to 2.01) and 1-year mortality (adjusted odds ratio per 10 units: 1.52; 95% CI: 1.11 to 2.07).
Conclusions
Among patients with multivessel disease and MI-related CS, CR is achieved only in one-fourth of the patients treated using an MV-PCI strategy. and the residual SYNTAX score is independently associated with early and late mortality.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Jan 2021; 77:144-155
Barthélémy O, Rouanet S, Brugier D, Vignolles N, ... Thiele H, Montalescot G
J Am Coll Cardiol: 18 Jan 2021; 77:144-155 | PMID: 33446307
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Abstract

Aortic Valve Replacement in Low-Risk Patients With Severe Aortic Stenosis Outside Randomized Trials.

Alperi A, Voisine P, Kalavrouziotis D, Dumont E, ... Mohammadi S, Rodés-Cabau J
Background
Recent randomized trials including low-risk patients showed positive results for transcatheter aortic valve replacement (TAVR) compared to surgical aortic valve replacement (SAVR), but patients with non-tricuspid aortic valve (NTAV), severe coronary artery disease (SevCAD), and those requiring concomitant mitral/tricuspid valve (CMTV) or concomitant ascending aorta replacement (CAAR) interventions were excluded.
Objectives
This study sought to evaluate the presence and impact of the main clinical variables not evaluated in TAVR versus SAVR trials (NTAV, SevCAD, and CMTV or CAAR intervention) in a large series of consecutive low-risk patients with severe aortic stenosis (SAS) undergoing SAVR.
Methods
Single-center study including consecutive patients with SAS and low surgical risk (Society of Thoracic Surgeons score of <4%) undergoing SAVR. Baseline, procedural characteristics, and 30-day outcomes were prospectively collected.
Results
Of 6,772 patients with SAS who underwent SAVR between 2000 and 2019, 5,310 (78.4%) exhibited a low surgical risk (mean Society of Thoracic Surgeons score: 1.94 ± 0.87%). Of these, 2,165 patients (40.8%) had at least 1 of the following: NTAV (n = 1,468, 27.6%), SevCAD (n = 307, 5.8%), CMTV (n = 306, 5.8%), and CAAR (n = 560, 10.5%). The 30-day mortality and stroke rates for the overall low-risk SAS cohort were 1.9% and 2.4%, respectively. The mortality rate was similar in the SevCAD (2.6%) and CAAR (2.1%) groups versus the rest of the cohort (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 0.85 to 3.75, and OR: 1.64; 95% CI: 0.88 to 3.05, respectively), lower in the NTAV group (0.9%; OR: 0.42; 95% CI: 0.22 to 0.81), and higher in the CMTV group (5.9%; OR: 2.61; 95% CI: 1.51 to 4.5).
Conclusions
In a real-world setting, close to one-half of the low-risk patients with SAS undergoing SAVR exhibited at least 1 major criterion not evaluated in TAVR versus SAVR randomized trials. Clinical outcomes were better than or similar to those predicted by surgical scores in all groups but those patients requiring CMTV intervention. These results may help determine the impact of implementing the results of TAVR-SAVR trials in real practice and may inform future trials in specific groups.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Jan 2021; 77:111-123
Alperi A, Voisine P, Kalavrouziotis D, Dumont E, ... Mohammadi S, Rodés-Cabau J
J Am Coll Cardiol: 18 Jan 2021; 77:111-123 | PMID: 33446305
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Abstract

Transcatheter Intervention for Congenital Defects Involving the Great Vessels: JACC Review Topic of the Week.

Goldstein BH, Kreutzer J

Since the development of balloon angioplasty and balloon-expandable endovascular stent technology in the 1970s and 1980s, percutaneous transcatheter intervention has emerged as a mainstay of therapy for congenital heart disease (CHD) lesions throughout the systemic and pulmonary vascular beds. Congenital lesions of the great vessels, including the aorta, pulmonary arteries, and patent ductus arteriosus, are each amenable to transcatheter intervention throughout the lifespan, from neonate to adult. In many cases, on-label devices now exist to facilitate these therapies. In this review, we seek to describe the contemporary approach to and outcomes from transcatheter management of major CHD lesions of the great vessels, with a focus on coarctation of the aorta, single- or multiple-branch pulmonary artery stenoses, and persistent patent ductus arteriosus. We further comment on the future of transcatheter therapies for these CHD lesions.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2021; 77:80-96
Goldstein BH, Kreutzer J
J Am Coll Cardiol: 04 Jan 2021; 77:80-96 | PMID: 33413945
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Abstract

Semilunar Valve Interventions for Congenital Heart Disease: JACC State-of-the-Art Review.

Morray BH, McElhinney DB

Transcatheter balloon valvuloplasty for the treatment of aortic and pulmonary valve stenosis was first described nearly 40 years ago. Since that time, the technique has been refined in an effort to optimize acute outcomes while reducing the long-term need for reintervention and valve replacement. Balloon pulmonary valvuloplasty is considered first-line therapy for pulmonary valve stenosis and generally results in successful relief of valvar obstruction. Larger balloon to annulus (BAR) diameter ratios can increase the risk for significant valvar regurgitation. However, the development of regurgitation resulting in right ventricular dilation and dysfunction necessitating pulmonary valve replacement is uncommon in long-term follow-up. Balloon aortic valvuloplasty has generally been the first-line therapy for aortic valve stenosis, although some contemporary studies have documented improved outcomes following surgical valvuloplasty in a subset of patients who achieve tri-leaflet valve morphology following surgical repair. Over time, progressive aortic regurgitation is common and frequently results in the need for aortic valve replacement. Neonates with critical aortic valve stenosis remain a particularly high-risk group. More contemporary data suggest that acutely achieving an aortic valve gradient <35 mm Hg with mild aortic regurgitation may improve long-term valve performance and reduce the need for valve replacement. Continued study will help to further improve outcomes and reduce the need for future reinterventions.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2021; 77:71-79
Morray BH, McElhinney DB
J Am Coll Cardiol: 04 Jan 2021; 77:71-79 | PMID: 33413944
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Abstract

Calcium-Induced Autonomic Denervation in Patients With Post-Operative Atrial Fibrillation.

Wang H, Zhang Y, Xin F, Jiang H, ... Wang Q, Po SS
Background
Post-operative atrial fibrillation (POAF) is associated with worse long-term cardiovascular outcomes.
Objectives
This study hypothesized that injecting calcium chloride (CaCl) into the major atrial ganglionated plexi (GPs) during isolated coronary artery bypass grafting (CABG) can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity.
Methods
This proof-of-concept study randomized 200 patients undergoing isolated, off-pump CABG to CaCl (n = 100) or sodium chloride (sham, n = 100) injection. Two milliliters of CaCl (5%) or sodium chloride (0.9%) was injected into the 4 major atrial GPs during CABG. All patients received 7-day continuous telemetry and Holter monitoring. The primary outcome was incidence of POAF (≥30 s) in 7 days. Secondary outcomes included length of hospitalization, POAF burden, average ventricular rate during AF, plasma level of inflammatory markers, and actionable antiarrhythmic therapy to treat POAF.
Results
The POAF incidence was reduced from 36% to 15% (hazard ratio: 0.366; 95% confidence interval: 0.211 to 0.635; p = 0.001). Length of hospitalization did not differ between the 2 groups. POAF burden (first 7 post-operative days), the use of amiodarone or esmolol, and the incidence of atrial couplets and nonsustained atrial tachyarrhythmias were significantly reduced in the CaCl group. Heart rate variability data showed a decrease in both high-frequency and low-frequency power in the CaCl group with a preserved low-frequency/high-frequency ratio, suggesting that the sympathetic/parasympathetic balance was not perturbed by CaCl injection.
Conclusions
Injection of CaCl into the 4 major atrial GPs reduced the POAF hazard by 63%. Inhibition of GP function by Ca-mediated neurotoxicity may underlie the therapeutic effect. (Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation; ChiCTR1800019276).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2021; 77:57-67
Wang H, Zhang Y, Xin F, Jiang H, ... Wang Q, Po SS
J Am Coll Cardiol: 04 Jan 2021; 77:57-67 | PMID: 33413942
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Abstract

Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study.

Luo J, le Cessie S, van Heemst D, Noordam R
Background
Previously, observational studies have identified associations between higher levels of dietary-derived antioxidants and lower risk of coronary heart disease (CHD), whereas randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation.
Objectives
The purpose of this study was to investigate possible causal associations between dietary-derived circulating antioxidants and primary CHD risk using 2-sample Mendelian randomization (MR).
Methods
Single-nucleotide polymorphisms for circulating antioxidants (vitamins E and C, retinol, β-carotene, and lycopene), assessed as absolute levels and metabolites, were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-CHD associations were obtained from 3 databases: the CARDIoGRAMplusC4D consortium (60,801 cases; 123,504 control subjects), UK Biobank (25,306 cases; 462,011 control subjects), and FinnGen study (7,123 cases; 89,376 control subjects). For each exposure, MR analyses were performed per outcome database and were subsequently meta-analyzed.
Results
Among an analytic sample of 768,121 individuals (93,230 cases), genetically predicted circulating antioxidants were not causally associated with CHD risk. For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval [CI]: 0.63 to 1.41) for retinol and 1.03 (95% CI: 0.97 to 1.10) for β-carotene per unit increase in ln-transformed antioxidant values. For metabolites, the odds ratio ranged between 0.93 (95% CI: 0.82 to 1.06) for γ-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels.
Conclusions
Evidence from our study did not support a protective effect of genetic predisposition to high dietary-derived antioxidant levels on CHD risk. Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2021; 77:45-54
Luo J, le Cessie S, van Heemst D, Noordam R
J Am Coll Cardiol: 04 Jan 2021; 77:45-54 | PMID: 33413940
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Abstract

Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease.

Zegard A, Okafor O, de Bono J, Kalla M, ... Stegemann B, Leyva F
Background
The \"gray zone\" of myocardial fibrosis (GZF) on cardiovascular magnetic resonance may be a substrate for ventricular arrhythmias (VAs).
Objectives
The purpose of this study was to determine whether GZF predicts sudden cardiac death (SCD) and VAs (ventricular fibrillation or sustained ventricular tachycardia) in patients with coronary artery disease (CAD) and a wide range of left ventricular ejection fractions (LVEFs).
Methods
In this retrospective study of CAD patients, the presence of myocardial fibrosis on visual assessment (MF) and GZF mass in patients with MF were assessed in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs.
Results
Among 979 patients (mean age [± SD]: 65.8 ± 12.3 years), 29 (2.96%) experienced SCD and 80 (8.17%) met the arrhythmic endpoint over median 5.82 years (interquartile range: 4.1 to 7.3 years). In the whole cohort, MF was strongly associated with SCD (hazard ratio: 10.1; 95% confidence interval [CI]: 1.42 to 1,278.9) and the arrhythmic endpoint (hazard ratio: 28.0; 95% CI: 4.07 to 3,525.4). In competing risks analyses, associations between LVEF <35% and SCD (subdistribution hazard ratio [sHR]: 2.99; 95% CI: 1.42 to 6.31) and the arrhythmic endpoint (sHR: 4.71; 95% CI: 2.97 to 7.47) were weaker. In competing risk analyses of the MF subcohort (n = 832), GZF using the 3SD method (GZF) >5.0 g was strongly associated with SCD (sHR: 10.8; 95% CI: 3.74 to 30.9) and the arrhythmic endpoint (sHR: 7.40; 95% CI: 4.29 to 12.8). Associations between LVEF <35% and SCD (sHR: 2.62; 95% CI: 1.24 to 5.52) and the arrhythmic endpoint (sHR: 4.14; 95% CI: 2.61 to 6.57) were weaker.
Conclusions
In CAD patients, MF plus quantified GZF mass was more strongly associated with SCD and VAs than LVEF. In selecting patients for implantable cardioverter-defibrillators, assessment of MF followed by quantification of GZF mass may be preferable to LVEF.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2021; 77:29-41
Zegard A, Okafor O, de Bono J, Kalla M, ... Stegemann B, Leyva F
J Am Coll Cardiol: 04 Jan 2021; 77:29-41 | PMID: 33413938
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Abstract

Association of Age With 10-Year Outcomes After Coronary Surgery in the Arterial Revascularization Trial.

Gaudino M, Di Franco A, Flather M, Gerry S, ... Fremes SE, Taggart DP
Background
The association of age with the outcomes of bilateral internal thoracic arteries (BITAs) versus single internal thoracic arteries (SITAs) for coronary bypass grafting (CABG) remains to be determined.
Objectives
The purpose of this study was to evaluate the association between age and BITA versus SITA outcomes in the Arterial Revascularization Trial.
Methods
The primary endpoints were all-cause mortality and a composite of major adverse events, including all-cause mortality, myocardial infarction, or stroke. Secondary endpoints were bleeding complications and sternal wound complications up to 6 months after surgery. Multivariable fractional polynomials analysis and log-rank tests were used.
Results
Age did not affect any of the explored outcomes in the overall BITA versus SITA comparison in the intention-to-treat analysis and in the analysis based on the number of arterial grafts received. However, when the intention-to-treat analysis was restricted to the populations of patients between age 50 and 70 years, younger patients in the BITA arm had a significantly lower incidence of major adverse events (p = 0.03).
Conclusions
Our results suggest that BITA may improve long-term outcome in younger patients, although more randomized data are needed to confirm this hypothesis.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2021; 77:18-26
Gaudino M, Di Franco A, Flather M, Gerry S, ... Fremes SE, Taggart DP
J Am Coll Cardiol: 04 Jan 2021; 77:18-26 | PMID: 33413936
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Abstract

Transcatheter Replacement of Transcatheter Versus Surgically Implanted Aortic Valve Bioprostheses.

Landes U, Sathananthan J, Witberg G, De Backer O, ... Leon MB, Webb JG
Background
Surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR) are now both used to treat aortic stenosis in patients in whom life expectancy may exceed valve durability. The choice of initial bioprosthesis should therefore consider the relative safety and efficacy of potential subsequent interventions.
Objectives
The aim of this study was to compare TAVR in failed transcatheter aortic valves (TAVs) versus surgical aortic valves (SAVs).
Methods
Data were collected on 434 TAV-in-TAV and 624 TAV-in-SAV consecutive procedures performed at centers participating in the Redo-TAVR international registry. Propensity score matching was applied, and 330 matched (165:165) patients were analyzed. Principal endpoints were procedural success, procedural safety, and mortality at 30 days and 1 year.
Results
For TAV-in-TAV versus TAV-in-SAV, procedural success was observed in 120 (72.7%) versus 103 (62.4%) patients (p = 0.045), driven by a numerically lower frequency of residual high valve gradient (p = 0.095), ectopic valve deployment (p = 0.081), coronary obstruction (p = 0.091), and conversion to open heart surgery (p = 0.082). Procedural safety was achieved in 116 (70.3%) versus 119 (72.1%) patients (p = 0.715). Mortality at 30 days was 5 (3%) after TAV-in-TAV and 7 (4.4%) after TAV-in-SAV (p = 0.570). At 1 year, mortality was 12 (11.9%) and 10 (10.2%), respectively (p = 0.633). Aortic valve area was larger (1.55 ± 0.5 cm vs. 1.37 ± 0.5 cm; p = 0.040), and the mean residual gradient was lower (12.6 ± 5.2 mm Hg vs. 14.9 ± 5.2 mm Hg; p = 0.011) after TAV-in-TAV. The rate of moderate or greater residual aortic regurgitation was similar, but mild aortic regurgitation was more frequent after TAV-in-TAV (p = 0.003).
Conclusions
In propensity score-matched cohorts of TAV-in-TAV versus TAV-in-SAV patients, TAV-in-TAV was associated with higher procedural success and similar procedural safety or mortality.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2021; 77:1-14
Landes U, Sathananthan J, Witberg G, De Backer O, ... Leon MB, Webb JG
J Am Coll Cardiol: 04 Jan 2021; 77:1-14 | PMID: 33413929
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Abstract

2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Ommen SR, Mital S, Burke MA, Day SM, ... Semsarian C, Sorajja P
Aim
This executive summary of the hypertrophic cardiomyopathy clinical practice guideline provides recommendations and algorithms for clinicians to diagnose and manage hypertrophic cardiomyopathy in adult and pediatric patients as well as supporting documentation to encourage their use.
Methods
A comprehensive literature search was conducted from January 1, 2010, to April 30, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases.
Structure
Many recommendations from the earlier hypertrophic cardiomyopathy guidelines have been updated with new evidence or a better understanding of earlier evidence. This summary operationalizes the recommendations from the full guideline and presents a combination of diagnostic work-up, genetic and family screening, risk stratification approaches, lifestyle modifications, surgical and catheter interventions, and medications that constitute components of guideline directed medical therapy. For both guideline-directed medical therapy and other recommended drug treatment regimens, the reader is advised to follow dosing, contraindications and drug-drug interactions based on product insert materials.

Copyright © 2020 American Heart Association, Inc., and the American College of Cardiology. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Dec 2020; 76:3022-3055
Ommen SR, Mital S, Burke MA, Day SM, ... Semsarian C, Sorajja P
J Am Coll Cardiol: 21 Dec 2020; 76:3022-3055 | PMID: 33229115
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Abstract

Prognostic Role of Hepatorenal Function Indexes in Patients With Ebstein Anomaly.

Egbe AC, Miranda WR, Dearani J, Kamath PS, Connolly HM
Background
Hepatorenal dysfunction is a risk factor for mortality in patients with chronic tricuspid regurgitation due to acquired heart disease. Ebstein anomaly is the most common cause of primary tricuspid regurgitation in adults with congenital heart disease, but the prevalence and prognostic implications of hepatorenal dysfunction are unknown in this population.
Objectives
The purpose of this study was to determine the risk factors and prognostic implications of hepatorenal dysfunction, as measured primarily by the use of model for end-stage liver disease excluding international normalized ratio (MELD-XI score), as well as looking at other associated factors.
Methods
This was a retrospective study of adults with Ebstein anomaly who received care at Mayo Clinic from 2003 to 2018.
Results
Of 692 patients, the median MELD-XI score was 10.2 (interquartile range: 9.4 to 13.3); 53 (8%) died and 3 (0.4%) underwent heart transplant. MELD-XI was an independent predictor of death/transplant (hazard ratio: 1.32; 95% confidence interval: 1.11 to 2.06; p < 0.001). In the subset of patients with serial MELD-XI scores (n = 416), temporal change in MELD-XI score (ΔMELD-XI) was also a predictor of death/transplant. In the subset of patients who underwent tricuspid valve surgery (n = 344), a post-operative improvement in MELD-XI score (ΔMELD-XI) was associated with improved long-term survival. Impaired right atrial (RA) reservoir strain and elevated estimated RA pressure were associated with worse baseline MELD-XI and ΔMELD-XI scores.
Conclusions
Hepatorenal dysfunction is a predictor of mortality in Ebstein anomaly, and RA dysfunction and hypertension are hemodynamic biomarkers that can identify patients at risk for deterioration in hepatorenal function and mortality. These data highlight the prognostic importance of noncardiac organ-system dysfunction, and provide complementary clinical risk stratification metrics for management of these patients.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Dec 2020; 76:2968-2976
Egbe AC, Miranda WR, Dearani J, Kamath PS, Connolly HM
J Am Coll Cardiol: 21 Dec 2020; 76:2968-2976 | PMID: 33334426
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Abstract

Transition From Temporary to Durable Circulatory Support Systems.

Saeed D, Potapov E, Loforte A, Morshuis M, ... Gummert J,
Background
The decision to implant durable mechanical circulatory systems (MCSs) in patients on extracorporeal life support (ECLS) is challenging due to expected poor outcomes in these patients.
Objectives
The aim of this study was to identify outcome predictors that may facilitate future patient selection and decision making.
Methods
The Durable MCS after ECLS registry is a multicenter retrospective study that gathered data on consecutive patients who underwent MCS implantation after ECLS between January 2010 and August 2018 in 11 high-volume European centers. Several perioperative parameters were collected. The primary endpoint was survival at 1 year after durable MCS implantation.
Results
A total of 531 durable MCSs after ECLS were implanted during this period. The average patient age was 53 ± 12 years old. ECLS cannulation was peripheral in 87% of patients and 33% of the patients had history of cardiopulmonary resuscitation before ECLS implantation. The 30-day, 1-year, and 3-year actuarial survival rates were 77%, 53%, and 43%, respectively. The following predictors for 1-year outcome have been observed: age, female sex, lactate value, Model of End-Stage Liver Disease XI score, history of atrial fibrillation, redo surgery, and body mass index >30 kg/m. On the basis of this data, a risk score and an app to estimate 1-year mortality was created.
Conclusions
The outcome in patients receiving durable MCS after ECLS remains limited, yet preoperative factors may allow differentiating futile patients from those with significant survival benefit.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 21 Dec 2020; 76:2956-2964
Saeed D, Potapov E, Loforte A, Morshuis M, ... Gummert J,
J Am Coll Cardiol: 21 Dec 2020; 76:2956-2964 | PMID: 33334424
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Abstract

Diastolic Function and Clinical Outcomes After Transcatheter Aortic Valve Replacement: PARTNER 2 SAPIEN 3 Registry.

Ong G, Pibarot P, Redfors B, Weissman NJ, ... Douglas PS, Hahn RT
Background
Few studies have evaluated if diastolic function could predict outcomes in patients with aortic stenosis.
Objectives
The authors aimed to assess the association between diastolic dysfunction (DD) and outcomes in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR).
Methods
Baseline, 30-day, and 1- and 2-year transthoracic echocardiograms from the PARTNER (Placement of Aortic Transcatheter Valves) 2 SAPIEN 3 registry were analyzed by a consortium of core laboratories and divided into the American Society of Echocardiography DD groups.
Results
Among the 1,750 included, 682 (54.4%) had grade 1 DD, 352 (28.1%) had grade 2 DD, 168 (13.4%) had grade 3 DD, and 51 (4.1%) had indeterminate DD grade. Incremental baseline grades of DD were associated with an increase in combined 1- and 2-year cardiovascular (CV) death/rehospitalization (all p < 0.002) and all-cause death at 2 years (p = 0.01) but not at 1 year. Improvement in DD grade/grade 1 DD at 30 days post-TAVR was seen in 70.8% patients. Patients with improvement in ≥1 grade of DD/grade 1 DD had reduced 1-year CV death/rehospitalization (p < 0.001) and increased 2-year survival (p = 0.01). Baseline grade 3 DD was a predictor of 1-year CV death/rehospitalization (hazard ratio: 2.73; 95% confidence interval: 1.07 to 6.98; p = 0.04). Improvement in DD grade/grade 1 DD at 30 days was protective for 1-year CV death/rehospitalizations (hazard ratio: 0.39; 95% confidence interval: 0.19 to 0.83; p = 0.01).
Conclusions
In the PARTNER 2 SAPIEN 3 registry, baseline DD was a predictor of up to 2 years clinical outcomes in patients who underwent TAVR. Improvement in DD grade at 30 days was associated with improvement in short-term clinical outcomes. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - PARTNER II - PARTNERII - S3 Intermediate [PARTNERII S3i]; NCT03222128; PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - High Risk and Nested Registry 7 [PII S3HR/NR7]; NCT03222141).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Dec 2020; 76:2940-2951
Ong G, Pibarot P, Redfors B, Weissman NJ, ... Douglas PS, Hahn RT
J Am Coll Cardiol: 21 Dec 2020; 76:2940-2951 | PMID: 33334422
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Abstract

Incidence and Predictors of Out-of-Hospital Cardiac Arrest Within 90 Days After Myocardial Infarction.

Faxén J, Jernberg T, Hollenberg J, Gadler F, Herlitz J, Szummer K
Background
The risk of sudden cardiac death (SCD) is high early after myocardial infarction (MI). Current knowledge and guidelines mainly rely on results from older clinical trials and registry studies. Left ventricular ejection fraction (LVEF) alone has not been proven a reliable predictor of SCD.
Objectives
This study sought to identify the incidence and additional predictors of SCD early after MI in a contemporary nationwide setting.
Methods
The authors used data from SWEDEHEART, the Swedish Cardiopulmonary Resuscitation Registry, and the Swedish Pacemaker and Implantable Cardioverter-Defibrillator (ICD) Registry. Cases of MI, which had undergone coronary angiography and were discharged alive between 2009 to 2017 without a prior ICD, were followed up to 90 days. Cox regression models were used to assess associations between clinical parameters and out-of-hospital cardiac arrest (OHCA).
Results
Among 121,379 cases, OHCA occurred in 349 (0.29%) and non-OHCA death in 2,194 (1.8%). A total of 6 variables (male sex, diabetes, estimated glomerular filtration rate <30 ml/min/1.73 m, Killip class ≥II, new-onset atrial fibrillation/flutter, and impaired LVEF [reference ≥50%] categorized as 40% to 49%, 30% to 39%, and <30%) were identified as independent predictors, were assigned points, and were grouped into 3 categories, where the incidence of OHCA ranged from 0.12% to 2.0% and non-OHCA death from 0.76% to 11.7%. Stratified by LVEF <40% alone, the incidence of OHCA was 0.20% and 0.76% and for non-OHCA death 1.1% and 4.9%.
Conclusions
In this nationwide study, the incidence of OHCA within 90 days after MI was <0.3%. A total of 5 clinical parameters in addition to LVEF predicted OHCA and non-OHCA death better than LVEF alone.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Dec 2020; 76:2926-2936
Faxén J, Jernberg T, Hollenberg J, Gadler F, Herlitz J, Szummer K
J Am Coll Cardiol: 21 Dec 2020; 76:2926-2936 | PMID: 33334420
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Abstract

Reliability of Office, Home, and Ambulatory Blood Pressure Measurements and Correlation With Left Ventricular Mass.

Schwartz JE, Muntner P, Kronish IM, Burg MM, ... Bigger JT, Shimbo D
Background
Determining the reliability and predictive validity of office blood pressure (OBP), ambulatory BP (ABP), and home BP (HBP) can inform which is best for diagnosing hypertension and estimating risk of cardiovascular disease.
Objectives
This study aimed to assess the reliability of OBP, HBP, and ABP and evaluate their associations with left ventricular mass index (LVMI) in untreated persons.
Methods
The Improving the Detection of Hypertension (IDH) study, a community-based observational study, enrolled 408 participants who had OBP assessed at 3 visits, and completed 3 weeks of HBP, 2 24-h ABP recordings, and a 2-dimensional echocardiogram. Mean age was 41.2 ± 13.1 years, 59.5% were women, 25.5% African American, and 64.0% Hispanic.
Results
The reliability of 1 week of HBP, 3 office visits with mercury sphygmomanometry, and 24-h ABP were 0.938, 0.894, and 0.846 for systolic and 0.918, 0.847, and 0.843 for diastolic BP, respectively. The correlations among OBP, HBP, and ABP, corrected for regression dilution bias, were 0.74 to 0.89. After multivariable adjustment including OBP and 24-h ABP, 10 mm Hg higher systolic and diastolic HBP were associated with 5.07 (standard error [SE]: 1.48) and 3.92 (SE: 2.14) g/m higher LVMI, respectively. After adjustment for HBP, neither systolic or diastolic OBP nor ABP was associated with LVMI.
Conclusions
OBP, HBP, and ABP assess somewhat distinct parameters. Compared with OBP (3 visits) or 24-h ABP, systolic and diastolic HBP (1 week) were more reliable and more strongly associated with LVMI. These data suggest that 1 week of HBP monitoring may be the best approach for diagnosing hypertension.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Dec 2020; 76:2911-2922
Schwartz JE, Muntner P, Kronish IM, Burg MM, ... Bigger JT, Shimbo D
J Am Coll Cardiol: 21 Dec 2020; 76:2911-2922 | PMID: 33334418
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Abstract

Inflammatory Bowel Disease and Atherosclerotic Cardiovascular Disease: JACC Review Topic of the Week.

Cainzos-Achirica M, Glassner K, Zawahir HS, Dey AK, ... Mehta NN, Nasir K

Chronic inflammatory diseases including human immunodeficiency virus infection, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus predispose to atherosclerotic cardiovascular disease (ASCVD). Inflammatory bowel disease (IBD) is a common chronic inflammatory condition, and the United States has the highest prevalence worldwide. IBD has so far been overlooked as a contributor to the burden of ASCVD among young and middle-age adults, but meta-analyses of cohort studies suggest that IBD is an independent risk factor for ASCVD. This review discusses the epidemiological links between IBD and ASCVD and potential mechanisms underlying these associations. ASCVD risk management of patients with IBD is challenging because of their young age and the inability of current risk scores to fully capture their increased risk. The role of IBD in current primary prevention guidelines is evaluated, and strategies for enhanced ASCVD risk reduction in patients with IBD are outlined. Finally, the authors discuss knowledge gaps and future research directions in this innovative field.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 14 Dec 2020; 76:2895-2905
Cainzos-Achirica M, Glassner K, Zawahir HS, Dey AK, ... Mehta NN, Nasir K
J Am Coll Cardiol: 14 Dec 2020; 76:2895-2905 | PMID: 33303079
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Abstract

Cardiopulmonary Impact of Particulate Air Pollution in High-Risk Populations: JACC State-of-the-Art Review.

Newman JD, Bhatt DL, Rajagopalan S, Balmes JR, ... Zhang J, Brook RD

Fine particulate air pollution <2.5 μm in diameter (PM) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 14 Dec 2020; 76:2878-2894
Newman JD, Bhatt DL, Rajagopalan S, Balmes JR, ... Zhang J, Brook RD
J Am Coll Cardiol: 14 Dec 2020; 76:2878-2894 | PMID: 33303078
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Abstract

Unconventional Natural Gas Development and Hospitalization for Heart Failure in Pennsylvania.

McAlexander TP, Bandeen-Roche K, Buckley JP, Pollak J, ... McEvoy JW, Schwartz BS
Background
Growing literature linking unconventional natural gas development (UNGD) to adverse health has implicated air pollution and stress pathways. Persons with heart failure (HF) are susceptible to these stressors.
Objectives
This study sought to evaluate associations between UNGD activity and hospitalization among HF patients, stratified by both ejection fraction (EF) status (reduced [HFrEF], preserved [HFpEF], not classifiable) and HF severity.
Methods
We evaluated the odds of hospitalization among patients with HF seen at Geisinger from 2008 to 2015 using electronic health records. We assigned metrics of UNGD activity by phase (pad preparation, drilling, stimulation, and production) 30 days before hospitalization or a frequency-matched control selection date. We assigned phenotype status using a validated algorithm.
Results
We identified 9,054 patients with HF with 5,839 hospitalizations (mean age 71.1 ± 12.7 years; 47.7% female). Comparing 4th to 1st quartiles, adjusted odds ratios (95% confidence interval) for hospitalization were 1.70 (1.35 to 2.13), 0.97 (0.75 to 1.27), 1.80 (1.35 to 2.40), and 1.62 (1.07 to 2.45) for pad preparation, drilling, stimulation, and production metrics, respectively. We did not find effect modification by HFrEF or HFpEF status. Associations of most UNGD metrics with hospitalization were stronger among those with more severe HF at baseline.
Conclusions
Three of 4 phases of UNGD activity were associated with hospitalization for HF in a large sample of patients with HF in an area of active UNGD, with similar findings by HFrEF versus HFpEF status. Older patients with HF seem particularly vulnerable to adverse health impacts from UNGD activity.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Dec 2020; 76:2862-2874
McAlexander TP, Bandeen-Roche K, Buckley JP, Pollak J, ... McEvoy JW, Schwartz BS
J Am Coll Cardiol: 14 Dec 2020; 76:2862-2874 | PMID: 33303076
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Abstract

Transcatheter Pulmonary Valve Replacement With the Sapien Prosthesis.

Shahanavaz S, Zahn EM, Levi DS, Aboulhousn JA, ... Balzer DT, McElhinney DB
Background
There are limited published data focused on outcomes of transcatheter pulmonary valve replacement (TPVR) with either a Sapien XT or Sapien 3 (S3) valve.
Objectives
This study sought to report short-term outcomes in a large cohort of patients who underwent TPVR with either a Sapien XT or S3 valve.
Methods
Data were entered retrospectively into a multicenter registry for patients who underwent attempted TPVR with a Sapien XT or S3 valve. Patient-related, procedural, and short-term outcomes data were characterized overall and according to type of right ventricular outflow tract (RVOT) anatomy.
Results
Twenty-three centers enrolled a total of 774 patients: 397 (51%) with a native/patched RVOT; 183 (24%) with a conduit; and 194 (25%) with a bioprosthetic valve. The S3 was used in 78% of patients, and the XT was used in 22%, with most patients receiving a 29-mm (39%) or 26-mm (34%) valve. The implant was technically successful in 754 (97.4%) patients. Serious adverse events were reported in 67 patients (10%), with no difference between RVOT anatomy groups. Fourteen patients underwent urgent surgery. Nine patients had a second valve implanted. Among patients with available data, tricuspid valve injury was documented in 11 (1.7%), and 9 others (1.3%) had new moderate or severe regurgitation 2 grades higher than pre-implantation, for 20 (3.0%) total patients with tricuspid valve complications. Valve function at discharge was excellent in most patients, but 58 (8.5%) had moderate or greater pulmonary regurgitation or maximum Doppler gradients >40 mm Hg. During limited follow-up (n = 349; median: 12 months), 9 patients were diagnosed with endocarditis, and 17 additional patients underwent surgical valve replacement or valve-in-valve TPVR.
Conclusions
Acute outcomes after TPVR with balloon-expandable valves were generally excellent in all types of RVOT. Additional data and longer follow-up will be necessary to gain insight into these issues.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Dec 2020; 76:2847-2858
Shahanavaz S, Zahn EM, Levi DS, Aboulhousn JA, ... Balzer DT, McElhinney DB
J Am Coll Cardiol: 14 Dec 2020; 76:2847-2858 | PMID: 33303074
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Abstract

Echocardiography-Guided Risk Stratification for Long QT Syndrome.

Sugrue A, van Zyl M, Enger N, Mancl K, ... Asirvatham SJ, Ackerman MJ
Background
The ability to identify those patients at the highest phenotypic risk for long QT syndrome (LQTS)-associated life-threatening cardiac events remains suboptimal.
Objectives
This study sought to validate the association between electromechanical window (EMW) negativity, as derived from echocardiography, and symptomatic versus asymptomatic status in patients with LQTS.
Methods
We analyzed a cohort of 651 patients with LQTS (age 26 ± 17 years; 60% females; 158 symptomatic; 51% LQTS type 1; 33% LQTS type 2; 11% LQTS type 3; 5% multiple mutations) and 50 healthy controls. EMW was calculated as the difference between the interval from QRS onset to aortic valve closure midline, as derived for continuous-wave Doppler, and the electrocardiogram-derived QT interval for the same beat.
Results
A negative EMW was found among nearly all patients with LQTS compared to controls, with more profound EMW negativity in patients with symptomatic LQTS compared to those with asymptomatic LQTS (-52 ± 38 ms vs. -18 ± 29 ms; p < 0.0001). Logistic regression identified EMW, heart rate-corrected QT interval (QTc), female sex, and LQTS genotype as univariate predictors of symptomatic status. After multivariate analysis, EMW remained an independent predictor of symptomatic status (odds ratio for each 10-ms decrease in EMW: 1.37; 95% confidence interval: 1.27 to 1.48; p < 0.0001). EMW outperformed QTc in predicting symptomatic patients (area under the curve: 0.78 vs. 0.70; p = 0.01). After training and implementation, EMW correlation from echocardiographic sonographers showed excellent reliability (intraclass correlation coefficient: 0.93; 95% confidence interval: 0.89 to 0.96).
Conclusions
In this validation study, patients with a history of LQTS-associated life-threatening cardiac events had a more profoundly negative EMW. EMW outperformed heart rate-corrected QT interval as a predictor of symptomatic status. EMW is now a clinically validated risk factor. In December 2019, our institution\'s echocardiography clinical practice committee approved use of EMW for patients with LQTS, making it a routinely reported echocardiographic finding.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Dec 2020; 76:2834-2843
Sugrue A, van Zyl M, Enger N, Mancl K, ... Asirvatham SJ, Ackerman MJ
J Am Coll Cardiol: 14 Dec 2020; 76:2834-2843 | PMID: 33303072
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Abstract

Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction.

Rossitto G, Mary S, McAllister C, Neves KB, ... Petrie MC, Delles C
Background
Microvascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated.
Objectives
This study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na excess.
Methods
Patients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na, and K) analyses; and 2) venous occlusion plethysmography to assess peripheral microvascular filtration coefficient (measuring capillary fluid extravasation) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation).
Results
Skin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue × min × mm Hg vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue × min × mm Hg; p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue × min × mm Hg vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue × min × mm Hg; p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001).
Conclusions
Peripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target.

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

J Am Coll Cardiol: 14 Dec 2020; 76:2817-2829
Rossitto G, Mary S, McAllister C, Neves KB, ... Petrie MC, Delles C
J Am Coll Cardiol: 14 Dec 2020; 76:2817-2829 | PMID: 33303070
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Abstract

Impact of Plaque Burden Versus Stenosis on Ischemic Events in Patients With Coronary Atherosclerosis.

Mortensen MB, Dzaye O, Steffensen FH, Bøtker HE, ... Blaha MJ, Nørgaard BL
Background
Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value.
Objectives
The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC).
Methods
Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease.
Results
During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD.
Conclusions
Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Dec 2020; 76:2803-2813
Mortensen MB, Dzaye O, Steffensen FH, Bøtker HE, ... Blaha MJ, Nørgaard BL
J Am Coll Cardiol: 14 Dec 2020; 76:2803-2813 | PMID: 33303068
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Abstract

2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

, Otto CM, Nishimura RA, Bonow RO, ... Thompson A, Toly C
Aim
This executive summary of the valvular heart disease guideline provides recommendations for clinicians to diagnose and manage valvular heart disease as well as supporting documentation to encourage their use.
Methods
A comprehensive literature search was conducted from January 1, 2010, to March 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected database relevant to this guideline.
Structure
Many recommendations from the earlier valvular heart disease guidelines have been updated with new evidence and provides newer options for diagnosis and treatment of valvular heart disease. This summary includes only the recommendations from the full guideline which focus on diagnostic work-up, the timing and choice of surgical and catheter interventions, and recommendations for medical therapy. The reader is referred to the full guideline for graphical flow charts, text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in developing these guidelines.

Copyright © 2020 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Dec 2020; epub ahead of print
, Otto CM, Nishimura RA, Bonow RO, ... Thompson A, Toly C
J Am Coll Cardiol: 09 Dec 2020; epub ahead of print | PMID: 33342587
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Abstract

Associations of Late Adolescent or Young Adult Cardiovascular Health With Premature Cardiovascular Disease and Mortality.

Perak AM, Ning H, Khan SS, Bundy JD, ... Van Horn LV, Lloyd-Jones DM
Background
When measured in adolescence or young adulthood, cardiovascular health (CVH) is associated with future subclinical cardiovascular disease (CVD), but data are lacking regarding CVD events or mortality.
Objectives
This study examined associations of CVH at ages 18 to 30 years with premature CVD and mortality.
Methods
This study analyzed data from the CARDIA (Coronary Artery Risk Development in Young Adults Study). CVH was scored at baseline (1985 to 1986) using Life\'s Simple 7 metrics and categorized as high (12 to 14 points), moderate (8 to 11), or low (0 to 7). CVD events and cause-specific mortality were adjudicated over 32 years of follow-up. Adjusted associations were estimated using Cox models and event rates and population attributable fractions were calculated by CVH category.
Results
Among 4,836 participants (mean age: 24.9 years, 54.8% female, 50.5% Black, mean education: 15.2 years), baseline CVH was high (favorable) in 28.8%, moderate in 65.0%, and low in 6.3%. During follow-up, 306 CVD events and 431 deaths occurred. The adjusted hazard ratios for high (vs. low) CVH were 0.14 (95% confidence interval [CI]: 0.09 to 0.22) for CVD and 0.07 (95% CI: 0.03 to 0.19) for CVD mortality, and the population attributable fractions for combined moderate or low (vs. high) CVH were 0.63 (95% CI: 0.47 to 0.74) for CVD and 0.81 (95% CI: 0.55 to 0.92) for CVD mortality. Among individuals with high CVH, event rates were low across sociodemographic subgroups (e.g., CVD rates per 1,000 person-years: age 18 to 24 years, 0.64; age 25 to 30 years, 0.65; men, 1.04; women, 0.36; Blacks, 0.90; Whites, 0.50; up to/through high-school education, 1.00; beyond high-school education, 0.61).
Conclusions
High CVH in late adolescence or young adulthood was associated with very low rates of premature CVD and mortality over 32 years, indicating the critical importance of maintaining high CVH.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Dec 2020; 76:2695-2707
Perak AM, Ning H, Khan SS, Bundy JD, ... Van Horn LV, Lloyd-Jones DM
J Am Coll Cardiol: 07 Dec 2020; 76:2695-2707 | PMID: 33181243
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Impact:
Abstract

Early Feasibility Studies for Cardiovascular Devices in the United States: JACC State-of-the-Art Review.

Holmes DR, Farb AA, Chip Hance R, Leon MB, ... Walkowiak J, Mack MJ

The development of technology to treat unmet clinical patient needs in the United States has been an important focus for the U.S. Food and Drug Administration and the 2016 Congressional 21st Century Cures Act. In response, a program of early feasibility studies (EFS) has been developed. One of the important issues has been the outmigration of the development and testing of medical devices from the United States. The EFS committee has developed and implemented processes to address issues to develop strategies for early treatment of these patient groups. Initial implementation of the U.S. Food and Drug Administration EFS program has been successful, but residual significant problems have hindered the opportunity to take full advantage of the program. These include delays in gaining Institutional Review Board approval, timeliness of budget and contractual negotiations, and lack of access to and enrollment of study subjects. This paper reviews improvements that have been made to the U.S. EFS ecosystem and outlines potential approaches to address remaining impediments to program success.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Dec 2020; 76:2786-2794
Holmes DR, Farb AA, Chip Hance R, Leon MB, ... Walkowiak J, Mack MJ
J Am Coll Cardiol: 07 Dec 2020; 76:2786-2794 | PMID: 33272373
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Impact:
Abstract

Post-Stroke Cardiovascular Complications and Neurogenic Cardiac Injury: JACC State-of-the-Art Review.

Sposato LA, Hilz MJ, Aspberg S, Murthy SB, ... Scheitz JF,

Over 1.5 million deaths worldwide are caused by neurocardiogenic syndromes. Furthermore, the consequences of deleterious brain-heart interactions are not limited to fatal complications. Cardiac arrhythmias, heart failure, and nonfatal coronary syndromes are also common. The brain-heart axis is implicated in post-stroke cardiovascular complications known as the stroke-heart syndrome, sudden cardiac death, and Takotsubo syndrome, among other neurocardiogenic syndromes. Multiple pathophysiological mechanisms with the potential to be targeted with novel therapies have been identified in the last decade. In the present state-of-the-art review, we describe recent advances in the understanding of anatomical and functional aspects of the brain-heart axis, cardiovascular complications after stroke, and a comprehensive pathophysiological model of stroke-induced cardiac injury.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Dec 2020; 76:2768-2785
Sposato LA, Hilz MJ, Aspberg S, Murthy SB, ... Scheitz JF,
J Am Coll Cardiol: 07 Dec 2020; 76:2768-2785 | PMID: 33272372
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Abstract

Hemodynamic and Clinical Implications of Impaired Pulmonary Vascular Reserve in the Fontan Circulation.

Egbe AC, Miranda WR, Anderson JH, Borlaug BA
Background
Pulmonary vascular disease, pulmonary endothelial dysfunction, liver fibrosis, renal disease, and exercise intolerance are common in adults with Fontan physiology. Although the pathophysiologic mechanisms linking these phenomena have been studied, certain aspects are not well understood.
Objectives
This study hypothesized that impaired pulmonary vascular reserve (VR) plays a central role linking these abnormalities, and that patients with abnormal pulmonary VR with exercise, compared with patients with normal VR, would display poorer pulmonary endothelial function, greater liver stiffness, more renal dysfunction, and poorer exercise capacity.
Methods
Symptomatic adults with the Fontan palliation (n = 29) underwent invasive cardiopulmonary exercise testing, echocardiography, and assessment of microvascular function. Abnormal pulmonary VR was defined by the slope of increase in pulmonary pressure relative to cardiac output with exercise >3 mm Hg/l/min. Pulmonary endothelial function was assessed using reactive hyperemia index. End-organ function was assessed using magnetic resonance elastography-derived liver stiffness, glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and peak oxygen consumption (Vo).
Results
Compared with individuals with normal VR (n = 8), those with abnormal VR (n = 21) displayed higher central and pulmonary venous pressures, and more severely impaired cardiac output and stroke volume responses to exertion, but similar pulmonary vascular resistance at rest. Patients with abnormal VR displayed more severely impaired reactive hyperemia index, increased liver stiffness, lower glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, and lower peak Vo. As compared to pulmonary vascular resistance at rest, slope of increase in pulmonary pressure relative to cardiac output displayed stronger correlations with reactive hyperemia index (r = -0.63 vs. r = -0.31; Meng test p = 0.009), magnetic resonance elastography-derived liver stiffness (r = 0.47 vs. r = 0.29; Meng test p = 0.07), glomerular filtration rate (r = -0.52 vs. r = -0.24; Meng test p = 0.03), N-terminal pro-B-type natriuretic peptide (r = 0.56 vs. r = 0.17; Meng test p = 0.02), and peak Vo (r = -0.63 vs. r = -0.26; Meng test p = 0.02).
Conclusions
Pulmonary vascular limitations in Fontan physiology are related to pulmonary endothelial and end-organ dysfunction, suggesting a mechanistic link between these commonly observed findings, and these abnormalities are more apparent during exercise testing, with little relationship at rest.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Dec 2020; 76:2755-2763
Egbe AC, Miranda WR, Anderson JH, Borlaug BA
J Am Coll Cardiol: 07 Dec 2020; 76:2755-2763 | PMID: 33272370
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Abstract

Effect of Empagliflozin on Hemodynamics in Patients With Heart Failure and Reduced Ejection Fraction.

Omar M, Jensen J, Frederiksen PH, Kistorp C, ... Schou M, Møller JE
Background
Inhibition of the sodium-glucose cotransporter-2 (SGLT2i) improves outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but the mechanism by which they improve outcomes remains unclear.
Objectives
This study aimed to investigate the effects of sodium-glucose cotransporter-2 inhibitor empagliflozin on central hemodynamics in patients with HF and HFrEF.
Methods
This investigator-initiated, double-blinded, placebo-controlled, randomized trial enrolled 70 patients with HFrEF from March 6, 2018, to September 10, 2019. Patients were assigned to empagliflozin of 10 mg or matching placebo once daily on guideline-driven HF therapy for 12 weeks. The primary outcome was ratio of pulmonary capillary wedge pressure (PCWP) to cardiac index (CI) at peak exercise after 12 weeks. Patients underwent right-heart catheterization at rest and during exercise at baseline and 12-week follow-up.
Results
Patients with HFrEF, mean age of 57 years, mean left-ventricular ejection fraction, 26%, and 12 (17%) with type 2 diabetes mellitus were randomized. There was no significant treatment effect on peak PCWP/CI (-0.13 mm Hg/l/min/m; 95% confidence interval: -1.60 to 1.34 mm Hg/l/min/m; p = 0.86). Considering hemodynamics over the full range of exercise loads, PCWP was significantly reduced (-2.40 mm Hg; 95% confidence interval: -3.96 to -0.84 mm Hg; p = 0.003), but not CI (-0.09 l/min/m; 95% confidence interval: -0.14 to 0.32 l/min/m; p = 0.448) by empagliflozin. This was consistent among patients with and without type 2 diabetes.
Conclusions
Among patients with stable HFrEF, empagliflozin for 12 weeks reduced PCWP compared with placebo. There was no significant improvement in neither CI nor PCWP/CI at rest or exercise.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Dec 2020; 76:2740-2751
Omar M, Jensen J, Frederiksen PH, Kistorp C, ... Schou M, Møller JE
J Am Coll Cardiol: 07 Dec 2020; 76:2740-2751 | PMID: 33272368
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Abstract

VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins.

Balling M, Afzal S, Varbo A, Langsted A, Davey Smith G, Nordestgaard BG
Background
Plasma apolipoprotein B (apoB) is a composite measure of all apoB-containing lipoproteins causing atherosclerotic cardiovascular disease; however, it is unclear which fraction of risk is explained by cholesterol and triglycerides, respectively, in very low-density lipoproteins (VLDLs).
Objectives
The authors tested the hypothesis that VLDL cholesterol and triglycerides each explain part of the myocardial infarction risk from apoB-containing lipoproteins.
Methods
Nested within 109,751 individuals from the Copenhagen General Population Study, the authors examined 25,480 subjects free of lipid-lowering therapy and myocardial infarction at study entry. All had measurements of plasma apoB (quantitating number of apoB-containing lipoproteins) and cholesterol and triglyceride content of VLDL, intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs).
Results
During a median 11 years of follow-up, 1,816 were diagnosed with myocardial infarction. Per 1-mmol/l higher levels, multivariable-adjusted hazard ratios for myocardial infarction were 2.07 (95% confidence interval [CI]: 1.81 to 2.36) for VLDL cholesterol, 1.19 (95% CI: 1.14 to 1.25) for VLDL triglycerides, 5.38 (95% CI: 3.73 to 7.75) for IDL cholesterol, and 1.86 (95% CI: 1.62 to 2.14) for LDL cholesterol. Per 1-g/l higher plasma apoB, the corresponding value was 2.21 (95% CI: 1.90 to 2.58). In a step-up Cox regression, risk factors for myocardial infarction entered by importance as VLDL cholesterol, systolic blood pressure, smoking, and IDL + LDL cholesterol, whereas VLDL triglycerides did not enter the model. VLDL cholesterol explained 50% and IDL + LDL cholesterol 29% of the risk of myocardial infarction from apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk.
Conclusions
VLDL cholesterol explained one-half of the myocardial infarction risk from elevated apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 07 Dec 2020; 76:2725-2735
Balling M, Afzal S, Varbo A, Langsted A, Davey Smith G, Nordestgaard BG
J Am Coll Cardiol: 07 Dec 2020; 76:2725-2735 | PMID: 33272366
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Abstract

Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease.

Castañer O, Pintó X, Subirana I, Amor AJ, ... Ortega E, Fitó M
Background
Genetic, observational, and clinical intervention studies indicate that circulating levels of triglycerides and cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol) can predict cardiovascular events.
Objectives
This study evaluated the association of triglycerides and remnant cholesterol (remnant-C) with major cardiovascular events in a cohort of older individuals at high cardiovascular risk.
Methods
This study determined the baseline lipid profile and searched for major adverse cardiovascular events (MACEs) in the high-risk primary prevention PREDIMED (Prevención con Dieta Mediterránea) trial population (mean age: 67 years; body mass index: 30 kg/m; 43% men; 48% with diabetes) after a median follow-up of 4.8 years. Unadjusted and adjusted Cox proportional hazard models were used to assess the association between lipid concentrations (either as continuous or categorical variables) and incident MACEs (N = 6,901; n cases = 263).
Results
In multivariable-adjusted analyses, triglycerides (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.06, per 10 mg/dl [0.11 mmol/l]; p < 0.001), non-high-density lipoprotein cholesterol (HDL-C) (HR: 1.05; 95% CI: 1.01 to 1.10, per 10 mg/dl [0.26 mmol/l]; p = 0.026), and remnant-C (HR: 1.21; 95% CI: 1.10 to 1.33, per 10 mg/dl [0.26 mmol/l]; p < 0.001), but not low-density lipoprotein cholesterol (LDL-C) or HDL-C, were associated with MACEs. Atherogenic dyslipidemia (triglycerides >150 mg/dl [1.69 mmol/l] and HDL-C <40 mg/dl [1.03 mmol/l] in men or <50 mg/dl [1.29 mmol/l] in women) was also associated with MACEs (HR: 1.44; 95% CI: 1.04 to 2.00; p = 0.030). Remnant-C ≥30 mg/dl (0.78 mmol/l) differentiated subjects at a higher risk of MACEs compared with those at lower concentrations, regardless of whether LDL-C levels were on target at ≤100 mg/dl (2.59 mmol/l).
Conclusions
In overweight or obese subjects at high cardiovascular risk, levels of triglycerides and remnant-C, but not LDL-C, were associated with cardiovascular outcomes independent of other risk factors.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 07 Dec 2020; 76:2712-2724
Castañer O, Pintó X, Subirana I, Amor AJ, ... Ortega E, Fitó M
J Am Coll Cardiol: 07 Dec 2020; 76:2712-2724 | PMID: 33272365
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Abstract

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

Roth GA, Mensah GA, Johnson CO, Addolorato G, ... Fuster V,

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.

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

J Am Coll Cardiol: 02 Dec 2020; epub ahead of print
Roth GA, Mensah GA, Johnson CO, Addolorato G, ... Fuster V,
J Am Coll Cardiol: 02 Dec 2020; epub ahead of print | PMID: 33309175
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Abstract

Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease.

Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, ... Stone GW,
Background
Coronary calcification hinders stent delivery and expansion and is associated with adverse outcomes. Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhancing vessel compliance and optimizing stent deployment.
Objectives
The purpose of this study was to assess the safety and effectiveness of IVL in severely calcified de novo coronary lesions.
Methods
Disrupt CAD III (NCT03595176) was a prospective, single-arm multicenter study designed for regulatory approval of coronary IVL. The primary safety endpoint was freedom from major adverse cardiovascular events (cardiac death, myocardial infarction, or target vessel revascularization) at 30 days. The primary effectiveness endpoint was procedural success. Both endpoints were compared with a pre-specified performance goal (PG). The mechanism of calcium modification was assessed in an optical coherence tomography (OCT) substudy.
Results
Patients (n = 431) were enrolled at 47 sites in 4 countries. The primary safety endpoint of the 30-day freedom from major adverse cardiovascular events was 92.2%; the lower bound of the 95% confidence interval was 89.9%, which exceeded the PG of 84.4% (p < 0.0001). The primary effectiveness endpoint of procedural success was 92.4%; the lower bound of the 95% confidence interval was 90.2%, which exceeded the PG of 83.4% (p < 0.0001). Mean calcified segment length was 47.9 ± 18.8 mm, calcium angle was 292.5 ± 76.5°, and calcium thickness was 0.96 ± 0.25 mm at the site of maximum calcification. OCT demonstrated multiplane and longitudinal calcium fractures after IVL in 67.4% of lesions. Minimum stent area was 6.5 ± 2.1 mm and was similar regardless of demonstrable fractures on OCT.
Conclusions
Coronary IVL safely and effectively facilitated stent implantation in severely calcified lesions.

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

J Am Coll Cardiol: 30 Nov 2020; 76:2635-2646
Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, ... Stone GW,
J Am Coll Cardiol: 30 Nov 2020; 76:2635-2646 | PMID: 33069849
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Abstract

Pre-Pregnancy Hypertension Among Women in Rural and Urban Areas of the United States.

Cameron NA, Molsberry R, Pierce JB, Perak AM, ... Lloyd-Jones DM, Khan SS
Background
Rates of maternal mortality are increasing in the United States with significant rural-urban disparities. Pre-pregnancy hypertension is a well-established risk factor for adverse maternal and offspring outcomes.
Objectives
The purpose of this study was to describe trends in maternal pre-pregnancy hypertension among women in rural and urban areas in 2007 to 2018 in order to inform community-engaged prevention and policy strategies.
Methods
We performed a nationwide, serial cross-sectional study using maternal data from all live births in women age 15 to 44 years between 2007 and 2018 (CDC Natality Database). Rates of pre-pregnancy hypertension were calculated per 1,000 live births overall and by urbanization status. Subgroup analysis in standard 5-year age categories was performed. We quantified average annual percentage change using Joinpoint Regression and rate ratios (95% confidence intervals [CIs]) to compare yearly rates between rural and urban areas.
Results
Among 47,949,381 live births to women between 2007 and 2018, rates of pre-pregnancy hypertension per 1,000 live births increased among both rural (13.7 to 23.7) and urban women (10.5 to 20.0). Two significant inflection points were identified in 2010 and 2016, with highest annual percentage changes between 2016 and 2018 in rural and urban areas. Although absolute rates were lower in younger compared with older women in both rural and urban areas, all age groups experienced similar increases. The rate ratios of pre-pregnancy hypertension in rural compared with urban women ranged from 1.18 (95% CI: 1.04 to 1.35) for ages 15 to 19 years to 1.51 (95% CI: 1.39 to 1.64) for ages 40 to 44 years in 2018.
Conclusions
Maternal burden of pre-pregnancy hypertension has nearly doubled in the past decade and the rural-urban gap has persisted.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 30 Nov 2020; 76:2611-2619
Cameron NA, Molsberry R, Pierce JB, Perak AM, ... Lloyd-Jones DM, Khan SS
J Am Coll Cardiol: 30 Nov 2020; 76:2611-2619 | PMID: 33183896
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Abstract

Cardiopulmonary Hemodynamics in Pulmonary Hypertension and Heart Failure: JACC Review Topic of the Week.

Maron BA, Kovacs G, Vaidya A, Bhatt DL, ... Guazzi M, Tedford RJ

Pulmonary hypertension (PH) is an independent risk factor for adverse clinical outcome, particularly in left heart disease (LHD) patients. Recent advances have clarified the mean pulmonary artery pressure (mPAP) range that is above normal and is associated with clinical events, including mortality. This progress has for the first time resulted in a new clinical definition of PH that is evidenced-based, is inclusive of mPAP >20 mm Hg, and emphasizes early diagnosis. Additionally, pulmonary vascular resistance (PVR) 2.2 to 3.0 WU, considered previously to be normal, appears to associate with elevated clinical risk. A revised approach to classifying PH patients as pre-capillary, isolated post-capillary, or combined pre-/post-capillary PH now guides point-of-care diagnosis, risk stratification, and treatment. Exercise hemodynamic or confrontational fluid challenge studies may also aid decision-making for patients with PH-LHD or otherwise unexplained dyspnea. This collective progress in pulmonary vascular and heart failure medicine reinforces the critical importance of accurate hemodynamic assessment.

Published by Elsevier Inc.

J Am Coll Cardiol: 30 Nov 2020; 76:2671-2681
Maron BA, Kovacs G, Vaidya A, Bhatt DL, ... Guazzi M, Tedford RJ
J Am Coll Cardiol: 30 Nov 2020; 76:2671-2681 | PMID: 33243385
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Abstract

Risk Factors for Morbidity and Mortality Following Hospitalization for Pericarditis.

Sigvardt FL, Hansen ML, Kristensen SL, Gustafsson F, ... Gislason GH, Madelaire C
Background
Viral or idiopathic pericarditis is a frequent condition, often considered benign, although prior studies have suggested that pericarditis is associated with both cardiovascular and noncardiovascular disease, for example, malignancy.
Objectives
This study sought to assess mortality risk and morbidity patterns in patients with incident viral or idiopathic pericarditis.
Methods
In nationwide Danish registries, we identified patients discharged with a first-time diagnosis of pericarditis from 1996 to 2016. Patients with a severe underlying heart condition were excluded. The patients were matched 1:10 with individuals from the general population by sex and year of birth. We assessed 5-year mortality using Kaplan-Meier and Cox proportional hazards models adjusted for baseline comorbidities and identified subsequent hospital admissions.
Results
We identified 7,988 patients with pericarditis and 79,880 matched control individuals. The absolute 5-year survival probability was 92.9% and 95.8% in the pericarditis and control groups, respectively (adjusted hazard ratio: 1.31; 95% confidence interval: 1.13 to 1.52). The greatest difference in mortality was seen the first year, and it was primarily driven by the female part of the population. The incidence rate per 1,000 person-years of new-onset, admission-required diagnosis was higher in the pericarditis group both for cardiovascular and noncardiovascular diseases.
Conclusions
We observed a higher mortality risk over 5 years in the pericarditis group, especially among the female patients, compared to matched control individuals. Furthermore, we observed a higher frequency of both cardiovascular and noncardiovascular hospital admissions, highlighting the need for focus on underlying morbidity in patients presenting with apparent viral or idiopathic pericarditis.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 30 Nov 2020; 76:2623-2631
Sigvardt FL, Hansen ML, Kristensen SL, Gustafsson F, ... Gislason GH, Madelaire C
J Am Coll Cardiol: 30 Nov 2020; 76:2623-2631 | PMID: 33243382
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Abstract

Pulmonary Hypertension in Transcatheter Mitral Valve Repair for Secondary Mitral Regurgitation: The COAPT Trial.

Ben-Yehuda O, Shahim B, Chen S, Liu M, ... Mack MJ, Stone GW
Background
Pulmonary hypertension worsens prognosis in patients with heart failure (HF) and secondary mitral regurgitation (SMR).
Objectives
This study sought to determine whether baseline pulmonary hypertension influences outcomes of transcatheter mitral valve repair (TMVr) in patients with HF with SMR.
Methods
In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, 614 patients with HF with moderate-to-severe or severe SMR were randomized to TMVr with the MitraClip plus guideline-directed medical therapy (GDMT) (n = 302) versus GDMT alone (n = 312). Baseline pulmonary artery systolic pressure (PASP) estimated from echocardiography was categorized as substantially increased (≥50 mm Hg) versus not substantially increased (<50 mm Hg).
Results
Among 528 patients, 184 (82 TMVr, 102 GDMT) had PASP of ≥50 mm Hg (mean: 59.1 ± 8.8 mm Hg) and 344 (171 TMVr, 173 GDMT) had PASP of <50 mm Hg (mean: 36.3 ± 8.1 mm Hg). Patients with PASP of ≥50 mm Hg had higher 2-year rates of death or HF hospitalization (HFH) compared to those with PASP of <50 mm Hg (68.8% vs. 49.1%; adjusted hazard ratio: 1.52; 95% confidence interval: 1.17 to 1.97; p = 0.002). Rates of death or HFH were reduced by TMVr versus GDMT alone, irrespective of baseline PASP (p = 0.45). TMVr reduced PASP from baseline to 30 days to a greater than GDMT alone (adjusted least squares mean: -4.0 vs. -0.9 mm Hg; p = 0.006), a change that was associated with reduced risk of death or HFH between 30 days and 2 years (adjusted hazard ratio: 0.91 per -5 mm Hg PASP; 95% confidence interval: 0.86 to 0.96; p = 0.0009).
Conclusions
Elevated PASP is associated with a worse prognosis in patients with HF with severe SMR. TMVr with the MitraClip reduced 30-day PASP and 2-year rates of death or HFH compared with GDMT alone, irrespective of PASP.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 30 Nov 2020; 76:2595-2606
Ben-Yehuda O, Shahim B, Chen S, Liu M, ... Mack MJ, Stone GW
J Am Coll Cardiol: 30 Nov 2020; 76:2595-2606 | PMID: 33243380
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Abstract

Brain Injury After Transcatheter Replacement of Bicuspid Versus Tricuspid Aortic Valves.

Fan J, Fang X, Liu C, Zhu G, ... Wang J, Leon MB
Background
An increasing number of bicuspid aortic valve (BAV) patients are undergoing transcatheter aortic valve replacement (TAVR), but the risk of brain injury in diffusion-weighted magnetic resonance imaging (DW-MRI) is currently unknown.
Objectives
This study sought to evaluate the risk of brain injury in BAV patients following TAVR.
Methods
A total of 204 consecutive severe aortic stenosis patients who underwent TAVR were enrolled. A total of 83 (40.7%) patients were BAV patients, and the other 121 patients were tricuspid aortic valve (TAV) patients. All patients received DW-MRI at baseline, and after TAVR.
Results
Median ages (76 years [interquartile range (IQR): 71 to 81 years] vs. 79 years [IQR: 74 to 83 years]; p = 0.004) and Society of Thoracic Surgeons scores (4.87 [IQR: 3.72 to 8.54] vs. 6.38 [IQR: 3.96 to 9.50]; p = 0.044) of the BAV and TAV patients were significantly different, while the overt stroke rates (2.4% vs. 1.7%; p = 0.704) were comparable between the 2 groups. BAV patients were associated with higher number of new lesions (4.0 [IQR: 1.0 to 8.0] vs. 2.0 [IQR: 1.0 to 5.0]; p = 0.008), total lesion volume (290 mm [IQR: 70 to 930 mm] vs. 140 mm [IQR: 35 to 480 mm]; p = 0.008), and the volume per lesion (70.0 mm [IQR: 45.0 to 115.0 mm] vs. 57.5 mm [IQR: 24.5 to 93.0 mm]; p = 0.037) in DW-MRI. Moreover, the proportion of patients with lesions larger than 1 cm (28.6% vs. 10.9%; p = 0.005) was higher in BAV patients than in TAV patients.
Conclusions
BAV patients may encounter more severe brain injuries not only due to greater number of lesions, but also due to larger lesion size in the early phase after TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294).

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

J Am Coll Cardiol: 30 Nov 2020; 76:2579-2590
Fan J, Fang X, Liu C, Zhu G, ... Wang J, Leon MB
J Am Coll Cardiol: 30 Nov 2020; 76:2579-2590 | PMID: 33243378
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Abstract

TEMPORARY REMOVAL: 2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Solution Set Oversight Committee.

, Kumbhani DJ, Cannon CP, Beavers CJ, ... Spinler SA, Thourani VH

This article has been temporarily removed as it was inadvertently posted ahead of an agreed-upon embargo. The article will be reinstated upon embargo expiry. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 25 Nov 2020; epub ahead of print
, Kumbhani DJ, Cannon CP, Beavers CJ, ... Spinler SA, Thourani VH
J Am Coll Cardiol: 25 Nov 2020; epub ahead of print | PMID: 33250267
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Abstract

TEMPORARY NOTICE: 2020 ACC/AHA/SVM/ACP Advanced Training Statement on Vascular Medicine (Revision of the 2004 ACC/ACP/SCAI/SVMB/SVS Clinical Competence Statement on Vascular Medicine and Catheter-Based Peripheral Vascular Interventions): A Report of the ACC Competency Management Committee.

, Creager MA, Hamburg NM, Calligaro KD, ... White Solaru K, Williams MS

This article has been temporarily removed as it was inadvertently posted ahead of an agreed-upon embargo. The article will be reinstated upon embargo expiry. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Copyright © 2020 American College of Cardiology Foundation, American Heart Association, Inc., and Society for Vascular Medicine. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 25 Nov 2020; epub ahead of print
, Creager MA, Hamburg NM, Calligaro KD, ... White Solaru K, Williams MS
J Am Coll Cardiol: 25 Nov 2020; epub ahead of print | PMID: 33250266
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Abstract

TEMPORARY NOTICE: 2021 ACC/AHA Key Data Elements and Definitions for Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Heart Failure).

, Bozkurt B, Hershberger RE, Butler J, ... Heidenreich PA, Weintraub WS

This article has been temporarily removed as it was inadvertently posted ahead of an agreed-upon embargo. The article will be reinstated upon embargo expiry. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 25 Nov 2020; epub ahead of print
, Bozkurt B, Hershberger RE, Butler J, ... Heidenreich PA, Weintraub WS
J Am Coll Cardiol: 25 Nov 2020; epub ahead of print | PMID: 33250265
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Impact:
Abstract

Timing of Oral P2Y Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

Tarantini G, Mojoli M, Varbella F, Caporale R, ... ,
Background
Although oral P2Y inhibitors are key in the management of patients with non-ST-segment elevation acute coronary syndrome, the optimal timing of their administration is not well defined.
Objectives
The purpose of this study was to compare downstream and upstream oral P2Y inhibitors administration strategies in patients with non-ST-segment elevation acute coronary syndrome undergoing invasive treatment.
Methods
We performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit).
Results
We randomized 1,449 patients to downstream or upstream oral P2Y inhibitor administration. A pre-specified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke; and Bleeding Academic Research Consortium type 3, 4, and 5 bleeding through day 30, did not differ significantly between the downstream and upstream groups (percent absolute risk reduction: -0.46; 95% repeated confidence interval: -2.90 to 1.90). These results were confirmed among patients undergoing percutaneous coronary intervention (72% of population) and regardless of the timing of coronary angiography (within or after 24 h from enrollment).
Conclusions
Downstream and upstream oral P2Y inhibitor administration strategies were associated with low incidence of ischemic and bleeding events and minimal numeric difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of 1 strategy over the other. (Downstream Versus Upstream Strategy for the Administration of P2Y Receptor Blockers In Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication [DUBIUS]; NCT02618837).

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 23 Nov 2020; 76:2450-2459
Tarantini G, Mojoli M, Varbella F, Caporale R, ... ,
J Am Coll Cardiol: 23 Nov 2020; 76:2450-2459 | PMID: 32882390
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Impact:
Abstract

STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement.

Carroll JD, Mack MJ, Vemulapalli S, Herrmann HC, ... Brindis RG, Bavaria JE

The STS-ACC TVT Registry (Society of Thoracic Surgeons-American College of Cardiology Transcatheter Valve Therapy Registry) from 2011 to 2019 has collected data on 276,316 patients undergoing transcatheter aortic valve replacement (TAVR) at sites in all U.S. states. Volumes have increased every year, exceeding surgical aortic valve replacement in 2019 (72,991 vs. 57,626), and it is now performed in all U.S. states. TAVR now extends from extreme- to low-risk patients. This is the first presentation on 8,395 low-risk patients treated in 2019. In 2019, for the entire cohort, femoral access increased to 95.3%, hospital stay was 2 days, and 90.3% were discharged home. Since 2011, the 30-day mortality rate has decreased (7.2% to 2.5%), stroke has started to decrease (2.75% to 2.3%), but pacemaker need is unchanged (10.9% to 10.8%). Alive with acceptable patient-reported outcomes is achieved in 8 of 10 patients at 1 year. The Registry is a national resource to improve care and analyze TAVR\'s evolution. Real-world outcomes, site performance, and the impact of coronavirus disease 2019 will be subsequently studied. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528).

Copyright © 2020 Society of Thoracic Surgeons and the American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 23 Nov 2020; 76:2492-2516
Carroll JD, Mack MJ, Vemulapalli S, Herrmann HC, ... Brindis RG, Bavaria JE
J Am Coll Cardiol: 23 Nov 2020; 76:2492-2516 | PMID: 33213729
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Impact:
Abstract

The Effect of Blood Lipids on the Left Ventricle: A Mendelian Randomization Study.

Aung N, Sanghvi MM, Piechnik SK, Neubauer S, Munroe PB, Petersen SE
Background
Cholesterol and triglycerides are among the most well-known risk factors for cardiovascular disease.
Objectives
This study investigated whether higher low-density lipoprotein (LDL) cholesterol and triglyceride levels and lower high-density lipoprotein cholesterol level are causal risk factors for changes in prognostically important left ventricular (LV) parameters.
Methods
One-sample Mendelian randomization (MR) of 17,311 European individuals from the UK Biobank with paired lipid and cardiovascular magnetic resonance data was performed. Two-sample MR was performed by using summary-level data from the Global Lipid Genetics Consortium (n = 188,577) and UK Biobank Cardiovascular Magnetic Resonance substudy (n = 16,923) for sensitivity analyses.
Results
In 1-sample MR analysis, higher LDL cholesterol was causally associated with higher LV end-diastolic volume (β = 1.85 ml; 95% confidence interval [CI]: 0.59 to 3.14 ml; p = 0.004) and higher LV mass (β = 0.81 g; 95% CI: 0.11 to 1.51 g; p = 0.023) and triglycerides with higher LV mass (β = 1.37 g; 95% CI: 0.45 to 2.3 g; p = 0.004). High-density lipoprotein cholesterol had no significant association with any LV parameter. Similar results were obtained by using 2-sample MR. Observational analyses were frequently discordant with those derived from MR.
Conclusions
MR analysis demonstrates that LDL cholesterol and triglycerides are associated with adverse changes in cardiac structure and function, in particular in relation to LV mass. These findings suggest that LDL cholesterol and triglycerides may have a causal effect in influencing cardiac morphology in addition to their established role in atherosclerosis.

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

J Am Coll Cardiol: 23 Nov 2020; 76:2477-2488
Aung N, Sanghvi MM, Piechnik SK, Neubauer S, Munroe PB, Petersen SE
J Am Coll Cardiol: 23 Nov 2020; 76:2477-2488 | PMID: 33213727
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Abstract

Acute Kidney Injury After Percutaneous Edge-to-Edge Mitral Repair.

Armijo G, Estevez-Loureiro R, Carrasco-Chinchilla F, Arzamendi D, ... Pan M, Nombela-Franco L
Background
In catheter-based procedures, acute kidney injury (AKI) is a frequent, serious complication ranging from 10% to 30%. In MitraClip (Abbott Vascular, Santa Clara, California), a usually contrast-free procedure, there is scarce data about its real incidence and impact.
Objectives
This study aimed to evaluate incidence, predictive factors, and midterm outcomes of AKI in patients with significant mitral regurgitation (MR) undergoing transcatheter valve repair with MitraClip.
Methods
A total of 721 patients undergoing MitraClip were included. AKI was defined as an absolute or a relative increase in serum creatinine of >0.3 mg/dl or ≥50%, respectively, or the need for hemodialysis during index hospitalization.
Results
The mean age of the patients was 72 ± 11 years (28.3% women). Median estimated glomerular filtration rate (eGFR) was 43.7 ml/min/1.73 m (interquartile range: 30.9 to 60.1 ml/min/1.73 m), and was <60 ml/min/1.73 m in 74.9% of the patients. AKI after MitraClip occurred in 106 patients (14.7%). Baseline hemoglobin (<11 g/dl) (odds ratio [OR]: 1.97; p = 0.003), urgent procedure (OR: 3.44; p = 0.003), and absence of device success (OR: 3.37; p < 0.001) were independent predictors of AKI. Patients with AKI had worse outcomes compared to those without AKI, including a higher proportion of in-hospital bleeding events (3.8% vs. 0.8%; p = 0.011), 2-year all-cause mortality (40.5% vs. 18.7%; p <0.001), and major adverse cardiac events (63.6% vs. 23.5%; p <0.001). Combination of AKI with significant residual MR after the procedure conferred even worst outcomes (2-year all-cause mortality 50.0% vs. 19.6%; p = 0.001, and major adverse cardiac events 70.0% vs. 18.9%; p < 0.001).
Conclusions
Despite being a \"zero-contrast\" procedure, one-sixth of patients undergoing transcatheter mitral valve repair had AKI, linked to device failure or other severe conditions. The occurrence of AKI was associated with worse outcomes, highlighting the importance to detect and reduce this complication in high-risk population.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 23 Nov 2020; 76:2463-2473
Armijo G, Estevez-Loureiro R, Carrasco-Chinchilla F, Arzamendi D, ... Pan M, Nombela-Franco L
J Am Coll Cardiol: 23 Nov 2020; 76:2463-2473 | PMID: 33213725
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Impact:
Abstract

Ticagrelor or Prasugrel in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

Valina C, Neumann FJ, Menichelli M, Mayer K, ... Schüpke S, Kastrati A
Background
Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI).
Objectives
This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management.
Methods
This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5.
Results
The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month.
Conclusions
In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800).

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 23 Nov 2020; 76:2436-2446
Valina C, Neumann FJ, Menichelli M, Mayer K, ... Schüpke S, Kastrati A
J Am Coll Cardiol: 23 Nov 2020; 76:2436-2446 | PMID: 33213722
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Impact:
Abstract

Incorporating Coronary Calcification Into Pre-Test Assessment of the Likelihood of Coronary Artery Disease.

Winther S, Schmidt SE, Mayrhofer T, Bøtker HE, ... Bøttcher M, Knuuti J
Background
The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients referred for diagnostic testing has declined, warranting optimization of individualized diagnostic strategies.
Objectives
This study sought to present a simple, clinically applicable tool enabling estimation of the likelihood of obstructive CAD by combining a pre-test probability (PTP) model (Diamond-Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score (CACS).
Methods
The new tool was developed in a cohort of symptomatic patients (n = 41,177) referred for diagnostic testing. The risk factor-weighted clinical likelihood (RF-CL) was calculated through PTP and risk factors, while the CACS-weighted clinical likelihood (CACS-CL) added CACS. The 2 calculation models were validated in European and North American cohorts (n = 15,411) and compared with a recently updated PTP table.
Results
The RF-CL and CACS-CL models predicted the prevalence of obstructive CAD more accurately in the validation cohorts than the PTP model, and markedly increased the area under the receiver-operating characteristic curves of obstructive CAD: for the PTP model, 72 (95% confidence intervals [CI]: 71 to 74); for the RF-CL model, 75 (95% CI: 74 to 76); and for the CACS-CL model, 85 (95% CI: 84 to 86). In total, 38% of the patients in the RF-CL group and 54% in the CACS-CL group were categorized as having a low clinical likelihood of CAD, as compared with 11% with the PTP model.
Conclusions
A simple risk factor and CACS-CL tool enables improved prediction and discrimination of patients with suspected obstructive CAD. The tool empowers reclassification of patients to low likelihood of CAD, who need no further testing.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 23 Nov 2020; 76:2421-2432
Winther S, Schmidt SE, Mayrhofer T, Bøtker HE, ... Bøttcher M, Knuuti J
J Am Coll Cardiol: 23 Nov 2020; 76:2421-2432 | PMID: 33213720
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Impact:
Abstract

Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque.

Stone GW, Maehara A, Ali ZA, Held C, ... Erlinge D,
Background
Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild.
Objectives
This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques.
Methods
Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel-related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up.
Results
A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy-IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm, and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm compared with 3.0 ± 1.0 mm in GDMT alone-treated lesions (least square means difference: 3.9 mm; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone-treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion-related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone-treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12).
Conclusions
PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Nov 2020; 76:2289-2301
Stone GW, Maehara A, Ali ZA, Held C, ... Erlinge D,
J Am Coll Cardiol: 16 Nov 2020; 76:2289-2301 | PMID: 33069847
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Impact:
Abstract

2020 ACC Expert Consensus Decision Pathway on Management of Conduction Disturbances in Patients Undergoing Transcatheter Aortic Valve Replacement: A Report of the American College of Cardiology Solution Set Oversight Committee.

Lilly SM, Deshmukh AJ, Epstein AE, Ricciardi MJ, ... Velagapudi P, Wyman JF

Consensus regarding a reasonable strategy to manage cardiac conduction disturbances after transcatheter aortic valve replacement (TAVR) has been elusive. This is due to the absence of adequately powered, randomized controlled trials; the often transient nature of the conduction disturbances; evolving technologies; and the interplay of cardiology subspecialties involved. In the absence of high-quality trials, numerous practice styles have been developed, and prolonged observation, electrophysiological testing, and pre-emptive pacemaker implantation have been described. Although the 2013 European Society of Cardiology guidelines address pacing post-TAVR, they do not provide in-depth discussion of this topic. Furthermore, a summary and proposed strategy for this problem have not been published by cardiovascular societies in the United States, despite an interest in establishing best practices in TAVR, valvular heart disease, and cardiovascular implantable electrical devices. This document reviews existing data and experience regarding the management of conduction disturbances after TAVR and proposes an evidence-based expert consensus decision pathway for their management. Where evidence is lacking or insufficient, the recommendations herein are based on expert opinion.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Nov 2020; 76:2391-2411
Lilly SM, Deshmukh AJ, Epstein AE, Ricciardi MJ, ... Velagapudi P, Wyman JF
J Am Coll Cardiol: 16 Nov 2020; 76:2391-2411 | PMID: 33190683
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Impact:
Abstract

Interpreting the Kansas City Cardiomyopathy Questionnaire in Clinical Trials and Clinical Care: JACC State-of-the-Art Review.

Spertus JA, Jones PG, Sandhu AT, Arnold SV

To improve the patient-centeredness of care, patient-reported outcomes have been increasingly used to quantify patients\' symptoms, function, and quality of life. In heart failure, the Kansas City Cardiomyopathy Questionnaire (KCCQ) has been qualified by the U.S. Food and Drug Administration as a Clinical Outcome Assessment and recommended as a performance measure for quantifying the quality of care. By systematically asking the same questions reproducibly over time, the KCCQ can validly and sensitively capture the impact of heart failure on patients\' lives and is strongly associated with clinical events over time. This review describes how to interpret the KCCQ, how it should be analyzed in clinical trials to maximize the interpretability of results, and how it can be used in clinical practice and population health. By providing a deeper understanding of the KCCQ, it is hoped that its use can further improve the patient-centeredness of heart failure care.

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

J Am Coll Cardiol: 16 Nov 2020; 76:2379-2390
Spertus JA, Jones PG, Sandhu AT, Arnold SV
J Am Coll Cardiol: 16 Nov 2020; 76:2379-2390 | PMID: 33183512
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Impact:
Abstract

Clinical Features and Outcomes of Peripartum Cardiomyopathy in Nigeria.

Karaye KM, Sa\'idu H, Balarabe SA, Ishaq NA, ... Stewart S,
Background
Nigeria has the highest incidence of peripartum cardiomyopathy (PPCM) in the world. However, data on PPCM-related outcomes are limited.
Objectives
The purpose of this study was to examine the clinical profile, myocardial remodeling, and survival of patients with PPCM in Nigeria.
Methods
This study consecutively recruited 244 PPCM patients (median 7 months postpartum) at 14 sites in Nigeria and applied structured follow-up for a median of 17 months (interquartile range: 14 to 20 months). Left ventricular reverse remodeling (LVRR) was defined as the composite of left ventricular (LV) end-diastolic dimension <33 mm/m and absolute increase in left ventricular ejection fraction (LVEF) ≥10%. LV full recovery was defined as LVEF ≥55%.
Results
Overall, 45 (18.7%) patients died during follow-up. Maternal age <20 years (hazard ratio [HR]: 2.40; 95% confidence interval (CI): 1.27 to 4.54), hypotension (HR: 1.87; 95% CI: 1.02 to 3.43), tachycardia (HR: 2.38; 95% CI: 1.05 to 5.43), and LVEF <25% at baseline (HR: 2.11; 95% CI: 1.12 to 3.95) independently predicted mortality. Obesity (HR: 0.16; 95% CI: 0.04 to 0.55) and regular use of beta-blockers at 6-month follow-up (HR: 0.20; 95% CI: 0.09 to 0.41) were independently associated with reduced risk for mortality. In total, 48 patients (24.1%) achieved LVRR and 45 (22.6%) achieved LV full recovery. LVEF <25% at baseline (HR: 0.66; 95% CI: 0.47 to 0.92) and regular use of beta-blockers at 6-month follow-up (HR: 1.62; 95% CI: 1.17 to 2.25) independently determined the risk for LV full recovery. Progressive reverse remodeling of all cardiac chambers was observed. In total, 18 patients (7.4%) were hospitalized during the study.
Conclusions
This is the largest study of PPCM in Africa. Consistent with late presentations, the mortality rate was high, whereas frequencies of LVRR and LV full recovery were low. Several variables predicted poor outcomes, and regular use of beta-blockers correlated with late survival and LV functional recovery.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 16 Nov 2020; 76:2352-2364
Karaye KM, Sa'idu H, Balarabe SA, Ishaq NA, ... Stewart S,
J Am Coll Cardiol: 16 Nov 2020; 76:2352-2364 | PMID: 33183509
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Impact:
Abstract

Transcatheter Bariatric Embolotherapy for Weight Reduction in Obesity.

Reddy VY, Neužil P, Musikantow D, Sramkova P, ... Kipshidze N, Fried M
Background
Obesity is well-appreciated to result in poor cardiovascular and metabolic outcomes. Dietary and medical weight loss strategies are frequently unsuccessful and unsustainable. Bariatric surgery is quite effective, but is reserved for the most obese patients because of the associated intraoperative/post-operative risks. In preclinical and early clinical case series, a novel therapy, transcatheter bariatric embolotherapy (TBE) of the left gastric artery, has been reported to promote weight loss by reducing ghrelin, an appetite-stimulating hormone secreted from the gastric fundus.
Objectives
The purpose of this study was to examine TBE in a single-blind, sham procedure randomized trial.
Methods
Obese subjects (body mass index 35 to 55 kg/m) were randomized 1:1 to either sham or TBE targeting the left gastric artery using an occlusion balloon microcatheter to administer 300- to 500-μm embolic beads. All patients entered a lifestyle counseling program. Patients and physicians performing follow-up were blind to the allocated therapy. Endoscopy was performed at baseline and 1-week post-procedure. The primary endpoint was 6-month total body weight loss (TBWL).
Results
Eligible subjects (n = 44; age 45.5 ± 9.4 years; 8 men/36 women; body mass index 39.6 ± 3.8 kg/m) were randomized to undergo the sham or TBE procedure with no device-related complications and 1 vascular complication. Patients reported mild nausea and vomiting, and endoscopy revealed only minor self-limiting ulcers in 5 patients. At 6 months, in both the intention-to-treat and per-protocol populations, the TBWL was greater with TBE (7.4 kg/6.4% and 9.4 kg/8.3% loss, respectively) than sham (3.0 kg/2.8% and 1.9 kg/1.8%, respectively; p = 0.034/0.052 and p = 0.0002/0.0011, respectively). The TBWL was maintained with TBE at 12 months (intention-to-treat 7.8 kg/6.5% loss, per-protocol 9.3 kg/9.3% loss; p = 0.0011/0.0008, p = 0.0005/0.0005, respectively).
Conclusions
In this randomized pilot trial, we have established the proof-of-principle that transcatheter bariatric embolotherapy of the left gastric artery is well-tolerated and promotes clinically significant weight loss over a sham procedure.(The Lowering Weight in Severe Obesity by Embolization of the Gastric Artery Trial [LOSEIT]; NCT03185949).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Nov 2020; 76:2305-2317
Reddy VY, Neužil P, Musikantow D, Sramkova P, ... Kipshidze N, Fried M
J Am Coll Cardiol: 16 Nov 2020; 76:2305-2317 | PMID: 33183504
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Impact:
Abstract

Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy.

Thavendiranathan P, Negishi T, Somerset E, Negishi K, ... Marwick TH,
Background
In patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardio-protective therapy (CPT) is constrained by the low sensitivity of EF for minor changes in LV function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT.
Objective
To identify whether GLS-guided CPT prevents reduction in LVEF in patients undergoing potentially cardiotoxic chemotherapy, compared with usual care.
Methods
In this international multicenter prospective randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n=166) or >10% absolute reduction of LVEF (n=165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction >5% or >10% asymptomatic to <55%) over 1 year.
Results
Of 331 randomized patients, 2 died and 22 withdrew consent or were lost to follow-up. Among 307 patients (age 54±12 years, 94% women, baseline LVEF 59±6%, GLS -20.6±2.4%) with a median (IQR) follow-up of 1.02 (0.98-1.07) years, most (n=278) had breast cancer. HF risk factors were prevalent: 29% had hypertension and 13% had diabetes mellitus. At 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the two arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs 13.7%, p=0.02), and 1-year EF was 57±6% versus 55±7% (p=0.05). Patients diagnosed with CTRCD in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1±10.9% versus 2.9±7.4%, p=0.03).
Conclusions
Although the change in LVEF was not different between the two arms, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 15 Nov 2020; epub ahead of print
Thavendiranathan P, Negishi T, Somerset E, Negishi K, ... Marwick TH,
J Am Coll Cardiol: 15 Nov 2020; epub ahead of print | PMID: 33220426
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Impact:
Abstract

Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization.

Oyama K, Furtado RHM, Fagundes A, Zelniker TA, ... Sabatine MS, Bergmark BA
Background
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors induce plaque regression and reduce the risk of coronary revascularization overall.
Objectives
To evaluate the ability of PCSK9 inhibitors to reduce the risk of complex coronary atherosclerosis requiring revascularization.
Methods
FOURIER was a randomized trial of the PCSK9 inhibitor evolocumab vs. placebo in 27,564 patients with stable atherosclerosis on statin therapy followed for a median of 2.2 years. Clinical documentation of revascularization events was blindly reviewed to assess coronary anatomy and procedural characteristics. Complex revascularization was the composite of complex percutaneous coronary intervention (PCI) (as per previous analyses, >1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm) or coronary artery bypass grafting surgery (CABG).
Results
1,724 patients underwent coronary revascularization, including 1482 who underwent PCI, 296 who underwent CABG, and 54 both. Complex revascularization was performed in 632 (37%) patients. Evolocumab reduced the risk of any coronary revascularization by 22% (HR 0.78 [0.71-0.86]; P<0.001), simple PCI by 22% (HR 0.78, [0.70-0.88]; P<0.001), complex PCI by 33% (HR 0.67 [0.54-0.84]; P<0.001), CABG by 24% (HR 0.76 [0.60-0.96]; P=0.019), and complex revascularization by 29% (HR 0.71 [0.61-0.84]; P<0.001). The magnitude of the risk reduction with evolocumab in complex revascularization tended to increase over time (20%, 36%, and 41% risk reductions in 1, 2 and beyond 2 year).
Conclusions
Adding evolocumab to statin therapy significantly reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 10 Nov 2020; epub ahead of print
Oyama K, Furtado RHM, Fagundes A, Zelniker TA, ... Sabatine MS, Bergmark BA
J Am Coll Cardiol: 10 Nov 2020; epub ahead of print | PMID: 33197560
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Impact:
Abstract

Cardio-Oncology Education and Training: JACC Council Perspectives.

Alvarez-Cardona JA, Ray J, Carver J, Zaha V, ... Herrmann J,

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 09 Nov 2020; 76:2267-2281
Alvarez-Cardona JA, Ray J, Carver J, Zaha V, ... Herrmann J,
J Am Coll Cardiol: 09 Nov 2020; 76:2267-2281 | PMID: 33153587
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Abstract

Evaluation and Management of Patients With Stable Angina: Beyond the Ischemia Paradigm: JACC State-of-the-Art Review.

Ferraro R, Latina JM, Alfaddagh A, Michos ED, ... Fuster V, Arbab-Zadeh A

Coronary heart disease is a chronic, systemic disease with a wide range of associated symptoms, clinical outcomes, and health care expenditure. Adverse events from coronary heart disease can be mitigated or avoided with lifestyle and risk factor modifications, and medical therapy. These measures are effective in slowing the progression of atherosclerotic disease and in reducing the risk of thrombosis in the setting of plaque disruptions. With increasing effectiveness of prevention and medical therapy, the role of coronary artery revascularization has decreased and is largely confined to subgroups of patients with unacceptable angina, severe left ventricular systolic dysfunction, or high-risk coronary anatomy. There is a compelling need to allocate resources appropriately to improve prevention. Herein, we review the scientific evidence in support of medical therapy and revascularization for the management of patients with stable coronary heart disease and discuss implications for the evaluation of patients with stable angina and public policy.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Nov 2020; 76:2252-2266
Ferraro R, Latina JM, Alfaddagh A, Michos ED, ... Fuster V, Arbab-Zadeh A
J Am Coll Cardiol: 09 Nov 2020; 76:2252-2266 | PMID: 33153586
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Abstract

Congenital Muscular Mitral-Aortic Discontinuity Identified in Patients With Obstructive Hypertrophic Cardiomyopathy.

Ferrazzi P, Spirito P, Binaco I, Zyrianov A, ... Boni L, Iascone M
Background
The mitral valve is often structurally abnormal in hypertrophic cardiomyopathy (HCM). However, the mechanisms responsible for these abnormalities remain controversial. In 2016 we identified, at myectomy, muscular mitral-aortic discontinuity in 5 young patients with obstructive HCM.
Objectives
This study sought to confirm our preliminary findings and assess the prevalence of muscular mitral-aortic discontinuity in obstructive HCM.
Methods
At our center, from January 2017 to April 2018, the area between the anterior mitral leaflet and aortic valve was inspected at myectomy in 106 consecutive patients with HCM.
Results
Muscular mitral-aortic discontinuity was identified in 28 (26%) patients and was significantly more common in younger than older patients (age 39 ± 13 years vs. 58 ± 11 years; p < 0.001). Muscular discontinuity was present in each of 6 patients aged <30 years but only 1 (2.7%) of 37 aged ≥60 years. Pathogenic sarcomere mutations were identified in 22 (79%) of 28 patients with and 24 (31%) of 78 without discontinuity (p < 0.001) and were associated with discontinuity independently of age (p = 0.021). Discontinuity mean length was 7.3 mm and was inversely related to age (p = 0.022). At echocardiography, the anterior mitral leaflet was longer in patients with than those without discontinuity (34 ± 4 mm vs. 29 ± 5 mm; p < 0.001).
Conclusions
We report, for the first time, muscular mitral-aortic discontinuity in HCM. At myectomy, a long muscular discontinuity displaced the anterior mitral leaflet toward the apex in most young patients, was significantly associated with sarcomere mutations independent of age, and was extremely uncommon in older patients. These findings suggest that a long muscular mitral-aortic discontinuity could predispose to the development of outflow obstruction in young patients with sarcomere mutations.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Nov 2020; 76:2238-2247
Ferrazzi P, Spirito P, Binaco I, Zyrianov A, ... Boni L, Iascone M
J Am Coll Cardiol: 09 Nov 2020; 76:2238-2247 | PMID: 33153584
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Abstract

Lack of Association of Spontaneous Coronary Artery Dissection With Autoimmune Disease.

Kronzer VL, Tarabochia AD, Lobo Romero AS, Tan NY, ... Hayes SN, Tweet MS
Background
Case reports and referral-based studies suggest spontaneous coronary artery dissection (SCAD) is associated with autoimmune diseases and causes 2% to 4% of acute coronary syndromes.
Objectives
This study determined the association of SCAD with autoimmune diseases, together with incidence and recurrence, in a population-based study.
Methods
This case-control study took place from 1995 to 2018 within the Rochester Epidemiology Project. The study identified cases with SCAD from diagnosis codes and verified them using coronary angiography images, matching each case to 3 control subjects on age, sex, county, and years of medical history. Autoimmune disease history came from a validated, code-based definition. A multivariable logistic regression model calculated the odds ratio (OR) for SCAD among patients with a history of autoimmune disease, adjusting for race and body mass index.
Results
The study identified 114 cases with SCAD (mean age 51 years and 90% women) and 342 matched control subjects. Autoimmune disease occurred in 13 (11%) cases with SCAD and 40 (12%) control subjects (p = 0.93). Even after adjustment, autoimmune diseases were not associated with SCAD (OR: 0.81; 95% confidence interval [CI]: 0.40 to 1.66). SCAD incidence between 2010 and 2018 (2.7 per 100,000; 95% CI: 1.7 to 3.7) was 10-fold higher than the incidence between 1995 and 2009 (0.3 per 100,000; 95% CI: 0.0 to 0.6). SCAD recurrence was 10% (95% CI: 3% to 16%) at 5 years.
Conclusions
These findings suggested SCAD pathogenesis is noninflammatory and screening for autoimmune diseases based on SCAD alone is not warranted. The code-based incidence of SCAD has increased over time, highlighting the importance of considering SCAD among patients with acute coronary syndromes.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Nov 2020; 76:2226-2234
Kronzer VL, Tarabochia AD, Lobo Romero AS, Tan NY, ... Hayes SN, Tweet MS
J Am Coll Cardiol: 09 Nov 2020; 76:2226-2234 | PMID: 33153582
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Abstract

Complicated Carotid Artery Plaques as a Cause of Cryptogenic Stroke.

Kopczak A, Schindler A, Bayer-Karpinska A, Koch ML, ... Dichgans M, Saam T
Background
The underlying etiology of ischemic stroke remains unknown in up to 30% of patients.
Objectives
This study explored the causal role of complicated (American Heart Association-lesion type VI) nonstenosing carotid artery plaques (CAPs) in cryptogenic stroke (CS).
Methods
CAPIAS (Carotid Plaque Imaging in Acute Stroke) is an observational multicenter study that prospectively recruited patients aged older than 49 years with acute ischemic stroke that was restricted to the territory of a single carotid artery on brain magnetic resonance imaging (MRI) and unilateral or bilateral CAP (≥2 mm, NASCET [North American Symptomatic Carotid Endarterectomy Trial] <70%). CAP characteristics were determined qualitatively and quantitatively by high-resolution, contrast-enhanced carotid MRI at 3T using dedicated surface coils. The pre-specified study hypotheses were that that the prevalence of complicated CAP would be higher ipsilateral to the infarct than contralateral to the infarct in CS and higher in CS compared with patients with cardioembolic or small vessel stroke (CES/SVS) as a combined reference group. Patients with large artery stroke (LAS) and NASCET 50% to 69% stenosis served as an additional comparison group.
Results
Among 234 recruited patients, 196 had either CS (n = 104), CES/SVS (n = 79), or LAS (n = 19) and complete carotid MRI data. The prevalence of complicated CAP in patients with CS was significantly higher ipsilateral (31%) to the infarct compared with contralateral to the infarct (12%; p = 0.0005). Moreover, the prevalence of ipsilateral complicated CAP was significantly higher in CS (31%) compared with CES/SVS (15%; p = 0.02) and lower in CS compared with LAS (68%; p = 0.003). Lipid-rich and/or necrotic cores in ipsilateral CAP were significantly larger in CS compared with CES/SVS (p < 0.05).
Conclusions
These findings substantiate the role of complicated nonstenosing CAP as an under-recognized cause of stroke. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933).

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

J Am Coll Cardiol: 09 Nov 2020; 76:2212-2222
Kopczak A, Schindler A, Bayer-Karpinska A, Koch ML, ... Dichgans M, Saam T
J Am Coll Cardiol: 09 Nov 2020; 76:2212-2222 | PMID: 33153580
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Abstract

Influence of LDL-Cholesterol Lowering on Cardiovascular Outcomes in Patients With Diabetes Mellitus Undergoing Coronary Revascularization.

Farkouh ME, Godoy LC, Brooks MM, Mancini GBJ, ... Boden WE, Fuster V
Background
Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular events, especially in high-risk populations.
Objectives
This study sought to evaluate the influence of LDL-C on the incidence of cardiovascular events either following a coronary revascularization procedure (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or optimal medical therapy alone in patients with established coronary heart disease and type 2 diabetes (T2DM).
Methods
Patient-level pooled analysis of 3 randomized clinical trials was undertaken. Patients with T2DM were categorized according to the levels of LDL-C at 1 year following randomization. The primary endpoint was major adverse cardiac or cerebrovascular events ([MACCE] the composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke).
Results
A total of 4,050 patients were followed for a median of 3.9 years after the index 1-year assessment. Patients whose 1-year LDL-C remained ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE (17.2% vs. 13.3% vs. 13.1% for LDL-C between 70 and <100 mg/dl and LDL-C <70 mg/dl, respectively; p = 0.016). When compared with optimal medical therapy alone, patients with PCI experienced a MACCE reduction only if 1-year LDL-C was <70 mg/dl (hazard ratio: 0.61; 95% confidence interval: 0.40 to 0.91; p = 0.016), whereas CABG was associated with improved outcomes across all 1-year LDL-C strata. In patients with 1-year LDL-C ≥70 mg/dl, patients undergoing CABG had significantly lower MACCE rates as compared with PCI.
Conclusions
In patients with coronary heart disease with T2DM, lower LDL-C at 1 year is associated with improved long-term MACCE outcome in those eligible for either PCI or CABG. When compared with optimal medical therapy alone, PCI was associated with MACCE reductions only in those who achieved an LDL-C <70 mg/dl.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 09 Nov 2020; 76:2197-2207
Farkouh ME, Godoy LC, Brooks MM, Mancini GBJ, ... Boden WE, Fuster V
J Am Coll Cardiol: 09 Nov 2020; 76:2197-2207 | PMID: 33153578
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Abstract

Dietary Inflammatory Potential and Risk of Cardiovascular Disease Among Men and Women in the U.S.

Li J, Lee DH, Hu J, Tabung FK, ... Giovannucci EL, Hu FB
Background
Inflammation plays an important role in cardiovascular disease (CVD) development. Diet modulates inflammation; however, it remains unknown whether dietary patterns with higher inflammatory potential are associated with long-term CVD risk.
Objectives
This study sought to examine whether proinflammatory diets are associated with increased CVD risk.
Methods
We prospectively followed 74,578 women from the Nurses\' Health Study (NHS) (1984-2016), 91,656 women from the NHSII (1991-2015), and 43,911 men from the Health Professionals Follow-up Study (1986-2016) who were free of CVD and cancer at baseline. Diet was assessed by food frequency questionnaires every 4 years. The inflammatory potential of diet was evaluated using a food-based empirical dietary inflammatory pattern (EDIP) score that was pre-defined based on levels of 3 systemic inflammatory biomarkers.
Results
During 5,291,518 person-years of follow-up, we documented 15,837 incident CVD cases, including 9,794 coronary heart disease (CHD) cases and 6,174 strokes. In pooled analyses of the 3 cohorts, after adjustment for use of anti-inflammatory medications and CVD risk factors including body mass index, a higher dietary inflammatory potential, as indicated by higher EDIP scores, was associated with an increased risk of CVD (hazard ratio [HR] comparing the highest to lowest quintiles: 1.38; 95% confidence interval [CI]: 1.31 to 1.46; p for trend <0.001), CHD (HR: 1.46; 95% CI: 1.36 to 1.56; p for trend <0.001), and stroke (HR: 1.28; 95% CI: 1.17- to 1.39; p for trend <0.001). These associations were consistent across cohorts and between sexes, and they remained significant after further adjustment for other dietary quality indices. In a subset of study participants (n = 33,719), a higher EDIP was associated with a higher circulating profile of proinflammatory biomarkers, lower levels of adiponectin, and an unfavorable blood lipid profile (p < 0.001).
Conclusions
Dietary patterns with a higher proinflammatory potential were associated with higher CVD risk. Reducing the inflammatory potential of the diet may potentially provide an effective strategy for CVD prevention.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Nov 2020; 76:2181-2193
Li J, Lee DH, Hu J, Tabung FK, ... Giovannucci EL, Hu FB
J Am Coll Cardiol: 09 Nov 2020; 76:2181-2193 | PMID: 33153576
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Abstract

Randomized Trial of Empagliflozin in Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction.

Santos-Gallego CG, Vargas-Delgado AP, Requena JA, Garcia-Ropero A, ... Badimon JJ,
Background
Large clinical trials established the benefits of SGLT2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia OBJECTIVES: To assess the effect of empagliflozin on LV function and volumes, functional capacity and quality of life (QoL) in non-diabetic HFrEF patients.
Methods
In this double-blind, placebo-controlled trial, non-diabetic HFrEF patients (n=84) were randomized to empagliflozin or placebo for six months. The primary endpoint was change in left ventricle end-diastolic volume (LVEDV) and left ventricle end-systolic volume (LVESV) assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LVEF, peak oxygen consumption in the cardiopulmonary exercise test, 6-minute walk test, and quality of life
Results:
Empagliflozin was associated with a significant reduction of LVEDV (-25.1±26.0 vs -1.5±25.4mL for empagliflozin vs placebo, respectively, p<0.001) and LVESV (-26.6±20.5 vs -0.5±21.9 mL for empagliflozin vs placebo, p<0.001). Empagliflozin was associated with reductions in LV mass (-17.8±31.9 vs 4.1±13.4 g, for empagliflozin vs placebo, respectively, p<0.001) and improvements in LVEF (6±4.2 vs -0.1±3.9 p<0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1±2.6 vs -0.5±1.9mL/min/kg for empagliflozin vs placebo, respectively, p=0.017), oxygen uptake efficiency slope (111±267 vs -146±318, p<0.001), as well as in 6-minute walk test (81±64 vs -35±68 meters, p<0.001) and quality of life (KCCQ-12: 21±18 vs 2±15, p<0.001).
Conclusions
Empagliflozin administration to non-diabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for SGLT2 inhibitors in the treatment of HFrEF patients independently of their glycemic status.
Condensed abstract
In this double-blind, placebo-controlled, randomized EMPATROPISM clinical trial, empagliflozin administration to non-diabetic HFrEF patients on top of optimal medical treatment ameliorated cardiac remodeling, reduced LV volumes, decreased LV mass, increased LV systolic function, enhanced functional capacity (both peak oxygen consumption and 6-minute walk test), and improved quality of life when compared with placebo. The results of the EMPATROPISM trial support the use of SGLT2 inhibitors in the treatment of HFrEF patients independently of their diabetic status.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 08 Nov 2020; epub ahead of print
Santos-Gallego CG, Vargas-Delgado AP, Requena JA, Garcia-Ropero A, ... Badimon JJ,
J Am Coll Cardiol: 08 Nov 2020; epub ahead of print | PMID: 33197559
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Abstract

Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis.

Nitsche C, Scully PR, Patel KP, Kammerlander A, ... Mascherbauer J, Treibel TA
Background
Older patients with severe aortic stenosis (AS) are increasingly identified to have cardiac amyloidosis (CA). It is unknown whether dual AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR).
Objective
To identify clinical characteristics and outcomes of AS-CA compared to lone AS.
Methods
TAVR referrals at three international sites underwent blinded research-corelab 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) prior to intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain-CA (AL) via tissue biopsy. National registries captured all-cause mortality.
Results
407 patients (83.4±6.5 years, 49.8% male) were recruited. DPD was positive in n=48 (11.8%, Grade-1 3.9%[n=16] Grade-2/3 7.9%[n=32]); AL was diagnosed in one Grade-1. Grade-2/3 patients had worse functional capacity, biomarkers (NT-proBNP/hsTnT), and bi-ventricular remodeling. A clinical score (RAISE) using left-ventricular Remodeling (hypertrophy/diastolic dysfunction), Age, Injury (hsTnT), Systemic involvement, and Electrical abnormalities (RBBB/low-voltages) was developed to predict AS-CA presence (AUC 0.86, 95%CI 0.78-0.94, p<0.001). Heart Team decision (DPD-blinded) resulted in TAVR (333[81.6%]), surgical-AVR (10[2.5%]), or medical management (65[15.9%]). After median 1.7 years, 23% of patients had died. 1-year mortality was worse in all-comers AS-CA (Grade-1-3) than lone AS (24.5 vs 13.9%, p=0.05). TAVR improved survival versus medical management with AS-CA survival post-TAVR no different to lone AS (p=0.36).
Conclusion
Dual pathology of AS-CA is common in older AS patients and can be predicted clinically. AS-CA has worse clinical presentation and a trend towards worse prognosis, unless treated. TAVR should therefore not be withheld in AS-CA.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 04 Nov 2020; epub ahead of print
Nitsche C, Scully PR, Patel KP, Kammerlander A, ... Mascherbauer J, Treibel TA
J Am Coll Cardiol: 04 Nov 2020; epub ahead of print | PMID: 33181246
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Abstract

Chronic Thromboembolic Pulmonary Hypertension: JACC Focus Seminar.

Papamatheakis DG, Poch DS, Fernandes TM, Kerr KM, Kim NH, Fedullo PF

Chronic thromboembolic pulmonary hypertension (CTEPH) is the result of pulmonary arterial obstruction by organized thrombotic material stemming from incompletely resolved acute pulmonary embolism. The exact incidence of CTEPH is unknown but appears to approximate 2.3% among survivors of acute pulmonary embolism. Although ventilation/perfusion scintigraphy has been supplanted by computed tomographic pulmonary angiography in the diagnostic approach to acute pulmonary embolism, it has a major role in the evaluation of patients with suspected CTEPH, the presence of mismatched segmental defects being consistent with the diagnosis. Diagnostic confirmation of CTEPH is provided by digital subtraction pulmonary angiography, preferably performed at a center familiar with the procedure and its interpretation. Operability assessment is then undertaken to determine if the patient is a candidate for potentially curative pulmonary endarterectomy surgery. When pulmonary endarterectomy is not an option, pulmonary arterial hypertension-targeted pharmacotherapy and balloon pulmonary angioplasty represent potential therapeutic alternatives.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Nov 2020; 76:2155-2169
Papamatheakis DG, Poch DS, Fernandes TM, Kerr KM, Kim NH, Fedullo PF
J Am Coll Cardiol: 02 Nov 2020; 76:2155-2169 | PMID: 33121723
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Abstract

Antithrombotic Management of Venous Thromboembolism: JACC Focus Seminar.

Renner E, Barnes GD

Venous thromboembolism (VTE) is a significant public health burden. Management of anticoagulation is the mainstay of treatment for the vast majority of patients. The introduction of 4 direct oral anticoagulants beginning in 2010 has significantly affected selection of anticoagulants for patients with VTE. Treatment of VTE consists of 3 phases: the initial treatment (first 5 to 21 days), primary treatment (first 3 to 6 months), and secondary prevention (after the initial 3 to 6 months). Oral-only anticoagulation strategies are now available, using apixaban or rivaroxaban therapy, beginning in the initial treatment phase. In addition, low-dose anticoagulation with either apixaban or rivaroxaban can be used in the secondary prevention phase for appropriate patients. Use of the direct oral anticoagulants is now supported for many patients with cancer-associated VTE. Appropriate selection and monitoring of anticoagulants remains a critical element of high-quality care for patients with VTE.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Nov 2020; 76:2142-2154
Renner E, Barnes GD
J Am Coll Cardiol: 02 Nov 2020; 76:2142-2154 | PMID: 33121722
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Abstract

Venous Thromboembolism Associated With Pregnancy: JACC Focus Seminar.

Nichols KM, Henkin S, Creager MA

Venous thromboembolism (VTE), composed of pulmonary embolism and deep venous thrombosis, is a significant cause of maternal mortality in the developed world. Normal physiological changes of pregnancy increase coagulability, which is compounded by patient-inherited and acquired risk factors. Depending on these risks and peripartum stage, the benefits of thromboprophylaxis can outweigh potential side effects. Diagnosis requires cautious clinical acumen because many symptoms of normal pregnancy mimic those of VTE and algorithmic tools used in the nonpregnant population are not equally applicable. Choice of imaging technique must account for potential risk to the fetus and altered test accuracy (sensitivity and specificity) in the setting of pregnancy. When VTE is diagnosed, anticoagulation is the backbone of treatment, with more advanced therapies being options for those with right ventricular dysfunction or unstable hemodynamics. Overall, pregnancy-associated VTE is complex, and management decisions should be individualized and informed by patient preferences.

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

J Am Coll Cardiol: 02 Nov 2020; 76:2128-2141
Nichols KM, Henkin S, Creager MA
J Am Coll Cardiol: 02 Nov 2020; 76:2128-2141 | PMID: 33121721
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Abstract

Advanced Management of Intermediate- and High-Risk Pulmonary Embolism: JACC Focus Seminar.

Piazza G

Intermediate-risk (submassive) pulmonary embolism (PE) describes normotensive patients with evidence of right ventricular compromise, whereas high-risk (massive) PE comprises those who have experienced hemodynamic decompensation with hypotension, cardiogenic shock, or cardiac arrest. Together, these 2 syndromes represent the most clinically challenging manifestations of the PE spectrum. Prompt therapeutic anticoagulation remains the cornerstone of therapy for both intermediate- and high-risk PE. Patients with intermediate-risk PE who subsequently deteriorate despite anticoagulation and those with high-risk PE require additional advanced therapies, typically focused on pulmonary artery reperfusion. Strategies for reperfusion therapy include systemic fibrinolysis, surgical pulmonary embolectomy, and a growing number of options for catheter-based therapy. Multidisciplinary PE response teams can aid in selection of appropriate management strategies, especially where gaps in evidence exist and guideline recommendations are sparse.

Published by Elsevier Inc.

J Am Coll Cardiol: 02 Nov 2020; 76:2117-2127
Piazza G
J Am Coll Cardiol: 02 Nov 2020; 76:2117-2127 | PMID: 33121720
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Abstract

Cardiovascular Care for Pregnant Women With Cardiovascular Disease.

Magun E, DeFilippis EM, Noble S, LaSala A, ... D\'Alton ME, Haythe J
Background
Cardio-obstetrics refers to a team-based approach to maternal care that includes multidisciplinary collaboration among maternal fetal medicine, cardiology, and others.
Objectives
This study sought to describe clinical characteristics, maternal and fetal outcomes, and cardiovascular readmissions in a cohort of pregnant women with underlying cardiovascular disease (CVD) followed by a cardio-obstetrics team.
Methods
We identified patients evaluated by our cardio-obstetrics team from January 1, 2010, through December 31, 2019, at a quaternary care hospital in New York City. Information was collected regarding demographics, comorbidities, underlying CVD, medications, maternal and fetal outcomes, and cardiovascular readmissions. Each patient was assigned a Cardiac Disease in Pregnancy (CARPREG) II score based on her clinical characteristics and underlying CVD.
Results
During the study period, 306 pregnant women (median age 29 years, 52.9% Hispanic or Latino) with CVD were seen. Most women (74.2%) were insured through Medicaid. The most common forms of CVD included arrhythmia (n = 88, 28.8%), congenital heart disease (n = 72, 23.5%), and cardiomyopathy (n = 72, 23.5%). The median CARPREG II score was 3; 130 patients (42.5%) had a CARPREG II score ≥4. Gestational diabetes occurred in 11.4%, gestational hypertension in 9.5%, and preeclampsia in 12.1% of women. Intensive care unit admission was required for 27 patients (8.8%) during delivery. Median gestational age for delivery was 38 weeks (interquartile range: 37 to 39). Live birth occurred in 98% of pregnancies. One maternal death occurred within a year of delivery in a woman with Eisenmenger syndrome. Following delivery, 30-day readmission rate was 2% and the rate of readmission from 30 to 90 days postpartum was 4.6%. Median follow-up was 2.6 years.
Conclusions
In a population of primarily Medicaid-insured pregnant women managed by a cardio-obstetrics team, maternal outcomes were encouraging and readmission rates following delivery were low. Prospective studies are needed to evaluate the impact of cardio-obstetric models of care on maternal outcomes.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Nov 2020; 76:2102-2113
Magun E, DeFilippis EM, Noble S, LaSala A, ... D'Alton ME, Haythe J
J Am Coll Cardiol: 02 Nov 2020; 76:2102-2113 | PMID: 33121718
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Abstract

Circulating Omega-3 Fatty Acids and Incident Adverse Events in Patients With Acute Myocardial Infarction.

Lázaro I, Rueda F, Cediel G, Ortega E, ... Sala-Vila A, Bayés-Genís A
Background
Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function.
Objectives
The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years\' follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE.
Methods
The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography.
Results
During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox proportional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95% CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44 to 0.96, for a 1-SD increase).
Conclusions
Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI.

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

J Am Coll Cardiol: 02 Nov 2020; 76:2089-2097
Lázaro I, Rueda F, Cediel G, Ortega E, ... Sala-Vila A, Bayés-Genís A
J Am Coll Cardiol: 02 Nov 2020; 76:2089-2097 | PMID: 33121716
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Abstract

Effects of Canagliflozin on Amino-Terminal Pro-B-Type Natriuretic Peptide: Implications for Cardiovascular Risk Reduction.

Januzzi JL, Xu J, Li J, Shaw W, ... Neal B, Hansen MK
Background
Canagliflozin reduces cardiovascular events including hospitalization for heart failure (HHF) in patients with type 2 diabetes and cardiovascular risk. Elevated amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are associated with HF diagnosis and predict cardiovascular risk.
Objectives
The purpose of this study was to measure NT-proBNP in CANVAS (Canagliflozin Cardiovascular Assessment Study) participants.
Methods
Associations between baseline NT-proBNP and cardiovascular, renal, and mortality outcomes and intervention-associated changes were determined.
Results
Of the 4,330 participants in the CANVAS trial, NT-proBNP was measured in 3,587, 2,918, and 995 participants at baseline, 1 year, and 6 years, respectively. The median baseline NT-proBNP concentration was 91 pg/ml, and 39.3% had NT-proBNP ≥125 pg/ml. NT-proBNP was higher in those with investigator-reported HF (13% of participants at baseline) versus those without (187 pg/ml vs. 81 pg/ml), with substantial overlap between groups. By 1 year, NT-proBNP increased with placebo, whereas canagliflozin reduced NT-proBNP by 11% (geometric mean ratio for canagliflozin vs. placebo = 0.89 [95% confidence interval (CI): 0.84 to 0.94]; p < 0.001). Lower NT-proBNP with canagliflozin was also observed at 6 years (p = 0.004). In adjusted models, baseline NT-proBNP ≥125 pg/ml was prognostic for incident HHF (hazard ratio [HR]: 5.40; 95% CI: 2.67 to 10.9), HHF/cardiovascular death (HR: 3.52; 95% CI: 2.38 to 5.20), and all-cause death (HR: 2.53; 95% CI: 1.78 to 3.61). Mediation analyses suggested that 10.4% of the effects of canagliflozin on HHF were reflected in NT-proBNP lowering.
Conclusions
A substantial percentage of patients in the CANVAS trial had elevated NT-proBNP values. Canagliflozin reduced NT-proBNP concentrations versus placebo; however, reduction in NT-proBNP explained only a small proportion of the benefit of canagliflozin on HF events. (CANVAS [CANagliflozin cardioVascular Assessment Study]; NCT01032629).

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Nov 2020; 76:2076-2085
Januzzi JL, Xu J, Li J, Shaw W, ... Neal B, Hansen MK
J Am Coll Cardiol: 02 Nov 2020; 76:2076-2085 | PMID: 33121714
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Abstract

Coronavirus and Cardiometabolic Syndrome: JACC Focus Seminar.

Mechanick JI, Rosenson RS, Pinney SP, Mancini DM, Narula J, Fuster V

The coronavirus disease 2019 (COVID-19) pandemic exposes unexpected cardiovascular vulnerabilities and the need to improve cardiometabolic health. Four cardiometabolic drivers-abnormal adiposity, dysglycemia, dyslipidemia, and hypertension-are examined in the context of COVID-19. Specific recommendations are provided for lifestyle change, despite social distancing restrictions, and pharmacotherapy, particularly for those with diabetes. Inpatient recommendations emphasize diligent and exclusive use of insulin to avert hyperglycemia in the face of hypercytokinemia and potential islet cell injury. Continuation of statins is advised, but initiating statin therapy to treat COVID-19 is as yet unsubstantiated by the evidence. The central role of the renin-angiotensin system is discussed. Research, knowledge, and practice gaps are analyzed with the intent to motivate prompt action. An emerging model of COVID-related cardiometabolic syndrome encompassing events before, during the acute phase, and subsequently in the chronic phase is presented to guide preventive measures and improve overall cardiometabolic health so future viral pandemics confer less threat.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Oct 2020; 76:2024-2035
Mechanick JI, Rosenson RS, Pinney SP, Mancini DM, Narula J, Fuster V
J Am Coll Cardiol: 26 Oct 2020; 76:2024-2035 | PMID: 33092738
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Abstract

Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar.

Giustino G, Pinney SP, Lala A, Reddy VY, ... Halperin JL, Fuster V

The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection. Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019. What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities. Myocardial injury occurs in approximately one-quarter of hospitalized patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality. The central pathophysiology underlying cardiovascular injury is the interplay between virus binding to the angiotensin-converting enzyme 2 receptor and the impact this action has on the renin-angiotensin system, the body\'s innate immune response, and the vascular response to cytokine production. The purpose of this review was to describe the mechanisms underlying cardiovascular injury, including that of thromboembolic disease and arrhythmia, and to discuss their clinical sequelae.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Oct 2020; 76:2011-2023
Giustino G, Pinney SP, Lala A, Reddy VY, ... Halperin JL, Fuster V
J Am Coll Cardiol: 26 Oct 2020; 76:2011-2023 | PMID: 33092737
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Abstract

Coronavirus Historical Perspective, Disease Mechanisms, and Clinical Outcomes: JACC Focus Seminar.

Pinney SP, Giustino G, Halperin JL, Mechanick JI, ... Rosenson RS, Fuster V

The emergence of a new coronavirus disease (coronavirus disease 2019 [COVID-19]) has raised global concerns regarding the health and safety of a vulnerable population. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incites a profound inflammatory response leading to tissue injury and organ failure. COVID-19 is characterized by the bidirectional relationship between inflammation and thrombosis. The clinical syndrome is propelled by inflammation producing acute lung injury, large-vessel thrombosis, and in situ microthrombi that may contribute to organ failure. Myocardial injury is common, but true myocarditis is rare. Elderly patients, those with established cardiovascular disease, and mechanically ventilated patients face the highest mortality risk. Therapies for COVID-19 are evolving. The antiviral drug remdesivir, dexamethasone, transfusion of convalescent plasma, and use of antithrombotic therapy are promising. Most require additional prospective studies. Although most patients recover, those who survive severe illness may experience persistent physical and psychological disabilities.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Oct 2020; 76:1999-2010
Pinney SP, Giustino G, Halperin JL, Mechanick JI, ... Rosenson RS, Fuster V
J Am Coll Cardiol: 26 Oct 2020; 76:1999-2010 | PMID: 33092736
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Abstract

Proteomic Signatures of Heart Failure in Relation to Left Ventricular Ejection Fraction.

Adamo L, Yu J, Rocha-Resende C, Javaheri A, Head RD, Mann DL
Background
There is a growing recognition of the inherent limitations of the use of the left ventricular ejection fraction (LVEF) to accurately phenotype patients with heart failure (HF).
Objectives
The authors sought to identify unique proteomic signatures for patients with HF with reduced ejection fraction (HFrEF), HF with a midrange LVEF (HFmrEF), and HF with preserved ejection fraction (HFpEF), as well as to identify molecular differences between patients with ischemic and nonischemic HF.
Methods
We used high-content aptamer-based proteomics technology (SOMAscan) to interrogate the blood proteome of age- and sex-matched patients with HF within different LVEF groups.
Results
Within the Washington University Heart Failure Registry, we identified age/sex-matched patients within 3 LVEF categories: HFrEF (LVEF <40%), HFmrEF (LVEF 40% to 50%), and HFpEF (LVEF >50%). We found that patients with HFrEF, HFmrEF, and HFpEF had unique variations in circulating proteins that reflected distinct biological pathophysiologies. Bioinformatics analysis revealed that there were biological themes that were unique to patients with HFrEF, HFpEF, or HFmrEF. Comparative analyses of patients with HFmrEF with improved LVEF and patients with HFmrEF with unchanged LVEF revealed marked differences between these 2 patient populations and indicated that patients with recovered LVEF are more similar to patients with HFpEF than to patients with HFrEF. Moreover, there were marked differences in the proteomic signatures of patients with ischemic and nonischemic HF.
Conclusions
Viewed together, these findings suggest that it may be possible to use high-content multiplexed proteomics assays in combination with the clinical assessment of LVEF to more accurately identify clinical phenotypes of patients with HF.

Published by Elsevier Inc.

J Am Coll Cardiol: 26 Oct 2020; 76:1982-1994
Adamo L, Yu J, Rocha-Resende C, Javaheri A, Head RD, Mann DL
J Am Coll Cardiol: 26 Oct 2020; 76:1982-1994 | PMID: 33092734
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Abstract

Clinical and Angiographic Features of Patients With Out-of-Hospital Cardiac Arrest and Acute Myocardial Infarction.

Kosugi S, Shinouchi K, Ueda Y, Abe H, ... Uematsu M, Koretsune Y
Background
Sudden cardiac arrest is a serious complication of acute myocardial infarction (MI). Although in-hospital mortality from MI has decreased, the mortality of MI patients complicated with out-of-hospital cardiac arrest (OHCA) remains high. However, the features of acute MI patients with OHCA have not been well known.
Objectives
We sought to characterize the clinical and angiographic features of acute MI patients with OHCA comparing with those without OHCA.
Methods
We retrospectively analyzed 480 consecutive patients with acute MI undergoing percutaneous coronary intervention. Patients complicated with OHCA were compared with patients without OHCA.
Results
Of the patients, 141 (29%) were complicated with OHCA. Multivariate analysis revealed that age (odds ratio [OR]: 0.8; 95% confidence interval [CI]: 0.7 to 0.9 per 5 years; p < 0.001), estimated glomerular filtration rate (OR: 0.8; 95% CI: 0.7 to 0.8 per 10 ml/min/1.73 m; p < 0.001), peak creatine kinase-myocardial band (OR: 1.3; 95% CI: 1.2 to 1.4 per 10 U/l; p < 0.001), calcium-channel antagonists use (OR: 0.4; 95% CI: 0.2 to 0.7; p = 0.002), the culprit lesion at the left main coronary artery (OR: 5.3; 95% CI: 1.9 to 15.1; p = 0.002), and the presence of chronic total occlusion (OR: 2.9; 95% CI: 1.5 to 5.7; p = 0.001) were significantly associated with OHCA.
Conclusions
Younger age, no use of calcium-channel antagonists, worse renal function, larger infarct size, culprit lesion in the left main coronary artery, and having chronic total occlusion were associated with OHCA.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Oct 2020; 76:1934-1943
Kosugi S, Shinouchi K, Ueda Y, Abe H, ... Uematsu M, Koretsune Y
J Am Coll Cardiol: 26 Oct 2020; 76:1934-1943 | PMID: 33092729
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Abstract

Characteristics of Heart Failure Trials Associated With Under-Representation of Women as Lead Authors.

Whitelaw S, Thabane L, Mamas MA, Reza N, ... Douglas PS, Van Spall HGC
Background
Clinical trials change practice in cardiology, and leading them requires research training, mentorship, sponsorship, and networking. Women report challenges in obtaining these opportunities.
Objectives
The purpose of this review was to evaluate temporal trends in representation of women as authors in heart failure (HF) randomized controlled trials (RCTs) published in high-impact medical journals and explore RCT characteristics associated with women as lead authors.
Methods
We searched MEDLINE, EMBASE, and CINAHL for HF RCTs published in journals with an impact factor ≥10 between January 1, 2000, and May 7, 2019. We assessed temporal trends in the gender distribution of authors, and used multivariable logistic regression to determine characteristics associated with women as lead authors.
Results
We identified 10,596 unique articles, of which 403 RCTs met inclusion criteria. Women represented 15.6% (95% confidence interval [CI]: 12.2% to 19.6%), 12.9% (95% CI: 9.8% to 16.6%), and 11.4% (95% CI: 8.5% to 14.9%) of lead, senior, and corresponding authors, respectively. The proportion of women authors has not changed over time. Women had lower odds of lead authorship in RCTs that were multicenter (odds ratio [OR]: 0.58; 95% CI: 0.18 to 0.96; p = 0.037), were coordinated in North America (OR: 0.21; 95% CI: 0.08 to 0.70; p = 0.011) or Europe (OR: 0.33; 95% CI: 0.09 to 0.91; p = 0.039), tested drug interventions (OR: 0.42; 95% CI: 0.16 to 0.97; p = 0.043), or had men as the senior author (OR: 0.50; 95% CI: 0.21 to 0.93; p = 0.043).
Conclusions
Women are under-represented as authors of HF RCTs, with no change in temporal trends. Women had lower odds of lead authorship in RCTs that were multicenter, were coordinated in North America or Europe, tested drug interventions, or had men as senior authors.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Oct 2020; 76:1919-1930
Whitelaw S, Thabane L, Mamas MA, Reza N, ... Douglas PS, Van Spall HGC
J Am Coll Cardiol: 26 Oct 2020; 76:1919-1930 | PMID: 33092727
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This program is still in alpha version.