Journal: J Am Coll Cardiol

Sorted by: date / impact
Abstract

Comparison of Atrial Remodeling Caused by Sustained Atrial Flutter Versus Atrial Fibrillation.

Guichard JB, Naud P, Xiong F, Qi X, ... Da Costa A, Nattel S
Background
Atrial flutter (AFL) and atrial fibrillation (AF) are associated with AF-promoting atrial remodeling, but no experimental studies have addressed remodeling with sustained AFL.
Objectives
This study aimed to define the atrial remodeling caused by sustained atrial flutter (AFL) and/or atrial fibrillation (AF).
Methods
Intercaval radiofrequency lesions created a substrate for sustained isthmus-dependent AFL, confirmed by endocavity mapping. Four groups (6 dogs per group) were followed for 3 weeks: sustained AFL; sustained AF (600 beats/min atrial tachypacing); AF superimposed on an AFL substrate (AF+AFLs); sinus rhythm (SR) with an AFL substrate (SR+AFLs; control group). All dogs had atrioventricular-node ablation and ventricular pacemakers at 80 beats/min to control ventricular rate.
Results
Monitoring confirmed spontaneous AFL maintenance >99% of the time in dogs with AFL. At terminal open-chest study, left-atrial (LA) effective refractory period was reduced similarly with AFL, AF+AFLs and AF, while AF vulnerability to extrastimuli increased in parallel. Induced AF duration increased significantly in AF+AFLs and AF, but not AFL. Dogs with AF+AFLs had shorter cycle lengths and substantial irregularity versus dogs with AFL. LA volume increased in AF+AFLs and AF, but not dogs with AFL, versus SR+AFLs. Optical mapping showed significant conduction slowing in AF+AFLs and AF but not AFL, paralleling atrial fibrosis and collagen-gene upregulation. Left-ventricular function did not change in any group. Transcriptomic analysis revealed substantial dysregulation of inflammatory and extracellular matrix-signaling pathways with AF and AF+ALs but not AFL.
Conclusions
Sustained AFL causes atrial repolarization changes like those in AF but, unlike AF or AF+AFLs, does not induce structural remodeling. These results provide novel insights into AFL-induced remodeling and suggest that early intervention may be important to prevent irreversible fibrosis when AF intervenes in a patient with AFL.

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

J Am Coll Cardiol: 27 Jul 2020; 76:374-388
Guichard JB, Naud P, Xiong F, Qi X, ... Da Costa A, Nattel S
J Am Coll Cardiol: 27 Jul 2020; 76:374-388 | PMID: 32703507
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Abstract

Long-Term Outcomes of Implantable Cardioverter-Defibrillator Therapy in the SCD-HeFT.

Poole JE, Olshansky B, Mark DB, Anderson J, ... Bardy GH,
Background
The SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) randomized 2,521 patients with moderate heart failure (HF) to amiodarone, placebo drug, or implantable cardioverter-defibrillator (ICD) therapy. Original trial follow-up ended October 31, 2003. Over a median 45.5-month follow-up, amiodarone, compared with placebo, did not affect survival, whereas randomization to an ICD significantly decreased all-cause mortality by 23%.
Objectives
This study sought to describe the extended treatment group survival of the SCD-HeFT cohort.
Methods
Mortality outcomes for the 1,855 patients alive at the end of the SCD-HeFT trial were collected between 2010 and 2011. These data were combined with the 666 deaths from the original study to compare long-term outcomes overall and for key pre-specified subgroups.
Results
Median (25th to 75th percentiles) follow-up was 11.0 (10.0 to 12.2) years. On the basis of intention-to-treat analysis, the ICD group had overall survival benefit versus placebo drug (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.028). When treatment benefit was examined as a function of time from randomization, attenuation of the ICD benefit was observed after 6 years (p value for the interaction = 0.0015). Subgroup analysis revealed long-term ICD benefit varied according to HF etiology and New York Heart Association (NYHA) functional class: ischemic HF HR: 0.81; 95% CI: 0.69 to 0.95; p = 0.009; nonischemic HF HR: 0.97; 95% CI: 0.79 to 1.20; p = 0.802; NYHA functional class II HR: 0.76; 95% CI: 0.65 to 0.90; p = 0.001; NYHA functional class III HR: 1.06; 95% CI: 0.86 to 1.31; p = 0.575.
Conclusions
Follow-up of SCD-HeFT patients to 11 years demonstrated heterogenous treatment-related patterns of long-term survival with ICD benefit most evident at 11 years for ischemic HF patients and for those with NYHA functional class II symptoms at trial enrollment. (SCD-HeFT 10 Year Follow-up [SCD-HeFT10 Yr]; NCT01058837).

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

J Am Coll Cardiol: 27 Jul 2020; 76:405-415
Poole JE, Olshansky B, Mark DB, Anderson J, ... Bardy GH,
J Am Coll Cardiol: 27 Jul 2020; 76:405-415 | PMID: 32703511
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Abstract

Penetrance of Hypertrophic Cardiomyopathy in Sarcomere Protein Mutation Carriers.

Lorenzini M, Norrish G, Field E, Ochoa JP, ... Kaski JP, Elliott PM
Background
Predictive genetic screening of relatives of patients with hypertrophic cardiomyopathy (HCM) caused by sarcomere protein (SP) gene mutations is current standard of care, but there are few data on long-term outcomes in mutation carriers without HCM.
Objectives
The aim of this study was to determine the incidence of new HCM diagnosis in SP mutation carriers.
Methods
This was a retrospective analysis of adult and pediatric SP mutation carriers identified during family screening who did not fulfill diagnostic criteria for HCM at first evaluation.
Results
The authors evaluated 285 individuals from 156 families (median age 14.2 years [interquartile range: 6.8 to 31.6 years], 141 [49.5%] male individuals); 145 (50.9%) underwent cardiac magnetic resonance (CMR). Frequency of causal genes was as follows: MYBPC3 n = 123 (43.2%), MYH7 n = 69 (24.2%), TNNI3 n = 39 (13.7%), TNNT2 n = 34 (11.9%), TPM1 n = 9 (3.2%), MYL2 n = 6 (2.1%), ACTC1 n = 1 (0.4%), multiple mutations n = 4 (1.4%). Median follow-up was 8.0 years (interquartile range: 4.0 to 13.3 years) and 86 (30.2%) patients developed HCM; 16 of 50 (32.0%) fulfilled diagnostic criteria on CMR but not echocardiography. Estimated HCM penetrance at 15 years of follow-up was 46% (95% confidence interval [CI]: 38% to 54%). In a multivariable model adjusted for age and stratified for CMR, independent predictors of HCM development were male sex (hazard ratio [HR]: 2.91; 95% CI: 1.82 to 4.65) and abnormal electrocardiogram (ECG) (HR: 4.02; 95% CI: 2.51 to 6.44); TNNI3 variants had the lowest risk (HR: 0.19; 95% CI: 0.07 to 0.55, compared to MYBPC3).
Conclusions
Following a first negative screening, approximately 50% of SP mutation carriers develop HCM over 15 years of follow-up. Male sex and an abnormal ECG are associated with a higher risk of developing HCM. Regular CMR should be considered in long-term screening.

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

J Am Coll Cardiol: 03 Aug 2020; 76:550-559
Lorenzini M, Norrish G, Field E, Ochoa JP, ... Kaski JP, Elliott PM
J Am Coll Cardiol: 03 Aug 2020; 76:550-559 | PMID: 32731933
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Abstract

Transcatheter Valve-in-Valve Aortic Valve Replacement as an Alternative to Surgical Re-Replacement.

Deharo P, Bisson A, Herbert J, Lacour T, ... Cuisset T, Fauchier L
Background
Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) and redo surgical aortic valve replacement (SAVR) represent the 2 treatments for aortic bioprosthesis failure. Clinical comparison of both therapies remains limited by the number of patients analyzed.
Objectives
The purpose of this study was to analyze the outcomes of VIV TAVR versus redo SAVR at a nationwide level in France.
Methods
Based on the French administrative hospital-discharge database, the study collected information for patients treated for aortic bioprosthesis failure with isolated VIV TAVR or redo SAVR between 2010 and 2019. Propensity score matching was used for the analysis of outcomes.
Results
A total of 4,327 patients were found in the database. After matching on baseline characteristics, 717 patients were analyzed in each arm. At 30 days, VIV TAVR was associated with lower rates of the composite of all-cause mortality, all-cause stroke, myocardial infarction, and major or life-threatening bleeding (odds ratio: 0.62; 95% confidence interval: 0.44 to 0.88; p = 0.03). During follow-up (median 516 days), the combined endpoint of cardiovascular death, all-cause stroke, myocardial infarction, or rehospitalization for heart failure was not different between the 2 groups (odds ratio: 1.18; 95% confidence interval: 0.99 to 1.41; p = 0.26). Rehospitalization for heart failure and pacemaker implantation were more frequently reported in the VIV TAVR group. A time-dependent interaction between all-cause and cardiovascular mortality following VIV TAVR was reported (p-interaction <0.05).
Conclusions
VIV TAVR was observed to be associated with better short-term outcomes than redo SAVR. Major cardiovascular outcomes were not different between the 2 treatments during long-term follow-up.

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

J Am Coll Cardiol: 03 Aug 2020; 76:489-499
Deharo P, Bisson A, Herbert J, Lacour T, ... Cuisset T, Fauchier L
J Am Coll Cardiol: 03 Aug 2020; 76:489-499 | PMID: 32731926
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Abstract

Cardiac Pacing Training in Africa: Endorsed by the Africa Heart Rhythm Association (AFHRA): JACC International.

Rwebembera J, Jeilan M, Ajijola OA, Talle M, ... Chin A, Bonny A

The field of pacing in Africa has evolved in an uncoordinated way across the continent with significant variation in local expertise, cost, and utilization. There are many countries where pacemaker services do not meet one-hundredth of the national demand. Regional, national, and institutional standards for pacemaker qualification and credentials are lacking. This paper reviews the current needs for bradycardia pacing and evaluates what standards should be set to develop pacemaker services in a resource-constrained continent, including the challenges and opportunities of capacity building and training as well as standards for training programs (training prerequisites, case volumes, program content, and evaluation).

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

J Am Coll Cardiol: 27 Jul 2020; 76:465-472
Rwebembera J, Jeilan M, Ajijola OA, Talle M, ... Chin A, Bonny A
J Am Coll Cardiol: 27 Jul 2020; 76:465-472 | PMID: 32703517
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Abstract

Effect of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFpEF.

Cunningham JW, Claggett BL, O\'Meara E, Prescott MF, ... Solomon SD, Zile MR
Background
Myocardial fibrosis may contribute to the pathophysiology of heart failure with preserved ejection fraction. Given the biochemical targets of sacubitril/valsartan, this study hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix homeostasis are altered by sacubitril/valsartan compared with valsartan alone.
Objectives
This study investigated the effects of sacubitril/valsartan on biomarkers of extracellular matrix homeostasis and the association between biomarkers and the primary endpoint (total heart failure hospitalizations and cardiovascular death).
Methods
N-terminal propeptide of collagen I and III, tissue inhibitor of matrix metalloproteinase 1, carboxyl-terminal telopeptide of collagen type I, and soluble ST2 were measured at baseline (n = 1,135) and 16 (n = 1,113) and 48 weeks (n = 1,016) after randomization. The effects of sacubitril/valsartan on these biomarkers were compared with those of valsartan alone. Baseline biomarker values and changes from baseline to 16 weeks were related to primary endpoint.
Results
At baseline, all 5 biomarkers were higher than published referent control values. Sixteen weeks after randomization, sacubitril/valsartan decreased tissue inhibitor of matrix metalloproteinase 1 by 8% (95% confidence interval [CI]: 6% to 10%; p < 0.001), soluble ST2 by 4% (95% CI: 1% to 7%; p = 0.002), and N-terminal propeptide of collagen III by 3% (95% CI: 0% to 6%; p = 0.04) and increased carboxyl-terminal telopeptide of collagen type I by 4% (95% CI: 1% to 8%; p = 0.02) compared with valsartan alone, consistently in men and women and patients with left ventricular ejection fraction above or below the median of 57%. Higher levels of tissue inhibitor of matrix metalloproteinase 1 and soluble ST2 at baseline and increases in these markers at 16 weeks were associated with higher primary endpoint event rates.
Conclusions
Biomarkers reflecting extracellular matrix homeostasis are elevated in heart failure with preserved ejection fraction, favorably altered by sacubitril/valsartan, and have important prognostic value. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

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

J Am Coll Cardiol: 03 Aug 2020; 76:503-514
Cunningham JW, Claggett BL, O'Meara E, Prescott MF, ... Solomon SD, Zile MR
J Am Coll Cardiol: 03 Aug 2020; 76:503-514 | PMID: 32731928
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Abstract

Pathophysiology and Acute Management of Tachyarrhythmias in Pheochromocytoma: JACC Review Topic of the Week.

Nazari MA, Rosenblum JS, Haigney MC, Rosing DR, Pacak K

Pheochromocytomas, arising from chromaffin cells, produce catecholamines, epinephrine and norepinephrine. The tumor biochemical phenotype is defined by which of these exerts the greatest influence on the cardiovascular system when released into circulation in high amounts. Action on the heart and vasculature can cause potentially lethal arrhythmias, often in the setting of comorbid blood pressure derangements. In a review of electrocardiograms obtained on pheochromocytoma patients (n = 650) treated at our institution over the last decade, severe and refractory sinus tachycardia, atrial fibrillation, and ventricular tachycardia were found to be the most common or life-threatening catecholamine-induced tachyarrhythmias. These arrhythmias, arising from catecholamine excess rather than from a primary electrophysiologic substrate, require special considerations for treatment and complication avoidance. Understanding the synthesis and release of catecholamines, the adrenoceptors catecholamines bind to, and the cardiac and vascular response to epinephrine and norepinephrine underlies optimal management in catecholamine-induced tachyarrhythmias.

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

J Am Coll Cardiol: 27 Jul 2020; 76:451-464
Nazari MA, Rosenblum JS, Haigney MC, Rosing DR, Pacak K
J Am Coll Cardiol: 27 Jul 2020; 76:451-464 | PMID: 32703516
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Abstract

Randomized Trials Versus Common Sense and Clinical Observation: JACC Review Topic of the Week.

Fanaroff AC, Califf RM, Harrington RA, Granger CB, ... Alexander JH, Lopes RD

Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine.

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

J Am Coll Cardiol: 03 Aug 2020; 76:580-589
Fanaroff AC, Califf RM, Harrington RA, Granger CB, ... Alexander JH, Lopes RD
J Am Coll Cardiol: 03 Aug 2020; 76:580-589 | PMID: 32731936
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Abstract

Atherosclerotic Cardiovascular Disease Risk Stratification Based on Measurements of Troponin and Coronary Artery Calcium.

Sandoval Y, Bielinski SJ, Daniels LB, Blaha MJ, ... Decker PA, Jaffe AS
Background
Low values of high-sensitivity cardiac troponin (hs-cTn) and coronary artery calcium (CAC) scores of zero are associated with a low risk for atherosclerotic cardiovascular disease (ASCVD).
Objectives
The purpose of this study was to evaluate baseline hs-cTnT and CAC in relation to ASCVD.
Methods
Baseline hs-cTnT (limit of detection [LoD] 3 ng/l) and CAC measurements were analyzed across participants age 45 to 84 years without clinical cardiovascular disease from the prospective MESA (Multi-Ethnic Study of Atherosclerosis) in relationship to incident ASCVD.
Results
Among 6,749 participants, 1,002 ASCVD events occurred during a median follow-up of 15 years. Participants with detectable CAC (20.1 vs. 5.0 events per 1,000 person-years; adjusted hazard ratio [HR]: 2.35; 95% confidence interval [CI]: 2.0 to 2.76; p < 0.001) and detectable hs-cTnT (15.4 vs. 5.2 per 1,000 person-years; adjusted HR: 1.47; 95% CI: 1.21 to 1.77; p < 0.001) had higher rates of ASCVD than those with undetectable results. Individuals with undetectable hs-cTnT (32%) had similar risk for ASCVD as did those with a CAC of zero (50%) (5.2 vs. 5.0 per 1,000 person-years). Together, hs-cTnT and CAC (discordance 38%) resulted in the following ASCVD event rates: hs-cTnT < LoD/CAC = 0: 2.8 per 1,000 person-years (reference), hs-cTnT ≥ LoD/CAC = 0: 6.8 per 1,000 person-years (HR: 1.59; 95% CI: 1.17 to 2.16; p = 0.003), hs-cTnT < LoD/CAC > 0: 11.1 per 1,000 person-years (HR: 2.74; 95% CI: 1.96 to 3.83; p < 0.00001), and hs-cTnT ≥ LoD/CAC > 0: 22.6 per 1,000 person-years (HR: 3.50; 95% CI: 2.60 to 4.70; p < 0.00001).
Conclusions
An undetectable hs-cTnT identifies patients with a similar, low risk for ASCVD as those with a CAC score of zero. The increased risk among those with discordant results supports their conjoined use for risk prediction.

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

J Am Coll Cardiol: 27 Jul 2020; 76:357-370
Sandoval Y, Bielinski SJ, Daniels LB, Blaha MJ, ... Decker PA, Jaffe AS
J Am Coll Cardiol: 27 Jul 2020; 76:357-370 | PMID: 32703505
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Abstract

Relationship of Ventricular Morphology and Atrioventricular Valve Function to Long-Term Outcomes Following Fontan Procedures.

Moon J, Shen L, Likosky DS, Sood V, ... Bove EL, Si MS
Background
The influence of ventricular morphology on Fontan outcomes is controversial.
Objectives
This study hypothesized that dysfunction of the single right ventricle (RV) and right atrioventricular valve regurgitation (AVVR) increases over time and adversely impacts late outcomes following a Fontan operation. A single-center retrospective study was performed.
Methods
From 1985 through 2018, 1,162 patients underwent the Fontan procedure at our center and were included in this study. Transplant and takedown free survival, ventricular, and atrioventricular valve dysfunction after Fontan were analyzed. Death or heart transplantation information was obtained from the National Death Index and the Scientific Registry of Transplant Recipients.
Results
The follow-up rate was 99%. Morphologic RV was present in 58% of patients. Transplant and takedown free survival were 91%, 75%, and 71% at 10 years, 20 years, and 25 years, respectively. Morphologic RV was an independent risk factor for transplant, takedown free survival (hazard ratio: 2.4; p = 0.008). The AVVR, which preceded ventricular dysfunction in most cases, was associated with the development of ventricular dysfunction after Fontan (odds ratio: 4.3; 95% confidence interval: 2.7 to 6.7; p < 0.001). Furthermore, AVVR and ventricular dysfunction progressed over time after Fontan, especially in the RV (AVVR: p < 0.0001, ventricular dysfunction: p < 0.0001).
Conclusions
Morphologic RV is negatively associated with the long-term survival following the Fontan, possibly due to a tendency toward progressive AVVR and deterioration of the single ventricle function. Additional volume overload caused by AVVR may be one of the main factors accelerating the dysfunction of the single RV, implying that early valve intervention may be warranted.

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

J Am Coll Cardiol: 27 Jul 2020; 76:419-431
Moon J, Shen L, Likosky DS, Sood V, ... Bove EL, Si MS
J Am Coll Cardiol: 27 Jul 2020; 76:419-431 | PMID: 32703513
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Abstract

Cardiovascular and Bleeding Risks Associated With Nonsteroidal Anti-Inflammatory Drugs After Myocardial Infarction.

Kang DO, An H, Park GU, Yum Y, ... Seo HS, Choi CU
Background
Limited data are available regarding the risk for adverse clinical events with concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment after myocardial infarction (MI).
Objectives
The aim of this study was to investigate the risk for cardiovascular and bleeding events according to groups of antithrombotic medications and subtypes of NSAIDs in patients with MI.
Methods
This was a nationwide cohort study to enroll a study population from the Health Insurance Review and Assessment Service database in Korea between 2009 and 2013. Patients were divided into groups on the basis of the prescribed antithrombotic medications. The primary and secondary outcomes were thromboembolic cardiovascular and clinically relevant bleeding events. The risk for adverse clinical events was assessed by ongoing NSAID treatment and subtypes of NSAIDs.
Results
In total, 108,232 patients (mean age 64.2 ± 12.8 years, 72.1% men, mean follow-up duration 2.3 ± 1.8 years) with first diagnosed MI were enrolled. Concomitant NSAID treatment significantly increased the risk for cardiovascular events (hazard ratio [HR]: 6.96; 95% confidence interval [CI]: 6.24 to 6.77; p < 0.001) and bleeding events (HR: 4.08; 95% CI: 3.51 to 4.73; p < 0.001) compared with no NSAID treatment. Among NSAID subtypes, the risk for cardiovascular and bleeding events was lowest with the use of celecoxib (HR: 4.65; 95% CI: 3.17 to 6.82; p < 0.001, and 3.44; 95% CI: 2.20 to 5.39; p < 0.001, respectively) and meloxicam (HR: 3.03; 95% CI: 1.68 to 5.47; p < 0.001, and 2.80; 95% CI: 1.40 to 5.60; p < 0.001, respectively).
Conclusions
Concomitant NSAID treatment significantly increased the risk for cardiovascular and bleeding events after MI. Although NSAID treatment should be avoided after MI, celecoxib and meloxicam could be considered as alternative options in cases in which NSAID use is unavoidable.

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

J Am Coll Cardiol: 03 Aug 2020; 76:518-529
Kang DO, An H, Park GU, Yum Y, ... Seo HS, Choi CU
J Am Coll Cardiol: 03 Aug 2020; 76:518-529 | PMID: 32731930
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Abstract

Targeting RNA With Antisense Oligonucleotides and Small Interfering RNA: JACC State-of-the-Art Review.

Katzmann JL, Packard CJ, Chapman MJ, Katzmann I, Laufs U

There is an unmet clinical need to reduce residual cardiovascular risk attributable to apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein and remnant particles. Pharmacological targeting of messenger RNA represents an emerging, innovative approach. Two major classes of agents have been developed-antisense oligonucleotides and small interfering RNA. Early problems with their use have been overcome by conjugation with N-acetylgalactosamine, an adduct that targets their delivery to the primary site of action in the liver. Using these agents to inhibit the translation of key regulatory proteins such as PCSK9, apolipoprotein CIII, apolipoprotein(a), and angiopoietin-like 3 has been shown to be effective in attenuating dyslipidemic states. Cardiovascular outcome trials with N-acetylgalactosamine-conjugated RNA-targeting drugs are ongoing. The advantages of these agents include long dosing intervals of up to 6 months and the potential to regulate the abundance of any disease-related protein. Long-term safety has yet to be demonstrated in large-scale clinical trials.

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

J Am Coll Cardiol: 03 Aug 2020; 76:563-579
Katzmann JL, Packard CJ, Chapman MJ, Katzmann I, Laufs U
J Am Coll Cardiol: 03 Aug 2020; 76:563-579 | PMID: 32731935
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Abstract

Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review.

Marquis-Gravel G, Moliterno DJ, Francis DP, Jüni P, ... Zannad F, Goodman SG

The role of percutaneous coronary interventions in addition to medical therapy for patients with stable coronary artery disease continues to be debated in routine clinical practice, despite more than 2 decades of randomized controlled trials. The residual uncertainty arises from particular challenges facing revascularization trials. Which endpoint do doctors care about, and which do patients care about? Which participants should be enrolled? What background medical therapy should we use? When is placebo control relevant? In this paper, we discuss how these questions can be approached and examine the merits and disadvantages of possible options. Engaging multiple stakeholders, including patients, researchers, regulators, and funders, to ensure the design elements are methodologically valid and clinically meaningful should be an aspirational goal in the development of future trials.

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

J Am Coll Cardiol: 27 Jul 2020; 76:435-450
Marquis-Gravel G, Moliterno DJ, Francis DP, Jüni P, ... Zannad F, Goodman SG
J Am Coll Cardiol: 27 Jul 2020; 76:435-450 | PMID: 32703515
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Abstract

Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease.

Maddahi J, Lazewatsky J, Udelson JE, Berman DS, ... Knuuti J, Orlandi C
Background
Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer.
Objectives
This study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m-labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated.
Methods
In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data.
Results
Sensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated.
Conclusions
Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710).

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

J Am Coll Cardiol: 27 Jul 2020; 76:391-401
Maddahi J, Lazewatsky J, Udelson JE, Berman DS, ... Knuuti J, Orlandi C
J Am Coll Cardiol: 27 Jul 2020; 76:391-401 | PMID: 32703509
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Abstract

Long-Term Adverse Cardiac Outcomes in Patients With Sarcoidosis.

Yafasova A, Fosbøl EL, Schou M, Gustafsson F, ... Køber L, Butt JH
Background
It is estimated that 5% of patients with sarcoidosis have clinically manifest cardiac involvement, although autopsy and imaging studies suggest a significantly higher prevalence of cardiac involvement. There is a paucity of contemporary data on the risk of adverse cardiac outcomes, particularly heart failure (HF), in patients with sarcoidosis.
Objectives
The purpose of this study was to examine the long-term risk of HF and other adverse cardiac outcomes in patients with sarcoidosis compared with matched control subjects.
Methods
In this cohort study, all patients age ≥18 years with newly diagnosed sarcoidosis (1996 to 2016) were identified through Danish nationwide registries and matched 1:4 by age, sex, and comorbidities with control subjects from the background population without sarcoidosis.
Results
Of the 12,042 patients diagnosed with sarcoidosis, 11,834 patients were matched with 47,336 subjects from the background population (median age: 42.8 years [25th to 75th percentile: 33.1 to 55.8 years], 54.3% men). The median follow-up was 8.2 years. Absolute 10-year risks of outcomes were as follows: HF: 3.18% (95% confidence interval [CI]: 2.83% to 3.57%) for sarcoidosis patients and 1.72% (95% CI: 1.58% to 1.86%) for the background population; the composite of ICD implantation, ventricular arrhythmias, and cardiac arrest: 0.96% (95% CI: 0.77% to 1.18%) for sarcoidosis patients and 0.45% (95% CI: 0.38% to 0.53%) for the background population; the composite of pacemaker implantation, atrioventricular block, and sinoatrial dysfunction: 0.94% (95% CI: 0.75% to 1.16%) for sarcoidosis patients and 0.51% (95% CI: 0.44% to 0.59%) for the background population; atrial fibrillation or flutter: 3.44% (95% CI: 3.06% to 3.84%) for sarcoidosis patients and 2.66% (95% CI: 2.49% to 2.84%) for the background population; and all-cause mortality: 10.88% (95% CI: 10.23% to 11.55%) for sarcoidosis patients and 7.43% (95% CI: 7.15% to 7.72%) for the background population.
Conclusions
Patients with sarcoidosis had a higher associated risk of HF and other adverse cardiac outcomes compared with matched control subjects.

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

J Am Coll Cardiol: 17 Aug 2020; 76:767-777
Yafasova A, Fosbøl EL, Schou M, Gustafsson F, ... Køber L, Butt JH
J Am Coll Cardiol: 17 Aug 2020; 76:767-777 | PMID: 32792073
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Abstract

Cardiovascular Effects of ADHD Therapies: JACC Review Topic of the Week.

Torres-Acosta N, O\'Keefe JH, O\'Keefe CL, Lavie CJ

Although the prevalence of attention-deficit/hyperactivity disorder (ADHD) has been stable over the past 3 decades, prescriptions of sympathomimetic stimulants have steadily increased in the United States. This study consisted of a systematic review of PubMed articles screened for ADHD medications and potential cardiovascular toxicity as well as nondrug strategies for managing ADHD. The cumulative body of data showed that ADHD medications cause modest elevations in resting heart rate and blood pressure. Other adverse effects reported with ADHD stimulants included arrhythmia, nonischemic cardiomyopathy, Takotsubo cardiomyopathy, and sudden death. However, such reports did not imply causation, and there was a paucity of randomized trial evidence addressing long-term safety of ADHD medications, particularly among adults. Further studies are essential to clarify the risks and benefits of ADHD stimulant medications and to explore nonpharmacological options, including regular exercise and omega-3 fatty acids, which could be helpful for improving ADHD symptoms.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 17 Aug 2020; 76:858-866
Torres-Acosta N, O'Keefe JH, O'Keefe CL, Lavie CJ
J Am Coll Cardiol: 17 Aug 2020; 76:858-866 | PMID: 32792083
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Abstract

Role of Cardiac Lymphatics in Myocardial Edema and Fibrosis: JACC Review Topic of the Week.

Brakenhielm E, González A, Díez J

The cardiac lymphatic network plays a key role in regulation of myocardial extracellular volume and immune cell homeostasis. In different pathological conditions cardiac lymphatics undergo significant remodeling, with insufficient lymphatic function and/or lymphangiogenesis leading to fluid accumulation and development of edema. Additionally, by modulating the reuptake of tissue-infiltrating immune cells, lymphatics regulate immune responses. Available evidence suggests that both edema and inadequate immune response resolution may contribute to extracellular matrix remodeling and interstitial myocardial fibrosis. Interestingly, stimulation of lymphangiogenesis has been shown to improve cardiac function and reduce the progression of myocardial fibrosis during heart failure development after myocardial infarction. This review goes through the available clinical and experimental data supporting a role for cardiac lymphatics in cardiac disease, focusing on the current evidence linking poor cardiac lymphatic transport to the fibrogenic process and discussing potential avenues for novel biomarkers and therapeutic targets to limit cardiac fibrosis and dysfunction.

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

J Am Coll Cardiol: 10 Aug 2020; 76:735-744
Brakenhielm E, González A, Díez J
J Am Coll Cardiol: 10 Aug 2020; 76:735-744 | PMID: 32762908
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Abstract

Identification of Undetected Monogenic Cardiovascular Disorders.

Abdulrahim JW, Kwee LC, Alenezi F, Sun AY, ... Khouri MG, Shah SH
Background
Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed.
Objectives
The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses in a cardiovascular cohort.
Methods
Exomes from 8,574 individuals referred for cardiac catheterization were analyzed. Pathogenic/likely pathogenic (P/LP) variants associated with MCVD (cardiomyopathies, arrhythmias, connective tissue disorders, and familial hypercholesterolemia were identified. Electronic health records (EHRs) were reviewed for individuals harboring P/LP variants who were predicted to develop disease (G+). G+ individuals who did not have a documented relevant diagnosis were classified into groups of whether they may represent missed diagnoses (unknown, unlikely, possible, probable, or definite) based on relevant diagnostic criteria/features for that disease.
Results
In total, 159 P/LP variants were identified; 2,361 individuals harbored at least 1 P/LP variant, of whom 389 G+ individuals (4.5% of total cohort) were predicted to have at least 1 MCVD. EHR review of 342 G+ individuals predicted to have 1 MCVD with sufficient EHR data revealed that 52 had been given the relevant clinical diagnosis. The remaining 290 individuals were classified as potentially having an MCVD as follows: 193 unlikely (66.6%), 50 possible (17.2%), 30 probable (10.3%), and 17 definite (5.9%). Grouping possible, probable, definite, and known diagnoses, 149 were considered to have an MCVD. Novel MCVD pathogenic variants were identified in 16 individuals.
Conclusions
Overall, 149 individuals (1.7% of cohort) had MCVDs, but only 35% were diagnosed. These patients represents a \"missed opportunity,\" which could be addressed by greater use of genetic testing of patients seen by cardiologists.

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

J Am Coll Cardiol: 17 Aug 2020; 76:797-808
Abdulrahim JW, Kwee LC, Alenezi F, Sun AY, ... Khouri MG, Shah SH
J Am Coll Cardiol: 17 Aug 2020; 76:797-808 | PMID: 32792077
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Abstract

Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac Arrest.

Ameloot K, Jakkula P, Hästbacka J, Reinikainen M, ... Dens J, Skrifvars MB
Background
In patients with shock after acute myocardial infarction (AMI), the optimal level of pharmacologic support is unknown. Whereas higher doses may increase myocardial oxygen consumption and induce arrhythmias, diastolic hypotension may reduce coronary perfusion and increase infarct size.
Objectives
This study aimed to determine the optimal mean arterial pressure (MAP) in patients with AMI and shock after cardiac arrest.
Methods
This study used patient-level pooled analysis of post-cardiac arrest patients with shock after AMI randomized in the Neuroprotect (Neuroprotective Goal Directed Hemodynamic Optimization in Post-cardiac Arrest Patients; NCT02541591) and COMACARE (Carbon Dioxide, Oxygen and Mean Arterial Pressure After Cardiac Arrest and Resuscitation; NCT02698917) trials who were randomized to MAP 65 mm Hg or MAP 80/85 to 100 mm Hg targets during the first 36 h after admission. The primary endpoint was the area under the 72-h high-sensitivity troponin-T curve.
Results
Of 235 patients originally randomized, 120 patients had AMI with shock. Patients assigned to the higher MAP target (n = 58) received higher doses of norepinephrine (p = 0.004) and dobutamine (p = 0.01) and reached higher MAPs (86 ± 9 mm Hg vs. 72 ± 10 mm Hg, p < 0.001). Whereas admission hemodynamics and angiographic findings were all well-balanced and revascularization was performed equally effective, the area under the 72-h high-sensitivity troponin-T curve was lower in patients assigned to the higher MAP target (median: 1.14 μg.72 h/l [interquartile range: 0.35 to 2.31 μg.72 h/l] vs. median: 1.56 μg.72 h/l [interquartile range: 0.61 to 4.72 μg. 72 h/l]; p = 0.04). Additional pharmacologic support did not increase the risk of a new cardiac arrest (p = 0.88) or atrial fibrillation (p = 0.94). Survival with good neurologic outcome at 180 days was not different between both groups (64% vs. 53%, odds ratio: 1.55; 95% confidence interval: 0.74 to 3.22).
Conclusions
In post-cardiac arrest patients with shock after AMI, targeting MAP between 80/85 and 100 mm Hg with additional use of inotropes and vasopressors was associated with smaller myocardial injury.

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

J Am Coll Cardiol: 17 Aug 2020; 76:812-824
Ameloot K, Jakkula P, Hästbacka J, Reinikainen M, ... Dens J, Skrifvars MB
J Am Coll Cardiol: 17 Aug 2020; 76:812-824 | PMID: 32792079
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Abstract

Heart Failure With Recovered Left Ventricular Ejection Fraction: JACC Scientific Expert Panel.

Wilcox JE, Fang JC, Margulies KB, Mann DL

Reverse left ventricular (LV) remodeling and recovery of LV function are associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction. A growing body of evidence suggests that even among patients who experience a complete normalization of LV ejection fraction, a significant proportion will develop recurrent LV dysfunction accompanied by recurrent heart failure events. This has led to intense interest in understanding how to manage patients with heart failure with recovered ejection fraction (HFrecEF). Because of the lack of a standard definition for HFrecEF, and the paucity of clinical data with respect to the natural history of HFrecEF patients, there are no current guidelines on how these patients should be followed up and managed. Accordingly, this JACC Scientific Expert Panel reviews the biology of reverse LV remodeling and the clinical course of patients with HFrecEF, as well as provides guidelines for defining, diagnosing, and managing patients with HFrecEF.

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

J Am Coll Cardiol: 10 Aug 2020; 76:719-734
Wilcox JE, Fang JC, Margulies KB, Mann DL
J Am Coll Cardiol: 10 Aug 2020; 76:719-734 | PMID: 32762907
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Abstract

Transvalvular Ventricular Unloading Before Reperfusion in Acute Myocardial Infarction.

Swain L, Reyelt L, Bhave S, Qiao X, ... O\'Neill W, Kapur NK
Background
Myocardial damage due to acute ST-segment elevation myocardial infarction (STEMI) remains a significant global health problem. New approaches to limit myocardial infarct size and reduce progression to heart failure after STEMI are needed. Mechanically reducing left ventricular (LV) workload (LV unloading) before coronary reperfusion is emerging as a potential approach to reduce infarct size.
Objectives
Given the central importance of mitochondria in reperfusion injury, we hypothesized that compared with immediate reperfusion (IR), LV unloading before reperfusion improves myocardial energy substrate use and preserves mitochondrial structure and function.
Methods
To explore the effect of LV unloading duration on infarct size, we analyzed data from the STEMI-Door to Unload (STEMI-DTU) trial and then tested the effect of LV unloading on ischemia and reperfusion injury, cardiac metabolism, and mitochondrial function in swine models of acute myocardial infarction.
Results
The duration of LV unloading before reperfusion was inversely associated with infarct size in patients with large anterior STEMI. In preclinical models, LV unloading reduced the expression of hypoxia-sensitive proteins and myocardial damage due to ischemia alone. LV unloading with a transvalvular pump (TV-P) but not with venoarterial extracorporeal membrane oxygenation (ECMO) reduced infarct size. Using unbiased and blinded metabolic profiling, TV-P improved myocardial energy substrate use and preserved mitochondrial structure including cardiolipin content after reperfusion compared with IR or ECMO. Functional testing in mitochondria isolated from the infarct zone showed an intact mitochondrial structure including cardiolipin content, preserved activity of the electron transport chain including mitochondrial complex I, and reduced oxidative stress with TV-P-supported reperfusion but not with IR or ECMO.
Conclusions
These novel findings identify that transvalvular unloading limits ischemic injury before reperfusion, improves myocardial energy substrate use, and preserves mitochondrial structure and function after reperfusion.

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

J Am Coll Cardiol: 10 Aug 2020; 76:684-699
Swain L, Reyelt L, Bhave S, Qiao X, ... O'Neill W, Kapur NK
J Am Coll Cardiol: 10 Aug 2020; 76:684-699 | PMID: 32762903
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Abstract

Prevalence and Prognostic Significance of Malnutrition in Patients With Acute Coronary Syndrome.

Raposeiras Roubín S, Abu Assi E, Cespón Fernandez M, Barreiro Pardal C, ... Ibanez B, Íñiguez Romo A
Background
Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its prognostic impact in patients with acute coronary syndrome (ACS) is not well known.
Objectives
This study sought to report the prevalence, clinical associations, and prognostic consequences of malnutrition in patients with ACS.
Methods
In this study, the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI) was applied to 5,062 consecutive patients with ACS. The relationships between malnutrition risk and all-cause mortality and major cardiovascular events (MACEs) (cardiovascular mortality, reinfarction, or ischemic stroke) were examined.
Results
According to the CONUT score, NRI, and PNI, 11.2%, 39.5%, and 8.9% patients were moderately or severely malnourished, respectively; 71.8% were at least mildly malnourished by at least 1 score. Although worse scores were most strongly related to lower body mass index, between 8.4% and 36.7% of patients with a body mass index of ≥25 kg/m were moderately or severely malnourished, depending on the nutritional index used. During a median follow-up of 3.6 years (interquartile range: 1.3 to 5.3 years), 830 (16.4%) patients died, and 1,048 (20.7%) had MACEs. Compared with good nutritional status, malnutrition was associated with significantly increased risk for all-cause death (adjusted hazard ratio for moderate and severe degrees of malnutrition, respectively: 2.02 [95% confidence interval (CI): 1.65 to 2.49] and 3.65 [95% CI: 2.41 to 5.51] for the CONUT score, 1.40 [95% CI: 1.17 to 1.68] and 2.87 [95% CI: 2.17 to 3.79] for the NRI, and 1.71 [95% CI: 1.37 to 2.15] and 1.95 [95% CI: 1.55 to 2.45] for the PNI score; p values <0.001 for all nutritional indexes). Similar results were found for the CONUT score and PNI regarding MACEs. All risk scores improve the predictive ability of the GRACE (Global Registry of Acute Coronary Events) risk score for both all-cause mortality and MACEs.
Conclusions
Malnutrition is common among patients with ACS and is strongly associated with increased mortality and cardiovascular events. Clinical trials are needed to prospectively evaluate the efficacy of nutritional interventions on outcomes in patients with ACS.

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

J Am Coll Cardiol: 17 Aug 2020; 76:828-840
Raposeiras Roubín S, Abu Assi E, Cespón Fernandez M, Barreiro Pardal C, ... Ibanez B, Íñiguez Romo A
J Am Coll Cardiol: 17 Aug 2020; 76:828-840 | PMID: 32792081
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Abstract

Focused Transesophageal Echocardiography During Cardiac Arrest Resuscitation: JACC Review Topic of the Week.

Teran F, Prats MI, Nelson BP, Kessler R, ... Arntfield RT, Bahner D

Focused transthoracic echocardiography (TTE) during cardiac arrest resuscitation can enable the characterization of myocardial activity, identify potentially treatable pathologies, assist with rhythm interpretation, and provide prognostic information. However, an important limitation of TTE is the difficulty obtaining interpretable images due to external and patient-related limiting factors. Over the last decade, focused transesophageal echocardiography (TEE) has been proposed as a tool that is ideally suited to image patients in extremis-those in cardiac arrest and periarrest states. In addition to the same diagnostic and prognostic role provided by TTE images, TEE provides unique advantages including the potential to optimize the quality of chest compressions, shorten cardiopulmonary resuscitation interruptions, guide resuscitative procedures, and provides a continuous image of myocardial activity. This review discusses the rationale, supporting evidence, opportunities, and challenges, and proposes a research agenda for the use of focused TEE in cardiac arrest with the goal to improve resuscitation outcomes.

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

J Am Coll Cardiol: 10 Aug 2020; 76:745-754
Teran F, Prats MI, Nelson BP, Kessler R, ... Arntfield RT, Bahner D
J Am Coll Cardiol: 10 Aug 2020; 76:745-754 | PMID: 32762909
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Abstract

Lipoprotein(a) and Family History Predict Cardiovascular Disease Risk.

Mehta A, Virani SS, Ayers CR, Sun W, ... Ballantyne CM, Khera A
Background
Elevated lipoprotein(a) (Lp[a]) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.
Objectives
The aim of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.
Methods
Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.
Results
Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.
Conclusions
Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions.

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

J Am Coll Cardiol: 17 Aug 2020; 76:781-793
Mehta A, Virani SS, Ayers CR, Sun W, ... Ballantyne CM, Khera A
J Am Coll Cardiol: 17 Aug 2020; 76:781-793 | PMID: 32792075
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Abstract

Presentation and Outcome of Arrhythmic Mitral Valve Prolapse.

Essayagh B, Sabbag A, Antoine C, Benfari G, ... Michelena H, Enriquez-Sarano M
Background
Mitral valve prolapse (MVP) is often considered benign but recent suggestion of an arrhythmic MVP (AMVP) form remains incompletely defined and uncertain.
Objectives
This study determined ventricular arrhythmia prevalence, severity, phenotypical context, and independent impact on outcome in patients with MVP.
Methods
A cohort of 595 (age 65 ± 16 years; 278 women) consecutive patients with MVP and comprehensive clinical, arrhythmia (24-h Holter monitoring) and Doppler-echocardiographic characterization, was identified. Long-term outcomes were analyzed.
Results
Ventricular arrhythmia was frequent (43% with at least ventricular ectopy ≥5%), most often moderate (ventricular tachycardia [VT]; 120 to 179 beats/min) in 27%, and rarely severe (VT ≥180 beats/min) in 9%. Presence of ventricular arrhythmia was associated with male sex, bileaflet prolapse, marked leaflet redundancy, mitral annulus disjunction (MAD), a larger left atrium and left ventricular end-systolic diameter, and T-wave inversion/ST-segment depression (all p ≤ 0.001). Severe ventricular arrhythmia was independently associated with presence of MAD, leaflet redundancy, and T-wave inversion/ST-segment depression (all p < 0.0001) but not with mitral regurgitation severity or ejection fraction. Overall mortality after arrhythmia diagnosis (8 years; 13 ± 2%) was strongly associated with arrhythmia severity (8 years; 10 ± 2% for no/trivial, 15 ± 3% for mild and/or moderate, and 24 ± 7% for severe arrhythmia; p = 0.02). Excess mortality was substantial for severe arrhythmia (univariate hazard ratio [HR]: 2.70; 95% confidence interval [CI]: 1.27 to 5.77; p = 0.01 vs. no/trivial arrhythmia), even after it was comprehensively adjusted, including for MVP characteristics (adjusted HR: 2.94; 95% CI: 1.36 to 6.36; p = 0.006) and by time-dependent analysis (adjusted HR: 3.25; 95% CI: 1.56 to 6.78; p = 0.002). Severe arrhythmia was also associated with higher rates of mortality, defibrillator implantation, VT ablation (adjusted HR: 4.68; 95% CI: 2.45 to 8.92; p < 0.0001), particularly under medical management (adjusted HR: 5.80; 95% CI: 2.75 to 12.23; p < 0.0001), and weakly post-mitral surgery (adjusted HR: 3.69; 95% CI: 0.93 to 14.74; p = 0.06).
Conclusions
In this large cohort of patients with MVP, ventricular arrhythmia by Holter monitoring was frequent but rarely severe. AMVP was independently associated with phenotype dominated by MAD, marked leaflet redundancy, and repolarization abnormalities. Long-term severe arrhythmia was independently associated with notable excess mortality and reduced event-free survival, particularly under medical management. Therefore, AMVP is a clinical entity strongly associated with outcome and warrants careful risk assessment and well-designed clinical trials.

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

J Am Coll Cardiol: 10 Aug 2020; 76:637-649
Essayagh B, Sabbag A, Antoine C, Benfari G, ... Michelena H, Enriquez-Sarano M
J Am Coll Cardiol: 10 Aug 2020; 76:637-649 | PMID: 32762897
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Abstract

Performance of Guideline Recommendations for Prevention of Myocardial Infarction in Young Adults.

Zeitouni M, Nanna MG, Sun JL, Chiswell K, Peterson ED, Navar AM
Background
The 2018 cholesterol guidelines of the American Heart Association and the American College of Cardiology (AHA/ACC) changed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) eligibility criteria for primary prevention to include multiple risk enhancers and novel intensive lipid-lowering therapies for secondary prevention.
Objectives
This study sought to determine how guideline changes affected identification for preventive therapy in young adults with premature myocardial infarction (MI).
Methods
The study identified adults presenting with first MI at Duke University Medical Center in Durham, North Carolina. Statin therapy eligibility was determined using the 2013 ACC/AHA and 2018 AHA/ACC guidelines criteria. The study also determined potential eligibility for intensive lipid-lowering therapies (very high risk) under the 2018 AHA/ACC guidelines, by assessing the composite of all-cause death, recurrent MI, or stroke rates in adults considered \"very high risk\" versus not.
Results
Among 6,639 patients with MI, 41% were <55 years of age (\"younger\"), 35% were 55 to 65 years of age (\"middle-aged\"), and 24% were 66 to 75 years of age (\"older\"). Younger adults were more frequently smokers (52% vs. 38% vs. 22%, respectively) and obese (42% vs. 34% vs. 31%, respectively), with metabolic syndrome (21% vs. 19% vs. 17%, respectively) and higher low-density lipoprotein cholesterol (117 vs. 107 vs. 103 mg/dl, respectively) (p trend <0.01 for all). Pre-MI, fewer younger adults met guideline indications for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) therapy than middle-aged and older adults. The 2018 guideline identified fewer younger adults eligible for statin therapy at the time of their MI than the 2013 guideline (46.4% vs. 56.7%; p < 0.01). Younger patients less frequently met very high-risk criteria for intensive secondary prevention lipid-lowering therapy (28.3% vs. 40.0% vs. 81.4%, respectively; p < 0.01). Over a median 8 years of follow-up, very high-risk criteria were associated with increased risk of major adverse cardiovascular events in individuals <55 years of age (hazard ratio: 2.09; 95% confidence interval: 1.82 to 2.41; p < 0.001), as was the case in older age groups (p interaction = 0.54).
Conclusions
Most younger patients with premature MI are not identified as statin candidates before their event on the basis of the 2018 guidelines, and most patients with premature MI are not recommended for intensive post-MI lipid management.

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

J Am Coll Cardiol: 10 Aug 2020; 76:653-664
Zeitouni M, Nanna MG, Sun JL, Chiswell K, Peterson ED, Navar AM
J Am Coll Cardiol: 10 Aug 2020; 76:653-664 | PMID: 32762899
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Abstract

Machine Learning Assessment of Left Ventricular Diastolic Function Based on Electrocardiographic Features.

Kagiyama N, Piccirilli M, Yanamala N, Shrestha S, ... Narula J, Sengupta PP
Background
Left ventricular (LV) diastolic dysfunction is recognized as playing a major role in the pathophysiology of heart failure; however, clinical tools for identifying diastolic dysfunction before echocardiography remain imprecise.
Objectives
This study sought to develop machine-learning models that quantitatively estimate myocardial relaxation using clinical and electrocardiography (ECG) variables as a first step in the detection of LV diastolic dysfunction.
Methods
A multicenter prospective study was conducted at 4 institutions in North America enrolling a total of 1,202 subjects. Patients from 3 institutions (n = 814) formed an internal cohort and were randomly divided into training and internal test sets (80:20). Machine-learning models were developed using signal-processed ECG, traditional ECG, and clinical features and were tested using the test set. Data from the fourth institution was reserved as an external test set (n = 388) to evaluate the model generalizability.
Results
Despite diversity in subjects, the machine-learning model predicted the quantitative values of the LV relaxation velocities (e\') measured by echocardiography in both internal and external test sets (mean absolute error: 1.46 and 1.93 cm/s; adjusted R = 0.57 and 0.46, respectively). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that the estimated e\' discriminated the guideline-recommended thresholds for abnormal myocardial relaxation and diastolic and systolic dysfunction (LV ejection fraction) the internal (area under the curve [AUC]: 0.83, 0.76, and 0.75) and external test sets (0.84, 0.80, and 0.81), respectively. Moreover, the estimated e\' allowed prediction of LV diastolic dysfunction based on multiple age- and sex-adjusted reference limits (AUC: 0.88 and 0.94 in the internal and external sets, respectively).
Conclusions
A quantitative prediction of myocardial relaxation can be performed using easily obtained clinical and ECG features. This cost-effective strategy may be a valuable first clinical step for assessing the presence of LV dysfunction and may potentially aid in the early diagnosis and management of heart failure patients.

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

J Am Coll Cardiol: 24 Aug 2020; 76:930-941
Kagiyama N, Piccirilli M, Yanamala N, Shrestha S, ... Narula J, Sengupta PP
J Am Coll Cardiol: 24 Aug 2020; 76:930-941 | PMID: 32819467
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Abstract

Loop Diuretic Prescription and 30-Day Outcomes in Older Patients With Heart Failure.

Faselis C, Arundel C, Patel S, Lam PH, ... Fonarow GC, Ahmed A
Background
Heart failure (HF) is a major source of morbidity and mortality. Fluid retention and shortness of breath are its cardinal manifestations for which loop diuretics are used. Although their usefulness is well accepted, less is known about their role in improving clinical outcomes.
Objectives
The purpose of this study was to determine the relationship between loop diuretics and clinical outcomes in patients with HF.
Methods
Of the 25,345 older patients hospitalized for HF in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 9,866 (39%) received no pre-admission diuretics. The study excluded 1,083 patients receiving dialysis and 847 discharged on thiazide diuretics. Of the remaining 7,936 patients, 5,568 (70%) were prescribed loop diuretics at discharge. Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort.
Results
Matched patients (n = 4,382) had a mean age of 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality occurred in 4.9% (107 of 2,191) and 6.6% (144 of 2,191) of patients in the loop diuretic and no loop diuretic groups, respectively (HR when the use of loop diuretics was compared with nonuse: 0.73; 95% CI: 0.57 to 0.94; p = 0.016). Patients in the loop diuretic group had a significantly lower risk of 30-day HF readmission (HR: 0.79; 95% CI: 0.63 to 0.99; p = 0.037) but not of 30-day all-cause readmission (HR: 0.89; 95% CI: 0.79 to 1.01; p = 0.081). None of the associations was statistically significant during 60 days of follow-up.
Conclusions
Hospitalized older patients not taking diuretics prior to hospitalization for HF decompensation who received a discharge prescription for loop diuretics had significantly better 30-day clinical outcomes than those not discharged on loop diuretics. These findings provide new information about short-term clinical benefits associated with loop diuretic use in HF.

Published by Elsevier Inc.

J Am Coll Cardiol: 10 Aug 2020; 76:669-679
Faselis C, Arundel C, Patel S, Lam PH, ... Fonarow GC, Ahmed A
J Am Coll Cardiol: 10 Aug 2020; 76:669-679 | PMID: 32762901
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Abstract

Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians.

Wang M, Menon R, Mishra S, Patel AP, ... Gupta R, Khera AV
Background
Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.
Objectives
This analysis used summary statistics from a prior genome-wide association study to derive a new GPS for South Asians.
Methods
This GPS was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPS reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPS reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.
Results
The GPS, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPS distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each).
Conclusions
The new GPS has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.

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

J Am Coll Cardiol: 10 Aug 2020; 76:703-714
Wang M, Menon R, Mishra S, Patel AP, ... Gupta R, Khera AV
J Am Coll Cardiol: 10 Aug 2020; 76:703-714 | PMID: 32762905
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Abstract

Imaging of Clinically Unrecognized Myocardial Fibrosis in Patients With Suspected Coronary Artery Disease.

Antiochos P, Ge Y, Steel K, Bingham S, ... Kwong RY,
Background
Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia.
Objectives
This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia.
Methods
In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE).
Results
UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE.
Conclusions
In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891).

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

J Am Coll Cardiol: 24 Aug 2020; 76:945-957
Antiochos P, Ge Y, Steel K, Bingham S, ... Kwong RY,
J Am Coll Cardiol: 24 Aug 2020; 76:945-957 | PMID: 32819469
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Abstract

Pulmonary Artery Denervation for Patients With Residual Pulmonary Hypertension After Pulmonary Endarterectomy.

Romanov A, Cherniavskiy A, Novikova N, Edemskiy A, ... Martynyuk TV, Steinberg JS
Background
Pulmonary artery denervation (PADN) procedure has not been applied to patients with residual chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA).
Objectives
This study sought to assess the safety and efficacy of PADN using remote magnetic navigation in patients with residual CTEPH after PEA.
Methods
Fifty patients with residual CTEPH despite medical therapy at least 6 months after PEA, who had mean pulmonary artery pressure ≥25 mm Hg or pulmonary vascular resistance (PVR) > 400 dyn‧s‧cm based on right heart catheterization were randomized to treatment with PADN (PADN group; n = 25) using remote magnetic navigation for ablation or medical therapy with riociguat (MED group; n = 25). In the MED group, a sham procedure with mapping but no ablation was performed. The primary endpoint was PVR at 12 months after randomization. Key secondary endpoint included 6-min walk test.
Results
After PADN procedure, 2 patients (1 in each group) developed groin hematoma that resolved without any consequences. At 12 months, mean PVR reduction was 258 ± 135 dyn‧s‧cm in the PADN group versus 149 ± 73 dyn‧s‧cm in the MED group, mean between-group difference was 109 dyn‧s‧cm (95% confidence interval: 45 to 171; p = 0.001). The 6-min walk test distance was significantly increased in the PADN group as compared to distance in the MED group (470 ± 84 m vs. 399 ± 116 m, respectively; p = 0.03).
Conclusions
PADN in patients with residual CTEPH resulted in substantial reduction of PVR at 12 months of follow-up, accompanied by improved 6-min walk test.

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

J Am Coll Cardiol: 24 Aug 2020; 76:916-926
Romanov A, Cherniavskiy A, Novikova N, Edemskiy A, ... Martynyuk TV, Steinberg JS
J Am Coll Cardiol: 24 Aug 2020; 76:916-926 | PMID: 32819465
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Abstract

Raising the Evidentiary Bar for Guideline Recommendations for TAVR: JACC Review Topic of the Week.

Kaul S

On August 16, 2019, the U.S. Food and Drug Administration approved expanding the indication for transcatheter aortic valve replacement (TAVR) to low-risk patients with symptomatic severe aortic stenosis. The decision was based on the results of 2 pivotal trials that confirmed superiority (PARTNER [Placement of Aortic Transcatheter Valves] 3) or noninferiority (Evolut Low Risk [LR]) of TAVR as compared with SAVR at 1- and 2-year follow-up, respectively. As compared with intermediate-risk cohorts, the sample size in these trials was smaller and the total number of primary endpoint events was nearly 3 times as low (193 vs. 615). The total number of deaths from any cause or disabling stroke at 1 year in the low-risk cohorts was 62, which is substantially lower than the numbers in intermediate-, high-, and inoperable-risk cohorts. In Evolut LR, only 137 of 1,403 patients (9.8%) completed the 2-year follow-up, with 91.2% requiring model-based imputation. Thus, the quantum of evidence is insufficient for endorsing TAVR as the preferred intervention for these patients.

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

J Am Coll Cardiol: 24 Aug 2020; 76:985-991
Kaul S
J Am Coll Cardiol: 24 Aug 2020; 76:985-991 | PMID: 32819472
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Abstract

Sex Differences in All-Cause Mortality in the Decade Following Complex Coronary Revascularization.

Hara H, Takahashi K, van Klaveren D, Wang R, ... Serruys PW,
Background
The poorer prognosis of coronary artery disease in females compared with males is related mainly to differences in baseline characteristics. In the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial, the effect of treatment with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting surgery (CABG) on mortality at 5 years differed significantly between females and males; however, the optimal revascularization beyond 5 years according to sex has not been evaluated.
Objectives
The aim of this study was to investigate the impact of sex on mortality and sex-treatment interaction at 10 years.
Methods
The SYNTAXES (SYNTAX Extended Survival) study evaluated vital status up to 10 years in 1,800 patients with de novo 3-vessel and/or left main coronary artery disease randomized to treatment with PCI or CABG in the SYNTAX trial. All-cause death at 10 years was separately evaluated in female and male patients with complex coronary artery disease.
Results
Of 1,800 patients, 402 (22.3%) were female and 1,398 (77.7%) were males. Females had a higher 10-year mortality rate compared with males (32.8% vs. 24.7%; log-rank p = 0.002), but female sex was not an independent predictor of mortality (adjusted hazard ratio: 1.02; 95% confidence interval: 0.76 to 1.36). Mortality at 10 years tended to be lower after CABG than after PCI, with a similar treatment effect for female and male patients (adjusted hazard ratio for females: 0.90 [95% confidence interval: 0.54 to 1.51]; adjusted hazard ratio for males: 0.76 [95% confidence interval: 0.56 to 1.02]; p for interaction = 0.952).
Conclusions
Female sex was not an independent predictor of mortality at 10 years in patients with complex coronary artery disease. The interaction between sex and treatment with PCI or CABG that was observed at 5 years was no longer present at 10 years. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972).

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

J Am Coll Cardiol: 24 Aug 2020; 76:889-899
Hara H, Takahashi K, van Klaveren D, Wang R, ... Serruys PW,
J Am Coll Cardiol: 24 Aug 2020; 76:889-899 | PMID: 32819461
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Abstract

Survival and Right Ventricular Function After Surgical Management of Acute Pulmonary Embolism.

Goldberg JB, Spevack DM, Ahsan S, Rochlani Y, ... Lansman S, Malekan R
Background
Acute pulmonary embolism (PE) is associated with high morbidity and mortality because of right ventricular (RV) failure. There is evidence suggesting surgical therapy (surgical embolectomy or venoarterial extracorporeal membrane oxygenation [ECMO]) is safe and effective.
Objectives
The aim of this study was to assess the safety and efficacy of surgical management of acute PE.
Methods
Surgical embolectomy and/or venoarterial ECMO were compared, between 2005 and 2019, for massive PE (MPE) versus high-risk submassive PE (SMPE). RV recovery was defined as improvements in central venous pressure, pulmonary artery systolic pressure, RV/left ventricular ratio, and RV fractional area change.
Results
One hundred thirty-six patients with PE (92 with SMPE and 44 with MPE) were identified. Patients with MPE more often presented with syncope (59.1% [26 of 44] vs. 25.0% [23 of 92]; p = 0.0003), Glasgow Coma Scale score ≤4 (22.7% [10 of 44] vs. 0% [0 of 92]), and failed thrombolysis (18.2% [8 of 44] vs. 4.3% [3 of 92]; p = 0.008). Pre-operative cardiopulmonary resuscitation occurred in 43.2% of patients with MPE (19 of 44). Most patients with SMPE were treated with embolectomy (98.9% [91 of 92]), while ECMO was used more in those with MPE (ECMO in 40.9% [18 of 44], embolectomy in 59.1% [26 of 44]). RV function improved as measured by central venous pressure (from 23.4 ± 4.9 to 10.5 ± 3.1 mm Hg), pulmonary artery systolic pressure (from 60.6 ± 14.2 to 33.8 ± 10.7 mm Hg), RV/left ventricular ratio (from 1.19 ± 0.33 to 0.87 ± 0.23; p < 0.005), and fractional area change (from 26.8 to 41.0; p < 0.005). Mortality was 4.4% (6 of 136; SMPE, 1.1% [1 of 92]; MPE, 11.6% [5 of 44]). Subgroup analysis showed morbidity and mortality were highly associated with pre-operative cardiopulmonary resuscitation.
Conclusions
Surgical management of patients with MPE and high-risk SMPE is safe and highly effective at achieving RV recovery.

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

J Am Coll Cardiol: 24 Aug 2020; 76:903-911
Goldberg JB, Spevack DM, Ahsan S, Rochlani Y, ... Lansman S, Malekan R
J Am Coll Cardiol: 24 Aug 2020; 76:903-911 | PMID: 32819463
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Abstract

Spontaneous Coronary Artery Dissection: JACC State-of-the-Art Review.

Hayes SN, Tweet MS, Adlam D, Kim ESH, ... Price JE, Rose CH

Over the past decade, spontaneous coronary artery dissection (SCAD) has emerged as an important cause of myocardial infarction, particularly among younger women. The pace of knowledge acquisition has been rapid, but ongoing challenges include accurately diagnosing SCAD and improving outcomes. Many SCAD patients experience substantial post-SCAD symptoms, recurrent SCAD, and psychosocial distress. Considerable uncertainty remains about optimal management of associated conditions, risk stratification and prevention of complications, recommendations for physical activity, reproductive planning, and the role of genetic evaluations. This review provides a clinical update on the diagnosis and management of patients with SCAD, including pregnancy-associated SCAD and pregnancy after SCAD, and highlight high-priority knowledge gaps that must be addressed.

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

J Am Coll Cardiol: 24 Aug 2020; 76:961-984
Hayes SN, Tweet MS, Adlam D, Kim ESH, ... Price JE, Rose CH
J Am Coll Cardiol: 24 Aug 2020; 76:961-984 | PMID: 32819471
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Abstract

Atrial Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation.

Reddy YNV, Obokata M, Verbrugge FH, Lin G, Borlaug BA
Background
Paroxysmal and permanent atrial fibrillation (AF) are common in heart failure with preserved ejection fraction (HFpEF).
Objectives
This study sought to determine the implications of left atrial (LA) myopathy and dysrhythmia across the spectrum of AF burden in HFpEF.
Methods
Consecutive patients with HFpEF (n = 285) and control subjects (n = 146) underwent invasive exercise testing and echocardiographic assessment of cardiac structure, function, and pericardial restraint.
Results
Patients with HFpEF were categorized into stages of AF progression: 181 (65%) had no history of AF, 49 (18%) had paroxysmal AF, and 48 (17%) had permanent AF. Patients with permanent AF were more congested with greater pulmonary vascular disease and lower cardiac output. LA volumes increased, while LA compliance, LA reservoir strain, and right ventricular function decreased with increasing AF burden. The presence of permanent AF was characterized by a distinct pathophysiology, with greater total heart volume caused by atrial dilatation, leading to elevated filling pressures through heightened pericardial restraint. Survival decreased with increasing AF burden. Ten-year progression to permanent AF was common, particularly in paroxysmal AF (52%), and the likelihood of AF progression increased with higher AF stage, poorer LA compliance, and lower LA strain.
Conclusions
LA compliance and mechanics progressively decline with increasing AF burden in HFpEF, increasing risk for new onset AF and progressive AF. These changes promote development of a unique phenotype of HFpEF characterized by heightened ventricular interaction, right heart failure, and worsening pulmonary vascular disease. Further study is required to identify therapeutic interventions targeting LA myopathy to improve outcomes in HFpEF.

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

J Am Coll Cardiol: 31 Aug 2020; 76:1051-1064
Reddy YNV, Obokata M, Verbrugge FH, Lin G, Borlaug BA
J Am Coll Cardiol: 31 Aug 2020; 76:1051-1064 | PMID: 32854840
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Abstract

Pulmonary Hypertension in HFpEF and HFrEF: JACC Review Topic of the Week.

Guazzi M, Ghio S, Adir Y

Pulmonary hypertension (PH) associated with left heart disease, or Group 2 PH, includes heart failure, valvular heart diseases, and congenital heart diseases. Although it is axiomatic that in PH due to heart failure the increase in pulmonary pressure is directly related to an enhanced left atrial pressure, which is common to both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), there has been limited attention over the years on the potential differences in terms of driving mechanisms, pathophysiology, and clinical phenotypes. Major differences between HFpEF and HFrEF are the underlying causes, associated comorbidities, and cardiac remodeling. This suggests that despite similar hemodynamic profiles, there may be some disparities in PH development. A focused knowledge on the differences between the 2 syndromes has relevant implications to seek new, personalized, and timely treatments for Group 2 PH. The purpose of the present review is to highlight the mechanisms and clinical phenotypes of PH in HFpEF and HFrEF.

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

J Am Coll Cardiol: 31 Aug 2020; 76:1102-1111
Guazzi M, Ghio S, Adir Y
J Am Coll Cardiol: 31 Aug 2020; 76:1102-1111 | PMID: 32854845
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Abstract

Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists.

Ambrosy AP, Braunwald E, Morrow DA, DeVore AD, ... Velazquez EJ,
Background
The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction.
Objectives
The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results.
Methods
The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission.
Results
At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro-B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups.
Conclusions
Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).

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

J Am Coll Cardiol: 31 Aug 2020; 76:1034-1048
Ambrosy AP, Braunwald E, Morrow DA, DeVore AD, ... Velazquez EJ,
J Am Coll Cardiol: 31 Aug 2020; 76:1034-1048 | PMID: 32854838
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Abstract

Pulsed Field Ablation in Patients With Persistent Atrial Fibrillation.

Reddy VY, Anic A, Koruth J, Petru J, ... Kawamura I, Neuzil P
Background
Unlike for paroxysmal atrial fibrillation (AF), pulmonary vein isolation (PVI) alone is considered insufficient for many patients with persistent AF. Adjunctive ablation of the left atrial posterior wall (LAPW) may improve outcomes, but is limited by both the difficulty of achieving lesion durability and concerns of damage to the esophagus-situated behind the LAPW.
Objectives
This study sought to assess the safety and lesion durability of pulsed field ablation (PFA) for both PVI and LAPW ablation in persistent AF.
Methods
PersAFOne is a single-arm study evaluating biphasic, bipolar PFA using a multispline catheter for PVI and LAPW ablation under intracardiac echocardiographic guidance. A focal PFA catheter was used for cavotricuspid isthmus ablation. No esophageal protection strategy was used. Invasive remapping was mandated at 2 to 3 months to assess lesion durability.
Results
In 25 patients, acute PVI (96 of 96 pulmonary veins [PVs]; mean ablation time: 22 min; interquartile range [IQR]: 15 to 29 min) and LAPW ablation (24 of 24 patients; median ablation time: 10 min; IQR: 6 to 13 min) were 100% acutely successful with the multispline PFA catheter alone. Using the focal PFA catheter, acute cavotricuspid isthmus block was achieved in 13 of 13 patients (median: 9 min; IQR: 6 to 12 min). The median total procedure time was 125 min (IQR: 108 to 166 min) (including a median of 28 min [IQR: 25 to 33 min] for voltage mapping), with a median of 16 min (IQR: 12 to 23 min) fluoroscopy. Post-procedure esophagogastroduodenoscopy and repeat cardiac computed tomography revealed no mucosal lesions or PV narrowing, respectively. Invasive remapping demonstrated durable isolation (defined by entrance block) in 82 of 85 PVs (96%) and 21 of 21 LAPWs (100%) treated with the pentaspline catheter. In 3 patients, there was localized scar regression of the LAPW ablation, albeit without conduction breakthrough.
Conclusions
The unique safety profile of PFA potentiated efficient, safe, and durable PVI and LAPW ablation. This extends the potential role of PFA beyond paroxysmal to persistent forms of AF. (Pulsed Fields for Persistent Atrial Fibrillation [PersAFOne]; NCT04170621).

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

J Am Coll Cardiol: 31 Aug 2020; 76:1068-1080
Reddy VY, Anic A, Koruth J, Petru J, ... Kawamura I, Neuzil P
J Am Coll Cardiol: 31 Aug 2020; 76:1068-1080 | PMID: 32854842
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Abstract

Bicuspid Aortic Valve Morphology and Outcomes After Transcatheter Aortic Valve Replacement.

Yoon SH, Kim WK, Dhoble A, Milhorini Pio S, ... Makkar RR,
Background
Bicuspid aortic stenosis accounts for almost 50% of patients undergoing surgical aortic valve replacement in the younger patients. Expanding the indication of transcatheter aortic valve replacement (TAVR) toward lower-risk and younger populations will lead to increased use of TAVR for patients with bicuspid aortic valve (BAV) stenosis despite the exclusion of bicuspid anatomy in all pivotal clinical trials.
Objectives
This study sought to evaluate the association of BAV morphology and outcomes of TAVR with the new-generation devices.
Methods
Patients with BAV confirmed by central core laboratory computed tomography (CT) analysis were included from the international multicenter BAV TAVR registry. BAV morphology including the number of raphe, calcification grade in raphe, and leaflet calcium volume were assessed with CT analysis in a masked fashion. Primary outcomes were all-cause mortality at 1 and 2 years, and secondary outcomes included 30-day major endpoints and procedural complications.
Results
A total of 1,034 CT-confirmed BAV patients with a mean age of 74.7 years and Society of Thoracic Surgeons score of 3.7% underwent TAVR with contemporary devices (n = 740 with Sapien 3; n = 188 with Evolut R/Pro; n = 106 with others). All-cause 30-day, 1-year, and 2-year mortality was 2.0%, 6.7%, and 12.5%, respectively. Multivariable analysis identified calcified raphe and excess leaflet calcification (defined as more than median calcium volume) as independent predictors of 2-year all-cause mortality. Both calcified raphe plus excess leaflet calcification were found in 269 patients (26.0%), and they had significantly higher 2-year all-cause mortality than those with 1 or none of these morphological features (25.7% vs. 9.5% vs. 5.9%; log-rank p < 0.001). Patients with both morphological features had higher rates of aortic root injury (p < 0.001), moderate-to-severe paravalvular regurgitation (p = 0.002), and 30-day mortality (p = 0.016).
Conclusions
Outcomes of TAVR in bicuspid aortic stenosis depend on valve morphology. Calcified raphe and excess leaflet calcification were associated with increased risk of procedural complications and midterm mortality. (Bicuspid Aortic Valve Stenosis Transcatheter Aortic Valve Replacement Registry; NCT03836521).

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

J Am Coll Cardiol: 31 Aug 2020; 76:1018-1030
Yoon SH, Kim WK, Dhoble A, Milhorini Pio S, ... Makkar RR,
J Am Coll Cardiol: 31 Aug 2020; 76:1018-1030 | PMID: 32854836
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Abstract

Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation: The COAPT Trial.

Grayburn PA, Sannino A, Cohen DJ, Kar S, ... Mack MJ, Stone GW
Background
Transcatheter mitral valve repair with the MitraClip results in marked clinical improvement in some but not all patients with secondary mitral regurgitation (MR) and heart failure (HF).
Objectives
This study sought to evaluate the clinical predictors of a major response to treatment in the COAPT trial.
Methods
Patients with HF and severe MR who were symptomatic on maximally tolerated guideline-directed medical therapy (GDMT) were randomly assigned to MitraClip plus GDMT or GDMT alone. Super-responders were defined as those alive without HF hospitalization and with ≥20-point improvement in the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score at 12 months. Responders were defined as those alive without HF hospitalization and with a 5 to <20-point KCCQ-OS improvement at 12 months. Nonresponders were those who either died, were hospitalized for HF, or had <5-point improvement in KCCQ-OS at 12 months.
Results
Among 614 enrolled patients, 41 (6.7%) had missing KCCQ-OS data and could not be classified. At 12 months, there were 79 super-responders (27.2%), 55 responders (19.0%), and 156 nonresponders (53.8%) in the MitraClip arm compared with 29 super-responders (10.2%), 46 responders (16.3%), and 208 nonresponders (73.5%) in the GDMT-alone arm (overall p < 0.0001). Independent baseline predictors of clinical responder status were lower serum creatinine and KCCQ-OS scores and treatment assignment to MitraClip. MR grade and estimated right ventricular systolic pressure at 30 days were improved to a greater degree in super-responders and responders but not in nonresponders.
Conclusions
Baseline predictors of clinical super-responders in patients with HF and severe secondary MR in the COAPT trial were lower serum creatinine, KCCQ-OS score and MitraClip treatment. Improved MR severity and reduced right ventricular systolic pressure at 30 days are associated with a long-term favorable clinical response after transcatheter mitral valve repair. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

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

J Am Coll Cardiol: 31 Aug 2020; 76:1007-1014
Grayburn PA, Sannino A, Cohen DJ, Kar S, ... Mack MJ, Stone GW
J Am Coll Cardiol: 31 Aug 2020; 76:1007-1014 | PMID: 32854834
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Abstract

Contemporary Management of Severe Acute Kidney Injury and Refractory Cardiorenal Syndrome: JACC Council Perspectives.

Jentzer JC, Bihorac A, Brusca SB, Del Rio-Pertuz G, ... Solomon MA,

Acute kidney injury (AKI) and cardiorenal syndrome (CRS) are increasingly prevalent in hospitalized patients with cardiovascular disease and remain associated with poor short- and long-term outcomes. There are no specific therapies to reduce mortality related to either AKI or CRS, apart from supportive care and volume status management. Acute renal replacement therapies (RRTs), including ultrafiltration, intermittent hemodialysis, and continuous RRT are used to manage complications of medically refractory AKI and CRS and may restore normal electrolyte, acid-base, and fluid balance before renal recovery. Patients who require acute RRT have a significant risk of mortality and long-term dialysis dependence, emphasizing the importance of appropriate patient selection. Despite the growing use of RRT in the cardiac intensive care unit, there are few resources for the cardiovascular specialist that integrate the epidemiology, diagnostic workup, and medical management of AKI and CRS with an overview of indications, multidisciplinary team management, and transition off of RRT.

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

J Am Coll Cardiol: 31 Aug 2020; 76:1084-1101
Jentzer JC, Bihorac A, Brusca SB, Del Rio-Pertuz G, ... Solomon MA,
J Am Coll Cardiol: 31 Aug 2020; 76:1084-1101 | PMID: 32854844
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Abstract

Epicardial Adipose Tissue Accumulation Confers Atrial Conduction Abnormality.

Nalliah CJ, Bell JR, Raaijmakers AJA, Waddell HM, ... Delbridge LMD, Kalman JM
Background
Clinical studies have reported that epicardial adipose tissue (EpAT) accumulation associates with the progression of atrial fibrillation (AF) pathology and adversely affects AF management. The role of local cardiac EpAT deposition in disease progression is unclear, and the electrophysiological, cellular, and molecular mechanisms involved remain poorly defined.
Objectives
The purpose of this study was to identify the underlying mechanisms by which EpAT influences the atrial substrate for AF.
Methods
Patients without AF undergoing coronary artery bypass surgery were recruited. Computed tomography and high-density epicardial electrophysiological mapping of the anterior right atrium were utilized to quantify EpAT volumes and to assess association with the electrophysiological substrate in situ. Excised right atrial appendages were analyzed histologically to characterize EpAT infiltration, fibrosis, and gap junction localization. Co-culture experiments were used to evaluate the paracrine effects of EpAT on cardiomyocyte electrophysiology. Proteomic analyses were applied to identify molecular mediators of cellular electrophysiological disturbance.
Results
Higher local EpAT volume clinically correlated with slowed conduction, greater electrogram fractionation, increased fibrosis, and lateralization of cardiomyocyte connexin-40. In addition, atrial conduction heterogeneity was increased with more extensive myocardial EpAT infiltration. Cardiomyocyte culture studies using multielectrode arrays showed that cardiac adipose tissue-secreted factors slowed conduction velocity and contained proteins with capacity to disrupt intermyocyte electromechanical integrity.
Conclusions
These findings indicate that atrial pathophysiology is critically dependent on local EpAT accumulation and infiltration. In addition to myocardial architecture disruption, this effect can be attributed to an EpAT-cardiomyocyte paracrine axis. The focal adhesion group proteins are identified as new disease candidates potentially contributing to arrhythmogenic atrial substrate.

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

J Am Coll Cardiol: 07 Sep 2020; 76:1197-1211
Nalliah CJ, Bell JR, Raaijmakers AJA, Waddell HM, ... Delbridge LMD, Kalman JM
J Am Coll Cardiol: 07 Sep 2020; 76:1197-1211 | PMID: 32883413
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Abstract

Long-Term Survival After Surgical or Percutaneous Revascularization in Patients With Diabetes and Multivessel Coronary Disease.

Tam DY, Dharma C, Rocha R, Farkouh ME, ... Fremes SE, Lee DS
Background
There remains a paucity of real-world observational evidence comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with diabetes and multivessel coronary artery disease (CAD).
Objectives
This study compared early and long-term outcomes of PCI versus CABG in patients with diabetes.
Methods
Clinical and administrative databases in Ontario, Canada were linked to obtain records of all patients with diabetes with angiographic evidence of 2- or 3-vessel CAD who were treated with either PCI or isolated CABG from 2008 to 2017. A 1:1 propensity score match was performed to account for baseline differences. All-cause mortality and the composite of myocardial infarction, repeat revascularization, stroke, or death (termed major cardiovascular and cerebrovascular events [MACCEs]) were compared between the matched groups using a stratified log-rank test and Cox proportional hazards model.
Results
A total of 4,519 and 9,716 patients underwent PCI and CABG, respectively. Before matching, patients who underwent CABG were significantly younger (age 65.7 years vs. 68.3 years), were more likely to be men (78% vs. 73%) and had more severe CAD. Propensity score matching based on 23 baseline covariates yielded 4,301 well-balanced pairs. There was no difference in early mortality between PCI and CABG (2.4% vs. 2.3%; p = 0.721) after matching. The median and maximum follow-ups were 5.5 and 11.5 years, respectively. All-cause mortality (hazard ratio [HR]: 1.39; 95% CI: 1.28 to 1.51) and overall MACCEs (HR: 1.99; 95% CI: 1.86 to 2.12) were significantly higher with PCI compared with CABG.
Conclusions
In patients with multivessel CAD and diabetes, CABG was associated with improved long-term mortality and freedom from MACCEs compared with PCI.

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

J Am Coll Cardiol: 07 Sep 2020; 76:1153-1164
Tam DY, Dharma C, Rocha R, Farkouh ME, ... Fremes SE, Lee DS
J Am Coll Cardiol: 07 Sep 2020; 76:1153-1164 | PMID: 32883408
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Abstract

Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies: JACC State-of-the-Art Review.

Abdelrahman KM, Chen MY, Dey AK, Virmani R, ... Narula J, Mehta NN

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit.

Published by Elsevier Inc.

J Am Coll Cardiol: 07 Sep 2020; 76:1226-1243
Abdelrahman KM, Chen MY, Dey AK, Virmani R, ... Narula J, Mehta NN
J Am Coll Cardiol: 07 Sep 2020; 76:1226-1243 | PMID: 32883417
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Abstract

Association of Family History With Incidence and Outcomes of Aortic Dissection.

Chen SW, Kuo CF, Huang YT, Lin WT, ... Chang SH, Chu PH
Background
Aortic dissection (AD) is a life-threatening emergency. However, the heritability and association of family history with late outcomes are unclear.
Objectives
The purpose of this study was to evaluate the effect of family history of AD on the incidence and prognosis of AD and estimate the heritability and environmental contribution in AD in Taiwan.
Methods
Both cross-sectional and cohort studies were conducted using Taiwan National Health Insurance database. A registry parent-offspring relationship algorithm was used to reconstruct the genealogy of this population for heritability estimation. The cross-sectional study included 23,868 patients with a diagnosis of AD in 2015. The prevalence and adjusted relative risks (RRs) were evaluated, and the liability threshold model was used to examine the effects of heritability and environmental factors. Furthermore, a 1:10 propensity score-matched cohort comprising AD patients with or without a family history of AD was included to compare late outcomes in the cohort study.
Results
A family history of AD in first-degree relatives was associated with an RR of 6.82 (95% confidence interval [CI]: 5.12 to 9.07). The heritability of AD was estimated to be 57.0% for genetic factors, and 3.1% and 40.0% for shared and nonshared environmental factors, respectively. After excluding individuals with Marfan syndrome or bicuspid aortic valve, a family history of AD was associated with an RR of 6.56 (95% CI: 4.92 to 8.77) for AD. Furthermore, patients with AD and a family history of AD had a higher risk of later aortic surgery than those with AD without a family history (subdistribution hazard ratio: 1.40; 95% CI: 1.12 to 1.76).
Conclusions
A family history of AD was a strong risk factor for AD. Furthermore, patients with AD with a family history of AD had a higher risk of later aortic surgery than those with no family history of AD.

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

J Am Coll Cardiol: 07 Sep 2020; 76:1181-1192
Chen SW, Kuo CF, Huang YT, Lin WT, ... Chang SH, Chu PH
J Am Coll Cardiol: 07 Sep 2020; 76:1181-1192 | PMID: 32883411
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Abstract

Program Directors Survey on Diversity in Cardiovascular Training Programs.

Damp JB, Cullen MW, Soukoulis V, Tam MC, ... Theriot P, Weissman G
Background
Women and minorities are under-represented in cardiovascular disease (CVD) specialties. It remains unknown how characteristics of the CVD learning environment affect diversity and how program directors (PDs) approach these critical issues.
Objectives
The second annual Cardiovascular PD Survey aimed to investigate characteristics of the CVD learning environment that may affect diversity and strategies PDs use to approach these issues.
Methods
The survey contained 20 questions examining U.S.-based CVD PD perceptions of diversity in CVD and related characteristics of the CVD fellowship learning environment.
Results
In total, 58% of PDs completed the survey. Responding programs demonstrated geographic diversity. The majority were university-based or -affiliated. A total of 86% of PDs felt diversity in CVD as a field needs to increase, and 70% agreed that training programs could play a significant role in this. In total, 89% of PDs have attempted to increase diversity in fellowship recruitment. The specific strategies used were associated with PD sex and the presence of under-represented minority trainees in the program. PDs identified lack of qualified candidates and overall culture of cardiology as the 2 most significant barriers to augmenting diversity. A majority of programs have support systems in place for minority fellows or specific gender groups, including procedures to report issues of harassment or an unsafe learning environment. PDs identified shared best practices for recruitment and implicit bias training, among others, as important resources in their efforts to support diversity in CVD training.
Conclusions
Diversity is important to CVD PDs. They are striving to increase it in their programs through recruitment and strategies directed toward the fellowship learning environment. The CVD community has opportunities to standardize strategies and provide national resources to support PDs in these critical efforts.

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

J Am Coll Cardiol: 07 Sep 2020; 76:1215-1222
Damp JB, Cullen MW, Soukoulis V, Tam MC, ... Theriot P, Weissman G
J Am Coll Cardiol: 07 Sep 2020; 76:1215-1222 | PMID: 32883415
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Abstract

Anticoagulation, Mortality, Bleeding and Pathology Among Patients Hospitalized with COVID-19: A Single Health System Study.

Nadkarni GN, Lala A, Bagiella E, Chang HL, ... Fayad ZA, Fuster V
Background
Thromboembolic disease is common in coronavirus disease-19 (COVID-19). There is limited evidence on association of in-hospital anticoagulation (AC) with outcomes and postmortem findings.
Objective
To examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies.
Methods
A retrospective analysis examining association of AC with mortality, intubation and major bleeding. We also conducted sub-analyses on association of therapeutic vs prophylactic AC initiated ≤48 hours from admission. We describe thromboembolic disease contextualized by pre-mortem AC among consecutive autopsies.
Results
Among 4,389 patients, median age was 65 years with 44% female. Compared to no AC (n=1530, 34.9%), therapeutic (n=900, 20.5%) and prophylactic AC (n=1959, 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]=0.53; 95%CI: 0.45-0.62, and aHR=0.50; 95%CI: 0.45-0.57, respectively), and intubation (aHR 0.69; 95%CI: 0.51-0.94, and aHR 0.72; 95% CI: 0.58-0.89, respectively). When initiated ≤48 hours from admission, there was no statistically significant difference between therapeutic (n=766) vs. prophylactic AC (n=1860) (aHR 0.86, 95%CI: 0.73-1.02; p=0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27/900 (3.0%) on therapeutic, 33/1959 (1.7%) on prophylactic, and 29/1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3/11 (27%) were on therapeutic AC.
Conclusions
AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared to prophylactic AC, therapeutic AC was associated with lower mortality, though not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 23 Aug 2020; epub ahead of print
Nadkarni GN, Lala A, Bagiella E, Chang HL, ... Fayad ZA, Fuster V
J Am Coll Cardiol: 23 Aug 2020; epub ahead of print | PMID: 32860872
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Abstract

Management and Outcomes of Patients With STEMI During the COVID-19 Pandemic in China.

Xiang D, Xiang X, Zhang W, Yi S, ... Huo Y, Ge J
Background
ST-segment elevation myocardial infarction (STEMI) is a fatal cardiovascular emergency requiring rapid reperfusion treatment. During the coronavirus disease-2019 (COVID-19) pandemic, medical professionals need to strike a balance between providing timely treatment for STEMI patients and implementing infection control procedures to prevent nosocomial spread of COVID-19 among health care workers and other vulnerable cardiovascular patients.
Objectives
This study evaluates the impact of the COVID-19 outbreak and China Chest Pain Center\'s modified STEMI protocol on the treatment and prognosis of STEMI patients in China.
Methods
Based on the data of 28,189 STEMI patients admitted to 1,372 Chest Pain Centers in China between December 27, 2019 and February 20, 2020, the study analyzed how the COVID-19 outbreak and China Chest Pain Center\'s modified STEMI protocol influenced the number of admitted STEMI cases, reperfusion strategy, key treatment time points, and in-hospital mortality and heart failure for STEMI patients.
Results
The COVID-19 outbreak reduced the number of STEMI cases reported to China Chest Pain Centers. Consistent with China Chest Pain Center\'s modified STEMI protocol, the percentage of patients undergoing primary percutaneous coronary intervention declined while the percentage of patients undergoing thrombolysis increased. With an average delay of approximately 20 min for reperfusion therapy, the rate of in-hospital mortality and in-hospital heart failure increased during the outbreak, but the rate of in-hospital hemorrhage remained stable.
Conclusions
There were reductions in STEMI patients\' access to care, delays in treatment timelines, changes in reperfusion strategies, and an increase of in-hospital mortality and heart failure during the COVID-19 pandemic in China.

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

J Am Coll Cardiol: 13 Aug 2020; epub ahead of print
Xiang D, Xiang X, Zhang W, Yi S, ... Huo Y, Ge J
J Am Coll Cardiol: 13 Aug 2020; epub ahead of print | PMID: 32828614
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Abstract

Interleukin-1Beta and Risk of Premature Death in Patients with Myocardial Infarction.

Silvain J, Kerneis M, Zeitouni M, Lattuca B, ... Montalescot G, Guerin M
Background
Inhibition of the interleukin-1β (IL-1β) innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high sensitivity C-reactive protein (hs-CRP).
Objectives
to assess the association between IL-1β level with all-cause mortality in patients with acute ST segment elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death.
Methods
IL-1β concentration was measured among 1398 ST segment elevation MI patients enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90-days and one-year using a multivariate-cox proportional regression analysis. Major cardiovascular events (MACE) were analyzed.
Results
IL-1β concentration measured at admission was associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR], 1.47 per 1SD increase; 95% CI, 1.16 to 1.87; p<0.002). The relation was nonlinear, and highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; 95%CI: 1.61-4.79, p=0.0002) and one-year (adjHR: 1.93; 95%CI: 1.21-3.06, p=0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACE at 90 days (adjHR: 2.42; 95% CI: 1.36-4.28, p=0.002 and 2.29; 95% CI: 1.31-4.01, p=0.004, respectively) and at one year (adjHR: 2.32; 95% CI: 1.36-3.97, p=0.002 and 2.35; 95% CI: 1.39-3.96, p=0.001, respectively).
Conclusion
IL-1β measured at admission in acute MI patients is independently associated with the risk of mortality and recurrent MACE.
Condensed abstract
In this observational prospective cohort study that included 1398 patients with ST segment elevation myocardial infarction, IL-1β concentration measured at admission was independently associated with all-cause mortality (adjusted hazard ratio [adjHR], 1.47 per 1SD increase; 95% CI, 1.16 to 1.87; p<0.002) and major cardiovascular event at 90 days and one year. The relation was nonlinear, and highest tertile of IL-1β was markedly associated with higher mortality rates at 90 days (adjHR: 2.78; 95%CI: 1.61-4.79, p=0.0002) and one-year (adjHR: 1.93; 95%CI: 1.21-3.06, p=0.005), regardless of the hs-CRP concentration.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 18 Aug 2020; epub ahead of print
Silvain J, Kerneis M, Zeitouni M, Lattuca B, ... Montalescot G, Guerin M
J Am Coll Cardiol: 18 Aug 2020; epub ahead of print | PMID: 32861811
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Abstract

Natural History of Functional Tricuspid Regurgitation Quantified by Cardiovascular Magnetic Resonance.

Zhan Y, Debs D, Khan MA, Nguyen DT, ... Zoghbi WA, Shah DJ
Background
Quantitation of tricuspid regurgitant (TR) severity can be challenging with conventional echocardiographic imaging and may be better evaluated using cardiovascular magnetic resonance (CMR).
Objectives
In patients with functional TR, this study sought to examine the relationship between TR volume (TRVol) and TR fraction (TRF) with all-cause mortality.
Methods
We examined 547 patients with functional TR using CMR to quantify TRVol and TRF. The primary outcome was all-cause mortality. Thresholds for mild, moderate, and severe TR were derived based on natural history outcome data.
Results
During a median follow-up of 2.6 years (interquartile range: 1.7 to 3.3 years), there were 93 deaths, with an estimated 5-year survival of 79% (95% confidence interval [CI]: 73% to 83%). After adjustment of clinical and imaging variables, including RV function, both TRF (adjusted hazard ratio [AHR] per 10% increment: 1.26; 95% CI: 1.10 to 1.45; p = 0.001) and TRVol (AHR per 10-ml increment: 1.15; 95% CI: 1.04 to 1.26; p = 0.004) were associated with mortality. Patients in the highest-risk strata of TRVol ≥45 ml or TRF ≥50% had the worst prognosis (AHR: 2.26; 95% CI: 1.36 to 3.76; p = 0.002 for TRVol and AHR: 2.60; 95% CI: 1.45 to 4.66; p = 0.001 for TRF).
Conclusions
This is the first study to use CMR to assess independent prognostic implications of functional TR. Both TRF and TRVol were associated with increased mortality after adjustment for clinical and imaging covariates, including right ventricular ejection fraction. A TRVol of ≥45 ml or TRF of ≥50% identified patients in the highest-risk strata for mortality. These CMR thresholds should be used for patient selection in future trials to determine if tricuspid valve intervention improves outcomes in this high-risk group.

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

J Am Coll Cardiol: 14 Sep 2020; 76:1291-1301
Zhan Y, Debs D, Khan MA, Nguyen DT, ... Zoghbi WA, Shah DJ
J Am Coll Cardiol: 14 Sep 2020; 76:1291-1301 | PMID: 32912443
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Abstract

Comparative Trends in Percutaneous Coronary Intervention in Japan and the United States, 2013 to 2017.

Inohara T, Kohsaka S, Spertus JA, Masoudi FA, ... Amano T, Nakamura M
Background
Adoption of the results of large-scale randomized controlled trials in percutaneous coronary intervention (PCI) may differ internationally, yet few studies have described the potential variations in PCI practice patterns.
Objectives
Using representative national registries, we compared temporal trends in procedural volume, patient characteristics, pre-procedural testing, procedural characteristics, and quality metrics in the United States and Japan.
Methods
The National Cardiovascular Data Registry CathPCI was used to describe care in the United States, and the J-PCI was used to assess practice patterns in Japan (numbers of participating hospitals: 1,752 in the United States and 1,108 in Japan). Both registries were summarized between 2013 and 2017.
Results
PCI volume increased by 15.8% in the United States from 550,872 in 2013 to 637,650 in 2017, primarily because of an increase in nonelective PCIs (p for trend <0.001). In Japan, the volume of PCIs increased by 36%, from 181,750 in 2013 to 247,274 in 2017, primarily because of an increase in elective PCIs (p for trend <0.001). The proportion of PCI cases for elective conditions was >2-fold greater in Japan (72.7%) than in the United States (33.8%; p < 0.001). Overall, the ratio of nonelective PCI (vs. elective PCI; 27.3% vs. 66.2%; p < 0.001) and the performance of noninvasive stress testing in patients with stable disease (15.2% vs. 55.3%; p < 0.001) was lower in Japan than in the United States. Computed tomography angiography was more commonly used in Japan (22.3% vs. 2.0%; p < 0.001).
Conclusions
Elective PCI is more than twice as common in Japan as in the United States in contemporary practice. Computed tomography angiography is much more frequently used pre-procedurally in Japan than in the United States.

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

J Am Coll Cardiol: 14 Sep 2020; 76:1328-1340
Inohara T, Kohsaka S, Spertus JA, Masoudi FA, ... Amano T, Nakamura M
J Am Coll Cardiol: 14 Sep 2020; 76:1328-1340 | PMID: 32912447
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Abstract

Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated with COVID-19 in the United States.

Matsubara D, Kauffman HL, Wang Y, Calderon-Anyosa R, ... Quartermain MD, Banerjee A
Background
Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of COVID-19, which has been termed multisystem inflammatory syndrome in children (MIS-C).
Objectives
This study aimed to analyze echocardiographic manifestations in MIS-C.
Methods
We retrospectively reviewed 28 MIS-C, 20 healthy controls and 20 classic Kawasaki disease (KD) patients. We reviewed echocardiographic parameters in acute phase of MIS-C and KD groups, and during subacute period in MIS-C group (interval: 5.2 ± 3 days).
Results
Only 1 case in MIS-C (4%) manifested coronary artery dilatation (z score=3.15) in acute phase, showing resolution during early follow up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters, were worse in MIS-C compared to KD. Moreover, MIS-C patients with myocardial injury (+) were more affected than myocardial injury (-) MIS-C with respect to all functional parameters. The strongest parameters to predict myocardial injury in MIS-C were global longitudinal strain (GLS), global circumferential strain (GCS), peak left atrial strain (LAS) and peak longitudinal strain of right ventricular free wall (RVFWLS) (Odds ratio: 1.45 (1.08-1.95), 1.39 (1.04-1.88), 0.84 (0.73-0.96), 1.59 (1.09-2.34) respectively). The preserved LVEF group in MIS-C showed diastolic dysfunction. During subacute period, LVEF returned to normal (median: from 54% to 64%, p<0.001) but diastolic dysfunction persisted.
Conclusions
Unlike classic KD, coronary arteries may be spared in early MIS-C, however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms.
Condensed abstract
Multisystem inflammatory syndrome in children (MIS-C) is an illness that resembles Kawasaki Disease (KD) or toxic shock, reported in children with a recent history of COVID-19 infection. This study analyzed echocardiographic manifestations of this illness. In our cohort of 28 MIS-C patients, left ventricular systolic and diastolic function were worse than in classic KD. These functional parameters correlated with biomarkers of myocardial injury. However, coronary arteries were typically spared. The strongest predictors of myocardial injury were global longitudinal strain, right ventricular strain, and left atrial strain. During subacute period, there was good recovery of systolic function, but diastolic dysfunction persisted.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 30 Aug 2020; epub ahead of print
Matsubara D, Kauffman HL, Wang Y, Calderon-Anyosa R, ... Quartermain MD, Banerjee A
J Am Coll Cardiol: 30 Aug 2020; epub ahead of print | PMID: 32890666
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Abstract

Nonculprit Lesion Severity and Outcome of Revascularization in Patients With STEMI and Multivessel Coronary Disease.

Sheth T, Pinilla-Echeverri N, Moreno R, Wang J, ... Cairns JA, Mehta SR
Background
In the COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial, angiography-guided percutaneous coronary intervention (PCI) of nonculprit lesions with the aim of complete revascularization reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (MI) and multivessel coronary artery disease.
Objectives
The purpose of this study was to determine the effect of nonculprit-lesion stenosis severity measured by quantitative coronary angiography (QCA) on the benefit of complete revascularization.
Methods
Among 4,041 patients randomized in the COMPLETE trial, nonculprit lesion stenosis severity was measured using QCA in the angiographic core laboratory in 3,851 patients with 5,355 nonculprit lesions. In pre-specified analyses, the treatment effect in patients with QCA stenosis ≥60% versus <60% on the first coprimary outcome of CV death or new MI and the second co-primary outcome of CV death, new MI, or ischemia-driven revascularization was determined.
Results
The first coprimary outcome was reduced with complete revascularization in the 2,479 patients with QCA stenosis ≥60% (2.5%/year vs. 4.2%/year; hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47 to 0.79), but not in the 1,372 patients with QCA stenosis <60% (3.0%/year vs. 2.9%/year; HR: 1.04; 95% CI: 0.72 to 1.50; interaction p = 0.02). The second coprimary outcome was reduced in patients with QCA stenosis ≥60% (2.9%/year vs. 6.9%/year; HR: 0.43; 95% CI: 0.34 to 0.54) to a greater extent than patients with QCA stenosis <60% (3.3%/year vs. 5.2%/year; HR: 0.65; 95% CI: 0.47 to 0.89; interaction p = 0.04).
Conclusions
Among patients with ST-segment elevation MI and multivessel coronary artery disease, complete revascularization reduced major CV outcomes to a greater extent in patients with stenosis severity of ≥60% compared with <60%, as determined by quantitative coronary angiography.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 14 Sep 2020; 76:1277-1286
Sheth T, Pinilla-Echeverri N, Moreno R, Wang J, ... Cairns JA, Mehta SR
J Am Coll Cardiol: 14 Sep 2020; 76:1277-1286 | PMID: 32912441
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Impact:
Abstract

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

Tarantini G, Mojoli M, Varbella F, Caporale R, ... Musumeci G,
Background
Although oral P2Y inhibitors are key in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS), the optimal timing of their administration is not well defined.
Objective
to compare downstream and upstream oral P2Y inhibitors administration strategies in NSTE-ACS patients undergoing invasive management.
Methods
We performed a randomized, adaptive, open-label, multi-center, 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 (PCI) were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was superiority of the downstream over the upstream strategy on the combination of efficacy and safety events (net clinical benefit).
Results
We randomized 1449 patients to downstream or upstream oral P2Y inhibitor administration. A prespecified 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, non-fatal myocardial infarction or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4 and 5 bleedings through day 30, did not differ significantly between the downstream and upstream groups (Absolute Risk Reduction (ARR%) -0.46 [-2.90; 1.90]).These results were confirmed among patients undergoing PCI (72% of population) and regardless of the timing of coronary angiography (within or after 24 hours from enrolment).
Conclusions
Downstream and upstream oral P2Y inhibitors administration strategies were associated with low incidence of ischemic and bleeding events and minimal numerical difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of one strategy over the other. [Funded by the Italian Society of Interventional Cardiology (SICI-GISE)].

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 25 Aug 2020; epub ahead of print
Tarantini G, Mojoli M, Varbella F, Caporale R, ... Musumeci G,
J Am Coll Cardiol: 25 Aug 2020; epub ahead of print | PMID: 32882390
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Impact:
Abstract

Impact of Tricuspid Regurgitation on Clinical Outcomes: The COAPT Trial.

Hahn RT, Asch F, Weissman NJ, Grayburn P, ... Mack MJ, Stone GW
Background
The presence of tricuspid regurgitation (TR) may affect prognosis in patients with mitral regurgitation (MR).
Objectives
This study sought to determine the impact of TR on outcomes in patients with heart failure and severe secondary MR randomized to guideline-directed medical therapy (GDMT) or edge-to-edge repair with the MitraClip in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.
Methods
A total of 614 patients with symptomatic heart failure with moderate to severe (3+) or severe (4+) secondary MR were randomized to maximally tolerated GDMT plus MitraClip or GDMT alone; 599 had core laboratory evaluable echocardiograms. Patients were divided into 2 groups by baseline TR severity: none/trace/mild TR (≤Mild TR) (n = 501 [83.6%]) and moderate/severe TR (≥Mod TR) (n = 98 [16.4%]). Two-year composite endpoints of death or heart failure hospitalization (HFH) and the individual endpoints were analyzed.
Results
Patients with ≥Mod TR were more likely to be New York Heart Association functional class III/IV (p < 0.0001) and have a Society of Thoracic Surgeons score of ≥8 (p < 0.0001), anemia (p = 0.02), chronic kidney disease (p = 0.003), and higher N-terminal pro-B-type natriuretic peptide (p = 0.02) than those with ≤Mild TR. Patients with ≥Mod TR had more severe MR (p = 0.0005) despite smaller left ventricular volumes (p = 0.005) and higher right ventricular systolic pressure (p < 0.0001). At 2 years, the composite rate of death or HFH was higher in patients with ≥Mod TR compared with ≤Mild TR treated with GDMT alone (83.0% vs. 64.3%; hazard ratio: 1.74; 95% confidence interval: 1.24 to 2.45; p = 0.001) but not following MitraClip (48.2% vs. 44.0%; hazard ratio: 1.14; 95% confidence interval: 0.71 to 1.84; p = 0.59). Rates of death or HFH, as well as death and HFH alone, were reduced by MitraClip compared with GDMT, irrespective of baseline TR grade (p = 0.16, 0.29, and 0.21 respectively).
Conclusions
Patients with severe secondary MR who also had ≥Mod TR had worse clinical and echocardiographic characteristics and worse clinical outcomes compared to those with ≤Mild TR. Within the COAPT trial, MitraClip improved outcomes in patients with and without ≥Mod TR severity compared with GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

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

J Am Coll Cardiol: 14 Sep 2020; 76:1305-1314
Hahn RT, Asch F, Weissman NJ, Grayburn P, ... Mack MJ, Stone GW
J Am Coll Cardiol: 14 Sep 2020; 76:1305-1314 | PMID: 32912445
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Impact:
Abstract

Mortality in Patients With Atrial Fibrillation Receiving Nonrecommended Doses of Direct Oral Anticoagulants.

Camm AJ, Cools F, Virdone S, Bassand JP, ... Kakkar AK,
Background
The recommended doses for direct oral anticoagulants (DOACs) to prevent stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) are described in specific regulatory authority approvals.
Objectives
The impact of DOAC dosing, according to the recommended guidance on all-cause mortality, stroke/SE, and major bleeding, was assessed at 2-year follow-up in patients with newly diagnosed AF.
Methods
Of a total of 34,926 patients enrolled (2013 to 2016) in the prospective GARFIELD-AF (Global Anticoagulant Registry in the FIELD-AF), 10,426 patients received a DOAC.
Results
The majority of patients (72.9%) received recommended dosing, 23.2% were underdosed, and 3.8% were overdosed. Nonrecommended dosing (underdosage and overdosage combined) compared with recommended dosing was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.48); HR: 1.25 (95% CI: 1.04 to 1.50) for underdosing, and HR: 1.19 (95% CI: 0.83 to 1.71) for overdosing. The excess deaths were cardiovascular including heart failure and myocardial infarction. The risks of stroke/SE and major bleeding were not significantly different irrespective of the level of dosing, although underdosed patients had a significantly lower risk of bleeding. A nonsignificant trend to higher risks of stroke/SE (HR: 1.51; 95% CI: 0.79 to 2.91) and major bleeding (HR: 1.29; 95% CI: 0.59 to 2.78) was observed in patients with overdosing.
Conclusions
In GARFIELD-AF, most patients received the recommended DOAC doses according to country-specific guidelines. Prescription of nonrecommended doses was associated with an increased risk of death, mostly cardiovascular death, compared with patients on recommended doses, after adjusting for baseline factors. (Global Anticoagulant Registry in the Field-AF [GARFIELD-AF]; NCT01090362).

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

J Am Coll Cardiol: 21 Sep 2020; 76:1425-1436
Camm AJ, Cools F, Virdone S, Bassand JP, ... Kakkar AK,
J Am Coll Cardiol: 21 Sep 2020; 76:1425-1436 | PMID: 32943160
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Abstract

Low-Density Lipoprotein Cholesterol and Adverse Cardiovascular Events After Percutaneous Coronary Intervention.

Sud M, Han L, Koh M, Abdel-Qadir H, ... Wijeysundera HC, Ko DT
Background
After percutaneous coronary interventions (PCIs), patients remain at high risk of developing late cardiovascular events. Although controlling low-density lipoprotein cholesterol (LDL-C) may improve outcomes after PCI, practice guidelines do not have specific recommendations on LDL-C management for this subgroup.
Objectives
The purpose of this study was to evaluate LDL-C testing and levels after PCIs, and to assess the association between LDL-C and longer-term cardiovascular events after PCIs.
Methods
All patients who received their first PCI from October 1, 2011, to September 30, 2014, in Ontario, Canada, were considered for inclusion. Patients who had LDL-C measurement within 6 months after PCI were categorized as: <70 mg/dl, 70 to <100 mg/dl, and ≥100 mg/dl. The primary composite outcome was cardiovascular death, myocardial infarction, coronary revascularization, and stroke through December 31, 2016.
Results
Among 47,884 included patients, 52% had LDL-C measured within 6 months of PCI and 57% had LDL-C <70 mg/dl. After a median 3.2 years, the rates of cardiovascular events were 55.2/1,000 person-years for the LDL-C <70 mg/dl group, 60.3/1,000 person-years for 70 to <100 mg/dl, and 94.0/1,000 person-years for ≥100 mg/dl. The adjusted subdistribution hazard ratios for cardiovascular events were 1.17 (95% confidence interval: 1.09 to 1.26) for LDL-C of 70 to <100 mg/dl, and 1.78 (95% confidence interval: 1.64 to 1.94) for LDL-C ≥100 mg/dl when compared with LDL-C <70 mg/dl.
Conclusions
One in 2 patients had LDL-C measured within 6 months after PCI, and only 57% had LDL-C <70 mg/dl. Higher levels of LDL-C were associated with an increased incidence of late cardiovascular events. Improved cholesterol management after PCI should be considered to improve the outcomes of these patients.

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

J Am Coll Cardiol: 21 Sep 2020; 76:1440-1450
Sud M, Han L, Koh M, Abdel-Qadir H, ... Wijeysundera HC, Ko DT
J Am Coll Cardiol: 21 Sep 2020; 76:1440-1450 | PMID: 32943162
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Impact:
Abstract

Revascularization in Patients With Left Main Coronary Artery Disease and Left Ventricular Dysfunction.

Park S, Ahn JM, Kim TO, Park H, ... Park DW,
Background
Left main coronary artery (LMCA) disease is associated with high mortality and morbidity due to a large area of jeopardized myocardium. However, the optimal revascularization strategy for patients with LMCA disease and left ventricular dysfunction is still unclear.
Objectives
This study sought to examine long-term comparative outcomes after percutaneous coronary intervention (PCI) or a coronary artery bypass grafting (CABG) according to the severity of left ventricular dysfunction.
Methods
The authors evaluated a total of 3,488 patients with LMCA disease who underwent CABG (n = 1,355) or PCI (n = 2,133) from the IRIS-MAIN (Interventional Research Incorporation Society-Left MAIN Revascularization) registry. Left ventricular function was categorized according to left ventricular ejection fraction (LVEF) as normal function (LVEF ≥55%), mild dysfunction (LVEF ≥45% to <55%), moderate dysfunction (LVEF ≥35% to <45%), or severe dysfunction (LVEF <35%). The primary outcome was a composite of death, myocardial infarction, or stroke.
Results
Among the overall patient population, 2,641 (75.7%) patients had normal LVEF and 403 (11.6%), 260 (7.5%), and 184 (5.3%) had mild, moderate, and severe left ventricular dysfunction at baseline, respectively. Compared with CABG, PCI was associated with a higher adjusted risk of primary outcomes in patients with moderate (hazard ratio [HR]: 2.23; 95% confidence interval [CI]: 1.17 to 4.28) or severe (HR: 2.45; 95% CI: 1.27 to 4.73) dysfunction. In contrast, PCI and CABG had similar risks of the primary outcomes in patients with normal (HR: 0.80; 95% CI: 0.59 to 1.07) or mild (HR: 1.17; 95% CI: 0.63 to 2.17) dysfunction (p for interaction = 0.004).
Conclusions
In the revascularization of LMCA disease, PCI was associated with an inferior primary composite outcome of death, MI, or stroke compared with CABG in patients with moderate or severe left ventricular dysfunction. However, the risk for the primary outcome was comparable between PCI and CABG in those with normal or mild left ventricular dysfunction. (Observational Study for Left Main Disease Treatment; NCT01341327).

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

J Am Coll Cardiol: 21 Sep 2020; 76:1395-1406
Park S, Ahn JM, Kim TO, Park H, ... Park DW,
J Am Coll Cardiol: 21 Sep 2020; 76:1395-1406 | PMID: 32943156
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Impact:
Abstract

Impact of Transcatheter Aortic Valve Replacement on Severity of Chronic Kidney Disease.

Cubeddu RJ, Asher CR, Lowry AM, Blackstone EH, ... Svensson LG,
Background
The effect of transcatheter aortic valve replacement (TAVR) on kidney function stage in patients with aortic stenosis remains poorly understood. We hypothesized that in some patients, TAVR results in improved kidney function by alleviating cardiorenal syndrome.
Objectives
The purpose of this study was to assess change in chronic kidney disease (CKD) stage following TAVR, identify variables associated with pre- and post-TAVR estimated glomerular filtration rate (eGFR), and assess association of post-TAVR eGFR with mortality.
Methods
Patients (n = 5,190) receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) 1, 2, and PARTNER 2 S3 trials between April 2007 and October 2014 were included. Pre-TAVR and procedural variables associated with post-TAVR eGFR, change in CKD stage at ≤7 days post-TAVR, and association of post-TAVR eGFR on intermediate-term mortality were assessed.
Results
At baseline, CKD stage ≥2 was present in 91% of patients. CKD stage either improved or was unchanged following TAVR in the majority of patients (77% stage 1, 90% stage 2, 89% stage 3A, 94% stage 3B, and 99% stage 4). Progression to CKD stage 5 occurred in 1 (0.035%) of 2,892 patients within 7 days post-TAVR. Of 3,546 patients in whom data were available, 70 (2.0%) underwent post-TAVR dialysis. Higher pre-TAVR eGFR and transfemoral approach were strongly associated with higher post-TAVR eGFR. Lower baseline and longitudinal post-TAVR eGFR were associated with lower intermediate-term survival.
Conclusions
In patients with severe aortic stenosis undergoing TAVR, even with baseline impaired eGFR, CKD stage is more likely to stay the same or improve than worsen. Aortic stenosis may contribute to cardiorenal syndrome that improves with TAVR.

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

J Am Coll Cardiol: 21 Sep 2020; 76:1410-1421
Cubeddu RJ, Asher CR, Lowry AM, Blackstone EH, ... Svensson LG,
J Am Coll Cardiol: 21 Sep 2020; 76:1410-1421 | PMID: 32943158
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Impact:
Abstract

Sex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart Failure.

Suthahar N, Lau ES, Blaha MJ, Paniagua SM, ... Ho JE, de Boer RA
Background
Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear.
Objectives
The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF.
Methods
The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio.
Results
Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001).
Conclusions
CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.

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

J Am Coll Cardiol: 21 Sep 2020; 76:1455-1465
Suthahar N, Lau ES, Blaha MJ, Paniagua SM, ... Ho JE, de Boer RA
J Am Coll Cardiol: 21 Sep 2020; 76:1455-1465 | PMID: 32943164
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Impact:
Abstract

A Pesco-Mediterranean Diet With Intermittent Fasting: JACC Review Topic of the Week.

O\'Keefe JH, Torres-Acosta N, O\'Keefe EL, Saeed IM, ... Smith SE, Ros E

As opportunistic omnivores, humans are evolutionarily adapted to obtain calories and nutrients from both plant and animal food sources. Today, many people overconsume animal products, often-processed meats high in saturated fats and chemical additives. Alternatively, strict veganism can cause nutritional deficiencies and predispose to osteopenia, sarcopenia, and anemia. A logical compromise is a plant-rich diet with fish/seafood as principal sources of animal food. This paper reviews cumulative evidence regarding diet and health, incorporating data from landmark clinical trials of the Mediterranean diet and recommendations from recent authoritative guidelines, to support the hypothesis that a Pesco-Mediterranean diet is ideal for optimizing cardiovascular health. The foundation of this diet is vegetables, fruits, nuts, seeds, legumes, whole grains, and extra-virgin olive oil with fish/seafood and fermented dairy products. Beverages of choice are water, coffee, and tea. Time-restricted eating is recommended, whereby intermittent fasting is done for 12 to 16 h each day.

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

J Am Coll Cardiol: 21 Sep 2020; 76:1484-1493
O'Keefe JH, Torres-Acosta N, O'Keefe EL, Saeed IM, ... Smith SE, Ros E
J Am Coll Cardiol: 21 Sep 2020; 76:1484-1493 | PMID: 32943166
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Impact:
Abstract

Trial Design Principles for Patients at High Bleeding Risk Undergoing PCI: JACC Scientific Expert Panel.

Capodanno D, Morice MC, Angiolillo DJ, Bhatt DL, ... Urban P, Mehran R

Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting.

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

J Am Coll Cardiol: 21 Sep 2020; 76:1468-1483
Capodanno D, Morice MC, Angiolillo DJ, Bhatt DL, ... Urban P, Mehran R
J Am Coll Cardiol: 21 Sep 2020; 76:1468-1483 | PMID: 32943165
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Impact:
Abstract

Time Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk.

Domanski MJ, Tian X, Wu CO, Reis JP, ... Lloyd-Jones DM, Fuster V
Background
Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown.
Objectives
Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages.
Methods
This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death.
Results
During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p < 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively).
Conclusions
Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.

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

J Am Coll Cardiol: 28 Sep 2020; 76:1507-1516
Domanski MJ, Tian X, Wu CO, Reis JP, ... Lloyd-Jones DM, Fuster V
J Am Coll Cardiol: 28 Sep 2020; 76:1507-1516 | PMID: 32972526
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Abstract

Impact of Peri-Procedural Myocardial Infarction on Outcomes After Revascularization.

Hara H, Serruys PW, Takahashi K, Kawashima H, ... Mack MJ,
Background
Numerous definitions for peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) surgery exist.
Objectives
The purpose of this study was to investigate the PMI rates according to various definitions, their clinically relevant association with all-cause mortality at 10 years, and their impact on composite endpoints at 5 years in the SYNTAXES (Synergy between PCI with Taxus and Cardiac Surgery Extended Survival) trial.
Methods
PMI was classified as a myocardial infarction occurring within 48 h of the procedure according to definitions of the SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries), ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches), and EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials; the Fourth Universal Definition of MI; and the Society for Cardiovascular Angiography and Interventions (SCAI). Of the 1,800 patients enrolled, 1,652 with creatine kinase and/or creatine kinase-myocardial band (CK-MB) post-procedure were included. The association between PMI and mortality was analyzed by Cox regression.
Results
PMI rates according to the SYNTAX and Fourth Universal Definition of MI, both of which required CK-MB elevation and electrocardiographic evidence of permanent myocardial damage, were 2.7% and 3.0%, respectively, in the PCI arm versus 2.4% and 2.1%, respectively, in the CABG arm. PMI rates according to the SCAI or EXCEL definition were higher in the PCI (5.7%) and CABG (16.5%) arms. PMIs according to the SYNTAX and Fourth Universal Definition of MI were more strongly associated with mortality than EXCEL and SCAI PMIs defined by isolated enzyme elevation when CK-MB was more than 10 times ULN. The impact of these \"enzyme-driven events\" on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year.
Conclusions
The rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).

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

J Am Coll Cardiol: 05 Oct 2020; 76:1622-1639
Hara H, Serruys PW, Takahashi K, Kawashima H, ... Mack MJ,
J Am Coll Cardiol: 05 Oct 2020; 76:1622-1639 | PMID: 33004127
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Impact:
Abstract

Ross Procedures in Children With Previous Aortic Valve Surgery.

Buratto E, Wallace FRO, Fricke TA, Brink J, ... Brizard CP, Konstantinov IE
Background
The Ross procedure in children is performed either as a primary operation, or a secondary operation after initial aortic valve surgery.
Objectives
The study aimed to determine whether the outcomes of primary and secondary Ross procedure are similar.
Methods
All patients who underwent Ross procedure between 1995 and 2018 were included in the study. Outcomes were compared between those who had primary Ross procedure and those who had secondary Ross procedure, after aortic valve surgery. Propensity score matching for baseline characteristics and risk factors for death and reoperation was performed.
Results
Of 140 Ross procedures, 51.4% (n = 72 of 140) were primary operations, while 48.6% (n = 68 of 140) were secondary operations. Patients undergoing primary Ross procedure tended to be older (median age 8.6 years vs. 7.0 years; p = 0.10) and have a higher weight (28.9 kg vs. 19.4 kg; p = 0.07). There were no significant differences in survival or freedom from reoperation in the unmatched cohort. Propensity score matching resulted in 50 well-matched pairs. In the matched cohort, survival at 10 years was 90.0% (95% confidence interval [CI]: 77.5% to 95.7%) in the primary Ross group, compared with 96.8% (95% CI: 79.2% to 99.5%) in the secondary Ross group (p = 0.04). Freedom from autograft reoperation at 10 years was 82% (95% CI: 64.1% to 91.5%) in the primary Ross group, compared with 97.0% (95% CI: 80.4% to 99.6%) in the secondary Ross group (p = 0.03).
Conclusions
Secondary Ross procedure performed after initial aortic valve surgery achieves superior long-term survival and freedom from autograft reoperation compared with primary Ross procedure. A strategy of initial aortic valve repair followed by delayed Ross procedure may provide better long-term survival and freedom from autograft reoperation.

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Sep 2020; 76:1564-1573
Buratto E, Wallace FRO, Fricke TA, Brink J, ... Brizard CP, Konstantinov IE
J Am Coll Cardiol: 28 Sep 2020; 76:1564-1573 | PMID: 32972534
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Abstract

Trends and Outcomes of Restenosis After Coronary Stent Implantation in the United States.

Moussa ID, Mohananey D, Saucedo J, Stone GW, ... Moses JW, Simonton C
Background
There is a paucity of data on the burden of in-stent restenosis (ISR) in the United States as well as on its presentation and appropriate treatment strategies.
Objectives
This study aims to provide an analysis of the temporal trends, clinical presentation, treatment strategies, and in-hospital outcomes of patients undergoing percutaneous coronary intervention (PCI) for ISR in the United States.
Methods
This study is a retrospective analysis of data collected in the Diagnostic Catheterization and Percutaneous Coronary Intervention (CathPCI) registry of the National Cardiovascular Data Registry (NCDR) between 2009 and 2017. Of the total patients undergoing PCI, we identified those undergoing PCI for ISR lesions. For comparison of in-hospital outcomes, propensity-score matching was employed.
Results
Among the 5,100,394 patients undergoing PCI, 10.6% of patients underwent PCI for ISR lesions. Patients with bare-metal stent ISR declined from 2.6% in 2009 Q3 to 0.9% in 2017 Q2 (p < 0.001), and drug-eluting stent ISR rose from 5.4% in 2009 Q3 to 6.3% in 2017 Q2 (p < 0.001). Patients with ISR PCI were less likely to present with non-ST-segment elevation myocardial infarction (MI) (18.7% vs. 22.5%; p < 0.001) or ST-segment elevation MI (8.5% vs. 15.7%; p < 0.001). In the propensity-matched population of patients, there were no significant differences between patients with ISR and non-ISR PCI for in-hospital complications and hospital length of stay.
Conclusions
ISR represents approximately 10% of all PCI and is treated most commonly with another stent. Approximately 25% of patients present with acute MI. In-hospital outcomes of patients with ISR PCI are comparable with those undergoing non-ISR PCI.

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

J Am Coll Cardiol: 28 Sep 2020; 76:1521-1531
Moussa ID, Mohananey D, Saucedo J, Stone GW, ... Moses JW, Simonton C
J Am Coll Cardiol: 28 Sep 2020; 76:1521-1531 | PMID: 32972528
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Impact:
Abstract

Machine Learning Improves Cardiovascular Risk Definition for Young, Asymptomatic Individuals.

Sánchez-Cabo F, Rossello X, Fuster V, Benito F, ... García-Ruiz JM, Lara-Pezzi E
Background
Clinical practice guidelines recommend assessment of subclinical atherosclerosis using imaging techniques in individuals with intermediate atherosclerotic cardiovascular risk according to standard risk prediction tools.
Objectives
The purpose of this study was to develop a machine-learning model based on routine, quantitative, and easily measured variables to predict the presence and extent of subclinical atherosclerosis (SA) in young, asymptomatic individuals. The risk of having SA estimated by this model could be used to refine risk estimation and optimize the use of imaging for risk assessment.
Methods
The Elastic Net (EN) model was built to predict SA extent, defined by a combined metric of the coronary artery calcification score and 2-dimensional vascular ultrasound. The performance of the model for the prediction of SA extension and progression was compared with traditional risk scores of cardiovascular disease (CVD). An external independent cohort was used for validation.
Results
EN-PESA (Progression of Early Subclinical Atherosclerosis) yielded a c-statistic of 0.88 for the prediction of generalized subclinical atherosclerosis. Moreover, EN-PESA was found to be a predictor of 3-year progression independent of the baseline extension of SA. EN-PESA assigned an intermediate to high cardiovascular risk to 40.1% (n = 1,411) of the PESA individuals, a significantly larger number than atherosclerotic CVD (n = 267) and SCORE (Systematic Coronary Risk Evaluation) (n = 507) risk scores. In total, 86.8% of the individuals with an increased risk based on EN-PESA presented signs of SA at baseline or a significant progression of SA over 3 years.
Conclusions
The EN-PESA model uses age, systolic blood pressure, and 10 commonly used blood/urine tests and dietary intake values to identify young, asymptomatic individuals with an increased risk of CVD based on their extension and progression of SA. These individuals are likely to benefit from imaging tests or pharmacological treatment. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

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

J Am Coll Cardiol: 05 Oct 2020; 76:1674-1685
Sánchez-Cabo F, Rossello X, Fuster V, Benito F, ... García-Ruiz JM, Lara-Pezzi E
J Am Coll Cardiol: 05 Oct 2020; 76:1674-1685 | PMID: 33004133
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Impact:
Abstract

Association of Bioprosthetic Aortic Valve Leaflet Calcification on Hemodynamic and Clinical Outcomes.

Zhang B, Salaun E, Côté N, Wu Y, ... Pibarot P, Clavel MA
Background
The prognostic value of aortic valve calcification (AVC) measured by using multidetector computed tomography imaging has been well validated in native aortic stenosis, and sex-specific thresholds have been proposed. However, few data are available regarding the impact of leaflet calcification on outcomes after biological aortic valve replacement (AVR).
Objectives
The goal of this study was to analyze the association of quantitative bioprosthetic leaflet AVC with hemodynamic and clinical outcomes, as well as its possible interaction with sex.
Methods
From 2008 to 2010, a total of 204 patients were prospectively enrolled with a median of 7.0 years (interquartile range: 5.1 to 9.2 years) after biological surgical AVR. AVC measured by using the Agatston method was indexed to the cross-sectional area of aortic annulus measured by echocardiography to calculate the AVC density (AVCd). Presence of hemodynamic valve deterioration (HVD; increase in mean gradient [MG] ≥10 mm Hg and/or increase in transprosthetic regurgitation ≥1) was assessed by echocardiography in 137 patients at the 3-year follow-up. The primary clinical endpoint was mortality or aortic valve re-intervention.
Results
There was no significant sex-related difference in the relationship between bioprosthetic AVCd and the progression of MG. Baseline AVCd showed an independent association with HVD at 3 years. During follow-up, there were 134 (65.7%) deaths (n = 100) or valve re-interventions (n = 47). AVCd ≥58 AU/cm was independently associated with an increased risk of mortality or aortic valve re-intervention (adjusted hazard ratio: 2.23; 95% confidence interval: 1.44 to 3.35; p < 0.001). The AVCd threshold combined with an MG progression threshold of 10 mm Hg amplified the stratification of patients at risk (log-rank, p < 0.001). The addition of AVCd threshold into the prediction model including traditional risk factors improved outcome prediction (net classification improvement: 0.25, p = 0.04; likelihood ratio test, p < 0.001).
Conclusions
Aortic bioprosthetic leaflet calcification is strongly and independently associated with HVD and the risk of death or aortic valve re-intervention. As opposed to native aortic stenosis, there is no sex-related differences in the relationship between AVCd and hemodynamic or clinical outcomes.

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

J Am Coll Cardiol: 12 Oct 2020; 76:1737-1748
Zhang B, Salaun E, Côté N, Wu Y, ... Pibarot P, Clavel MA
J Am Coll Cardiol: 12 Oct 2020; 76:1737-1748 | PMID: 33032735
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Abstract

Type A Aortic Dissection-Experience Over 5 Decades: JACC Historical Breakthroughs in Perspective.

Zhu Y, Lingala B, Baiocchi M, Tao JJ, ... Fischbein MP, Woo YJ

The Stanford classification of aortic dissection was described in 1970. The classification proposed that type A aortic dissection should be surgically repaired immediately, whereas type B aortic dissection can be treated medically. Since then, diagnostic tools and management of acute type A aortic dissection (ATAAD) have undergone substantial evolution. This paper evaluated historical changes of ATAAD repair at Stanford University since the establishment of the aortic dissection classification 50 years ago. The surgical approaches to the proximal and distal extent of the aorta, cerebral perfusion methods, and cannulation strategies were reviewed. Additional analyses using patients who underwent ATAAD repair at Stanford University from 1967 through December 2019 were performed to further illustrate the Stanford experience in the management of ATAAD. While technical complexity increased over time, post-operative survival continued to improve. Further investigation is warranted to delineate factors associated with the improved outcomes observed in this study.

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

J Am Coll Cardiol: 05 Oct 2020; 76:1703-1713
Zhu Y, Lingala B, Baiocchi M, Tao JJ, ... Fischbein MP, Woo YJ
J Am Coll Cardiol: 05 Oct 2020; 76:1703-1713 | PMID: 33004136
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Abstract

Implications of Alternative Definitions of Peri-Procedural Myocardial Infarction After Coronary Revascularization.

Gregson J, Stone GW, Ben-Yehuda O, Redfors B, ... Serruys PW, Pocock SJ
Background
Varying definitions of procedural myocardial infarction (PMI) are in widespread use.
Objectives
This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial.
Methods
The pre-specified protocol definition of PMI (PMI) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMI) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMI, troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined.
Results
PMI occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference -2.4%; 95% confidence interval [CI]: -4.4% to -0.5%; p = 0.015). The corresponding rates of PMI were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMI and PMI were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMI was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (p = 0.86). Conversely, PMI was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (p = 0.004). Results were similar for all-cause mortality and with varying PMI biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality.
Conclusions
The rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMI was associated with similar hazard after PCI and CABG, whereas PMI was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776).

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

J Am Coll Cardiol: 05 Oct 2020; 76:1609-1621
Gregson J, Stone GW, Ben-Yehuda O, Redfors B, ... Serruys PW, Pocock SJ
J Am Coll Cardiol: 05 Oct 2020; 76:1609-1621 | PMID: 33004126
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Abstract

Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review.

Astrup A, Magkos F, Bier DM, Brenna JT, ... Yusuf S, Krauss RM

The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods.

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

J Am Coll Cardiol: 17 Aug 2020; 76:844-857
Astrup A, Magkos F, Bier DM, Brenna JT, ... Yusuf S, Krauss RM
J Am Coll Cardiol: 17 Aug 2020; 76:844-857 | PMID: 32562735
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Abstract

Intracranial Arterial Calcification: Prevalence, Risk Factors, and Consequences: JACC Review Topic of the Week.

Bartstra JW, van den Beukel TC, Van Hecke W, Mali WPTM, ... de Jong PA, den Harder AM

Intracranial large and small arterial calcifications are a common incidental finding on computed tomography imaging in the general population. Here we provide an overview of the published reports on prevalence of intracranial arterial calcifications on computed tomography imaging and histopathology in relation to risk factors and clinical outcomes. We performed a systematic search in Medline, with a search filter using synonyms for computed tomography scanning, (histo)pathology, different intracranial arterial beds, and calcification. We found that intracranial calcifications are a frequent finding in all arterial beds with the highest prevalence in the intracranial internal carotid artery. In general, prevalence increases with age. Longitudinal studies on calcification progression and intervention studies are warranted to investigate the possible causal role of calcification on clinical outcomes. This might open up new therapeutic directions in stroke and dementia prevention and the maintenance of the healthy brain.

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

J Am Coll Cardiol: 28 Sep 2020; 76:1595-1604
Bartstra JW, van den Beukel TC, Van Hecke W, Mali WPTM, ... de Jong PA, den Harder AM
J Am Coll Cardiol: 28 Sep 2020; 76:1595-1604 | PMID: 32972537
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Abstract

Association Between Left Ventricular Noncompaction and Vigorous Physical Activity.

de la Chica JA, Gómez-Talavera S, García-Ruiz JM, García-Lunar I, ... Ibáñez B, Fuster V
Background
Left ventricular (LV) hypertrabeculation fulfilling noncompaction cardiomyopathy criteria has been detected in athletes. However, the association between LV noncompaction (LVNC) phenotype and vigorous physical activity (VPA) in the general population is disputed.
Objectives
The aim of this study was to assess the relationship between LVNC phenotype on cardiac magnetic resonance (CMR) imaging and accelerometer-measured physical activity (PA) in a cohort of middle-aged nonathlete participants in the PESA (Progression of Early Subclinical Atherosclerosis) study.
Methods
In PESA participants (n = 4,184 subjects free of cardiovascular disease), PA was measured by waist-secured accelerometers. CMR was performed in 705 subjects (mean age 48 ± 4 years, 16% women). VPA was recorded as total minutes per week. The study population was divided into 6 groups: no VPA and 5 sex-specific quintiles of VPA rate (Q1 to Q5). The Petersen criterion for LVNC was evaluated in all subjects undergoing CMR. For participants meeting this criterion (noncompacted-to-compacted ratio ≥2.3), 3 more restrictive LVNC criteria were also evaluated (Jacquier, Grothoff, and Stacey).
Results
LVNC phenotype prevalence according to the Petersen criterion was significantly higher among participants in the highest VPA quintile (Q5 = 30.5%) than in participants with no VPA (14.2%). The Jacquier and Grothoff criteria were also more frequently fulfilled in participants in the highest VPA quintile (Jacquier Q5 = 27.4% vs. no VPA = 12.8% and Grothoff Q5 = 15.8% vs. no VPA = 7.1%). The prevalence of the systolic Stacey LVNC criterion was low (3.6%) and did not differ significantly between no VPA and Q5.
Conclusions
In a community-based study, VPA was associated with a higher prevalence of CMR-detected LVNC phenotype according to diverse established criteria. The association between VPA and LVNC phenotype was independent of LV volumes. According to these data, vigorous recreational PA should be considered as a possible but not uncommon determinant of LV hypertrabeculation in asymptomatic subjects.

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

J Am Coll Cardiol: 12 Oct 2020; 76:1723-1733
de la Chica JA, Gómez-Talavera S, García-Ruiz JM, García-Lunar I, ... Ibáñez B, Fuster V
J Am Coll Cardiol: 12 Oct 2020; 76:1723-1733 | PMID: 33032733
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Abstract

Cardiovascular Biomarkers and Imaging in Older Adults: JACC Council Perspectives.

Forman DE, de Lemos JA, Shaw LJ, Reuben DB, ... Rich MW,

Whereas the burgeoning population of older adults is intrinsically vulnerable to cardiovascular disease, the utility of many management precepts that were validated in younger adults is often unclear. Whereas biomarker- and imaging-based tests are a major part of cardiovascular disease care, basic assumptions about their use and efficacy cannot be simply extrapolated to many older adults. Biology, physiology, and body composition change with aging, with important influences on cardiovascular disease testing procedures and their interpretation. Furthermore, clinical priorities of older adults are more heterogeneous, potentially undercutting the utility of testing data that are collected. The American College of Cardiology and the National Institutes on Aging, in collaboration with the American Geriatrics Society, convened, at the American College of Cardiology Heart House, a 2-day multidisciplinary workshop, \"Diagnostic Testing in Older Adults with Cardiovascular Disease,\" to address these issues. This review summarizes key concepts, clinical limitations, and important opportunities for research.

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

J Am Coll Cardiol: 28 Sep 2020; 76:1577-1594
Forman DE, de Lemos JA, Shaw LJ, Reuben DB, ... Rich MW,
J Am Coll Cardiol: 28 Sep 2020; 76:1577-1594 | PMID: 32972536
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Abstract

Targeting Cyclic Guanosine Monophosphate to Treat Heart Failure: JACC Review Topic of the Week.

Emdin M, Aimo A, Castiglione V, Vergaro G, ... Metra M, Senni M

The significant morbidity and mortality associated with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. Reduced cyclic guanosine monophosphate levels contribute to HF progression. Among molecules modulating the nitric oxide (NO)-GMP-phosphodiesterase (PDE) pathway, the evaluation of nitrates, synthetic natriuretic peptides (NP), and NP analogs has yielded mixed results. Conversely, sacubitril/valsartan, combining NP degradation inhibition through neprilysin and angiotensin receptor blockade, has led to groundbreaking findings in HFrEF. Other strategies to increase tissue cyclic guanosine monophosphate have been attempted, such as PDE-3 or PDE-5 inhibition (with negative or neutral results), NO-independent soluble guanylate cyclase (sGC) activation, or enhancement of sGC sensitivity to endogenous NO. Following the positive results of the phase 3 VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial on the sGC stimulator vericiguat in HFrEF, the main open questions are the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF and of vericiguat in HFpEF.

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

J Am Coll Cardiol: 12 Oct 2020; 76:1795-1807
Emdin M, Aimo A, Castiglione V, Vergaro G, ... Metra M, Senni M
J Am Coll Cardiol: 12 Oct 2020; 76:1795-1807 | PMID: 33032741
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Abstract

Sex Differences in Incident and Recurrent Coronary Events and All-Cause Mortality.

Peters SAE, Colantonio LD, Chen L, Bittner V, ... Muntner P, Woodward M
Background
Women have lower age-specific rates of incident coronary heart disease (CHD) than men. It is unclear whether women remain at lower risk for CHD events versus men following a myocardial infarction (MI).
Objectives
This study assessed sex differences in recurrent MI, recurrent CHD events, and mortality among patients with MI and compared these associations with sex differences in a control group without a history of CHD.
Methods
This study analyzed data for 171,897 women and 167,993 men age 21 years or older with health insurance in the United States who had a MI hospitalization in 2015 or 2016. Patients with a MI were frequency matched by age and calendar year to 687,588 women and 671,972 men without CHD. Beneficiaries were followed until December 2017 for MI, CHD (i.e., MI or coronary revascularization), and in Medicare for all-cause mortality.
Results
Age-standardized rates of MI per 1,000 person-years were 4.5 in women and 5.7 in men without CHD (hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.62 to 0.67) and 60.2 in women and 59.8 in men with MI (HR: 0.94; 95% CI: 0.92 to 0.96). CHD rates in women versus men were 6.3 versus 10.7 among those without CHD (HR: 0.53; 95% CI: 0.51 to 0.54) and 84.5 versus 99.3 among those with MI (HR: 0.87; 95% CI: 0.85 to 0.89). All-cause mortality rates in women versus men were 63.7 versus 59.0 among those without CHD (HR: 0.72; 95% CI: 0.71 to 0.73) and 311.6 versus 284.5 among those with MI (HR: 0.90; 95% CI: 0.89 to 0.92).
Conclusions
The lower risk for MI, CHD, and all-cause mortality in women versus men is considerably attenuated following a MI.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 12 Oct 2020; 76:1751-1760
Peters SAE, Colantonio LD, Chen L, Bittner V, ... Muntner P, Woodward M
J Am Coll Cardiol: 12 Oct 2020; 76:1751-1760 | PMID: 33032737
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Abstract

Effect of Anti-Inflammatory Drugs on Clinical Outcomes in Patients With Malignant Pericardial Effusion.

Kim SR, Kim EK, Cho J, Chang SA, ... Lee SC, Park SW
Background
Pericardiocentesis (PCC) with extended catheter drainage has become a relatively safe procedure to control pericardial effusion (PE), but little is known about long-term outcomes after PCC in malignant PE.
Objectives
This study evaluated the effects of anti-inflammatory agents on long-term outcomes after effective drainage of PE in active cancer patients.
Methods
From May 2007 to December 2018, 445 patients with malignant PE who underwent echocardiography-guided PCC were enrolled. Clinical, laboratory, echocardiographic and procedural findings, and clinical outcome data were collected. Use of anti-inflammatory agents including colchicine, nonsteroidal anti-inflammatory drugs, or steroids after PCC was also analyzed. Colchicine was administered in a dose of 0.6 mg orally, twice a day for 2 months. The primary outcome was defined as a composite of all-cause death and re-PCC or pericardial window operation due to recurred PE.
Results
The procedure was successful in 97.0% of the cases, with 1 procedure-related death. During the follow-up of 2 years, 26.1% of patients developed recurrent PE, and 46.0% developed constrictive pericarditis. The colchicine treatment group showed a significantly lower risk of composite events (adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [CI]: 0.49 to 0.87; p = 0.003) as well as all-cause death (aHR: 0.60; 95% CI: 0.45 to 0.81; p = 0.001) than did the noncolchicine group. On propensity score matching, colchicine after PCC was consistently associated with a lower composite events (aHR: 0.55; 95% CI: 0.37 to 0.82; p = 0.003).
Conclusions
In cancer patients with malignant PE, PCC with extended drainage can be an appropriate therapeutic option and shows low complication rate. Patients receiving colchicine after successful PCC showed significant improvement in clinical outcome.

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

J Am Coll Cardiol: 28 Sep 2020; 76:1551-1561
Kim SR, Kim EK, Cho J, Chang SA, ... Lee SC, Park SW
J Am Coll Cardiol: 28 Sep 2020; 76:1551-1561 | PMID: 32972532
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Abstract

Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging for Detection of Coronary Artery Disease.

Arai AE, Schulz-Menger J, Berman D, Mahrholdt H, ... Pennell DJ,
Background
Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies.
Objectives
The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging.
Methods
Two international, single-vendor, phase 3 clinical trials of near identical design, \"GadaCAD1\" and \"GadaCAD2,\" were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD.
Results
Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2.
Conclusions
Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.

Published by Elsevier Inc.

J Am Coll Cardiol: 28 Sep 2020; 76:1536-1547
Arai AE, Schulz-Menger J, Berman D, Mahrholdt H, ... Pennell DJ,
J Am Coll Cardiol: 28 Sep 2020; 76:1536-1547 | PMID: 32972530
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Abstract

Cardiac Troponin for Assessment of Myocardial Injury in COVID-19: JACC Review Topic of the Week.

Sandoval Y, Januzzi JL, Jaffe AS

Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death. These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations. The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients. Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury. The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.

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

J Am Coll Cardiol: 07 Sep 2020; 76:1244-1258
Sandoval Y, Januzzi JL, Jaffe AS
J Am Coll Cardiol: 07 Sep 2020; 76:1244-1258 | PMID: 32652195
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Abstract

Preeclampsia-Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review.

Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S

Preeclampsia is a hypertensive disorder of pregnancy. It affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality. Hypertension and proteinuria are the cornerstone of the disease, though systemic organ dysfunction may ensue. The clinical syndrome begins with abnormal placentation with subsequent release of antiangiogenic markers, mediated primarily by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). High levels of sFlt-1 and sEng result in endothelial dysfunction, vasoconstriction, and immune dysregulation, which can negatively impact every maternal organ system and the fetus. This review comprehensively examines the pathogenesis of preeclampsia with a specific focus on the mechanisms underlying the clinical features. Delivery is the only definitive treatment. Low-dose aspirin is recommended for prophylaxis in high-risk populations. Other treatment options are limited. Additional research is needed to clarify the pathophysiology, and thus, identify potential therapeutic targets for improved treatment and, ultimately, outcomes of this prevalent disease.

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

J Am Coll Cardiol: 05 Oct 2020; 76:1690-1702
Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S
J Am Coll Cardiol: 05 Oct 2020; 76:1690-1702 | PMID: 33004135
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Impact:
Abstract

Inhibition of Interleukin-1β and Reduction in Atherothrombotic Cardiovascular Events in the CANTOS Trial.

Everett BM, MacFadyen JG, Thuren T, Libby P, Glynn RJ, Ridker PM
Background
Inflammation reduction with the interleukin (IL)-1β inhibitor canakinumab significantly reduces the first major adverse cardiovascular event in patients with prior myocardial infarction (MI) and residual inflammatory risk (high-sensitivity C-reactive protein ≥ 2 mg/l). However, the effect of canakinumab on the total number of cardiovascular events, including recurrent events collected after a first event, is unknown.
Objectives
This study sought to determine whether randomly allocated canakinumab would reduce the total burden of serious cardiovascular events.
Methods
We randomized 10,061 patients to placebo or canakinumab 50 mg, 150 mg, or 300 mg once every 3 months and compared the rates of the composite of all serious cardiovascular events (MI, stroke, coronary revascularization, and cardiovascular death) in active versus placebo groups. We used negative binomial regression to account for correlations among repeated events in the same person and to estimate rate ratios and 95% confidence intervals.
Results
During a median of 3.7 years of follow-up, 3,417 total serious cardiovascular events occurred in 2,003 individuals among the 10,061 unique patients randomized. Canakinumab reduced the rates of total serious cardiovascular events, with rates per 100 person-years in the placebo, 50 mg, 150 mg, and 300 mg canakinumab groups of 10.4, 8.4, 8.3, and 8.2, respectively. The corresponding rate ratios (95% confidence intervals) compared with placebo were 0.80 (0.69 to 0.93) for 50 mg, 0.79 (0.68 to 0.92) for 150 mg, and 0.78 (0.67 to 0.91) for 300 mg.
Conclusions
Anti-inflammatory therapy with canakinumab significantly reduced the total number of cardiovascular events in patients with prior MI and evidence of residual inflammatory risk. (Cardiovascular Risk Reduction Study [Reduction in Recurrent Major CV Disease Events] (CANTOS); NCT01327846.

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

J Am Coll Cardiol: 05 Oct 2020; 76:1660-1670
Everett BM, MacFadyen JG, Thuren T, Libby P, Glynn RJ, Ridker PM
J Am Coll Cardiol: 05 Oct 2020; 76:1660-1670 | PMID: 33004131
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Impact:
Abstract

Inflammation as a Predictor of Recurrent Ventricular Tachycardia After Ablation in Patients With Myocarditis.

Peretto G, Sala S, Basso C, Rizzo S, ... Mazzone P, Della Bella P
Background
Little is known about the risk stratification of patients with myocarditis undergoing ventricular tachycardia (VT) ablation.
Objectives
This study sought to describe VT ablation results and identify factors associated with arrhythmia recurrences in a cohort of patients with myocarditis.
Methods
The authors enrolled 125 consecutive patients with myocarditis, undergoing VT ablation. Before ablation, disease stage was evaluated, to identify active (AM) versus previous myocarditis (PM). The primary study endpoint was assessment of VT recurrences by 12-month follow-up. Predictors of VT recurrences were retrospectively identified.
Results
All patients (age 51 ± 14 years, 91% men, left ventricular ejection fraction 52% ± 9%) had history of myocarditis diagnosed by endomyocardial biopsy (59%) and/or cardiac magnetic resonance (90%). Furthermore, all had multiple episodes of drug-refractory VTs. Multimodal pre-procedural staging identified 47 patients with AM (38%) and 78 patients with PM (62%). All patients showed low-voltage areas (LVA) at electroanatomical map (97% epicardial or endoepicardial); of them, 25 (20%) had wide borderzone (WBZ, constituting >50% of the whole LVA). VT recurrences were documented in 25 patients (20%) by 12 months, and in 43 (34%) by last follow-up (median 63 months; interquartile range: 39 to 87). At multivariable analysis, AM stage was the only predictor of VT recurrences by 12 months (hazard ratio: 9.5; 95% confidence interval: 2.6 to 35.3; p < 0.001), whereas both AM stage and WBZ were associated with arrhythmia recurrences anytime during follow-up. No VT episodes were found after redo ablation was performed in 23 patients during PM stage.
Conclusion
Our findings suggest that VT ablation should be avoided during AM, but is often of benefit for recurrent VT after the acute phase of myocarditis.

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

J Am Coll Cardiol: 05 Oct 2020; 76:1644-1656
Peretto G, Sala S, Basso C, Rizzo S, ... Mazzone P, Della Bella P
J Am Coll Cardiol: 05 Oct 2020; 76:1644-1656 | PMID: 33004129
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Abstract

Incidence, Characteristics, Predictors, and Outcomes of Surgical Explantation After Transcatheter Aortic Valve Replacement.

Hirji SA, Percy ED, McGurk S, Malarczyk A, ... Shah PB, Kaneko T
Background
Currently, there is a paucity of information on surgical explantation after transcatheter aortic valve replacement (TAVR).
Objectives
The purpose of this study was to examine the incidence, patient characteristics, predictors, and outcomes of surgical explantation after TAVR using a population-based, nationally representative database.
Methods
We analyzed the Medicare Provider profile to include all U.S. patients undergoing TAVR from 2012 to 2017. Time to surgical explant was calculated from the index TAVR discharge to surgical explantation. Post-operative survival was assessed using time-dependent Cox proportional hazard regression analysis and landmark analysis.
Results
The incidence of surgical explantation was 0.2% (227 of 132,633 patients), and was 0.28% and 0.14% in the early and newer TAVR era, respectively. The median time to surgical explant was 212 days, whereas 8.8% and 70.9% underwent surgical explantation within 30 days and 1 year, respectively. The primary indication for reintervention was bioprosthetic failure (79.3%). Compared with the no-explant cohort, the explant cohort was significantly younger (mean age 73.7 years vs. 81.7 years), with a lower prevalence of heart failure (55.9% vs. 65.8%) but more likely a lower-risk profile cohort (15% vs. 2.4%; all p < 0.05). The 30-day and 1-year mortality rates were 13.2% and 22.9%, respectively, and did not vary by either time to surgical explant or TAVR era, or between patients with versus without endocarditis (all p > 0.05). The time-dependent Cox regression analysis demonstrated a higher mortality in those with surgical explantation (hazard ratio: 4.03 vs. no-explant group; 95% confidence interval: 1.81 to 8.98). Indication, time-to-surgical-explant, and year of surgical explantation were not associated with worse post-explantation survival (all p > 0.05).
Conclusions
The present study provides updated evidence on the incidence, timing, and outcomes of surgical explantation of a TAVR prosthesis. Although the overall incidence was low, short-term mortality was high. These findings stress the importance of future mechanistic studies on TAVR explantation and may have implications on lifetime management of aortic stenosis, particularly in younger patients.

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

J Am Coll Cardiol: 19 Oct 2020; 76:1848-1859
Hirji SA, Percy ED, McGurk S, Malarczyk A, ... Shah PB, Kaneko T
J Am Coll Cardiol: 19 Oct 2020; 76:1848-1859 | PMID: 33059830
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Abstract

Structural Deterioration of Transcatheter Versus Surgical Aortic Valve Bioprostheses in the PARTNER-2 Trial.

Pibarot P, Ternacle J, Jaber WA, Salaun E, ... Hahn RT,
Background
It is unknown whether transcatheter valves will have similar durability as surgical bioprosthetic valves. Definitions of structural valve deterioration (SVD), based on valve related reintervention or death, underestimate the incidence of SVD.
Objectives
This study sought to determine and compare the 5-year incidence of SVD, using new standardized definitions based on echocardiographic follow-up of valve function, in intermediate-risk patients with severe aortic stenosis given transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial and registry.
Methods
In the PARTNER 2A trial, patients were randomly assigned to receive either TAVR with the SAPIEN XT or SAVR, whereas in the SAPIEN 3 registry, patients were assigned to TAVR with the SAPIEN 3. The primary endpoint was the incidence of SVD, that is, the composite of SVD-related hemodynamic valve deterioration during echocardiographic follow-up and/or SVD-related bioprosthetic valve failure (BVF) at 5 years.
Results
Compared with SAVR, the SAPIEN-XT TAVR cohort had a significantly higher 5-year exposure adjusted incidence rates (per 100 patient-years) of SVD (1.61 ± 0.24% vs. 0.63 ± 0.16%), SVD-related BVF (0.58 ± 0.14% vs. 0.12 ± 0.07%), and all-cause (structural or nonstructural) BVF (0.81 ± 0.16% vs. 0.27 ± 0.10%) (p ≤ 0.01 for all). The 5-year rates of SVD (0.68 ± 0.18% vs. 0.60 ± 0.17%; p = 0.71), SVD-related BVF (0.29 ± 0.12% vs. 0.14 ± 0.08%; p = 0.25), and all-cause BVF (0.60 ± 0.15% vs. 0.32 ± 0.11%; p = 0.32) in SAPIEN 3 TAVR were not significantly different to a propensity score matched SAVR cohort. The 5-year rates of SVD and SVD-related BVF were significantly lower in SAPIEN 3 versus SAPIEN XT TAVR matched cohorts.
Conclusions
Compared with SAVR, the second-generation SAPIEN XT balloon-expandable valve has a higher 5-year rate of SVD, whereas the third-generation SAPIEN 3 has a rate of SVD that was not different from SAVR. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves - PII A [PARTNERII A]; NCT01314313; The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - PARTNER II - PARTNERII - S3 Intermediate [PARTNERII S3i]; NCT03222128).

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

J Am Coll Cardiol: 19 Oct 2020; 76:1830-1843
Pibarot P, Ternacle J, Jaber WA, Salaun E, ... Hahn RT,
J Am Coll Cardiol: 19 Oct 2020; 76:1830-1843 | PMID: 33059828
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Abstract

Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease: The Disrupt CAD III Study.

Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, ... Waksman R, 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.
Objective
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 (MACE: cardiac death, myocardial infarction or target vessel revascularization) at 30 days. The primary effectiveness endpoint was procedural success. Both endpoints were compared to a pre-specified performance goal (PG). The mechanism of calcium modification was assessed in an optical coherence tomography (OCT) sub-study.
Results
Patients (n=431) were enrolled at 47 sites in four countries. The primary safety endpoint of the 30-day freedom from MACE was 92.2%; the lower bound of the 95% confidence interval (CI) was 89.5% 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% CI 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 multi-plane and longitudinal calcium fractures after IVL in 67.4% of lesions. Minimum stent area was 6.5 ± 2.1mm 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: 09 Oct 2020; epub ahead of print
Hill JM, Kereiakes DJ, Shlofmitz RA, Klein AJ, ... Waksman R, Stone GW
J Am Coll Cardiol: 09 Oct 2020; epub ahead of print | PMID: 33069849
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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
We 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 non-obstructive stenosis not intended for PCI but with IVUS plaque burden ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) vs. GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (non-powered) safety endpoint was randomized target lesion failure (TLF; cardiac death, target vessel-related MI or clinically-driven target lesion revascularization) at 24 months. The secondary (non-powered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (MACE; 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 NIRS-IVUS median plaque burden was 73.7%, median MLA was 2.9 mm, and median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and 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% CI 3.3-4.5, P<0.0001). TLF 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 MACE occurred in 4.3% BVS-treated patients vs. 10.7% GDMT alone-treated patients (OR 0.38, 95% CI 0.11-1.28, 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.

Copyright © 2020. Published by Elsevier Inc.

J Am Coll Cardiol: 21 Sep 2020; epub ahead of print
Stone GW, Maehara A, Ali ZA, Held C, ... Erlinge D,
J Am Coll Cardiol: 21 Sep 2020; epub ahead of print | PMID: 33069847
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Abstract

Challenges in Cardiac and Pulmonary Sarcoidosis: JACC State-of-the-Art Review.

Trivieri MG, Spagnolo P, Birnie D, Liu P, ... Fayad ZA, Judson MA

Sarcoidosis is a complex disease with heterogeneous clinical presentations that can affect virtually any organ. Although the lung is typically the most common organ involved, combined pulmonary and cardiac sarcoidosis (CS) account for most of the morbidity and mortality associated with this disease. Pulmonary sarcoidosis can be asymptomatic or result in impairment in quality of life and end-stage, severe, and/or life-threatening disease. The latter outcome is seen almost exclusively in those with fibrotic pulmonary sarcoidosis, which accounts for 10% to 20% of pulmonary sarcoidosis patients. CS is problematic to diagnose and may cause significant morbidity and death from heart failure or ventricular arrhythmias. The diagnosis of CS usually requires surrogate cardiac imaging biomarkers, as endomyocardial biopsy has relatively low yield, even with directed electrophysiological mapping. Treatment of CS is often multifactorial, involving a combination of antigranulomatous therapy and pharmacotherapy for cardiac arrhythmias and/or heart failure in addition to device placement and cardiac transplantation.

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

J Am Coll Cardiol: 19 Oct 2020; 76:1878-1901
Trivieri MG, Spagnolo P, Birnie D, Liu P, ... Fayad ZA, Judson MA
J Am Coll Cardiol: 19 Oct 2020; 76:1878-1901 | PMID: 33059834
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Abstract

Molecular Imaging of Apoptosis in Atherosclerosis by Targeting Cell Membrane Phospholipid Asymmetry.

Chaudhry F, Kawai H, Johnson KW, Narula N, ... Fuster V, Narula J
Background
Apoptosis in atherosclerotic lesions contributes to plaque vulnerability by lipid core enlargement and fibrous cap attenuation. Apoptosis is associated with exteriorization of phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the cell membrane. Although PS-avid radiolabeled annexin-V has been employed for molecular imaging of high-risk plaques, PE-targeted imaging in atherosclerosis has not been studied.
Objectives
This study sought to evaluate the feasibility of molecular imaging with PE-avid radiolabeled duramycin in experimental atherosclerotic lesions in a rabbit model and compare duramycin targeting with radiolabeled annexin-V.
Methods
Of the 27 rabbits, 21 were fed high-cholesterol, high-fat diet for 16 weeks. Nine of the 21 rabbits received Tc-duramycin (test group), 6 received Tc-linear duramycin (duramycin without PE-binding capability, negative radiotracer control group), and 6 received Tc-annexin-V for radionuclide imaging. The remaining normal chow-fed 6 animals (disease control group) received Tc-duramycin. In vivo microSPECT/microCT imaging was performed, and the aortas were explanted for ex vivo imaging and for histological characterization of atherosclerosis.
Results
A significantly higher duramycin uptake was observed in the test group compared with that of disease control and negative radiotracer control animals; duramycin uptake was also significantly higher than the annexin-V uptake. Quantitative duramycin uptake, represented as the square root of percent injected dose per cm (√ID/cm) of abdominal aorta was >2-fold higher in atherosclerotic lesions in test group (0.08 ± 0.01%) than in comparable regions of disease control animals (0.039 ± 0.0061%, p = 3.70·10). Mean annexin uptake (0.060 ± 0.010%) was significantly lower than duramycin (p = 0.001). Duramycin uptake corresponded to the lesion severity and macrophage burden. The radiation burden to the kidneys was substantially lower with duramycin (0.49% ID/g) than annexin (5.48% ID/g; p = 4.00·10).
Conclusions
Radiolabeled duramycin localizes in lipid-rich areas with high concentration of apoptotic macrophages in the experimental atherosclerosis model. Duramycin uptake in atherosclerotic lesions was significantly greater than annexin-V uptake and produced significantly lower radiation burden to nontarget organs.

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

J Am Coll Cardiol: 19 Oct 2020; 76:1862-1874
Chaudhry F, Kawai H, Johnson KW, Narula N, ... Fuster V, Narula J
J Am Coll Cardiol: 19 Oct 2020; 76:1862-1874 | PMID: 33059832
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This program is still in alpha version.