Journal: J Am Coll Cardiol

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Abstract

Mechanical Left Ventricular Unloading in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation.

Grandin EW, Nunez JI, Willar B, Kennedy K, ... Shaefi S, Garan AR
Background
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) increases left ventricular (LV) afterload, potentially provoking LV distention and impairing recovery. LV mechanical unloading (MU) with intra-aortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) can prevent LV distension, potentially at the risk of more complications, and net clinical benefit remains uncertain.
Objectives
This study aims to determine the association between MU and outcomes for patients undergoing VA-ECMO.
Methods
The authors queried the Extracorporeal Life Support Organization registry for adults receiving peripheral VA-ECMO from 2010 to 2019 and stratified them by MU with IABP or pVAD. The primary outcome was in-hospital mortality; secondary outcomes included on-support mortality and complications during VA-ECMO.
Results
Among 12,734 VA-ECMO patients, 3,399 (26.7%) received MU: 2,782 (82.9%) IABP and 580 (17.1%) pVAD. MU patients were older (age 56.3 vs 52.7 years) and, before extracorporeal membrane oxygenation, more often required >2 vasopressors (41.7% vs 27.2%) and had respiratory (21.1% vs 15.9%), renal (24.6% vs 15.8%), and liver failure (4.4% vs 3.1%) (all P < 0.001). MU patients had lower in-hospital mortality (56.6% vs 59.3%, P = 0.006), which persisted in multivariable modeling (adjusted OR [aOR]: 0.84; 95% CI: 0.77-0.92; P < 0.001). MU was associated with more cannula site bleeding (aOR: 1.25; 95% CI: 1.11-1.40; P < 0.001) and hemolysis (aOR: 1.27; 95% CI: 1.03-1.57; P = 0.02). Compared to pVAD, MU patients with IABP had similar mortality (aOR: 0.80; 95% CI: 0.64-1.01; P = 0.06) and less medical bleeding (aOR: 0.45; 95% CI: 0.31-0.64; P < 0.001), cannula site bleeding (aOR: 0.72; 95% CI: 0.54-0.96; P = 0.03), and renal injury (aOR: 0.78; 95% CI: 0.62-0.98; P = 0.03).
Conclusions
Among adults receiving VA-ECMO, MU was associated with lower in-hospital mortality despite increased complications including hemolysis and cannulation site bleeding. Compared to pVAD, MU with IABP was associated with similar mortality and lower complication rates.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Apr 2022; 79:1239-1250
Grandin EW, Nunez JI, Willar B, Kennedy K, ... Shaefi S, Garan AR
J Am Coll Cardiol: 05 Apr 2022; 79:1239-1250 | PMID: 35361346
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Abstract

Long-Term Outcomes of Patients Requiring Unplanned Repeated Interventions After Surgery for Congenital Heart Disease.

Sengupta A, Gauvreau K, Kohlsaat K, Colan SD, ... Del Nido PJ, Nathan M
Background
Unplanned catheter-based or surgical reinterventions after congenital heart operations are independently associated with operative mortality and increased postoperative length of stay.
Objectives
This study assessed the long-term outcomes of transplant-free survivors of hospital discharge requiring predischarge reinterventions after congenital cardiac surgery.
Methods
Data from patients who required predischarge reinterventions in the anatomic area of repair after congenital cardiac surgery and survived to hospital discharge at a quaternary referral center from January 2011 to December 2019 were retrospectively reviewed. Previously published echocardiographic criteria were used to assess the severity of persistent residual lesions at discharge (Grade 1, no residua; Grade 2, minor residua; and Grade 3, major residua). Outcomes included postdischarge (late) mortality or transplant and unplanned reintervention. Associations between predischarge residual lesion severity and outcomes were assessed by using Cox or competing risk models, adjusting for baseline patient characteristics, case complexity, and preoperative risk factors.
Results
Among the 408 patients who met entry criteria, there were 58 (14.2%) postdischarge deaths or transplants and 208 (51.0%) late reinterventions at a median follow-up of 3.0 years (IQR: 1.1-6.8 years). Greater predischarge residual lesion severity was associated with worse transplant-free survival and freedom from reintervention (both, P < 0.05). On multivariable analyses, Grade 3 patients had an increased risk of postdischarge mortality or transplant (HR: 4.8; 95% CI: 2.0-11; P < 0.001) and late reintervention (subdistribution HR: 2.1; 95% CI: 1.4-3.1; P < 0.001) vs Grade 1 patients.
Conclusions
Among transplant-free survivors requiring predischarge reinterventions after congenital cardiac surgery, those with persistent major residua have significantly worse long-term outcomes. These high-risk patients warrant closer surveillance.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2489-2499
Sengupta A, Gauvreau K, Kohlsaat K, Colan SD, ... Del Nido PJ, Nathan M
J Am Coll Cardiol: 28 Jun 2022; 79:2489-2499 | PMID: 35738709
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Abstract

Becoming a Parent During Cardiovascular Training.

Oliveros E, Burgess S, Nadella N, Davidson L, ... DeFaria Yeh D, Park K
Background
Specialty training in cardiovascular diseases is consistently perceived to have adverse job conditions and interfere with family life. There is a dearth of universal workforce support for trainees who become parents during training.
Objectives
This study sought to identify parental policies across cardiovascular training programs internationally.
Methods
An Internet-based international survey study available from August 2020 to October 2020 was sent via social media. The survey was administered 1 time and anonymously. Participants shared experiences regarding parental benefits/policies and perception of barriers for trainees. Participants were divided into 3 groups: training program directors, trainees pregnant during cardiology fellowship, and trainees not pregnant during training.
Results
A total of 417 replies were received from physicians, including 47 responses (11.3%) from training program directors, 146 responses (35%) from current or former trainees pregnant during cardiology training, and 224 responses (53.7%) from current or former trainees that were not pregnant during cardiology training. Among trainees, 280 (67.1%) were parents during training. Family benefits and policies were not uniformly available across institutions, and knowledge regarding the existence of such policies was low. Average parental leave ranged from 1 to 2 months in the United States compared with >4 months outside the United States, and in all countries, paternity leave was uncommon (only 11 participants [2.6%]). Coverage during family leave was primarily provided by peers (n = 184 [44.1%]), and 168 (91.3%) were without additional monetary or time compensation.
Conclusions
This is the first international survey evaluating and comparing parental benefits and policies among cardiovascular training programs. There is great variability among institutions, highlighting disparities in real-world experiences.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2119-2126
Oliveros E, Burgess S, Nadella N, Davidson L, ... DeFaria Yeh D, Park K
J Am Coll Cardiol: 31 May 2022; 79:2119-2126 | PMID: 35618349
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Abstract

Early Coronary Atherosclerosis in Women With Previous Preeclampsia.

Hauge MG, Damm P, Kofoed KF, Ersbøll AS, ... Gustafsson F, Linde JJ
Background
Women with previous preeclampsia have an increased risk of coronary artery disease later in life.
Objectives
This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population.
Methods
Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA.
Results
A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity.
Conclusions
Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2310-2321
Hauge MG, Damm P, Kofoed KF, Ersbøll AS, ... Gustafsson F, Linde JJ
J Am Coll Cardiol: 14 Jun 2022; 79:2310-2321 | PMID: 35680182
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Abstract

Cardiovascular Risks of Hydroxychloroquine vs Methotrexate in Patients With Rheumatoid Arthritis.

D\'Andrea E, Desai RJ, He M, Glynn RJ, ... Weinblatt ME, Kim SC
Background
Hydroxychloroquine is often used as a first-line treatment of rheumatoid arthritis despite limited evidence on its cardiovascular risk.
Objectives
We conducted a cardiovascular safety evaluation comparing hydroxychloroquine to methotrexate among patients with rheumatoid arthritis.
Methods
Using Medicare data (2008-2016), we identified 54,462 propensity score-matched patients with rheumatoid arthritis, aged ≥65 years, who initiated hydroxychloroquine or methotrexate. Primary outcomes were sudden cardiac arrest or ventricular arrythmia (SCA/VA) and major adverse cardiovascular event (MACE). Secondary outcomes were cardiovascular mortality, all-cause mortality, myocardial infarction, stroke, and hospitalized heart failure (HF). We also examined treatment effect modification by history of HF.
Results
Hydroxychloroquine was not associated with risk of SCA/VA (HR: 1.03; 95% CI: 0.79-1.35) or MACE (HR: 1.07; 95% CI: 0.97-1.18) compared with methotrexate. In patients with history of HF, hydroxychloroquine initiators had a higher risk of MACE (HR: 1.30; 95% CI: 1.08-1.56), cardiovascular mortality (HR: 1.34; 95% CI: 1.06-1.70), all-cause mortality (HR: 1.22; 95% CI: 1.04-1.43), myocardial infarction (HR: 1.74; 95% CI: 1.25-2.42), and hospitalized HF (HR: 1.29; 95% CI: 1.07-1.54) compared to methotrexate initiators. Cardiovascular risks were not different in patients without history of HF except for an increased hospitalized HF risk (HR: 1.57; 95% CI: 1.30-1.90) among hydroxychloroquine initiators.
Conclusions
In older patients with rheumatoid arthritis, hydroxychloroquine and methotrexate showed similar SCA/VA and MACE risks; however, hydroxychloroquine initiators with history of HF had higher risks of MACE, cardiovascular mortality, all-cause mortality, and myocardial infarction. An increased hospitalized HF risk was observed among hydroxychloroquine initiators regardless of an HF history.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2022; 80:36-46
D'Andrea E, Desai RJ, He M, Glynn RJ, ... Weinblatt ME, Kim SC
J Am Coll Cardiol: 05 Jul 2022; 80:36-46 | PMID: 35772915
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Abstract

Outcomes Associated With Peripheral Artery Disease in Myocardial Infarction With Cardiogenic Shock.

Mihatov N, Mosarla RC, Kirtane AJ, Parikh SA, ... Yeh RW, Secemsky EA
Background
Mortality rates for patients presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remain high despite advances in revascularization strategies and mechanical circulatory support (MCS) devices.
Objectives
This study sought to elucidate the association between comorbid lower extremity peripheral artery disease (PAD) and outcomes in CS and AMI.
Methods
PAD status was defined in Medicare beneficiaries hospitalized with CS and AMI from October 1, 2015 to June 30, 2018. Primary outcomes ascertained through December 31, 2018 included in- and out-of-hospital mortality. Secondary outcomes included bleeding, amputation, stroke, and lower extremity revascularization. Multivariable regression models with adjustment for confounders were used to estimate risk. Subgroup analyses included patients treated with MCS and those who underwent coronary revascularization.
Results
Among 71,690 patients, 5.9% (N = 4,259) had PAD. Mean age was 77.8 ± 7.9 years, 58.7% were male, and 84.3% were White. Cumulative in-hospital mortality was 47.2%, with greater risk among those with PAD (56.3% vs 46.6% without PAD; adjusted OR: 1.50; 95% CI: 1.40-1.59). PAD patients also had greater risk of in-hospital amputation (1.6% vs 0.2%; adjusted OR: 7.0; 95% CI: 5.26-9.37) and out-of-hospital mortality (67.9% vs 40.7%; adjusted HR: 1.78; 95% CI: 1.67-1.90). MCS was less frequently utilized in PAD patients (21.5% vs 38.6% without PAD; P < 0.001) and was associated with higher mortality, need for lower extremity revascularization, and amputation risk. Findings were consistent in patients who underwent coronary revascularization.
Conclusions
Among patients presenting with AMI and CS, PAD was associated with worse limb outcomes and survival. In addition to lower MCS utilization rates, those with PAD who received MCS had increased mortality, lower extremity revascularization, and amputation rates.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Apr 2022; 79:1223-1235
Mihatov N, Mosarla RC, Kirtane AJ, Parikh SA, ... Yeh RW, Secemsky EA
J Am Coll Cardiol: 05 Apr 2022; 79:1223-1235 | PMID: 35361344
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Abstract

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy.

Norrish G, Cleary A, Field E, Cervi E, ... Elliott PM, Kaski JP
Background
Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized.
Objectives
The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years.
Methods
Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years.
Results
At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age.
Conclusions
Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.

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

J Am Coll Cardiol: 24 May 2022; 79:1986-1997
Norrish G, Cleary A, Field E, Cervi E, ... Elliott PM, Kaski JP
J Am Coll Cardiol: 24 May 2022; 79:1986-1997 | PMID: 35589160
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Abstract

Prospective Evaluation of Autonomic Dysfunction in Post-Acute Sequela of COVID-19.

Jamal SM, Landers DB, Hollenberg SM, Turi ZG, ... Tancredi J, Parrillo JE
Background
Patients with PASC often report symptoms of orthostatic intolerance and autonomic dysfunction. Numerous case reports link Postural Orthostatic Tachycardia Syndrome (POTS) to PASC. No prospective analysis has been performed.
Objective
We performed head-up tilt table (HUTT) testing in symptomatic Post-Acute Sequela of COVID-19 (PASC) patients to evaluate for orthostatic intolerance suggestive of autonomic dysfunction.
Methods
We performed a prospective, observational evaluation of patients with PASC complaining of poor exertional tolerance, tachycardia with minimal activity or positional change, and palpitations. Exclusion criteria included pregnancy, pre-PASC autonomic dysfunction or syncope, or another potential explanation of PASC symptoms. All subjects underwent HUTT.
Results
Twenty-four patients with the described PASC symptoms were included. HUTT was performed a mean of 5.8 ± 3.5 months after symptom onset. Twenty-three of the 24 had orthostatic intolerance on HUTT, with 4 demonstrating POTS, 15 provoked orthostatic intolerance (POI) after nitroglycerin, 3 neurocardiogenic syncope, and one orthostatic hypotension. Compared to those with POTS, patients with POI described significantly earlier improvement of symptoms.
Conclusions
This prospective evaluation of HUTT in PASC patients revealed orthostatic intolerance on HUTT suggestive of autonomic dysfunction in nearly all subjects. Those with POI may be further along the path of clinical recovery than those demonstrating POTS.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 28 Mar 2022; epub ahead of print
Jamal SM, Landers DB, Hollenberg SM, Turi ZG, ... Tancredi J, Parrillo JE
J Am Coll Cardiol: 28 Mar 2022; epub ahead of print | PMID: 35381331
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Abstract

Trends in Clinical Characteristics, Management Strategies and Outcomes of STEMI Patients with COVID-19.

Garcia S, Dehghani P, Stanberry L, Grines C, ... Yildiz M, Henry TD
Background
We previously reported high in-hospital mortality for STEMI patients with COVID-19 treated in the early phase of the pandemic.
Objectives
To describe trends of COVID-19 patients with STEMI during the course of the pandemic.
Methods
The North American COVID-19 STEMI (NACMI) registry is a prospective, investigator initiated, multi-center, observational registry of hospitalized STEMI patients with confirmed or suspected COVID-19 infection in North America. We compared trends in clinical characteristics, management and outcomes of patients treated in the first year of the pandemic (1/2020 to 12/2020) versus those treated in the second year (1/2021 to 12/2021).
Results
A total of 586 COVID positive (+) patients with STEMI were included in the present analysis; 227 treated in Y2020 and 359 treated in Y2021. Patients\' characteristics changed over time. Relative to Y2020, the proportion of Caucasian patients was higher (58% vs. 39%, p<0.001), patients presented more frequently with typical ischemic symptoms (59% vs 51%, p=0.04), were less likely to have shock pre-PCI (13% vs 18%, p=0.07) or pulmonary manifestations (33% vs. 47%, p=0.001) in Y2021. In-hospital mortality decreased from 33% (Y2020) to 23% (Y2021) (p=0.008). In Y2021, none of the 22 vaccinated patients expired in hospital, whereas in-hospital death was recorded in 37 (22%) of unvaccinated patients (p=0.009).
Conclusions
Significant changes have occurred in the clinical characteristics and outcomes of STEMI patients with COVID-19 infection during the course of the pandemic.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 25 Mar 2022; epub ahead of print
Garcia S, Dehghani P, Stanberry L, Grines C, ... Yildiz M, Henry TD
J Am Coll Cardiol: 25 Mar 2022; epub ahead of print | PMID: 35390486
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Abstract

Call for Formalized Pathways in Vascular Medicine Training: JACC Review Topic of the Week.

Eberhardt RT, Bonaca MP, Abu Daya H, Garcia LA, ... Young MN, Piazza G
The burden of vascular diseases and complexity of their management have been growing. Vascular medicine specialists may help to bridge gaps in care, especially as part of multidisciplinary teams. However, there is a limited number of vascular medicine specialists because of constraints in training. Despite established pathways for training in vascular medicine, there are obstacles that restrict completion of training in dedicated programs. A key factor is lack of funding as a result of inadequate recognition by key national accrediting and credentialing organizations. A concerted effort is required to overcome the obstacles to expand vascular medicine training programs and ultimately the pool of vascular medicine specialists. Well-trained vascular medicine specialists will be well positioned to ease the burden of vascular disease and optimize patient outcomes.

Copyright © 2022 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2129-2139
Eberhardt RT, Bonaca MP, Abu Daya H, Garcia LA, ... Young MN, Piazza G
J Am Coll Cardiol: 31 May 2022; 79:2129-2139 | PMID: 35618351
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Abstract

Cigarette Smoking, Cessation, and Risk of Heart Failure With Preserved and Reduced Ejection Fraction.

Ding N, Shah AM, Blaha MJ, Chang PP, Rosamond WD, Matsushita K
Background
Smoking is well-recognized as a risk factor for heart failure (HF). However, few studies have evaluated the prospective association of cigarette smoking and smoking cessation with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) as distinct phenotypes.
Objectives
The aim of this study was to quantify the association of cigarette smoking and smoking cessation with the incidence of HFpEF and HFrEF.
Methods
In 9,345 ARIC (Atherosclerosis Risk In Communities) study White and Black participants without history of HF at baseline in 2005 (age range 61-81 years), we quantified the associations of several established cigarette smoking parameters (smoking status, pack-years, intensity, duration, and years since cessation) with physician-adjudicated incident acute decompensated HF using multivariable Cox models.
Results
Over a median follow-up of 13.0 years, there were 1,215 incident HF cases. Compared with never smokers, current cigarette smoking was similarly associated with HFpEF and HFrEF, with adjusted HRs ∼2. There was a dose-response relationship for pack-years of smoking and HF. A more extended period of smoking cessation was associated with a lower risk of HF, but significantly elevated risk persisted up to a few decades for HFpEF and HFrEF.
Conclusions
All cigarette smoking parameters consistently showed significant and similar associations with HFpEF and HFrEF. Smoking cessation significantly reduced the risk of HF, but excess HF risk persisted for a few decades. Our results strengthened the evidence that smoking is an important modifiable risk factor for HF and highlighted the importance of smoking prevention and cessation for the prevention of HF, including HFpEF.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2298-2305
Ding N, Shah AM, Blaha MJ, Chang PP, Rosamond WD, Matsushita K
J Am Coll Cardiol: 14 Jun 2022; 79:2298-2305 | PMID: 35680180
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Abstract

Care Models for Acute Chest Pain That Improve Outcomes and Efficiency: JACC State-of-the-Art Review.

Dawson LP, Smith K, Cullen L, Nehme Z, ... Taylor AJ, Stub D
Existing assessment pathways for acute chest pain are often resource-intensive, prolonged, and expensive. In this review, the authors describe existing chest pain pathways and current issues at the patient and system level, and provide an overview of recent advances in chest pain research that could inform improved outcomes for both patients and health systems. There are multiple avenues to improve existing models of chest pain care, including novel risk stratification pathways incorporating highly sensitive point-of-care troponin assays; new devices available before first medical contact that could allow clinicians to access vital signs and electrocardiogram data; artificial intelligence and precision medicine tools that may guide indications for further testing; and strategies to improve hospital benchmarking and performance monitoring to standardize care. Improving the speed and accuracy of chest pain diagnosis and management should be a priority for researchers and is likely to translate to substantive benefits for patients and health systems.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2333-2348
Dawson LP, Smith K, Cullen L, Nehme Z, ... Taylor AJ, Stub D
J Am Coll Cardiol: 14 Jun 2022; 79:2333-2348 | PMID: 35680185
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Abstract

Magnetically Controlled Capsule Endoscopy for Assessment of Antiplatelet Therapy-Induced Gastrointestinal Injury.

Han Y, Liao Z, Li Y, Zhao X, ... Li Z, Stone GW
Background
Gastrointestinal bleeding is the most frequent major complication of antiplatelet therapy. In patients at low bleeding risk, however, clinically overt gastrointestinal bleeding is relatively uncommon.
Objectives
The authors sought to assess the effects of different antiplatelet regimens on gastrointestinal mucosal injury by means of a novel magnetically controlled capsule endoscopy system in patients at low bleeding risk.
Methods
Patients (n = 505) undergoing percutaneous coronary intervention in whom capsule endoscopy demonstrated no ulcerations or bleeding (although erosions were permitted) after 6 months of dual antiplatelet therapy (DAPT) were randomly assigned to aspirin plus placebo (n = 168), clopidogrel plus placebo (n = 169), or aspirin plus clopidogrel (n = 168) for an additional 6 months. The primary endpoint was the incidence of gastrointestinal mucosal injury (erosions, ulceration, or bleeding) at 6-month or 12-month capsule endoscopy.
Results
Gastrointestinal mucosal injury through 12 months was less with single antiplatelet therapy (SAPT) than with DAPT (94.3% vs 99.2%; P = 0.02). Aspirin and clopidogrel monotherapy had similar effects. Among 68 patients without any gastrointestinal injury at randomization (including no erosions), SAPT compared with DAPT caused less gastrointestinal injury (68.1% vs 95.2%; P = 0.006), including fewer new ulcers (8.5% vs 38.1%; P = 0.009). Clinical gastrointestinal bleeding from 6 to 12 months was less with SAPT than with DAPT (0.6% vs 5.4%; P = 0.001).
Conclusions
Despite being at low risk of bleeding, nearly all patients receiving antiplatelet therapy developed gastrointestinal injury, although overt bleeding was infrequent. DAPT for 6 months followed by SAPT with aspirin or clopidogrel from 6 to 12 months resulted in less gastrointestinal mucosal injury and clinical bleeding compared with DAPT through 12 months. (OPT-PEACE [Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by Ankon Magnetically Controlled Capsule Endoscopy]; NCT03198741).

Copyright © 2022 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 17 Jan 2022; 79:116-128
Han Y, Liao Z, Li Y, Zhao X, ... Li Z, Stone GW
J Am Coll Cardiol: 17 Jan 2022; 79:116-128 | PMID: 34752902
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Abstract

Arterial Ultrasound Testing to Predict Atherosclerotic Cardiovascular Events.

Nicolaides AN, Panayiotou AG, Griffin M, Tyllis T, ... Avraamides C, Martin RM
Background
Studies have indicated that the presence and size of subclinical atherosclerotic plaques improve the prediction of atherosclerotic cardiovascular events (ASCVE) over and above that provided by conventional risk factors alone. However, the relative contribution of different ultrasonographic measurements and sites of measurements on the 10-year ASCVD risk is largely unknown.
Objectives
Our aims were to determine the relative performance of carotid intima-media thickness, plaque thickness, and plaque area in 10-year ASCVD prediction when added to conventional risk factors as well as whether the vascular territory of these measurements, carotid or common femoral bifurcation, and the number of bifurcations with plaque (NBP) influence prediction.
Methods
We enrolled 985 adults (mean age: 58.1 ± 10.2 years) free of atherosclerotic cardiovascular disease. Conventional risk factors were recorded, and both carotid and common femoral bifurcations were scanned with ultrasonography. The primary endpoint was a composite of first-time fatal or nonfatal ASCVE.
Results
Over a mean ± SD follow-up of 13.2 ± 3.7 years, ASCVE occurred in 154 (15.6%) participants. By adding different plaque measurements to conventional risk factors in a Cox model, net reclassification improvement was 10.4% with maximum intima-media thickness, 9.5% with carotid plaque thickness, and 14.2% with carotid plaque area. It increased to 16.1%, 16.6%, and 16.6% (P < 0.0001) by adding measurements from 4 bifurcations: NBP, total plaque thickness, and total plaque area, respectively.
Conclusions
NBP, total plaque thickness, or total plaque area from both the carotid and common femoral bifurcations provides a better prediction of future ASCVE than measurements from a single site. The results need to be validated in an independent cohort.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:1969-1982
Nicolaides AN, Panayiotou AG, Griffin M, Tyllis T, ... Avraamides C, Martin RM
J Am Coll Cardiol: 24 May 2022; 79:1969-1982 | PMID: 35589158
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Abstract

Cardiovascular Outcomes in Aortopathy: GenTAC Registry of Genetically Triggered Aortic Aneurysms and Related Conditions.

Holmes KW, Markwardt S, Eagle KA, Devereux RB, ... Roman MJ, GenTAC Investigators
Background
The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.
Objectives
The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.
Methods
The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome (LDS) (n = 121) were analyzed.
Results
The 25% probability of elective proximal aortic aneurysm surgery was 30 years for LDS (95% CI: 18-37 years), followed by MFS (34 years; 95% CI: 32-36 years), nsHTAD (52 years; 95% CI: 48-56 years), and BAV (55 years; 95% CI: 53-58 years). Any dissection surgery 25% probability was highest in LDS (38 years; 95% CI: 33-53 years) followed by MFS (51 years; 95% CI: 46-57 years) and nsHTAD (54 years; 95% CI: 51-61 years). BAV experienced the largest relative frequency of elective surgery to any dissection surgery (254/33 = 7.7), compared with MFS (273/112 = 2.4), LDS (35/16 = 2.2), or nsHTAD (82/76 = 1.1). With MFS as the reference population, risk of any dissection surgery or cardiovascular mortality was lowest in BAV patients (HR: 0.13; 95% CI: 0.08-0.18; HR: 0.13; 95%: CI: 0.06-0.27, respectively). The greatest risk of mortality was seen in patients with vEDS.
Conclusions
Marfan and LDS cohorts demonstrate age and event profiles congruent with the current understanding of syndromic aortopathies. BAV events weigh toward elective replacement with relatively few dissection surgeries. Nonsyndromic HTAD patients experience near equal probability of dissection vs prophylactic surgery, possibly because of failure of early diagnosis.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2069-2081
Holmes KW, Markwardt S, Eagle KA, Devereux RB, ... Roman MJ, GenTAC Investigators
J Am Coll Cardiol: 31 May 2022; 79:2069-2081 | PMID: 35618343
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Abstract

Reduced Heart Failure and Mortality in Patients Receiving Statin Therapy Before Initial Acute Coronary Syndrome.

Bugiardini R, Yoon J, Mendieta G, Kedev S, ... Badimon L, Cenko E
Background
There is uncertainty regarding the impact of statins on the risk of atherosclerotic cardiovascular disease (ASCVD) and its major complication, acute heart failure (AHF).
Objectives
The aim of this study was to investigate whether previous statin therapy translates into lower AHF events and improved survival from AHF among patients presenting with an acute coronary syndrome (ACS) as a first manifestation of ASCVD.
Methods
Data were drawn from the International Survey of Acute Coronary Syndromes Archives. The study participants consisted of 14,542 Caucasian patients presenting with ACS without previous ASCVD events. Statin users before the index event were compared with nonusers by using inverse probability weighting models. Estimates were compared by test of interaction on the log scale. Main outcome measures were the incidence of AHF according to Killip class and the rate of 30-day all-cause mortality in patients presenting with AHF.
Results
Previous statin therapy was associated with a significantly decreased rate of AHF on admission (4.3% absolute risk reduction; risk ratio [RR]: 0.72; 95% CI: 0.62-0.83) regardless of younger (40-75 years) or older age (interaction P = 0.27) and sex (interaction P = 0.22). Moreover, previous statin therapy predicted a lower risk of 30-day mortality in the subset of patients presenting with AHF on admission (5.2 % absolute risk reduction; RR: 0.71; 95% CI: 0.50-0.99).
Conclusions
Among adults presenting with ACS as a first manifestation of ASCVD, previous statin therapy is associated with a reduced risk of AHF and improved survival from AHF. (International Survey of Acute Coronary Syndromes [ISACS] Archives; NCT04008173).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:2021-2033
Bugiardini R, Yoon J, Mendieta G, Kedev S, ... Badimon L, Cenko E
J Am Coll Cardiol: 24 May 2022; 79:2021-2033 | PMID: 35589164
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Abstract

Socioeconomic Status and Risk of Bleeding After Mechanical Aortic Valve Replacement.

Dalén M, Persson M, Glaser N, Sartipy U
Background
Whether low socioeconomic status (SES) is associated with increased risk of anticoagulation-related adverse events in patients with mechanical heart valves is unknown.
Objectives
This study sought to investigate the impact of patients\' SES on the risk of bleeding after mechanical aortic valve replacement (AVR).
Methods
This nationwide population-based cohort study included all patients aged 18-70 years who underwent mechanical AVR in Sweden from 1997 to 2018. Data were obtained from the SWEDEHEART register and other national health data registers. The exposure was quartiles of household disposable income. The primary outcome was hospitalization for a bleeding event.
Results
Among 5974 patients, the absolute risk for bleeding after 20 years of follow-up was 20% (95% CI: 17%-24%) in the lowest income quartile (Q1) and 16% (95% CI: 13%-20%) in the highest quartile (Q4). The risk of bleeding decreased with increasing income level and was significantly lower in patients in income level Q3 (HR: 0.77; 95% CI: 0.60-0.99) and Q4 (HR: 0.68; 95% CI: 0.50-0.92) than Q1. The risk of death from intracranial hemorrhage was five times higher in the lowest income quartile than the age- and sex-matched general Swedish population (standardized mortality ratio: 5.0; 95% CI: 3.3-7.4).
Conclusions
We observed a strong association between SES and risk of bleeding among patients who underwent mechanical AVR. These findings suggest suboptimal anticoagulation treatment in patients with lower SES and the need for strategies to optimize anticoagulation treatment in patients with a mechanical heart valve. (Health-Data Register Studies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950).

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

J Am Coll Cardiol: 28 Jun 2022; 79:2502-2513
Dalén M, Persson M, Glaser N, Sartipy U
J Am Coll Cardiol: 28 Jun 2022; 79:2502-2513 | PMID: 35738711
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Abstract

Natural and Modified History of Atrioventricular Valve Regurgitation in Patients With Fontan Circulation.

King G, Buratto E, Celermajer DS, Grigg L, ... d\'Udekem Y, Konstantinov IE
Background
Atrioventricular valve (AVV) regurgitation is increasingly prevalent in patients with a Fontan circulation.
Objectives
We sought to determine the impact of ventricular dominance and AVV operation on outcomes in patients with a Fontan circulation and ≥moderate AVV regurgitation.
Methods
We conducted a retrospective study, including propensity score matching analysis, of 1,703 patients who survived Fontan operation in Australia and New Zealand from 1987 to 2021.
Results
Patients undergoing AVV operation were more likely to have right ventricular (RV) dominance or an atrioventricular septal defect. In the entire cohort, death or transplantation after Fontan operation was significantly higher in patients who underwent AVV operation before or at Fontan completion compared with those who did not (20 years: 18%; 95% CI: 8%-26% vs 13%; 95% CI: 10%-15%; P = 0.03). After propensity score matching, including for RV dominance, there was no significant difference in death or transplantation between the groups (20 years: 18%; 95% CI: 8%-26% vs 16%; 95% CI: 10%-22%; P = 0.41). Only patients with RV dominance who developed ≥moderate AVV regurgitation after Fontan operation were at increased risk of death or transplantation (HR: 2.8; 95% CI: 1.4-5.3; P < 0.01). In patients with left ventricular dominance, there was no significant difference in death or transplantation between patients with ≥moderate AVV regurgitation compared with those with <moderate regurgitation (P = 0.8).
Conclusions
RV dominance, but not AVV surgery itself, was associated with poor outcomes. Moderate or greater AVV regurgitation after Fontan operation is associated with a significantly increased risk of death or transplantation, only in patients with RV dominance.

Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Mar 2022; epub ahead of print
King G, Buratto E, Celermajer DS, Grigg L, ... d'Udekem Y, Konstantinov IE
J Am Coll Cardiol: 12 Mar 2022; epub ahead of print | PMID: 35331598
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Abstract

Transcatheter Closure of Atrial and Ventricular Septal Defects: JACC Focus Seminar.

Turner ME, Bouhout I, Petit CJ, Kalfa D
The field of congenital interventional cardiology has experienced tremendous growth in recent years. Beginning with the development of early devices for transcatheter closure of septal defects in the 1970s and 1980s, such technologies have evolved to become a mainstay of treatment for many atrial septal defects (ASDs) and ventricular septal defects (VSDs). Percutaneous device closure is now the preferred approach for the majority of secundum ASDs. It is also a viable treatment option for selected VSDs, though limitations still exist. In this review, the authors describe the current state of transcatheter closure of ASDs and VSDs in children and adults, including patient selection, procedural approach, and outcomes. Potential areas for future evolution and innovation are also discussed.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2022; 79:2247-2258
Turner ME, Bouhout I, Petit CJ, Kalfa D
J Am Coll Cardiol: 07 Jun 2022; 79:2247-2258 | PMID: 35654496
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Abstract

Gender Differences in Takotsubo Syndrome.

Arcari L, Núñez Gil IJ, Stiermaier T, El-Battrawy I, ... Eitel I, Santoro F
Background
Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized.
Objectives
The aim of the present study is to describe TTS sex differences.
Methods
TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger.
Results
In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52).
Conclusions
Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2085-2093
Arcari L, Núñez Gil IJ, Stiermaier T, El-Battrawy I, ... Eitel I, Santoro F
J Am Coll Cardiol: 31 May 2022; 79:2085-2093 | PMID: 35618345
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Abstract

Immune Checkpoint Therapies and Atherosclerosis: Mechanisms and Clinical Implications: JACC State-of-the-Art Review.

Vuong JT, Stein-Merlob AF, Nayeri A, Sallam T, Neilan TG, Yang EH
Immune checkpoint inhibitor therapy has revolutionized the treatment of advanced malignancies in recent years. Numerous reports have detailed the myriad of possible adverse inflammatory effects of immune checkpoint therapies, including within the cardiovascular system. However, these reports have been largely limited to myocarditis. The critical role of inflammation and adaptive immunity in atherosclerosis has been well characterized in preclinical studies, and several emerging clinical studies indicate a potential role of immune checkpoint targeting therapies in the development and exacerbation of atherosclerosis. In this review, we provide an overview of the role of T-cell immunity in atherogenesis and describe the molecular effects and clinical associations of both approved and investigational immune checkpoint therapy on atherosclerosis. We also highlight the role of cholesterol metabolism in oncogenesis and discuss the implications of these associations on future treatment and monitoring of atherosclerotic cardiovascular disease in the oncologic population receiving immune checkpoint therapy.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jan 2022; 79:577-593
Vuong JT, Stein-Merlob AF, Nayeri A, Sallam T, Neilan TG, Yang EH
J Am Coll Cardiol: 14 Jan 2022; 79:577-593 | PMID: 35144750
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Abstract

Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction.

Zhao Y, Lu X, Wan F, Gao L, ... Ji Y, Pu J
Background
Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear.
Objectives
This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI.
Methods
Study patient data were obtained from the database of the EARLY-MYO-CMR (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI) registry, which was a prospective, multicenter registry of patients with ST-segment elevation myocardial infarction (STEMI) undergoing cardiac magnetic resonance (CMR) imaging after reperfusion therapy. The primary endpoint was CMR-defined post-reperfusion infarct size. A secondary clinical endpoint was the composite of major adverse cardiac events (MACE) during follow-up. Potential mechanisms were explored with the use of preclinical animal AMI models.
Results
Of 706 patients enrolled in the EARLY-MYO-CMR registry, 412 patients with STEMI were ultimately included. Shift work was associated with increased CMR-defined infarct size (β = 5.94%; 95% CI: 2.94-8.94; P < 0.0001). During a median follow-up of 5.0 years, shift work was associated with increased risks of MACE (adjusted HR: 1.92; 95% CI: 1.12-3.29; P = 0.017). Consistent with clinical findings, shift work simulation in mice and sheep significantly augmented reperfusion injury in AMI. Mechanism studies identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that played a crucial role in mediating the detrimental effects of shift work on myocardial injury.
Conclusions
The current study provided novel findings that shift work increases myocardial infarction reperfusion injury. It identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that might play a crucial role in mediating this process. (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI [EARLY-MYO-CMR] registry; NCT03768453).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2097-2115
Zhao Y, Lu X, Wan F, Gao L, ... Ji Y, Pu J
J Am Coll Cardiol: 31 May 2022; 79:2097-2115 | PMID: 35618347
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Abstract

Definitions and Standardized Endpoints for Treatment of Coronary Bifurcations.

Lunardi M, Louvard Y, Lefèvre T, Stankovic G, ... Onuma Y, Bifurcation Academic Research Consortium and European Bifurcation Club
The Bifurcation Academic Research Consortium (Bif-ARC) project originated from the need to overcome the paucity of standardization and comparability between studies involving bifurcation coronary lesions. This document is the result of a collaborative effort between academic research organizations and the most renowned interventional cardiology societies focused on bifurcation lesions in Europe, the United States, and Asia. This consensus provides standardized definitions for bifurcation lesions; the criteria to judge the side branch relevance; the procedural, mechanistic, and clinical endpoints for every type of bifurcation study; and the follow-up methods. Considering the complexity of bifurcation lesions and their evaluation, detailed instructions and technical aspects for site and core laboratory analysis of bifurcation lesions are also reported. The recommendations included within this consensus will facilitate pooled analyses and the effective comparison of data in the future, improving the clinical relevance of trials in bifurcation lesions, and the quality of care in this subset of patients.

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

J Am Coll Cardiol: 13 May 2022; epub ahead of print
Lunardi M, Louvard Y, Lefèvre T, Stankovic G, ... Onuma Y, Bifurcation Academic Research Consortium and European Bifurcation Club
J Am Coll Cardiol: 13 May 2022; epub ahead of print | PMID: 35597684
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Abstract

Transcatheter Cardiac Interventions in the Newborn: JACC Focus Seminar.

Barry OM, Bouhout I, Turner ME, Petit CJ, Kalfa DM
For neonates with critical congenital heart disease requiring intervention, transcatheter approaches for many conditions have been established over the past decades. These interventions may serve to stabilize or palliate to surgical next steps or effectively primarily treat the condition. Many transcatheter interventions have evidence-based records of effectiveness and safety, which have led to widespread acceptance as first-line therapies. Other techniques continue to innovatively push the envelope and challenge the optimal strategies for high-risk neonates with right ventricular outflow tract obstruction or ductal-dependent pulmonary blood flow. In this review, the most commonly performed neonatal transcatheter interventions will be described to illustrate the current state of the field and highlight areas of future opportunity.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2022; 79:2270-2283
Barry OM, Bouhout I, Turner ME, Petit CJ, Kalfa DM
J Am Coll Cardiol: 07 Jun 2022; 79:2270-2283 | PMID: 35654498
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Abstract

Pericardial Effusion Provoking Atrial Fibrillation After Cardiac Surgery: JACC Review Topic of the Week.

Gaudino M, Di Franco A, Rong LQ, Cao D, ... DiMaio JM, Girardi LN
Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Patients who develop POAF are more likely to experience adverse outcomes, including increased rates of death, stroke, heart failure, and hospitalizations, and higher hospital costs. Understanding the mechanisms underlying POAF is important to improve patients\' outcome and optimize health systems\' efficiency. Beyond classic pathogenic hypotheses, emerging evidence suggests that postoperative pericardial effusion and localized pericardial inflammation may trigger POAF. This hypothesis is supported by data from nonhuman animal models and a growing body of evidence showing that reducing postoperative pericardial effusion might reduce POAF incidence. In this review, we summarize the classic pathophysiology theories of POAF following cardiac surgery and discuss new etiologic mechanisms with a specific focus on the role of pericardial effusion and inflammation.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2529-2539
Gaudino M, Di Franco A, Rong LQ, Cao D, ... DiMaio JM, Girardi LN
J Am Coll Cardiol: 28 Jun 2022; 79:2529-2539 | PMID: 35738715
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Abstract

Interventions for Congenital Atrioventricular Valve Dysfunction: JACC Focus Seminar.

Barry OM, Bouhout I, Kodali SK, George I, ... Petit CJ, Kalfa D
Innovation and creativity have led to tremendous advancements in the care and management of patients with congenital heart disease (CHD) that have resulted in considerably increased survival. Catheter-based interventions have contributed significantly to these advancements. However, catheter-based interventions for congenital lesions of the atrioventricular (AV) valves have been limited in scope and effectiveness mainly because of patient size and anatomical challenges. Thus, surgical repair and replacement for congenital AV valve lesions have remained the preferred therapy. However, the ongoing transcatheter heart valve revolution has led to techniques and technologies that are changing the landscape, particularly for adult CHD patients. Many devices for AV valve repair and replacement are being studied in adult patients without CHD, and translation of select practices to CHD patients has begun, with many more to come. Transcatheter AV valve interventions represent exciting opportunities for the growing numbers of adult CHD patients.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2022; 79:2259-2269
Barry OM, Bouhout I, Kodali SK, George I, ... Petit CJ, Kalfa D
J Am Coll Cardiol: 07 Jun 2022; 79:2259-2269 | PMID: 35654497
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Impact:
Abstract

Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data.

Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, ... Heymans SRB, Prasad SK
Background
Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction.
Objectives
The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification.
Methods
Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years).
Results
In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005).
Conclusions
Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine.

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

J Am Coll Cardiol: 07 Jun 2022; 79:2219-2232
Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, ... Heymans SRB, Prasad SK
J Am Coll Cardiol: 07 Jun 2022; 79:2219-2232 | PMID: 35654493
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Abstract

Diabetes and Progression of Heart Failure: The Atherosclerosis Risk In Communities (ARIC) Study.

Echouffo-Tcheugui JB, Ndumele CE, Zhang S, Florido R, ... Shah AM, Selvin E
Background
The influence of diabetes on progression from preclinical heart failure (HF) stages to overt HF is poorly understood.
Objectives
The purpose of this study was to characterize the influence of diabetes on the progression from preclinical HF stages (A or B based on the 2021 Universal Definition) to overt HF.
Methods
We included 4,774 adults with preclinical HF (stage A [n = 1,551] or B [n = 3,223]) who attended the ARIC (Atherosclerosis Risk In Communities) study Visit 5 (2011-2013). Within each stage (A or B), we assessed the associations of diabetes and glycemic control (hemoglobin A1C [HbA1C] <7% vs ≥7%) with progression to HF, and of cross-categories of HF stages (A vs B), diabetes, and glycemic control with incident HF.
Results
Among the participants (mean age 75.4 years, 58% women, 20% Black), there were 470 HF events during 8.6 years of follow-up. Stage B participants with HbA1C ≥7% experienced clinical HF at a younger age than those with controlled diabetes or without diabetes (mean age 80 years vs 83 years vs 82 years; P < 0.001). HbA1C ≥7% was more strongly associated with HF in stage B (HR: 1.83; 95% CI: 1.33-2.51) compared with stage A (HR: 1.52; 95% CI: 0.53-4.38). In cross-categories of preclinical HF stage and HbA1C, participants with stage B and HbA1C ≥7% had increased risk of HF progression compared with stage A without diabetes (HR: 7.56; 95% CI: 4.68-12.20).
Conclusions
Among older adults with preclinical HF stages, uncontrolled diabetes was associated with substantial risk of HF progression. Our results suggest that targeting diabetes early in the HF process is critical.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2285-2293
Echouffo-Tcheugui JB, Ndumele CE, Zhang S, Florido R, ... Shah AM, Selvin E
J Am Coll Cardiol: 14 Jun 2022; 79:2285-2293 | PMID: 35680178
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Abstract

Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols.

Takahashi T, Samuels BA, Li W, Parikh MA, ... Kobayashi Y, Microvascular Network
Background
Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm.
Objectives
We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols.
Methods
PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock.
Results
A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95% CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as ≥90% diameter reduction (1.0%; 95% CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95% CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100 μg and 200 μg.
Conclusions
Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2367-2378
Takahashi T, Samuels BA, Li W, Parikh MA, ... Kobayashi Y, Microvascular Network
J Am Coll Cardiol: 21 Jun 2022; 79:2367-2378 | PMID: 35710187
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Impact:
Abstract

Elevated Remnant Cholesterol Reclassifies Risk of Ischemic Heart Disease and Myocardial Infarction.

Doi T, Langsted A, Nordestgaard BG
Background
Elevated remnant cholesterol causes ischemic heart disease.
Objectives
We tested the hypothesis that the inclusion of elevated remnant cholesterol will lead to appropriate reclassification of individuals who later experience myocardial infarction and ischemic heart disease.
Methods
For >10 years we followed up 41,928 white Danish individuals from the Copenhagen General Population Study without a history of ischemic cardiovascular disease, diabetes, and statin use. Using predefined cut points for elevated remnant cholesterol, we calculated net reclassification index (NRI) from below to above 5%, 7.5%, and/or 10% 10-year occurrence of myocardial infarction and ischemic heart disease defined as a composite of death from ischemic heart disease, myocardial infarction, and coronary revascularization.
Results
For individuals with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P < 0.001) of myocardial infarction and 21% (P < 0.001) of ischemic heart disease were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Consequently, the addition of remnant cholesterol levels yielded NRI of 10% (95% CI: 1%-20%) for myocardial infarction and 5% (95% CI: -3% to 13%) for ischemic heart disease. Correspondingly, when reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% (P < 0.001) of individuals with myocardial infarction and 41% (P < 0.001) with ischemic heart disease were reclassified appropriately, leading to NRI of respectively 20% (95% CI: 9%-31%) and 11% (95% CI: 2%-21%).
Conclusions
Elevated remnant cholesterol levels considerably improve myocardial infarction and ischemic heart disease risk prediction.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2383-2397
Doi T, Langsted A, Nordestgaard BG
J Am Coll Cardiol: 21 Jun 2022; 79:2383-2397 | PMID: 35710189
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Impact:
Abstract

Prospective Evaluation of Cardiovascular Risk 10 Years After a Hypertensive Disorder of Pregnancy.

Levine LD, Ky B, Chirinos JA, Koshinksi J, ... Koelper N, Lewey J
Background
Hypertensive disorders of pregnancy (HDP) are associated with increased risk of cardiovascular disease (CVD) 20-30 years later; however, cardiovascular (CV) risk in the decade after HDP is less studied.
Objectives
The purpose of this study was to evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier.
Methods
This is a prospective study of patients with and without a diagnosis of HDP ≥10 years earlier (2005-2007) who underwent in-person visits with echocardiography, arterial tonometry, and flow-mediated dilation of the brachial artery.
Results
A total of 135 patients completed assessments (84 with and 51 without a history of HDP); 85% self-identified as Black. Patients with a history of HDP had a 2.4-fold increased risk of new hypertension compared with those without HDP (56.0% vs. 23.5%; adjusted relative risk: 2.4; 95% CI: 1.39-4.14) with no differences in measures of left ventricular structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function. Patients who developed hypertension, regardless of HDP history, had greater left ventricular remodeling, including greater relative wall thickness; worse diastolic function, including lower septal and lateral e\' and E/A ratio; more abnormal longitudinal strain; and higher effective arterial elastance than patients without hypertension.
Conclusions
We found a 2.4-fold increased risk of hypertension 10 years after HDP. Differences in noninvasive measures of CV risk were driven mostly by the hypertension diagnosis, regardless of HDP history, suggesting that the known long-term risk of CVD after HDP may primarily be a consequence of hypertension development.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2401-2411
Levine LD, Ky B, Chirinos JA, Koshinksi J, ... Koelper N, Lewey J
J Am Coll Cardiol: 21 Jun 2022; 79:2401-2411 | PMID: 35710191
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Abstract

Medicare Coverage and Out-of-Pocket Costs of Quadruple Drug Therapy for Heart Failure.

Faridi KF, Dayoub EJ, Ross JS, Dhruva SS, Ahmad T, Desai NR
Background
Beta-blockers, angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), known as quadruple therapy, are recommended for patients with heart failure with reduced ejection fraction (HFrEF).
Objectives
This study sought to determine Medicare coverage and out-of-pocket (OOP) costs of quadruple therapy and regimens excluding ARNI or SGLT2i.
Methods
This study assessed cost sharing, prior authorization, and step therapy in all 4,068 Medicare prescription drug plans in 2020. OOP costs were determined during the standard coverage period and annually based on the Medicare Part D standard benefit, inclusive of deductible, standard coverage, coverage gap, and catastrophic coverage.
Results
Tier ≥3 cost sharing was required by 99.1% of plans for ARNI and 98.5% for at least 1 SGLT2i. Only ARNI required prior authorization (24.3% of plans), and step therapy was required only for SGLT2is (5.4%) and eplerenone (0.8%). The median 30-day standard coverage OOP cost of quadruple therapy was $94 (IQR: $84-$100), including $47 (IQR: $40-$47) for ARNI and $45 (IQR: $40-$47) for SGLT2i. The median annual OOP cost of quadruple therapy was $2,217 (IQR: $1,956-$2,579) compared with $1,319 (IQR: $1,067-$1,675) when excluding SGLT2i and $1,322 (IQR: $1,025-$1,588) when including SGLT2i and substituting an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ARNI. The median 30-day OOP cost of generic regimens was $3 (IQR: $0-$9).
Conclusions
Medicare drug plans restrict coverage of quadruple therapy through cost sharing, with OOP costs that are substantially higher than generic regimens. Quadruple therapy may be unaffordable for many Medicare patients with HFrEF unless medication prices and cost sharing are reduced.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2516-2525
Faridi KF, Dayoub EJ, Ross JS, Dhruva SS, Ahmad T, Desai NR
J Am Coll Cardiol: 28 Jun 2022; 79:2516-2525 | PMID: 35738713
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Impact:
Abstract

False Lumen Flow Assessment by Magnetic Resonance Imaging and Long-Term Outcomes in Uncomplicated Aortic Dissection.

Evangelista A, Pineda V, Guala A, Bijnens B, ... Ferreira I, Rodríguez-Palomares J
Background
Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist.
Objectives
The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters.
Methods
One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD.
Results
After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter >45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events.
Conclusions
High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter >45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 21 Jun 2022; 79:2415-2427
Evangelista A, Pineda V, Guala A, Bijnens B, ... Ferreira I, Rodríguez-Palomares J
J Am Coll Cardiol: 21 Jun 2022; 79:2415-2427 | PMID: 35710193
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Impact:
Abstract

Causes, Angiographic Characteristics, and Management of Premature Myocardial Infarction: JACC State-of-the-Art Review.

Rallidis LS, Xenogiannis I, Brilakis ES, Bhatt DL
Among patients presenting with acute myocardial infarction (AMI), the proportion of young individuals has increased in recent years. Although coronary atherosclerosis is less extensive in young patients with AMI, with higher prevalence of single-vessel disease and rare left main involvement, the long-term prognosis is not benign. Young patients with AMI with obstructive coronary artery disease have similar risk factors as older patients except for higher prevalence of smoking, lipid disorders, and family history of premature coronary artery disease, and lower prevalence of diabetes mellitus and hypertension. Smoking cessation is by far the most effective secondary preventive measure. Myocardial infarction with nonobstructive coronary arteries is a relatively common clinical entity (10%-20%) among young patients with AMI, with intravascular and cardiac magnetic resonance imaging being key for diagnosis and potentially treatment. Spontaneous coronary artery dissection is a frequent pathogenetic mechanism of AMI among young women, requiring a high degree of suspicion, especially in the peripartum period.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2431-2449
Rallidis LS, Xenogiannis I, Brilakis ES, Bhatt DL
J Am Coll Cardiol: 21 Jun 2022; 79:2431-2449 | PMID: 35710195
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Impact:
Abstract

Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study.

Florido R, Daya NR, Ndumele CE, Koton S, ... Platz EA, Selvin E
Background
More than 80% of adult patients diagnosed with cancer survive long term. Long-term complications of cancer and its therapies may increase the risk of cardiovascular disease (CVD), but prospective studies using adjudicated cancer and CVD events are lacking.
Objectives
The aim of this study was to assess the risk of CVD in cancer survivors in a prospective community-based study.
Methods
We included 12,414 ARIC (Atherosclerosis Risk In Communities) study participants. Cancer diagnoses were ascertained via linkage with state registries supplemented with medical records. Incident CVD outcomes were coronary heart disease (CHD), heart failure (HF), stroke, and a composite of these. We used multivariable Poisson and Cox regressions to estimate the association of cancer with incident CVD.
Results
Mean age was 54 years, 55% were female, and 25% were Black. A total of 3,250 participants (25%) had incident cancer over a median 13.6 years of follow-up. Age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for cardiovascular risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37; 95% CI: 1.26-1.50), HF (HR: 1.52; 95% CI: 1.38-1.68), and stroke (HR: 1.22; 95% CI: 1.03-1.44), but not CHD (HR: 1.11; 95% CI: 0.97-1.28). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk.
Conclusions
Compared with persons without cancer, adult cancer survivors have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors. There is an unmet need to define strategies for CVD prevention in this high-risk population.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2022; 80:22-32
Florido R, Daya NR, Ndumele CE, Koton S, ... Platz EA, Selvin E
J Am Coll Cardiol: 05 Jul 2022; 80:22-32 | PMID: 35772913
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Impact:
Abstract

Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers.

Rade JJ, Barton BA, Vasan RS, Kronsberg SS, ... Kakouros N, Kickler TA
Background
Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor.
Objectives
This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use.
Methods
Stable thromboxane B2 metabolites (TXB2-M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 ± 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB2-M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling.
Results
In 1,363 (44.8%) participants taking ASA at the index examination, median TXB2-M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB2-M were significantly associated with all-cause and cardiovascular mortality irrespective of ASA use (HR: 1.96 and 2.41, respectively; P < 0.0001 for both) for TXB2-M in the highest quartile based on ASA use compared with lower quartiles, and remained significant after adjustment for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P ≤ 0.005 for both). In 2,353 participants without CVD, TXB2-M were associated with cardiovascular mortality in ASA nonusers (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, while ASA use was associated with all-cause mortality in those with low (adjusted HR: 1.46; 95% CI: 1.14-1.87) but not elevated TXB2-M.
Conclusions
Systemic thromboxane generation is an independent risk factor for all-cause and cardiovascular mortality irrespective of ASA use, and its measurement may be useful for therapy modification, particularly in those without CVD.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; epub ahead of print
Rade JJ, Barton BA, Vasan RS, Kronsberg SS, ... Kakouros N, Kickler TA
J Am Coll Cardiol: 24 May 2022; epub ahead of print | PMID: 35660296
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Impact:
Abstract

Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age.

Böhm M, Butler J, Filippatos G, Ferreira JP, ... Anker SD, EMPEROR-Preserved Trial Committees and Investigators
Background
Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied.
Objectives
The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction).
Methods
We grouped patients (n = 5,988) according to their baseline age (<65 years [n = 1,199], 65-74 years [n = 2,214], 75-79 years [n = 1,276], ≥80 years [n = 1,299]). We explored the influence of age on empagliflozin effects on CVD or HFH (primary outcome), total HFH, rate of decline in estimated glomerular filtration rate, health-related quality of life with the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score, and frequency of adverse events.
Results
Considering only patients on placebo, the incidence of primary outcomes (P trend = 0.02) and CVD (P trend = 0.003) increased with age. Empagliflozin reduced primary outcomes (P trend = 0.33), first HFH (P trend = 0.22), and first and recurrent HFH (P trend = 0.11) across all age groups with an effect being similar at ≥75 years (P interaction = 0.22) or >80 years (P interaction = 0.51). Empagliflozin improved Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52 and attenuated the decline of estimated glomerular filtration rate without age interaction (P = 0.48 and P = 0.32, respectively). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the age groups.
Conclusions
Empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age was not associated with reduced efficacy or meaningful intolerability. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT0305951).

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

J Am Coll Cardiol: 05 Jul 2022; 80:1-18
Böhm M, Butler J, Filippatos G, Ferreira JP, ... Anker SD, EMPEROR-Preserved Trial Committees and Investigators
J Am Coll Cardiol: 05 Jul 2022; 80:1-18 | PMID: 35772911
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Impact:
Abstract

LMNA Variants and Risk of Adult-Onset Cardiac Disease.

Lazarte J, Jurgens SJ, Choi SH, Khurshid S, ... Lunetta KL, Lubitz SA
Background
Genetic variants in LMNA may cause cardiac disease, but population-level contributions of variants to cardiac disease burden are not well-characterized.
Objectives
We sought to determine the frequency and contribution of rare LMNA variants to cardiomyopathy and arrhythmia risk among ambulatory adults.
Methods
We included 185,990 UK Biobank participants with whole-exome sequencing. We annotated rare loss-of-function and missense LMNA variants for functional effect using 30 in silico prediction tools. We assigned a predicted functional effect weight to each variant and calculated a score for each carrier. We tested associations between the LMNA score and arrhythmia (atrial fibrillation, bradyarrhythmia, ventricular arrhythmia) or cardiomyopathy outcomes (dilated cardiomyopathy and heart failure). We also examined associations for variants located upstream vs downstream of the nuclear localization signal.
Results
Overall, 1,167 (0.63%) participants carried an LMNA variant and 15,079 (8.11%) had an arrhythmia or cardiomyopathy event during a median follow-up of 10.9 years. The LMNA score was associated with arrhythmia or cardiomyopathy (OR: 2.21; P < 0.001) and the association was more significant when restricted to variants upstream of the nuclear localization signal (OR: 5.05; P < 0.001). The incidence rate of arrhythmia or cardiomyopathy was 8.43 per 1,000 person-years (95% CI: 6.73-10.12 per 1,000 person-years) among LMNA variant carriers and 6.38 per 1,000 person-years (95% CI: 6.27-6.50 per 1,000 person-years) among noncarriers. Only 3 (1.2%) of the variants were reported as pathogenic in ClinVar.
Conclusions
Middle-aged adult carriers of rare missense or loss-of-function LMNA variants are at increased risk for arrhythmia and cardiomyopathy.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2022; 80:50-59
Lazarte J, Jurgens SJ, Choi SH, Khurshid S, ... Lunetta KL, Lubitz SA
J Am Coll Cardiol: 05 Jul 2022; 80:50-59 | PMID: 35772917
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Impact:
Abstract

Balloon- Versus Self-Expanding Valve Systems for Treating Small Failed Surgical Aortic Bioprostheses: The LYTEN Trial.

Rodés-Cabau J, Abbas A, Serra V, Vilalta V, ... Pelletier-Beaumont E, Pibarot P
Background
Data comparing valve systems in the valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) field has been obtained from retrospective studies.
Objectives
To compare the hemodynamic results between the balloon-expandable SAPIEN (3/ULTRA) (BEV) and self-expanding Evolut (R/PRO/PRO+) (SEV) valves in ViV-TAVR.
Methods
Patients with a failed small (≤23 mm) surgical valve. were randomized to receive a BEV or a SEV. The primary endpoint was valve hemodynamics (maximal/mean residual gradients; severe prosthesis patient mismatch [PPM] or moderate-severe aortic regurgitation [AR]) at 30 days as evaluated by Doppler-echocardiography.
Results
A total of 102 patients were randomized, and of these, 98 patients finally underwent a ViV-TAVR procedure (BEV: 46, SEV: 52). The procedure was successful in all cases, with no differences in clinical outcomes at 30 days between groups (no death or stroke events). Patients in the SEV group exhibited lower mean and maximal transvalvular gradient values (15±8 vs 23±8 mmHg, p˂0.001; 28±16 vs 40±13 mmHg, p ˂0.001), and a tendency towards a lower rate of severe PPM (44% vs. 64%, p=0.07). There were no cases of moderate-severe AR. 55 consecutive patients (SEV: 27, BEV: 28) underwent invasive valve hemodynamic evaluation during the procedure, with no differences in mean and peak transvalvular gradients between both groups (p=0.41 and p=0.70, respectively).
Conclusions
In patients with small failed aortic bioprostheses, ViV-TAVR with a SEV was associated with improved valve hemodynamics as evaluated by echocardiography. There were no differences between groups in intra-procedural invasive valve hemodynamics and 30-day clinical outcomes (NCT03520101).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 13 May 2022; epub ahead of print
Rodés-Cabau J, Abbas A, Serra V, Vilalta V, ... Pelletier-Beaumont E, Pibarot P
J Am Coll Cardiol: 13 May 2022; epub ahead of print | PMID: 35597385
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Impact:
Abstract

Inappropriate Sinus Tachycardia: Etiology, Pathophysiology, and Management: JACC Review Topic of the Week.

Ahmed A, Pothineni NVK, Charate R, Garg J, ... Gopinathannair R, Lakkireddy D
Inappropriate sinus tachycardia (IST) is a clinical syndrome that generally affects young patients and is associated with distressing symptoms. Although the most common symptom is palpitations, it can be accompanied by a myriad of symptoms, including anxiety, dizziness, presyncope, and syncope. The pathogenesis of IST is not well understood and considered multifactorial, with autonomic dysfunction being the central abnormality. IST is a diagnosis of exclusion. Management presents a clinical challenge. The overall efficacy of lifestyle modifications and medical therapy may be limited. Recent advances in catheter and surgical sinus node sparing ablation techniques have led to improvement in outcomes. In addition, increased focus has led to development of multimodality team-based interventions to improve outcomes in this group of patients. In this review, we discuss the mechanistic basis of IST, review current approaches to diagnosis, and outline contemporary therapeutic approaches.

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

J Am Coll Cardiol: 21 Jun 2022; 79:2450-2462
Ahmed A, Pothineni NVK, Charate R, Garg J, ... Gopinathannair R, Lakkireddy D
J Am Coll Cardiol: 21 Jun 2022; 79:2450-2462 | PMID: 35710196
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Impact:
Abstract

Diagnosis and Evaluation of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.

Maron BJ, Desai MY, Nishimura RA, Spirito P, ... Maron MS, Sherrid MV
Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited global heart disease, with complex phenotypic and genetic expression and natural history, affecting both genders and many races and cultures. Prevalence is 1:200-1:500, largely based on the disease phenotype with imaging, inferring that 750,000 Americans may be affected by HCM. However, cross-sectional data show that only a fraction are clinically diagnosed, suggesting under-recognition, with most clinicians exposed to small segments of the broad disease spectrum. Highly effective HCM management strategies have emerged, altering clinical course and substantially lowering mortality and morbidity rates. These advances underscore the importance of reliable HCM diagnosis with echocardiography and cardiac magnetic resonance. Family screening with noninvasive imaging will identify relatives with the HCM phenotype, while genetic analysis recognizes preclinical sarcomere gene carriers without left ventricular hypertrophy, but with the potential to transmit disease. Comprehensive initial patient evaluations are important for reliable diagnosis, accurate portrayal of HCM and family history, risk stratification, and distinguishing obstructive versus nonobstructive forms.

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

J Am Coll Cardiol: 31 Dec 2021; 79:372-389
Maron BJ, Desai MY, Nishimura RA, Spirito P, ... Maron MS, Sherrid MV
J Am Coll Cardiol: 31 Dec 2021; 79:372-389 | PMID: 35086660
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Impact:
Abstract

Trends and Disparities in Cardiometabolic Health Among U.S. Adults, 1999-2018.

O\'Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D
Background
Few studies have assessed U.S. cardiometabolic health trends-optimal levels of multiple risk factors and absence of clinical cardiovascular disease (CVD)-or its impact on health disparities.
Objectives
The purpose of this study was to investigate U.S. trends in optimal cardiometabolic health from 1999 to 2018.
Methods
We assessed proportions of adults with optimal cardiometabolic health, based on adiposity, blood glucose, blood lipids, blood pressure, and clinical CVD; and optimal, intermediate, and poor levels of each component among 55,081 U.S. adults in the National Health and Nutrition Examination Survey.
Results
In 2017-2018, only 6.8% (95% CI: 5.4%-8.1%) of U.S. adults had optimal cardiometabolic health, declining from 1999-2000 (P trend = 0.02). Among components of cardiometabolic health, the largest declines were for adiposity (optimal levels: 33.8%-24.0%; poor levels: 47.7%-61.9%) and glucose (optimal levels: 59.4%-36.9%; poor levels: 8.6%-13.7%) (P trend <0.001 for each). Optimal levels of blood lipids increased from 29.9%-37.0%, whereas poor decreased from 28.3%-14.7% (P trend <0.001). Trends over time for blood pressure and CVD were smaller. Disparities by age, sex, education, and race/ethnicity were evident in all years, and generally worsened over time. By 2017-2018, prevalence of optimal cardiometabolic health was lower among Americans with lower (5.0% [95% CI: 2.8%-7.2%]) vs higher education (10.3% [95% CI: 7.6%-13.0%]); and among Mexican American (3.2% [95% CI: 1.4%-4.9%]) vs non-Hispanic White (8.4% [95% CI: 6.3%-10.4%]) adults.
Conclusions
Between 1999 and 2000 and 2017 and 2018, U.S. cardiometabolic health has been poor and worsening, with only 6.8% of adults having optimal cardiometabolic health, and disparities by age, sex, education, and race/ethnicity. These novel findings inform the need for nationwide clinical and public health interventions to improve cardiometabolic health and health equity.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:138-151
O'Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D
J Am Coll Cardiol: 12 Jul 2022; 80:138-151 | PMID: 35798448
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Impact:
Abstract

Secular Trends in Risk Profiles Among Adults With Cardiovascular Disease in the United States.

Gao Y, Isakadze N, Duffy E, Sheng Q, ... Matsushita K, Martin SS
Background
Documenting trends in risk factors among individuals with cardiovascular disease (CVD) may inform policy and secondary prevention initiatives.
Objectives
This study aimed to examine 20-year trends in risk profiles among U.S. adults with CVD and any racial/ethnic disparities.
Methods
In this serial cross-sectional analysis of 6,335 adults with self-reported CVD participating in the National Health and Nutrition Examination Survey from 1999 through 2018, we calculated age- and sex-adjusted proportions with ideal risk factor attainment.
Results
The proportions with ideal hemoglobin A1c (<7% if diabetes or <5.7% if not) and body mass index (<25 kg/m2) worsened from 58.7% (95% CI: 55.2%-62.1%) to 52.4% (95% CI: 48.2%-56.6%) and 23.9% (95% CI: 21.5%-26.4%) to 18.2% (95% CI: 15.6%-21.2%) from 1999-2002 to 2015-2018, respectively. After initial improvement, the proportion with blood pressure <130/80 mm Hg declined from 52.1% (95% CI: 48.9%-55.4%) in 2007-2010 to 48.6% (95% CI: 44.2%-52.7%) in 2015-2018. The proportion with non-high-density lipoprotein cholesterol levels <100 mg/dL increased from 7.3% (95% CI: 5.6%-9.5%) in 1999-2002 to 30.3% (95% CI: 25.7%-35.5%) in 2015-2018. The proportions with ideal smoking, physical activity, and diet profiles were unchanged over time, and in 2015-2018 were 77.8% (95% CI: 73.6%-81.4%), 22.4% (95% CI: 19.3%-25.9%), and 1.3% (95% CI: 0.7%-2.6%). Worsening trends were observed in Hispanic adults for cholesterol, and in Black adults for smoking (both P < 0.05 for nonlinear and linear trends). Persistently lower ideal risk factor attainment was observed for blood pressure in Black adults and for hemoglobin A1c levels in Asian adults compared with White adults (all P < 0.05 for differences).
Conclusions
Trends in cardiovascular risk factor profiles in U.S. adults with CVD were suboptimal from 1999 through 2018, with persistent racial/ethnic disparities.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:126-137
Gao Y, Isakadze N, Duffy E, Sheng Q, ... Matsushita K, Martin SS
J Am Coll Cardiol: 12 Jul 2022; 80:126-137 | PMID: 35798447
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Impact:
Abstract

Analysis of Worsening Heart Failure Events in an Integrated Health Care System.

Ambrosy AP, Parikh RV, Sung SH, Tan TC, ... Cristino J, Go AS
Background
There is growing interest to disentangle worsening heart failure (WHF) from location of care and move away from hospitalization as a surrogate for acuity.
Objectives
The purpose of this study was to describe the incidence of WHF events across the care continuum from ambulatory encounters to hospitalizations.
Methods
We studied calendar year cohorts of adults with diagnosed heart failure (HF) from 2010-2019 within a large, integrated health care delivery system. Electronic health record (EHR) data were accessed for outpatient encounters, emergency department (ED) visits/observation stays, and hospitalizations. WHF was defined as ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Symptoms and signs were ascertained using natural language processing.
Results
We identified 103,138 eligible individuals with mean age 73.6 ± 13.7 years, 47.5% women, and mean left ventricular ejection fraction of 51.4% ± 13.7%. There were 1,136,750 unique encounters including 743,039 (65.4%) outpatient encounters, 224,670 (19.8%) ED visits/observation stays, and 169,041 (14.9%) hospitalizations. A total of 126,008 WHF episodes were identified, including 34,758 (27.6%) outpatient encounters, 28,301 (22.5%) ED visits/observation stays, and 62,949 (50.0%) hospitalizations. The annual incidence (events per 100 person-years) of WHF increased from 25 to 33 during the study period primarily caused by outpatient encounters (7 to 10) and ED visits/observation stays (4 to 7). The 30-day rate of hospitalizations for WHF ranged from 8.2% for outpatient encounters to 12.4% for hospitalizations.
Conclusions
ED visits/observation stays and outpatient encounters account for approximately one-half of WHF events, are driving the underlying growth in HF morbidity, and portend a poor short-term prognosis.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:111-122
Ambrosy AP, Parikh RV, Sung SH, Tan TC, ... Cristino J, Go AS
J Am Coll Cardiol: 12 Jul 2022; 80:111-122 | PMID: 35798445
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Impact:
Abstract

Carotid Artery Stenting: JACC State-of-the-Art Review.

White CJ, Brott TG, Gray WA, Heck D, ... Sachar R, Siddiqui A
Significant advances in the field of carotid artery stenting (CAS) have occurred, including new randomized trial data, recent professional societal statements for competency, new techniques and new devices that have been developed, and perhaps most importantly, our understanding of how to better select candidates for CAS to avoid periprocedural complications. The current Centers for Medicare and Medicaid Services coverage decision regarding CAS is outdated, and our review supports our recommendation to approve CAS in selected candidates who are symptomatic with a carotid stenosis ≥50% and ≤99% and for asymptomatic patients with carotid stenosis ≥70% and ≤99% for stroke prevention. Optimized CAS strategies have allowed experienced operators to better assess procedure risk before CAS and have led to continued improvement in CAS outcomes. New technologies including enhanced embolic protection devices and dual-layered stents should result in further improvement.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:155-170
White CJ, Brott TG, Gray WA, Heck D, ... Sachar R, Siddiqui A
J Am Coll Cardiol: 12 Jul 2022; 80:155-170 | PMID: 35798450
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Abstract

Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy.

Desai MY, Owens A, Geske JB, Wolski K, ... Sehnert AJ, Nissen SE
Background
Septal reduction therapy (SRT), surgical myectomy or alcohol ablation, is recommended for obstructive hypertrophic cardiomyopathy (oHCM) patients with intractable symptoms despite maximal medical therapy, but is associated with morbidity and mortality.
Objectives
This study sought to determine whether the oral myosin inhibitor mavacamten enables patients to improve sufficiently to no longer meet guideline criteria or choose to not undergo SRT.
Methods
Patients with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at rest/provocation who met guideline criteria for SRT were randomized, double blind, to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection fraction. The primary endpoint was the composite of the proportion of patients proceeding with SRT or who remained guideline-eligible after 16 weeks\' treatment.
Results
One hundred and twelve oHCM patients were enrolled, mean age 60 ± 12 years, 51% men, 93% New York Heart Association (NYHA) functional class III/IV, with a mean post-exercise LVOT gradient of 84 ± 35.8 mm Hg. After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients (17.9%) met guideline criteria or underwent SRT, difference (58.9%; 95% CI: 44.0%-73.9%; P < 0.001). Hierarchical testing of secondary outcomes showed significant differences (P < 0.001) favoring mavacamten, mean differences in post-exercise peak LVOT gradient -37.2 mm Hg; ≥1 NYHA functional class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53.
Conclusions
In oHCM patients with intractable symptoms, mavacamten significantly reduced the fraction of patients meeting guideline criteria for SRT after 16 weeks. Long-term freedom from SRT remains to be determined. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072).

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

J Am Coll Cardiol: 12 Jul 2022; 80:95-108
Desai MY, Owens A, Geske JB, Wolski K, ... Sehnert AJ, Nissen SE
J Am Coll Cardiol: 12 Jul 2022; 80:95-108 | PMID: 35798455
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Abstract

Staphylococcus Aureus Infective Endocarditis: JACC Patient Pathways.

Grapsa J, Blauth C, Chandrashekhar YS, Prendergast B, ... Mack M, Fuster V
A 19-year-old female patient presented with Staphylococcus aureus infective endocarditis, with suspected subdural brain hemorrhage, disseminated intravascular coagulopathy, and septic renal as well as spleen infarcts. The patient had extensive vegetations on the mitral and tricuspid valves and underwent urgent mitral and tricuspid repair. This paper discusses the clinical case and current evidence regarding the management and treatment of Staphylococcus aureus endocarditis.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2022; 79:88-99
Grapsa J, Blauth C, Chandrashekhar YS, Prendergast B, ... Mack M, Fuster V
J Am Coll Cardiol: 04 Jan 2022; 79:88-99 | PMID: 34794846
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Abstract

Eisenmenger Syndrome: JACC State-of-the-Art Review.

Arvanitaki A, Gatzoulis MA, Opotowsky AR, Khairy P, ... Mulder BJM, D\'Alto M
Although major breakthroughs in the field of pediatric cardiology, cardiac surgery, intervention, and overall care improved the outlook of congenital heart disease, Eisenmenger syndrome (ES) is still encountered and remains a complex clinical entity with multisystem involvement, including secondary erythrocytosis, increased thrombotic and bleeding diathesis, high arrhythmogenic risk, progressive heart failure, and premature death. Clearly, care for ES is best delivered in multidisciplinary expert centers. In this review, we discuss the considerable recent progress in understanding the complex pathophysiology of ES, means of prognostication, and improvement in clinical outcomes achieved with pulmonary arterial hypertension-targeted therapies. Additionally, we delineate areas of uncertainty in various aspects of care, discuss gaps in current evidence, and review current status in less privileged countries and propose initiatives to reduce disease burden. Finally, we propose the application of emerging technologies to enhance the delivery and quality of health care related to ES and beyond.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 29 Jan 2022; 79:1183-1198
Arvanitaki A, Gatzoulis MA, Opotowsky AR, Khairy P, ... Mulder BJM, D'Alto M
J Am Coll Cardiol: 29 Jan 2022; 79:1183-1198 | PMID: 35331414
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Abstract

Cardiovascular Complications of Interatrial Conduction Block: JACC State-of-the-Art Review.

Power DA, Lampert J, Camaj A, Bienstock SW, ... Bayés-de-Luna A, Fuster V
Interatrial block (IAB) is an electrocardiographic pattern describing the conduction delay between the right and left atria. IAB is classified into 3 degrees of block that correspond to decreasing conduction in the region of Bachmann\'s bundle. Although initially considered benign in nature, specific subsets of IAB have been associated with atrial arrhythmias, elevated thromboembolic stroke risk, cognitive impairment, and mortality. As the pathophysiologic relationships between IAB and stroke are reinforced, investigation has now turned to the potential benefit of early detection, atrial imaging, cardiovascular risk factor modification, antiarrhythmic pharmacotherapy, and stroke prevention with oral anticoagulation. This review provides a contemporary overview of the epidemiology, pathophysiology, diagnosis, and management of IAB, with a focus on future directions.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 29 Jan 2022; 79:1199-1211
Power DA, Lampert J, Camaj A, Bienstock SW, ... Bayés-de-Luna A, Fuster V
J Am Coll Cardiol: 29 Jan 2022; 79:1199-1211 | PMID: 35331415
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Abstract

Quantitative Myocardial Perfusion Predicts Outcomes in Patients With Prior Surgical Revascularization.

Seraphim A, Dowsing B, Rathod KS, Shiwani H, ... Kellman P, Manisty C
Background
Patients with previous coronary artery bypass graft (CABG) surgery typically have complex coronary disease and remain at high risk of adverse events. Quantitative myocardial perfusion indices predict outcomes in native vessel disease, but their prognostic performance in patients with prior CABG is unknown.
Objectives
In this study, we sought to evaluate whether global stress myocardial blood flow (MBF) and perfusion reserve (MPR) derived from perfusion mapping cardiac magnetic resonance (CMR) independently predict adverse outcomes in patients with prior CABG.
Methods
This was a retrospective analysis of consecutive patients with prior CABG referred for adenosine stress perfusion CMR. Perfusion mapping was performed in-line with automated quantification of MBF. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular events defined as nonfatal myocardial infarction and unplanned revascularization. Associations were evaluated with the use of Cox proportional hazards models after adjusting for comorbidities and CMR parameters.
Results
A total of 341 patients (median age 67 years, 86% male) were included. Over a median follow-up of 638 days (IQR: 367-976 days), 81 patients (24%) reached the primary outcome. Both stress MBF and MPR independently predicted outcomes after adjusting for known prognostic factors (regional ischemia, infarction). The adjusted hazard ratio (HR) for 1 mL/g/min of decrease in stress MBF was 2.56 (95% CI: 1.45-4.35) and for 1 unit of decrease in MPR was 1.61 (95% CI: 1.08-2.38).
Conclusions
Global stress MBF and MPR derived from perfusion CMR independently predict adverse outcomes in patients with previous CABG. This effect is independent from the presence of regional ischemia on visual assessment and the extent of previous infarction.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 29 Jan 2022; 79:1141-1151
Seraphim A, Dowsing B, Rathod KS, Shiwani H, ... Kellman P, Manisty C
J Am Coll Cardiol: 29 Jan 2022; 79:1141-1151 | PMID: 35331408
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Abstract

Comparative Costs of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot.

O\'Byrne ML, Glatz AC, Huang YV, Kelleman MS, ... McCracken CE, Goldstein BH
Background
Recent data have demonstrated that overall mortality and adverse events are not significantly different for primary repair (PR) and staged repair (SR) approaches to management of neonates with symptomatic tetralogy of Fallot (sTOF). Cost data can be used to compare the relative value (cost for similar outcomes) of these approaches and are a potentially more sensitive measure of morbidity.
Objectives
This study sought to compare the economic costs associated with PR and SR in neonates with sTOF.
Methods
Data from a multicenter retrospective cohort study of neonates with sTOF were merged with administrative data to compare total costs and cost per day alive over the first 18 months of life in a propensity score-adjusted analysis. A secondary analysis evaluated differences in department-level costs.
Results
In total, 324 subjects from 6 centers from January 2011 to November 2017 were studied (40% PR). The 18-month cumulative mortality (P = 0.18), procedural complications (P = 0.10), hospital complications (P = 0.94), and reinterventions (P = 0.22) did not differ between PR and SR. Total 18-month costs for PR (median $179,494 [IQR: $121,760-$310,721]) were less than for SR (median: $222,799 [IQR: $167,581-$327,113]) (P < 0.001). Cost per day alive (P = 0.005) and department-level costs were also all lower for PR. In propensity score-adjusted analyses, PR was associated with lower total cost (cost ratio: 0.73; P < 0.001) and lower department-level costs.
Conclusions
In this multicenter study of neonates with sTOF, PR was associated with lower costs. Given similar overall mortality between treatment strategies, this finding suggests that PR provides superior value.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 29 Jan 2022; 79:1170-1180
O'Byrne ML, Glatz AC, Huang YV, Kelleman MS, ... McCracken CE, Goldstein BH
J Am Coll Cardiol: 29 Jan 2022; 79:1170-1180 | PMID: 35331412
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Abstract

Longitudinal Outcomes of Subcutaneous or Transvenous Implantable Cardioverter-Defibrillators in Older Patients.

Friedman DJ, Qin L, Parzynski C, Heist EK, ... Curtis JP, Al-Khatib SM
Background
The subcutaneous (S-) implantable cardioverter-defibrillator (ICD) is an alternative to the transvenous (TV-) ICD that is increasingly implanted in younger patients; data on the safety and effectiveness of the S-ICD in older patients are lacking.
Objectives
The purpose of this study was to compare outcomes among older patients who received an S- or TV-ICD.
Methods
The authors compared S-ICD and single-chamber TV-ICD implants in Fee-For-Service Medicare beneficiaries using the National Cardiovascular Data Registry ICD Registry. Outcomes were ascertained from Medicare claims data. Cox regression or competing-risk models (with TV-ICD as reference) with overlap weights were used to compare death and nonfatal outcomes (device reoperation, device removal for infection, device reoperation without infection, and cardiovascular admission), respectively. Recurrent all-cause readmissions were compared using Anderson-Gill models.
Results
A total of 16,063 patients were studied (age 72.6 ± 5.9 years, 28.4% women, ejection fraction 28.3 ± 8.9%). Compared with TV-ICD patients (n = 15,072), S-ICD patients (n = 991, 6.2% overall) were more often Black, younger, and dialysis dependent and less likely to have history of atrial fibrillation or flutter. In adjusted analyses, there were no differences between device type and risk of all-cause mortality (HR: 1.020; 95% CI: 0.819-1.270), device reoperation (subdistribution [s] HR: 0.976; 95% CI: 0.645-1.479), device removal for infection (sHR: 0.614; 95% CI: 0.138-2.736), device reoperation without infection (sHR: 0.975; 95% CI: 0.632-1.506), cardiovascular readmission (sHR: 1.087; 95% CI: 0.912-1.295), or recurrent all-cause readmission (HR: 1.072; 95% CI: 0.990-1.161).
Conclusions
In a large representative national cohort of older patients undergoing ICD implantation, risk of death, device reoperation, device removal for infection, device reoperation without infection, and cardiovascular and all-cause readmission were similar among S- and TV-ICD recipients.

Published by Elsevier Inc.

J Am Coll Cardiol: 22 Jan 2022; 79:1050-1059
Friedman DJ, Qin L, Parzynski C, Heist EK, ... Curtis JP, Al-Khatib SM
J Am Coll Cardiol: 22 Jan 2022; 79:1050-1059 | PMID: 35300816
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Abstract

Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults.

Guasch-Ferré M, Li Y, Willett WC, Sun Q, ... Stampfer MJ, Hu FB
Background
Olive oil consumption has been shown to lower cardiovascular disease risk, but its associations with total and cause-specific mortality are unclear.
Objectives
The purpose of this study was to evaluate whether olive oil intake is associated with total and cause-specific mortality in 2 prospective cohorts of U.S. men and women.
Methods
The authors used multivariable-adjusted Cox proportional-hazards models to estimate HRs for total and cause-specific mortality among 60,582 women (Nurses\' Health Study, 1990-2018) and 31,801 men (Health Professionals Follow-up Study, 1990-2018) who were free of cardiovascular disease or cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years.
Results
During 28 years of follow-up, 36,856 deaths occurred. The multivariable-adjusted pooled HR for all-cause mortality among participants who had the highest consumption of olive oil (>0.5 tablespoon/day or >7 g/d) was 0.81 (95% CI: 0.78-0.84) compared with those who never or rarely consumed olive oil. Higher olive oil intake was associated with 19% lower risk of cardiovascular disease mortality (HR: 0.81; 95% CI: 0.75-0.87), 17% lower risk of cancer mortality (HR: 0.83; 95% CI: 0.78-0.89), 29% lower risk of neurodegenerative disease mortality (HR: 0.71; 95% CI: 0.64-0.78), and 18% lower risk of respiratory disease mortality (HR: 0.82; 95% CI: 0.72-0.93). In substitution analyses, replacing 10 g/d of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil was associated with 8%-34% lower risk of total and cause-specific mortality. No significant associations were observed when olive oil was compared with other vegetable oils combined.
Conclusions
Higher olive oil intake was associated with lower risk of total and cause-specific mortality. Replacing margarine, butter, mayonnaise, and dairy fat with olive oil was associated with lower risk of mortality.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Jan 2022; 79:101-112
Guasch-Ferré M, Li Y, Willett WC, Sun Q, ... Stampfer MJ, Hu FB
J Am Coll Cardiol: 18 Jan 2022; 79:101-112 | PMID: 35027106
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Abstract

Association of Lipoprotein(a) With Atherosclerotic Plaque Progression.

Kaiser Y, Daghem M, Tzolos E, Meah MN, ... Zheng KH, Dweck MR
Background
Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain.
Objectives
This study aims to investigate whether Lp(a) is associated with adverse plaque progression.
Methods
Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary computed tomography angiography at baseline and 12 months to assess progression of total, calcific, noncalcific, and low-attenuation plaque (necrotic core) in particular. High Lp(a) was defined as Lp(a) ≥ 70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score (a Scottish cardiovascular risk score comprised of age, sex, smoking, blood pressure, total and high-density lipoprotein [HDL]-cholesterol, diabetes, rheumatoid arthritis, and deprivation index).
Results
A total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, with median Lp(a) values of 100 (range: 82 to 115) mg/dL and 10 (range: 5 to 24) mg/dL in the high and low Lp(a) groups, respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2 ± 88.4 mm3 vs -0.7 ± 50.1 mm3; P = 0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β = 10.5% increase for each 50 mg/dL Lp(a), 95% CI: 0.7%-20.3%). There was no difference in total, calcific, and noncalcific plaque volume progression.
Conclusions
Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.

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

J Am Coll Cardiol: 25 Jan 2022; 79:223-233
Kaiser Y, Daghem M, Tzolos E, Meah MN, ... Zheng KH, Dweck MR
J Am Coll Cardiol: 25 Jan 2022; 79:223-233 | PMID: 35057907
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Abstract

Mineralocorticoid Receptor Antagonists and Empagliflozin in Patients With Heart Failure and Preserved Ejection Fraction.

Ferreira JP, Butler J, Zannad F, Filippatos G, ... Packer M, Anker SD
Background
Mineralocorticoid receptor antagonists (MRAs) may be beneficial in reducing heart failure (HF) hospitalizations in patients with HF with preserved ejection fraction. The effect of sodium-glucose cotransporter 2 inhibitors in patients with HF with preserved ejection fraction according to MRA background therapy has not been reported.
Objectives
The aim of this study was to examine the effect of empagliflozin in MRA users and nonusers in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) trial.
Methods
Survival analyses were conducted comparing the effects of empagliflozin vs placebo in MRA users and nonusers at baseline with treatment-by-MRA use interaction terms.
Results
A total of 5,988 patients were included, of whom 2,244 (37.5%) were using MRAs at baseline. MRA users had higher event rates than MRA nonusers (placebo group primary outcome 9.4 vs 8.2 events per 100 person-years). The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users (HR: 0.73 [95% CI: 0.62-0.87] and HR: 0.87 [95% CI: 0.71-1.06]; interaction P = 0.22). The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers than in MRA users (HR: 0.60 [95% CI: 0.47-0.77] and HR: 0.90 [95% CI: 0.68-1.19]; interaction P = 0.038). MRA users experienced almost twice as many hyperkalemia events as MRA nonusers, and empagliflozin reduced the risk for hyperkalemia or initiation of potassium binders regardless of MRA use (MRA nonusers: HR: 0.90 [95% CI: 0.69-1.19]; MRA users: HR: 0.74 [95% CI: 0.56-0.96]; interaction P = 0.29).
Conclusions
The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users. The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers. Empagliflozin reduced hyperkalemia, with no significant treatment-by-MRA subgroup interaction. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).

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

J Am Coll Cardiol: 29 Jan 2022; 79:1129-1137
Ferreira JP, Butler J, Zannad F, Filippatos G, ... Packer M, Anker SD
J Am Coll Cardiol: 29 Jan 2022; 79:1129-1137 | PMID: 35331406
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Abstract

Coronary Risk Estimation Based on Clinical Data in Electronic Health Records.

Petrazzini BO, Chaudhary K, Márquez-Luna C, Forrest IS, ... Nadkarni G, Do R
Background
Clinical features from electronic health records (EHRs) can be used to build a complementary tool to predict coronary artery disease (CAD) susceptibility.
Objectives
The purpose of this study was to determine whether an EHR score can improve CAD prediction and reclassification 1 year before diagnosis, beyond conventional clinical guidelines as determined by the pooled cohort equations (PCE) and a polygenic risk score for CAD.
Methods
We applied a machine learning framework using clinical features from the EHR in a multiethnic, clinical care cohort (BioMe) comprising 555 CAD cases and 6,349 control subjects and in a population-based cohort (UK Biobank) comprising 3,130 CAD cases and 378,344 control subjects for external validation.
Results
Compared with the PCE, the EHR score improved CAD prediction by 12% in the BioMe Biobank and by 9% in the UK Biobank. The EHR score reclassified 25.8% and 15.2% individuals in each cohort respectively, compared with the PCE score. We observed larger improvements in the EHR score over the PCE in a subgroup of individuals with low CAD risk, with 20% increased discrimination and 34.4% increased reclassification. In all models, the polygenic risk score for CAD did not improve CAD prediction, compared with the PCE or EHR score.
Conclusions
The EHR score resulted in increased prediction and reclassification for CAD, demonstrating its potential use for population health monitoring of short-term CAD risk in large health systems.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 29 Jan 2022; 79:1155-1166
Petrazzini BO, Chaudhary K, Márquez-Luna C, Forrest IS, ... Nadkarni G, Do R
J Am Coll Cardiol: 29 Jan 2022; 79:1155-1166 | PMID: 35331410
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Abstract

Lead-Related Venous Obstruction in Patients With Implanted Cardiac Devices: JACC Review Topic of the Week.

Zimetbaum P, Carroll BJ, Locke AH, Secemsky E, Schermerhorn M
Cardiac implantable electronic device implantation rates have increased in recent decades. Venous obstruction of the subclavian, brachiocephalic, or superior vena cava veins represents an important complication of implanted leads. These forms of venous obstruction can result in significant symptoms as well as present a barrier to the implantation of additional device leads. The risk factors for the development of these complications remain poorly understood, and diagnosis relies on clinical recognition and cross-sectional imaging. Anticoagulation remains the mainstay of treatment, and thrombus debulking, lead extraction, venoplasty, and stenting are all important therapeutic interventions. This review provides a multidisciplinary-based approach to the evaluation and management of cardiac implantable electronic device lead-associated venous obstruction.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 25 Jan 2022; 79:299-308
Zimetbaum P, Carroll BJ, Locke AH, Secemsky E, Schermerhorn M
J Am Coll Cardiol: 25 Jan 2022; 79:299-308 | PMID: 35057916
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Abstract

Editor-in-Chief\'s Top Picks From 2021.

Fuster V
Each week, I record audio summaries for every paper in JACC, as well as an issue summary. This process has become a true labor of love due to the time they require, but I am motivated by the sheer number of listeners (16M+), and it has allowed me to familiarize myself with every paper that we publish. Thus, I have selected the top 100 papers (both Original Investigations and Review Articles) from distinct specialties each year. In addition to my personal choices, I have included papers that have been the most accessed or downloaded on our websites, as well as those selected by the JACC Editorial Board members. In order to present the full breadth of this important research in a consumable fashion, we will present these abstracts in this issue of JACC, as well as their Central Illustrations and podcasts. The highlights comprise the following sections: Artificial Intelligence & Machine Learning (NEW section), Basic & Translational Research, Biomarkers (NEW section), Cardiac Failure & Myocarditis, Cardiomyopathies & Genetics, Cardio-Oncology, Cardiovascular Disease in Women, Coronary Disease & Interventions, Congenital Heart Disease, Coronavirus, Hypertension, Imaging, Metabolic & Lipid Disorders, Neurovascular Disease & Dementia, Promoting Health & Prevention, Rhythm Disorders & Thromboembolism, Vascular Medicine, and Valvular Heart Disease.1-100.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 22 Jan 2022; 79:695-753
Fuster V
J Am Coll Cardiol: 22 Jan 2022; 79:695-753 | PMID: 35177199
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Abstract

Propensity-Matched Comparison of the Ross Procedure and Prosthetic Aortic Valve Replacement in Adults.

El-Hamamsy I, Toyoda N, Itagaki S, Stelzer P, ... Erogova N, Adams DH
Background
There has recently been renewed interest in the Ross procedure in adults.
Objectives
The goal of this study was to compare long-term outcomes after the Ross procedure vs biological and mechanical aortic valve replacement (AVR) in adults (aged 18-50 years) undergoing aortic valve surgery.
Methods
Mandatory California and New York databases were queried between 1997 and 2014. Exclusion criteria included: ≥1 concomitant procedure, reoperations, infective endocarditis, intravenous drug use, hemodialysis, and out-of-state residency. Propensity matching (1:1:1) was used, resulting in 434 patients per group. The primary endpoint was all-cause mortality. Secondary endpoints were stroke, major bleeding, reoperation, and endocarditis. Median follow-up was 12.5 years (IQR: 9.3-15.7 years).
Results
At 15 years, actuarial survival after the Ross procedure was 93.1% (95% CI: 89.1%-95.7%), similar to that of the age-, sex-, and race-matched U.S. general population. It was significantly lower after biological AVR (HR: 0.42; 95% CI: 0.23-0.075; P = 0.003) and mechanical AVR (HR: 0.45; 95% CI: 0.26-0.79; P = 0.006). At 15 years, the Ross procedure was associated with a lower cumulative risk of reintervention (P = 0.008) and endocarditis (P = 0.01) than biological AVR. In contrast, at 15 years, the Ross procedure was associated with a higher cumulative incidence of reoperation (P < 0.001) but lower risks of stroke (P = 0.03) and major bleeding (P = 0.016) than mechanical AVR. Thirty-day mortality after valve-related complications was lowest after a reintervention.
Conclusions
In young adults, the Ross procedure is associated with better long-term survival and freedom from valve-related complications compared with prosthetic AVR. This confirms the notion that a living valve substitute in the aortic position translates into improved clinically relevant outcomes.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 01 Jan 2022; 79:805-815
El-Hamamsy I, Toyoda N, Itagaki S, Stelzer P, ... Erogova N, Adams DH
J Am Coll Cardiol: 01 Jan 2022; 79:805-815 | PMID: 35210036
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Abstract

Right Ventricular-Pulmonary Arterial Coupling and Afterload Reserve in Patients Undergoing Transcatheter Tricuspid Valve Repair.

Brener MI, Lurz P, Hausleiter J, Rodés-Cabau J, ... Taramasso M, Hahn RT
Background
The right ventricular (RV)-pulmonary arterial (PA) coupling ratio relates the efficiency with which RV stroke work is transferred into the PA. Lower ratios indicate an inadequate RV contractile response to increased afterload.
Objectives
This study sought to evaluate the prognostic significance of RV-PA coupling in patients with tricuspid regurgitation (TR) who were undergoing transcatheter tricuspid valve repair or replacement (TTVR).
Methods
The study investigators calculated RV-PA coupling ratios for patients enrolled in the global TriValve registry by dividing the tricuspid annular plane systolic excursion (TAPSE) by the PA systolic pressure (PASP) from transthoracic echocardiograms performed before the procedure and 30 days after the procedure. The primary endpoint was all-cause mortality at 1-year follow-up.
Results
Among 444 patients analyzed, their mean age was 76.9 ± 9.1 years, and 53.8% of the patients were female. The median TAPSE/PASP ratio was 0.406 mm/mm Hg (interquartile range: 0.308-0.567 mm/mm Hg). Sixty-three patients died within 1 year of TTVR, 21 with a TAPSE/PASP ratio >0.406 and 42 with a TAPSE/PASP ratio ≤0.406. In multivariable Cox regression analysis, a TAPSE/PASP ratio >0.406 vs ≤0.406 was associated with a decreased risk of all-cause mortality (HR: 0.57; 95% CI: 0.35-0.93; P = 0.023). In 234 (52.7%) patients with echocardiograms 30 days after TTVR, a decline in RV-PA coupling was independently associated with reduced odds of all-cause mortality (odds ratio [OR]: 0.42; 95% CI: 0.19-0.93; P = 0.032). The magnitude of TR reduction after TTVR (≥1+ vs <1+; OR: 2.53; 95% CI: 1.06-6.03; P = 0.037) was independently associated with a reduction in post-TTVR RV-PA coupling.
Conclusions
RV-PA coupling is a powerful, independent predictor of all-cause mortality in patients with TR undergoing TTVR. These data suggest that the TAPSE/PASP ratio can inform patient selection and prognostication following TTVR.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 08 Jan 2022; 79:448-461
Brener MI, Lurz P, Hausleiter J, Rodés-Cabau J, ... Taramasso M, Hahn RT
J Am Coll Cardiol: 08 Jan 2022; 79:448-461 | PMID: 35115101
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Impact:
Abstract

Inflammation, Aging, and Cardiovascular Disease: JACC Review Topic of the Week.

Liberale L, Badimon L, Montecucco F, Lüscher TF, Libby P, Camici GG
Aging and inflammation both contribute pivotally to cardiovascular (CV) and cerebrovascular disease, the leading causes of death and disability worldwide. The concept of inflamm-aging recognizes that low-grade inflammatory pathways observed in the elderly contribute to CV risk. Understanding the mechanisms that link inflammation and aging could reveal new therapeutic targets and offer options to cope with the growing aging population worldwide. This review reports recent scientific advances in the pathways through which inflamm-aging mediates age-dependent decline in CV function and disease onset and considers critically the translational potential of such concepts into everyday clinical practice.

Copyright © 2022 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 01 Jan 2022; 79:837-847
Liberale L, Badimon L, Montecucco F, Lüscher TF, Libby P, Camici GG
J Am Coll Cardiol: 01 Jan 2022; 79:837-847 | PMID: 35210039
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Abstract

A Score to Assess Mortality After Percutaneous Mitral Valve Repair.

Raposeiras-Roubin S, Adamo M, Freixa X, Arzamendi D, ... Grasso C, Estévez-Loureiro R
Background
Risk stratification for transcatheter edge-to-edge mitral valve repair (TEER) is paramount in the decision-making process for treating severe mitral regurgitation (MR).
Objectives
This study sought to create and validate a user-friendly score (MitraScore) to predict the risk of mortality in patients undergoing TEER.
Methods
The derivation cohort was based on a multicentric international registry that included 1,119 patients referred for TEER between 2012 and 2020. Score discrimination was assessed using Harrell\'s c-statistic, and the calibration was evaluated with the Gronnesby and Borgan goodness-of-fit test. An external validation was carried out in 725 patients from the GIOTTO registry.
Results
After multivariate analysis, we identified 8 independent predictors of mortality during the follow-up (2.1 ± 1.8 years): age ≥75 years, anemia, glomerular filtrate rate <60 mL/min/1.73 m2, left ventricular ejection fraction <40%, peripheral artery disease, chronic obstructive pulmonary disease, high diuretic dose, and no therapy with renin-angiotensin system inhibitors. The MitraScore was derived by assigning 1 point to each independent predictor. The c-statistic was 0.70. Per each point of the MitraScore, the relative risk of mortality increased by 55% (HR: 1.55; 95% CI: 1.44-1.67; P < 0.001). The discrimination and calibration for mortality prediction was better than those of EuroSCORE II (c-statistic 0.61) or Society of Thoracic Surgeons score (c-statistic 0.57). The MitraScore maintained adequate performance in the validation cohort (c-statistic 0.66). The score was also predictive for heart failure rehospitalization and was correlated with the probability of clinical improvement.
Conclusions
The MitraScore is a simple prediction algorithm for the prediction of follow-up mortality in patients treated with TEER.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 15 Jan 2022; 79:562-573
Raposeiras-Roubin S, Adamo M, Freixa X, Arzamendi D, ... Grasso C, Estévez-Loureiro R
J Am Coll Cardiol: 15 Jan 2022; 79:562-573 | PMID: 35144748
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Impact:
Abstract

Association of Donor Brain Death Due to Stroke With Prognosis After Heart Transplantation.

Mikami T, Itagaki S, Fujisaki T, Kuno T, ... Burns JD, Anyanwu AC
Background
The proximate cause of donor brain death is not considered a conventional risk factor in modern heart transplantation.
Objectives
This study aimed to investigate the effect of the cause of donor brain death on recipients.
Methods
Using the United Network for Organ Sharing registry, long-term mortality and allograft failure were compared in recipients who underwent heart transplantation in the United States from 2005 through 2018 between allograft recipients from donors with stroke as the cause of brain death (n = 3,761) vs nonstroke causes (n = 14,677). Inverse probability weighting was used for risk adjustment. Interactions were investigated between the cause of brain death and other conventional donor risk factors for recipient mortality.
Results
There was an interaction between the cause of brain death and donor age (Pinteraction = 0.008). When allografts were procured from donors aged 40 years or younger, stroke as the cause of brain death was associated with an increased risk of mortality (23% vs 19% at 5 years; HR: 1.17; 95% CI: 1.02-1.35) and allograft failure (HR: 1.30; 95% CI: 1.04-1.63). When donors were older than 40 years, the cause of brain death was not associated with outcomes.
Conclusions
As the cause of donor brain death, stroke had a substantially different effect on recipient and allograft survival depending on donor age. In the case of younger donor ages, stroke was associated with higher recipient mortality and allograft failure than other causes of brain death. The strength of this association decreased with increasing donor age such that the increased hazard was no longer present in donors older than approximately 40 years.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 22 Jan 2022; 79:1063-1072
Mikami T, Itagaki S, Fujisaki T, Kuno T, ... Burns JD, Anyanwu AC
J Am Coll Cardiol: 22 Jan 2022; 79:1063-1072 | PMID: 35300818
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Abstract

Association of Longitudinal High-Sensitivity Troponin T With Mortality in Patients With Chronic Kidney Disease.

Chesnaye NC, Al-Sodany E, Szummer K, Barany P, ... Jager KJ, Evans M
Background
Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed.
Objectives
This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD.
Methods
The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged ≥65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival.
Results
There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.0-6.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure.
Conclusions
Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 01 Jan 2022; 79:327-336
Chesnaye NC, Al-Sodany E, Szummer K, Barany P, ... Jager KJ, Evans M
J Am Coll Cardiol: 01 Jan 2022; 79:327-336 | PMID: 35086654
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Abstract

Anticoagulation in Patients With COVID-19: JACC Review Topic of the Week.

Farkouh ME, Stone GW, Lala A, Bagiella E, ... Palacios IF, Fuster V
Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).

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

J Am Coll Cardiol: 08 Jan 2022; 79:917-928
Farkouh ME, Stone GW, Lala A, Bagiella E, ... Palacios IF, Fuster V
J Am Coll Cardiol: 08 Jan 2022; 79:917-928 | PMID: 35241226
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Abstract

Discordance Between Standard Equations for Determination of LDL Cholesterol in Patients With Atherosclerosis.

Sajja A, Li HF, Spinelli KJ, Blumenthal RS, ... Martin SS, Gluckman TJ
Background
Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for guiding cholesterol-lowering therapy. Different methods currently exist to estimate LDL-C.
Objectives
This study sought to assess discordance of estimated LDL-C using the Friedewald, Sampson, and Martin/Hopkins equations.
Methods
Electronic health record data from patients with atherosclerotic cardiovascular disease and triglyceride (TG) levels of <400 mg/dL between October 1, 2015, and June 30, 2019, were retrospectively analyzed. LDL-C was estimated using the Friedewald, Sampson, and Martin/Hopkins equations. Patients were categorized as concordant if LDL-C was <70 mg/dL with each pairwise comparison of equations and as discordant if LDL-C was <70 mg/dL for the index equation and ≥70 mg/dL for the comparator.
Results
The study included 146,106 patients with atherosclerotic cardiovascular disease (mean age: 68 years; 56% male; 91% White). The Martin/Hopkins equation consistently estimated higher LDL-C values than the Friedewald and Sampson equations. Discordance rates were 15% for the Friedewald vs Martin/Hopkins comparison, 9% for the Friedewald vs Sampson comparison, and 7% for the Sampson vs Martin/Hopkins comparison. Discordance increased at lower LDL-C cutpoints and in those with elevated TG levels. Among patients with TG levels of ≥150 mg/dL, a >10 mg/dL difference in LDL-C was present in 67%, 27%, and 23% of patients when comparing the Friedewald vs Martin/Hopkins, Friedewald vs Sampson, and Sampson vs Martin/Hopkins equations, respectively.
Conclusions
Clinically meaningful differences in estimated LDL-C exist among equations, particularly at TG levels of ≥150 mg/dL and/or lower LDL-C levels. Reliance on the Friedewald and Sampson equations may result in the underestimation and undertreatment of LDL-C in those at increased risk.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 15 Jan 2022; 79:530-541
Sajja A, Li HF, Spinelli KJ, Blumenthal RS, ... Martin SS, Gluckman TJ
J Am Coll Cardiol: 15 Jan 2022; 79:530-541 | PMID: 35144744
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Abstract

Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week.

Taha K, Kirkels FP, Teske AJ, Asselbergs FW, ... Haugaa KH, Cramer MJ
Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 15 Jan 2022; 79:594-608
Taha K, Kirkels FP, Teske AJ, Asselbergs FW, ... Haugaa KH, Cramer MJ
J Am Coll Cardiol: 15 Jan 2022; 79:594-608 | PMID: 35144751
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Impact:
Abstract

Intramyocardial Hemorrhage and the \"Wave Front\" of Reperfusion Injury Compromising Myocardial Salvage.

Liu T, Howarth AG, Chen Y, Nair AR, ... Kumar A, Dharmakumar R
Background
Reperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size.
Objectives
Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not known.
Methods
We studied cardiac troponin kinetics (cTn) of ST-segment elevation MI patients (n = 70) classified by cardiovascular magnetic resonance to be hemorrhagic (70%) or nonhemorrhagic following primary percutaneous coronary intervention. To isolate the effects of hemorrhage from ischemic burden, we performed controlled canine studies (n = 25), and serially followed both cTn and MI size with time-lapse imaging.
Results
CTn was not different before reperfusion; however, an increase in cTn following primary percutaneous coronary intervention peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with hemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without hemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in hemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in hemorrhagic cases (P < 0.01).
Conclusions
Myocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2022; 79:35-48
Liu T, Howarth AG, Chen Y, Nair AR, ... Kumar A, Dharmakumar R
J Am Coll Cardiol: 04 Jan 2022; 79:35-48 | PMID: 34991787
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Impact:
Abstract

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Writing Committee Members, Lawton JS, Tamis-Holland JE, Bangalore S, ... Yong CM, Zwischenberger BA
Aim
The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use.
Methods
A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered.
Structure
Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

Copyright © 2022 The American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Jan 2022; 79:197-215
Writing Committee Members, Lawton JS, Tamis-Holland JE, Bangalore S, ... Yong CM, Zwischenberger BA
J Am Coll Cardiol: 18 Jan 2022; 79:197-215 | PMID: 34895951
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Abstract

Feasibility and Potential Impact of Heart Transplantation From Adult Donors After Circulatory Death.

Madan S, Saeed O, Forest SJ, Goldstein DJ, Jorde UP, Patel SR
Background
A shortage of donation after brain death (DBD) donors for heart transplantation (HT) persists. Recent improvements in organ procurement from donation after circulatory death (DCD) donors and promising early results of DCD-HTs from Europe and Australia have renewed interest in DCD-HT.
Objectives
The current study evaluated donor and recipient characteristics, early outcomes, and potential impact of adult DCD-HT in the United States.
Methods
The United Network for Organ Sharing registry was used to identify and compare adult DCD donors based on their use for HT between January 2020 and February 2021. Adult DCD-HTs with available post-HT outcomes data were compared with contemporary adult DBD-HTs during study period using Cox-regression analysis and propensity-matching.
Results
Of the 3,611 adult DCD donors referred during the study period, 136 were used for HT. DCD donors used for HT were younger (median age 29 years), and most were male (90%), and blood type O (79%). On comparing DCD-HT (n = 127) and DBD-HT (n = 2,961) meeting study criteria and with available data on post-HT outcomes, there was no significant difference in 30-day or 6-month mortality, primary graft failure up to 30 days, or other outcomes including in-hospital stroke, pacemaker insertion, hemodialysis, and post-HT length of hospital stay. Results were similar in propensity matched DCD-HT and DBD-HT cohorts. The number of potential adult DCD donors referred has increased substantially (n = 871 in 2010 to n = 3,045 in 2020), and the authors estimated that widespread adoption of DCD-HT could lead to approximately 300 additional adult HTs in the United States annually.
Conclusions
This preliminary analysis of adult DCD-HTs from the United States showed favorable early outcomes and suggested a potential for substantial increase in adult HT volumes with use of DCD donors.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Jan 2022; 79:148-162
Madan S, Saeed O, Forest SJ, Goldstein DJ, Jorde UP, Patel SR
J Am Coll Cardiol: 18 Jan 2022; 79:148-162 | PMID: 34922742
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Impact:
Abstract

Impact of Autophagy on Prognosis of Patients With Dilated Cardiomyopathy.

Kanamori H, Yoshida A, Naruse G, Endo S, ... Miyazaki T, Okura H
Background
Autophagy is a cellular process that degrades a cell\'s own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM).
Objectives
The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart.
Methods
Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy.
Results
The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period.
Conclusions
The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 01 Jan 2022; 79:789-801
Kanamori H, Yoshida A, Naruse G, Endo S, ... Miyazaki T, Okura H
J Am Coll Cardiol: 01 Jan 2022; 79:789-801 | PMID: 35210034
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Impact:
Abstract

Risk Stratification for Congenital Heart Surgery for ICD-10 Administrative Data (RACHS-2).

Allen P, Zafar F, Mi J, Crook S, ... Anderson BR, New York State CHS-COLOUR
Background
As the cardiac community strives to improve outcomes, accurate methods of risk stratification are imperative. Since adoption of International Classification of Disease-10th Revision (ICD-10) in 2015, there is no published method for congenital heart surgery risk stratification for administrative data.
Objectives
This study sought to develop an empirically derived, publicly available Risk Stratification for Congenital Heart Surgery (RACHS-2) tool for ICD-10 administrative data.
Methods
The RACHS-2 stratification system was iteratively and empirically refined in a training dataset of Pediatric Health Information Systems claims to optimize sensitivity and specificity compared with corresponding locally held Society of Thoracic Surgeons-Congenital Heart Surgery (STS-CHS) clinical registry data. The tool was validated in a second administrative data source: New York State Medicaid claims. Logistic regression was used to compare the ability of RACHS-2 in administrative data to predict operative mortality vs STAT Mortality Categories in registry data.
Results
The RACHS-2 system captured 99.6% of total congenital heart surgery registry cases, with 1.0% false positives. RACHS-2 predicted operative mortality in both training and validation administrative datasets similarly to STAT Mortality Categories in registry data. C-statistics for models for operative mortality in training and validation administrative datasets-adjusted for RACHS-2-were 0.76 and 0.84 (95% CI: 0.72-0.80 and 0.80-0.89); C-statistics for models for operative mortality-adjusted for STAT Mortality Categories-in corresponding clinical registry data were 0.75 and 0.84 (95% CI: 0.71-0.79 and 0.79-0.89).
Conclusions
RACHS-2 is a risk stratification system for pediatric cardiac surgery for ICD-10 administrative data, validated in 2 administrative-registry-linked datasets. Statistical code is publicly available upon request.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 08 Jan 2022; 79:465-478
Allen P, Zafar F, Mi J, Crook S, ... Anderson BR, New York State CHS-COLOUR
J Am Coll Cardiol: 08 Jan 2022; 79:465-478 | PMID: 35115103
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Impact:
Abstract

Reintervention and Survival After Transcatheter Pulmonary Valve Replacement.

McElhinney DB, Zhang Y, Levi DS, Georgiev S, ... Ewert P, Schubert S
Background
Transcatheter pulmonary valve (TPV) replacement (TPVR) has become the standard therapy for postoperative pulmonary outflow tract dysfunction in patients with a prosthetic conduit/valve, but there is limited information about risk factors for death or reintervention after this procedure.
Objectives
This study sought to evaluate mid- and long-term outcomes after TPVR in a large multicenter cohort.
Methods
International registry focused on time-related outcomes after TPVR.
Results
Investigators submitted data for 2,476 patients who underwent TPVR and were followed up for 8,475 patient-years. A total of 95 patients died after TPVR, most commonly from heart failure (n = 24). The cumulative incidence of death was 8.9% (95% CI: 6.9%-11.5%) 8 years after TPVR. On multivariable analysis, age at TPVR (HR: 1.04 per year; 95% CI: 1.03-1.06 per year; P < 0.001), a prosthetic valve in other positions (HR: 2.1; 95% CI: 1.2-3.7; P = 0.014), and an existing transvenous pacemaker/implantable cardioverter-defibrillator (HR: 2.1; 95% CI: 1.3-3.4; P = 0.004) were associated with death. A total of 258 patients underwent TPV reintervention. At 8 years, the cumulative incidence of any TPV reintervention was 25.1% (95% CI: 21.8%-28.5%) and of surgical TPV reintervention was 14.4% (95% CI: 11.9%-17.2%). Risk factors for surgical reintervention included age (0.95 per year [95% CI: 0.93-0.97 per year]; P < 0.001), prior endocarditis (2.5 [95% CI: 1.4-4.3]; P = 0.001), TPVR into a stented bioprosthetic valve (1.7 [95% CI: 1.2-2.5]; P = 0.007), and postimplant gradient (1.4 per 10 mm Hg [95% CI: 1.2-1.7 per 10 mm Hg]: P < 0.001).
Conclusions
These findings support the conclusion that survival and freedom from reintervention or surgery after TPVR are generally comparable to outcomes of surgical conduit/valve replacement across a wide age range.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2022; 79:18-32
McElhinney DB, Zhang Y, Levi DS, Georgiev S, ... Ewert P, Schubert S
J Am Coll Cardiol: 04 Jan 2022; 79:18-32 | PMID: 34991785
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Abstract

Maternal Cardiac Function at Midgestation and Development of Preeclampsia.

Gibbone E, Huluta I, Wright A, Nicolaides KH, Charakida M
Background
Preeclampsia (PE) is an independent risk factor for adverse maternal cardiovascular outcomes. The role of maternal cardiac function in the pathophysiology of PE remains unclear.
Objectives
This study sought to describe differences in cardiac function at midgestation between women who develop PE and those with uncomplicated pregnancy and to establish whether routine cardiac assessment at midgestation can improve performance of screening for PE achieved by established biomarkers.
Methods
Mean arterial pressure was measured, medical history was obtained, and left ventricular (LV) systolic and diastolic functions were assessed using standard echocardiography and speckle tracking imaging. Uterine artery pulsatility index and serum placental growth factor and soluble fms-like tyrosine kinase-1 were measured.
Results
In 4,795 pregnancies, 126 (2.6%) developed PE. Following multivariable analysis, peripheral vascular resistance was significantly higher and LV global longitudinal systolic strain, ejection fraction, cardiac output, and left atrial area were mildly lower in women who developed PE compared to those who did not. There was a weak association between maternal cardiovascular indices and biomarkers of placental perfusion and function. Cardiac indices did not improve the performance of screening for PE on top of maternal risk factors, mean arterial pressure, and biomarkers of placental perfusion and function.
Conclusion
Women who develop PE have an increase in peripheral vascular resistance and a mild reduction in LV functional cardiac indices long before PE development. However, cardiac indices do not improve the performance of screening for PE; thus, their routine clinical use is not advocated.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Jan 2022; 79:52-62
Gibbone E, Huluta I, Wright A, Nicolaides KH, Charakida M
J Am Coll Cardiol: 04 Jan 2022; 79:52-62 | PMID: 34991789
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Impact:
Abstract

Interventions for Frailty Among Older Adults With Cardiovascular Disease: JACC State-of-the-Art Review.

Ijaz N, Buta B, Xue QL, Mohess DT, ... Gerstenblith G, Damluji AA
With the aging of the world\'s population, a large proportion of patients seen in cardiovascular practice are older adults, but many patients also exhibit signs of physical frailty. Cardiovascular disease and frailty are interdependent and have the same physiological underpinning that predisposes to the progression of both disease processes. Frailty can be defined as a phenomenon of increased vulnerability to stressors due to decreased physiological reserves in older patients and thus leads to poor clinical outcomes after cardiovascular insults. There are various pathophysiologic mechanisms for the development of frailty: cognitive decline, physical inactivity, poor nutrition, and lack of social supports; these risk factors provide opportunity for various types of interventions that aim to prevent, improve, or reverse the development of frailty syndrome in the context of cardiovascular disease. There is no compelling study demonstrating a successful intervention to improve a global measure of frailty. Emerging data from patients admitted with heart failure indicate that interventions associated with positive outcomes on frailty and physical function are multidimensional and include tailored cardiac rehabilitation. Contemporary cardiovascular practice should actively identify patients with physical frailty who could benefit from frailty interventions and aim to deliver these therapies in a patient-centered model to optimize quality of life, particularly after cardiovascular interventions.

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

J Am Coll Cardiol: 08 Jan 2022; 79:482-503
Ijaz N, Buta B, Xue QL, Mohess DT, ... Gerstenblith G, Damluji AA
J Am Coll Cardiol: 08 Jan 2022; 79:482-503 | PMID: 35115105
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Abstract

Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.

Maron BJ, Desai MY, Nishimura RA, Spirito P, ... Maron MS, Sherrid MV
Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.5%/y. Palliative pharmacological strategies with currently available negative inotropic drugs can control symptoms over the short-term in some patients, but generally do not alter long-term clinical course. Notably, a substantial proportion of HCM patients (largely those identified without outflow obstruction) experience a stable/benign course without major interventions. The expert panel has critically appraised all available data and presented management insights and recommendations with concise principles for clinical decision-making.

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

J Am Coll Cardiol: 01 Jan 2022; 79:390-414
Maron BJ, Desai MY, Nishimura RA, Spirito P, ... Maron MS, Sherrid MV
J Am Coll Cardiol: 01 Jan 2022; 79:390-414 | PMID: 35086661
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Abstract

Benefit of Early Revascularization Based on Inducible Ischemia and Left Ventricular Ejection Fraction.

Rozanski A, Miller RJH, Gransar H, Han D, ... Thomson L, Berman DS
Background
The utility of performing early myocardial revascularization among patients presenting with inducible myocardial ischemia and low left ventricular ejection fraction (LVEF) is currently unknown.
Objectives
In this study, we sought to assess the relationship between stress-induced myocardial ischemia, revascularization, and all-cause mortality (ACM) among patients with normal vs low LVEF.
Methods
We evaluated 43,443 patients undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging from 1998 to 2017. Median follow-up was 11.4 years. Myocardial ischemia was assessed for its interaction between early revascularization and mortality. A propensity score was used to adjust for nonrandomization to revascularization, followed by multivariable Cox modeling adjusted for the propensity score and clinical variables to predict ACM.
Results
The frequency of myocardial ischemia varied markedly according to LVEF and angina, ranging from 6.7% among patients with LVEF ≥55% and no typical angina to 64.0% among patients with LVEF <45% and typical angina (P < 0.001). Among 39,883 patients with LVEF ≥45%, early revascularization was associated with increased mortality risk among patients without ischemia and lower mortality risk among patients with severe (≥15%) ischemia (HR: 0.70; 95% CI: 0.52-0.95). Among 3,560 patients with LVEF <45%, revascularization was not associated with mortality benefit among patients with no or mild ischemia, and was associated with decreased mortality among patients with moderate (10%-14%) (HR: 0.67; 95% CI: 0.49-0.91) and severe (≥15%) (HR: 0.55; 95% CI: 0.38-0.80) ischemia.
Conclusions
Within this cohort, early myocardial revascularization was associated with a significant reduction in mortality among both patients with normal LVEF and severe inducible myocardial ischemia and patients with low LVEF and moderate or severe inducible myocardial ischemia.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 19 Jul 2022; 80:202-215
Rozanski A, Miller RJH, Gransar H, Han D, ... Thomson L, Berman DS
J Am Coll Cardiol: 19 Jul 2022; 80:202-215 | PMID: 35835493
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Abstract

Criteria for Defining Stages of Cardiogenic Shock Severity.

Kapur NK, Kanwar M, Sinha SS, Thayer KL, ... Blumer V, Burkhoff D
Background
Risk-stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks uniform criteria defining each stage.
Objectives
The purpose of this study was to test parameters that define SCAI stages and explore their utility as predictors of in-hospital mortality in CS.
Methods
The CS Working Group registry includes patients from 17 hospitals enrolled between 2016 and 2021 and was used to define clinical profiles for CS. We selected parameters of hypotension and hypoperfusion and treatment intensity, confirmed their association with mortality, then defined formal criteria for each stage and tested the association between both baseline and maximum Stage and mortality.
Results
Of 3,455 patients, CS was caused by heart failure (52%) or myocardial infarction (32%). Mortality was 35% for the total cohort and higher among patients with myocardial infarction, out-of-hospital cardiac arrest, and treatment with increasing numbers of drugs and devices. Systolic blood pressure, lactate level, alanine transaminase level, and systemic pH were significantly associated with mortality and used to define each stage. Using these criteria, baseline and maximum stages were significantly associated with mortality (n = 1,890). Lower baseline stage was associated with a higher incidence of stage escalation and a shorter duration of time to reach maximum stage.
Conclusions
We report a novel approach to define SCAI stages and identify a significant association between baseline and maximum stage and mortality. This approach may improve clinical application of the staging system and provides new insight into the trajectory of hospitalized CS patients. (Cardiogenic Shock Working Group Registry [CSWG]; NCT04682483).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 19 Jul 2022; 80:185-198
Kapur NK, Kanwar M, Sinha SS, Thayer KL, ... Blumer V, Burkhoff D
J Am Coll Cardiol: 19 Jul 2022; 80:185-198 | PMID: 35835491
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Abstract

Contributions of the Women\'s Health Initiative to Cardiovascular Research: JACC State-of-the-Art Review.

LaMonte MJ, Manson JE, Anderson GL, Baker LD, ... Rossouw JE, WHI Investigators
The WHI (Women\'s Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2022; 80:256-275
LaMonte MJ, Manson JE, Anderson GL, Baker LD, ... Rossouw JE, WHI Investigators
J Am Coll Cardiol: 19 Jul 2022; 80:256-275 | PMID: 35835498
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Abstract

Subclinical Atherosclerosis in Young, Socioeconomically Vulnerable Hispanic and Non-Hispanic Black Adults.

Iglesies-Grau J, Fernandez-Jimenez R, Diaz-Munoz R, Jaslow R, ... Fayad ZA, Fuster V
Background
Non-Hispanic Black persons are at greater risk of cardiovascular (CV) events than other racial/ethnic groups; however, their differential vulnerability to early subclinical atherosclerosis is poorly understood.
Objectives
This work aims to study the impact of race/ethnicity on early subclinical atherosclerosis in young socioeconomically disadvantaged adults.
Methods
Bilateral carotid and femoral 3-dimensional vascular ultrasound examinations were performed on 436 adults (parents/caregivers and staff) with a mean age of 38.0 ± 11.1 years, 82.3% female, 66% self-reported as Hispanic, 34% self-reported as non-Hispanic Black, and no history of CV disease recruited in the FAMILIA (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health) trial from 15 Head Start preschools in Harlem (neighborhood in New York, New York, USA). The 10-year Framingham CV risk score was calculated, and the relationship between race/ethnicity and the presence and extent of subclinical atherosclerosis was analyzed with multivariable logistic and linear regression models.
Results
The mean 10-year Framingham CV risk was 4.0%, with no differences by racial/ethnic category. The overall prevalence of subclinical atherosclerosis was significantly higher in the non-Hispanic Black (12.9%) than in the Hispanic subpopulation (6.6%). After adjusting for 10-year Framingham CV risk score, body mass index, fruit and vegetable consumption, physical activity, and employment status, non-Hispanic Black individuals were more likely than Hispanic individuals to have subclinical atherosclerosis (OR: 3.45; 95% CI: 1.44-8.29; P = 0.006) and multiterritorial disease (P = 0.026).
Conclusions
After adjustment for classic CV risk, lifestyle, and socioeconomic factors, non-Hispanic Black younger adults seem more vulnerable to early subclinical atherosclerosis than their Hispanic peers, suggesting that the existence of emerging or undiscovered CV factors underlying the residual excess risk (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health [FAMILIA (Project 2)]; NCT02481401).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2022; 80:219-229
Iglesies-Grau J, Fernandez-Jimenez R, Diaz-Munoz R, Jaslow R, ... Fayad ZA, Fuster V
J Am Coll Cardiol: 19 Jul 2022; 80:219-229 | PMID: 35835495
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Abstract

Criteria for Referral of Patients With Advanced Heart Failure for Specialized Palliative Care.

Chang YK, Allen LA, McClung JA, Denvir MA, ... Collins A, Hui D
Background
Patients with advanced heart failure have substantial supportive care needs. Specialist palliative care can be beneficial, but it is unclear who is most appropriate for referral and when patients should be referred.
Objectives
We conducted a Delphi study of international experts to identify consensus referral criteria for specialist palliative care for patients with advanced heart failure.
Methods
Clinicians from 5 continents with expertise in the integration of cardiology and palliative care were asked to rate 34 disease-based, 24 needs-based, and 9 time-based criteria over 3 rounds. Consensus was defined a priori as ≥70% agreement. A criterion was coded as major if the experts endorsed that meeting that criterion alone was adequate to justify a referral.
Results
The response rate was 44 of 46 (96%), 41 of 46 (89%), and 43 of 46 (93%) in the first, second, and third rounds, respectively. Panelists reached consensus on 25 major criteria for specialist palliative care referral. The 25 major criteria were categorized under 6 topics, including \"advanced/refractory heart failure, comorbidities, and complications\" (eg, cardiac cachexia, cardiorenal syndrome) (n = 8), \"advanced heart failure therapies\" (eg, chronic inotropes, precardiac transplant) (n = 4), \"hospital utilization\" (eg, emergency room visits, hospitalization) (n = 2), \"prognostic estimate\" (n = 1), \"symptom burden/distress\" (eg, severe physical/emotional/spiritual distress) (n = 6), and \"decision making/social support\" (eg, goals-of-care discussions) (n = 4). The majority (68%) of major criteria had ≥90% agreement.
Conclusions
International experts reached consensus on a large number of criteria for referral to specialist palliative care. With further validation, these criteria may be useful for standardizing palliative care access in the inpatient and/or outpatient settings.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:332-344
Chang YK, Allen LA, McClung JA, Denvir MA, ... Collins A, Hui D
J Am Coll Cardiol: 26 Jul 2022; 80:332-344 | PMID: 35863850
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Abstract

Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy.

Goette A, Borof K, Breithardt G, Camm AJ, ... Kirchhof P, EAST-AFNET 4 Investigators
Background
Whether atrial fibrillation (AF) pattern or timing of AF therapy modifies the effectiveness of early rhythm control (ERC) is not known.
Objectives
This study sought to compare clinical characteristics and outcomes in patients presenting with different AF patterns on ERC vs usual care.
Methods
The effects of ERC were compared in first-diagnosed AF (FDAF), paroxysmal AF (paroxAF), and persistent AF (persAF) in this prespecified analysis of the EAST-AFNET 4 (Early treatment of atrial fibrillation for stroke prevention) trial. Associations between AF pattern and primary outcomes (first primary outcome: cardiovascular death, stroke, and hospitalization for heart failure and acute coronary syndrome; second primary outcome: nights spent in hospital per year) were compared over a mean follow-up of 5.1 years. Changes in health-related quality of life were assessed by the EQ-5D.
Results
FDAF patients (n = 1,048, enrolled 7 days after diagnosing AF) were slightly older (71 years of age, 48.0% female) than patients with paroxAF (n = 994, 70 years of age, 50.0% female) and persAF (n = 743, 70 years of age, 38.0% female). ERC reduced the primary outcome in all 3 AF patterns. Hospitalizations for acute coronary syndrome were highest in FDAF (incidence rate ratio [IRR]: 1.50; 95% CI: 0.83-2.69; P for interaction = 0.032) compared with paroxAF (IRR: 0.64; 95% CI: 0.32-1.25) and persAF (IRR: 0.50; 95% CI: 0.25-1.00). FDAF patients spent more nights in hospital (IRR: 1.38; 95% CI: 1.12-1.70; P for interaction = 0.004) than paroxAF (IRR: 0.84; 95% CI: 0.67-1.03), and persAF (IRR: 1.02; 95% CI: 0.80-1.30) patients. ERC improved health-related quality of life (EQ-5D score) in patients with paroxAF and persAF but not in patients with FDAF (P = 0.019).
Conclusions
ERC reduces the first primary composite outcome in all AF patterns. Patients with FDAF are at high risk for hospitalization and acute coronary syndrome, particularly on ERC. (Early treatment of atrial fibrillation for stroke prevention trial; ISRCTN04708680; Early Treatment of Atrial Fibrillation for Stroke Prevention Trial [EAST]; NCT01288352; Early treatment of Atrial fibrillation for Stroke prevention Trial [EAST]; EudraCT2010-021258-20).

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

J Am Coll Cardiol: 26 Jul 2022; 80:283-295
Goette A, Borof K, Breithardt G, Camm AJ, ... Kirchhof P, EAST-AFNET 4 Investigators
J Am Coll Cardiol: 26 Jul 2022; 80:283-295 | PMID: 35863844
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Abstract

Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.

Choi D, Waksman O, Shaik A, Mar P, ... Goonewardena SN, Rosenson RS
Background
Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19.
Objectives
This study sought to determine the association between estimated BV (eBV) and mortality among hospitalized COVID-19 patients.
Methods
The study population included 5,621 hospitalized COVID-19 patients at the Mount Sinai Health System from February 27, 2020, to November 27, 2021. eBV was calculated using the Walburn-Schneck model. Multivariate Cox proportional hazards models were used to evaluate the association between eBV and mortality. Considered covariates included age, sex, race, cardiovascular and metabolic comorbidities, in-house pharmacotherapy, and baseline inflammatory biomarkers.
Results
Estimated high-shear BV (eHSBV) and estimated low-shear BV were associated with increased in-hospital mortality. One-centipoise increases in eHSBV and estimated low-shear BV were associated with a 36.0% and 7.0% increase in death, respectively (P < 0.001). Compared with participants in the lowest quartile of eHSBV, those in the highest quartile of eHSBV had higher mortality (adjusted HR: 1.53; 95% CI: 1.27-1.84). The association was consistent among multiple subgroups, notably among patients without any comorbidities (adjusted HR: 1.69; 95% CI: 1.28-2.22).
Conclusions
Among hospitalized COVID-19 patients, increased eBV is significantly associated with higher mortality. This suggests that eBV can prognosticate patient outcomes in earlier stages of COVID-19, and that future therapeutics aimed at reducing WBV should be evaluated.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:316-328
Choi D, Waksman O, Shaik A, Mar P, ... Goonewardena SN, Rosenson RS
J Am Coll Cardiol: 26 Jul 2022; 80:316-328 | PMID: 35863848
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Abstract

Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults.

Barhoum P, Pineton de Chambrun M, Dorgham K, Kerneis M, ... Gorochov G, Hékimian G
Background
Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19-related myocarditis.
Objectives
This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19-related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A-).
Methods
A monocentric retrospective analysis of consecutive fulminant COVID-19-related myocarditis in a 26-bed intensive care unit (ICU).
Results
Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19-related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A- patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A- patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A- had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A- patients (54%) but in none of the MIS-A+ patients.
Conclusion
MIS-A+ and MIS-A- fulminant COVID-19-related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients\' management and further understanding of their pathophysiology.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:299-312
Barhoum P, Pineton de Chambrun M, Dorgham K, Kerneis M, ... Gorochov G, Hékimian G
J Am Coll Cardiol: 26 Jul 2022; 80:299-312 | PMID: 35863846
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Abstract

Spatially Distinct Genetic Determinants of Aortic Dimensions Influence Risks of Aneurysm and Stenosis.

Nekoui M, Pirruccello JP, Di Achille P, Choi SH, ... Lindsay ME, Ellinor PT
Background
The left ventricular outflow tract (LVOT) and ascending aorta are spatially complex, with distinct pathologies and embryologic origins. Prior work examined the genetics of thoracic aortic diameter in a single plane.
Objectives
We sought to elucidate the genetic basis for the diameter of the LVOT, aortic root, and ascending aorta.
Methods
Using deep learning, we analyzed 2.3 million cardiac magnetic resonance images from 43,317 UK Biobank participants. We computed the diameters of the LVOT, the aortic root, and at 6 locations of ascending aorta. For each diameter, we conducted a genome-wide association study and generated a polygenic score. Finally, we investigated associations between these scores and disease incidence.
Results
A total of 79 loci were significantly associated with at least 1 diameter. Of these, 35 were novel, and most were associated with 1 or 2 diameters. A polygenic score of aortic diameter approximately 13 mm from the sinotubular junction most strongly predicted thoracic aortic aneurysm (n = 427,016; mean HR: 1.42 per SD; 95% CI: 1.34-1.50; P = 6.67 × 10-21). A polygenic score predicting a smaller aortic root was predictive of aortic stenosis (n = 426,502; mean HR: 1.08 per SD; 95% CI: 1.03-1.12; P = 5 × 10-6).
Conclusions
We detected distinct genetic loci underpinning the diameters of the LVOT, aortic root, and at several segments of ascending aorta. We spatially defined a region of aorta whose genetics may be most relevant to predicting thoracic aortic aneurysm. We further described a genetic signature that may predispose to aortic stenosis. Understanding genetic contributions to proximal aortic diameter may enable identification of individuals at risk for aortic disease and facilitate prioritization of therapeutic targets.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Aug 2022; 80:486-497
Nekoui M, Pirruccello JP, Di Achille P, Choi SH, ... Lindsay ME, Ellinor PT
J Am Coll Cardiol: 02 Aug 2022; 80:486-497 | PMID: 35902171
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Abstract

Effects of Cyproheptadine on Mitral Valve Remodeling and Regurgitation After Myocardial Infarction.

Marsit O, Clavel MA, Paquin A, Deschênes V, ... Pibarot P, Beaudoin J
Background
Ischemic mitral regurgitation (MR) is primarily caused by left ventricle deformation, but leaflet thickening with fibrotic changes are also observed in the valve. Increased levels of 5-hydroxytryptamine (5-HT; ie, serotonin) are described after myocardial infarction (MI); 5-HT can induce valve fibrosis through the 5-HT type 2B receptor (5-HT2BR).
Objectives
This study aims to test the hypothesis that post-MI treatment with cyproheptadine (5-HT2BR antagonist) can prevent ischemic MR by reducing the effect of serotonin on mitral biology.
Methods
Thirty-six sheep were divided into 2 groups: inferior MI and inferior MI treated with cyproheptadine (0.5 mg/kg/d). Animals were followed for 90 days. Blood 5-HT, infarct size, left ventricular volume and function, MR fraction and mitral leaflet size were assessed. In a complementary in vitro study, valvular interstitial cells were exposed to pre-MI and post-MI serum collected from the experimental animals.
Results
Increased 5-HT levels were observed after MI in nontreated animals, but not in the group treated with cyproheptadine. Infarct size was similar in both groups (11 ± 3 g vs 9 ± 5 g; P = 0.414). At 90 days, MR fraction was 16% ± 7% in the MI group vs 2% ± 6% in the cyproheptadine group (P = 0.0001). The increase in leaflet size following MI was larger in the cyproheptadine group (+40% ± 9% vs +22% ± 12%; P = 0.001). Mitral interstitial cells overexpressed extracellular matrix genes when treated with post-MI serum, but not when exposed to post-MI serum collected from treated animals.
Conclusions
Cyproheptadine given after inferior MI reduces post-MI 5-HT levels, prevents valvular fibrotic remodeling, is associated with larger increase in mitral valve size and less MR.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Aug 2022; 80:500-510
Marsit O, Clavel MA, Paquin A, Deschênes V, ... Pibarot P, Beaudoin J
J Am Coll Cardiol: 02 Aug 2022; 80:500-510 | PMID: 35902173
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Abstract

Coronary In-Stent Restenosis: JACC State-of-the-Art Review.

Giustino G, Colombo A, Camaj A, Yasumura K, ... Kini A, Sharma SK
The introduction and subsequent iterations of drug-eluting stent technologies have substantially improved the efficacy and safety of percutaneous coronary interventions. However, the incidence of in-stent restenosis (ISR) and the resultant need for repeated revascularization still occur at a rate of 1%-2% per year. Given that millions of drug-eluting stents are implanted each year around the globe, ISR can be considered as a pathologic entity of public health significance. The mechanisms of ISR are multifactorial. Since the first description of the angiographic patterns of ISR, the advent of intracoronary imaging has further elucidated the mechanisms and patterns of ISR. The armamentarium and treatment strategies of ISR have also evolved over time. Currently, an individualized approach using intracoronary imaging to characterize the underlying substrate of ISR is recommended. In this paper, we comprehensively reviewed the incidence, mechanisms, and imaging characterization of ISR and propose a contemporary treatment algorithm.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:348-372
Giustino G, Colombo A, Camaj A, Yasumura K, ... Kini A, Sharma SK
J Am Coll Cardiol: 26 Jul 2022; 80:348-372 | PMID: 35863852
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Abstract

Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure.

Dukkipati SR, Holmes DR, Doshi SK, Kar S, ... Allocco DJ, Reddy VY
Background
In the U.S. Food and Drug Administration (FDA) clinical trials of left atrial appendage (LAA) closure, a postimplantation peridevice leak (PDL) of ≤5 mm (PDL≤5) was accepted as sufficient LAA \"closure.\" However, the clinical consequences of these PDLs on subsequent thromboembolism are poorly characterized.
Objectives
We sought to assess the impact of PDL≤5 on clinical outcomes after implantation of the Watchman device.
Methods
Using combined data from the FDA studies PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy), and CAP2 (Continued Access to PREVAIL), we assessed patients with successful device implantation for PDL by means of protocol-mandated transesophageal echocardiograms (TEEs) at 45 days and 1 year. Five-year outcomes were assessed as a function of the absence or presence of PDL≤5.
Results
The cohort included 1,054 patients: mean age 74 ± 8.3 years, 65% male, and CHA2DS2-VASc 4.1 ± 1.4. TEE imaging at 45 days revealed 634 patients (60.2%) without and 404 (38.3%) with PDL≤5, and 1-year TEE revealed 704 patients (71.6%) without and 272 (27.7%) with PDL≤5. The presence of PDL≤5 at 1 year, but not at 45 days, was associated with an increased 5-year risk of ischemic stroke or systemic embolism (adjusted HR: 1.94; 95% CI: 1.15-3.29; P = 0.014), largely driven by an increase in nondisabling stroke (HR: 1.97; 95% CI: 1.03-3.78; P = 0.04), while disabling or fatal stroke rates were similar (HR: 0.69; 95% CI: 0.19-2.46; P = 0.56). PDL≤5 was not associated with an increased risk of cardiovascular or unexplained death (HR: 1.20; P = 0.45) or all-cause death (HR: 0.87; P = 0.42).
Conclusions
PDL≤5 at 1 year after percutaneous LAA closure with the Watchman device are associated with increased thromboembolism, driven by increased nondisabling stroke, but similar mortality. (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [PROTECT-AF; NCT00129545]; Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy [PREVAIL; NCT01182441]; Continued Access to PREVAIL [CAP2; NCT01760291]).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 02 Aug 2022; 80:469-483
Dukkipati SR, Holmes DR, Doshi SK, Kar S, ... Allocco DJ, Reddy VY
J Am Coll Cardiol: 02 Aug 2022; 80:469-483 | PMID: 35902169
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Abstract

New Cardiovascular Risk Assessment Techniques for Primary Prevention: JACC Review Topic of the Week.

Verma KP, Inouye M, Meikle PJ, Nicholls SJ, Carrington MJ, Marwick TH
Risk factor-based models fail to accurately estimate risk in select populations, in particular younger individuals. A sizable number of people are also classified as being at intermediate risk, for whom the optimal preventive strategy could be more precise. Several personalized risk prediction tools, including coronary artery calcium scoring, polygenic risk scores, and metabolic risk scores may be able to improve risk assessment, pending supportive outcome data from clinical trials. Other tools may well emerge in the near future. A multidimensional approach to risk prediction holds the promise of precise risk prediction. This could allow for targeted prevention minimizing unnecessary costs and risks while maximizing benefits. High-risk individuals could also be identified early in life, creating opportunities to arrest the development of nascent coronary atherosclerosis and prevent future clinical events.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:373-387
Verma KP, Inouye M, Meikle PJ, Nicholls SJ, Carrington MJ, Marwick TH
J Am Coll Cardiol: 26 Jul 2022; 80:373-387 | PMID: 35863853
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Abstract

Standardized Definitions for Bioprosthetic Valve Dysfunction Following Aortic or Mitral Valve Replacement: JACC State-of-the-Art Review.

Pibarot P, Herrmann HC, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
Bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF) may be caused by structural or nonstructural valve dysfunction. Both surgical and transcatheter bioprosthetic valves have limited durability because of structural valve deterioration. The main objective of this summary of experts participating in a virtual workshop was to propose standardized definitions for nonstructural and structural BVD and BVF following aortic or mitral biological valve replacement with the goal of facilitating research reporting and implementation of these terms in clinical practice. Definitions of structural BVF, based on valve reintervention or death, underestimate the true incidence of BVF. However, definitions solely based on the presence of high transprosthetic gradient at a given echocardiogram during follow-up overestimate the incidence of structural BVD and BVF. Definitions of aortic or mitral structural BVD must therefore include the confirmation by imaging of permanent structural changes to the leaflets alongside evidence of deterioration in valve hemodynamic function at echocardiography follow-up.

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

J Am Coll Cardiol: 02 Aug 2022; 80:545-561
Pibarot P, Herrmann HC, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
J Am Coll Cardiol: 02 Aug 2022; 80:545-561 | PMID: 35902178
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