Journal: J Am Coll Cardiol

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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

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

Worldwide Disparities in Recovery of Cardiac Testing 1 Year Into COVID-19.

Einstein AJ, Hirschfeld C, Williams MC, Vitola JV, ... Paez D, INCAPS COVID 2 Investigators Group
Background
The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown.
Objectives
The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide.
Methods
The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic\'s onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery.
Results
Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians\' psychological stress were significant in predicting recovery of cardiac testing.
Conclusions
Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing.

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

J Am Coll Cardiol: 24 May 2022; 79:2001-2017
Einstein AJ, Hirschfeld C, Williams MC, Vitola JV, ... Paez D, INCAPS COVID 2 Investigators Group
J Am Coll Cardiol: 24 May 2022; 79:2001-2017 | PMID: 35589162
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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

Diagnosis and Management of Infective Endocarditis in People Who Inject Drugs: JACC State-of-the-Art Review.

Yucel E, Bearnot B, Paras ML, Zern EK, ... Wakeman SE, Sundt T
The incidence of injection drug use-associated infective endocarditis has been increasing rapidly over the last decade. Patients with drug use-associated infective endocarditis present an increasingly common clinical challenge with poor long-term outcomes and high reinfection and readmission rates. Their care raises issues unique to this population, including antibiotic selection and administration, indications for and ethical issues surrounding surgical intervention, and importantly management of the underlying substance use disorder to minimize the risk of reinfection. Successful treatment of these patients requires a broad understanding of these concerns. A multidisciplinary, collaborative approach providing a holistic approach to treating both the acute infection along with effectively addressing substance use disorder is needed to improve short-term and longer-term outcomes.

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

J Am Coll Cardiol: 24 May 2022; 79:2037-2057
Yucel E, Bearnot B, Paras ML, Zern EK, ... Wakeman SE, Sundt T
J Am Coll Cardiol: 24 May 2022; 79:2037-2057 | PMID: 35589166
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Abstract

Sodium Glucose Cotransporter-2 Inhibition for Acute Myocardial Infarction: JACC Review Topic of the Week.

Udell JA, Jones WS, Petrie MC, Harrington J, ... Hernandez AF, Butler J
Sodium glucose cotransporter-2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and chronic heart failure. SGLT2 inhibitors also reduce the risk of cardiovascular mortality and hospitalization for heart failure among patients with type 2 diabetes mellitus and a remote history of myocardial infarction (MI). As a result of the growing body of evidence in diverse disease states, and the hypothesized mechanisms of action, it is reasonable to consider the potential of SGLT2 inhibition to improve outcomes in patients with acute MI as well if initiated early after presentation. Whether these therapies are efficacious and safe to use early in the course of acute coronary heart disease remains relatively unexplored. Here, we describe the contemporary data and continuing evidence gap for considering the use of SGLT2 inhibitors early following an acute MI to reduce cardiovascular morbidity and mortality.

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

J Am Coll Cardiol: 24 May 2022; 79:2058-2068
Udell JA, Jones WS, Petrie MC, Harrington J, ... Hernandez AF, Butler J
J Am Coll Cardiol: 24 May 2022; 79:2058-2068 | PMID: 35589167
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Abstract

Distribution of Coronary Artery Calcium by Age, Sex, and Race Among Patients 30-45 Years Old.

Javaid A, Dardari ZA, Mitchell JD, Whelton SP, ... Villines TC, Blaha MJ
Background
Coronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged <45 years.
Objectives
The purpose of this study was to determine the probability of CAC >0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years.
Methods
We harmonized 3 datasets-CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort-to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques.
Results
The prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile.
Conclusions
In a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.

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

J Am Coll Cardiol: 17 May 2022; 79:1873-1886
Javaid A, Dardari ZA, Mitchell JD, Whelton SP, ... Villines TC, Blaha MJ
J Am Coll Cardiol: 17 May 2022; 79:1873-1886 | PMID: 35550683
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Abstract

Location of Aortic Enlargement and Risk of Type A Dissection at Smaller Diameters.

Ganapathi AM, Ranney DN, Peterson MD, Lindsay ME, ... Isselbacher EM, Hughes GC
Background
Previous work has demonstrated that more than one-half of acute type A aortic dissections (ATADs) occur at a maximal aortic diameter (MAD) of <5.5 cm. However, no analysis has investigated whether ATAD risk at smaller MADs is more common with modest dilation of the aortic root (AR) or supracoronary ascending aorta (AA) in patients without genetically triggered aortopathy.
Objectives
This study sought to determine if the segment of modest aortic dilation affects risk of ATAD.
Methods
Using the International Registry of Acute Aortic Dissection (IRAD) database from May 1996 to October 2016, we identified 667 ATAD patients with MAD <5.5 cm. Patients were stratified by location of the largest proximal aortic segment (AR or AA). Patients with known genetically triggered aortopathy were excluded. MADs at time of dissection were compared between AR and AA groups. Secondary outcomes included operation, postoperative outcomes, and long-term survival.
Results
Of patients with ATAD at an MAD <5.5 cm, 79.5% (n = 530) were in the AA group and 20.5% (n = 137) in the AR group. Modestly dilated ARs (median MAD 4.6 cm [IQR: 4.1-5.0 cm]) dissected at a significantly smaller diameter than modestly dilated AAs (median MAD 4.8 cm [IQR: 4.4-5.1 cm]) (P < 0.01). AR patients were significantly younger than AA patients (58.5 ± 13.0 years vs 63.2 ± 13.3 years; P < 0.01) and more commonly male (78% vs 65%; P < 0.01). Postoperative and long-term outcomes did not differ between groups.
Conclusions
ATAD appears to occur at smaller diameters in patients with modest dilation in the AR vs the AA (4.6 vs 4.8 cm). These findings may have implications for future consensus guidelines regarding the management of patients with aortic disease.

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

J Am Coll Cardiol: 17 May 2022; 79:1890-1897
Ganapathi AM, Ranney DN, Peterson MD, Lindsay ME, ... Isselbacher EM, Hughes GC
J Am Coll Cardiol: 17 May 2022; 79:1890-1897 | PMID: 35550685
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Abstract

Cardiovascular Risk Factors Mediate the Long-Term Maternal Risk Associated With Hypertensive Disorders of Pregnancy.

Stuart JJ, Tanz LJ, Rimm EB, Spiegelman D, ... Rexrode KM, Rich-Edwards JW
Background
Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, are associated with an increased risk of CVD.
Objectives
The purpose of this study was to evaluate associations between HDP and long-term CVD and identify the proportion of the association mediated by established CVD risk factors.
Methods
Parous participants without CVD in the Nurses\' Health Study II (n = 60,379) were followed for incident CVD from first birth through 2017. Cox proportional hazards models estimated HRs and 95% CIs for the relationship between HDP and CVD, adjusting for potential confounders, including prepregnancy body mass index, smoking, and parental history of CVD. To evaluate the proportion of the association jointly accounted for by chronic hypertension, hypercholesterolemia, type 2 diabetes, and changes in body mass index, we used the difference method.
Results
Women with HDP in first pregnancy had a 63% higher rate of CVD (95% CI: 1.37-1.94) compared with women with normotensive pregnancies. This association was mediated by established CVD risk factors (proportion mediated = 64%). The increased rate of CVD was higher for preeclampsia (HR: 1.72; 95% CI: 1.42-2.10) than gestational hypertension (HR: 1.41; 95% CI: 1.03-1.93). Established CVD risk factors accounted for 57% of the increased rate of CVD for preeclampsia but 84% for gestational hypertension (both P < 0.0001).
Conclusions
Established CVD risk factors arising after pregnancy explained most (84%) of the increased risk of CVD conferred by gestational hypertension and 57% of the risk among women with preeclampsia. Screening for chronic hypertension, hypercholesterolemia, type 2 diabetes, and overweight/obesity after pregnancy may be especially helpful in CVD prevention among women with a history of HDP.

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

J Am Coll Cardiol: 17 May 2022; 79:1901-1913
Stuart JJ, Tanz LJ, Rimm EB, Spiegelman D, ... Rexrode KM, Rich-Edwards JW
J Am Coll Cardiol: 17 May 2022; 79:1901-1913 | PMID: 35550687
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Abstract

Burden of Pediatric Heart Failure in the United States.

Amdani S, Marino BS, Rossano J, Lopez R, Schold JD, Tang WHW
Background
There are currently limited accurate national estimates for pediatric heart failure (HF).
Objectives
This study aims to describe the current burden of primary and comorbid pediatric HF in the United States.
Methods
International Classification of Diseases, Clinical Modification codes were used to identify HF cases and comorbidities from the Kids\' Inpatient Database, National Inpatient Sample, National Emergency Department (ED) Sample, and National Vital Statistics System for 2012 and 2016. To describe HF events, all visits/events among pediatric and adult subjects were included in the analysis. HF events were classified into 1 of 3 groups: 1) no HF; 2) primary HF; or 3) comorbid HF. We compared patients with and without HF and calculated unique event rates with age and sex standardization.
Results
Congenital heart disease, conduction disorders/arrhythmias, and cardiomyopathy were responsible for the majority of pediatric HF-related ED visits and hospitalizations. Compared to 2012, in 2016, there was an increase in comorbid HF ED visits (rate ratio: 1.93; P < 0.001) and primary HF hospitalizations (rate ratio: 1.14; P = 0.002). Pediatric HF burden was lower compared to adult HF; however, deaths in the ED and in-hospital were significantly more likely in children presenting with HF than adults.
Conclusions
The burden of pediatric HF continues to increase. Compared to adults with HF presenting to the ED and in-hospital, outcomes are inferior and per patient resource use is higher for children hospitalized with HF. National initiatives to understand risk factors for morbidity and mortality in pediatric HF and continued surveillance and mitigation of preventable risk factors may attenuate this uptrend.

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

J Am Coll Cardiol: 17 May 2022; 79:1917-1928
Amdani S, Marino BS, Rossano J, Lopez R, Schold JD, Tang WHW
J Am Coll Cardiol: 17 May 2022; 79:1917-1928 | PMID: 35550689
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Abstract

The Increasing Role of Rhythm Control in Patients With Atrial Fibrillation: JACC State-of-the-Art Review.

Camm AJ, Naccarelli GV, Mittal S, Crijns HJGM, ... Turakhia MP, Kirchhof P
The considerable mortality and morbidity associated with atrial fibrillation (AF) pose a substantial burden on patients and health care services. Although the management of AF historically focused on decreasing AF recurrence, it evolved over time in favor of rate control. Recently, more emphasis has been placed on reducing adverse cardiovascular outcomes using rhythm control, generally by using safe and effective rhythm-control therapies (typically antiarrhythmic drugs and/or AF ablation). Evidence increasingly supports early rhythm control in patients with AF that has not become long-standing, but current clinical practice and guidelines do not yet fully reflect this change. Early rhythm control may effectively reduce irreversible atrial remodeling and prevent AF-related deaths, heart failure, and strokes in high-risk patients. It has the potential to halt progression and potentially save patients from years of symptomatic AF; therefore, it should be offered more widely.

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

J Am Coll Cardiol: 17 May 2022; 79:1932-1948
Camm AJ, Naccarelli GV, Mittal S, Crijns HJGM, ... Turakhia MP, Kirchhof P
J Am Coll Cardiol: 17 May 2022; 79:1932-1948 | PMID: 35550691
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Abstract

Anticoagulation for Percutaneous Ventricular Assist Device-Supported Cardiogenic Shock: JACC Review Topic of the Week.

Vandenbriele C, Arachchillage DJ, Frederiks P, Giustino G, ... Price S, Chieffo A
Interest in the use of mechanical circulatory support for patients presenting with cardiogenic shock is growing rapidly. The Impella (Abiomed Inc), a microaxial, continuous-flow, short-term, ventricular assist device (VAD), requires meticulous postimplantation management. Because systemic anticoagulation is needed to prevent pump thrombosis, patients are exposed to increased bleeding risk, further aggravated by sepsis, thrombocytopenia, and high shear stress-induced acquired von Willebrand syndrome. The precarious balance between bleeding and thrombosis in percutaneous VAD-supported cardiogenic shock patients is often the main reason that patient outcomes are jeopardized, and there is a lack of data addressing optimal anticoagulation management strategies during percutaneous VAD support. Here, we present a parallel anti-Factor Xa/activated partial thromboplastin time-guided anticoagulation algorithm and discuss pitfalls of heparin monitoring in critically ill patients. This review will guide physicians toward a more standardized (anti)coagulation approach to tackle device-related morbidity and mortality in this critically ill patient group.

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

J Am Coll Cardiol: 17 May 2022; 79:1949-1962
Vandenbriele C, Arachchillage DJ, Frederiks P, Giustino G, ... Price S, Chieffo A
J Am Coll Cardiol: 17 May 2022; 79:1949-1962 | PMID: 35550692
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Abstract

Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement.

Généreux P, Pibarot P, Redfors B, Bax JJ, ... Leon MB, Cohen DJ
Background
The impact of aortic valve replacement (AVR) on progression/regression of extra-valvular cardiac damage and its association with subsequent prognosis is unknown.
Objectives
To describe evolution of cardiac damage post-AVR and its association with outcomes.
Methods
Patients undergoing transcatheter or surgical AVR from the PARTNER 2 and 3 trials were pooled and classified by cardiac damage stage at baseline and 1-year (Stage 0, no damage; Stage 1, left ventricular damage; Stage 2, left atrial or mitral valve damage; Stage 3, pulmonary vasculature or tricuspid valve damage; Stage 4, right ventricular damage). Proportional hazards models determined association between change in cardiac damage post-AVR and 2-year outcomes.
Results
Among 1974 patients, 121 (6.1%) were Stage 0, 287 (14.5%) Stage 1, 1014 (51.4%) Stage 2, 412 (20.9%) Stage 3, and 140 (7.1%) Stage 4 pre-AVR. Two-year mortality was associated with extent of cardiac damage at baseline and 1-year. Compared with baseline, cardiac damage improved in ∼15%, remained unchanged in ∼60%, and worsened in ∼25% of patients at 1-year. One-year change in cardiac damage stage was independently associated with mortality (adjHR for improvement=0.49; no change=1.0; worsening=1.95; p=0.023) and composite of death or heart failure hospitalization (adjHR for improvement=0.60; no change=1.0; worsening=2.25; p<0.001) at 2 years.
Conclusion
In patients undergoing AVR, extent of extravalvular cardiac damage at baseline and its change at 1-year have important prognostic implications. These findings suggest that earlier detection of AS and intervention prior to development of irreversible cardiac damage may improve global cardiac function and prognosis.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 14 May 2022; epub ahead of print
Généreux P, Pibarot P, Redfors B, Bax JJ, ... Leon MB, Cohen DJ
J Am Coll Cardiol: 14 May 2022; epub ahead of print | PMID: 35595203
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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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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

Antithrombotic Therapy After Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

Freeman JV, Higgins AY, Wang Y, Du C, ... Masoudi FA, Curtis JP
Background
Pivotal trials of percutaneous left atrial appendage occlusion (LAAO) used specific postprocedure treatment protocols.
Objectives
This study sought to evaluate patterns of postprocedure care after LAAO with the Watchman device in clinical practice and compare the risk of adverse events for different discharge antithrombotic strategies.
Methods
We evaluated patients in the LAAO Registry of the National Cardiovascular Data Registry who underwent LAAO with the Watchman device between 2016 and 2018. We assessed adherence to the full postprocedure trial protocol including standardized follow-up, imaging, and antithrombotic agents and then evaluated the most commonly used antithrombotic strategies and compared the rates and risk of adverse events at 45 days and 6 months by means of multivariable COX frailty regression.
Results
Among 31,994 patients undergoing successful LAAO, only 12.2% received the full postprocedure treatment protocol studied in pivotal trials; the most common protocol deviations were with discharge antithrombotic medications. The most common discharge medication strategies were warfarin and aspirin (36.9%), direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin only (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (5.0%). In multivariable Cox frailty regression, the adjusted risk of any adverse event through the 45-day follow-up visit were significantly lower for discharge on warfarin alone (HR: 0.692; 95% CI: 0.569-0.841) and DOAC alone (HR: 0.731; 95% CI: 0.574-0.930) compared with warfarin and aspirin. Warfarin alone retained lower risk at the 6-month follow-up.
Conclusions
In contemporary U.S. practice, practitioners rarely used the full U.S. Food and Drug Administration-approved postprocedure treatment protocols studied in pivotal trials of the Watchman device. Discharge after implantation on warfarin or DOAC without concomitant aspirin was associated with lower risk of adverse outcomes.

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

J Am Coll Cardiol: 10 May 2022; 79:1785-1798
Freeman JV, Higgins AY, Wang Y, Du C, ... Masoudi FA, Curtis JP
J Am Coll Cardiol: 10 May 2022; 79:1785-1798 | PMID: 35512858
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Abstract

High-Intensity Statin Use Among Patients With Atherosclerosis in the U.S.

Nelson AJ, Haynes K, Shambhu S, Eapen Z, ... Pagidipati NJ, Granger CB
Background
Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have improved the use of high-intensity statins is unknown.
Objectives
This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD.
Methods
In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities.
Results
Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence.
Conclusions
Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD.

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

J Am Coll Cardiol: 10 May 2022; 79:1802-1813
Nelson AJ, Haynes K, Shambhu S, Eapen Z, ... Pagidipati NJ, Granger CB
J Am Coll Cardiol: 10 May 2022; 79:1802-1813 | PMID: 35512860
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Abstract

Incidence of Sudden Cardiac Death in the European Union.

Jean-Philippe E, Lerner I, Valentin E, Folke F, ... Jouven X, ESCAPE-NET Investigators
Background
Although sudden cardiac death (SCD) is recognized as a high-priority public health topic, reliable estimates of the incidence of SCD or, more broadly, out-of-hospital cardiac arrest (OHCA), in the population are scarce, especially in the European Union.
Objectives
The study objective was to determine the incidence of SCD and OHCA in the European Union.
Methods
The study examined 4 large (ie, >2 million inhabitants) European population-based prospective registries collecting emergency medical services (EMS)-attended (ie, with attempted resuscitation) OHCA and SCD (OHCA without obvious extracardiac causes) for >5 consecutive years from January 2012 to December 2017 in the Paris region (France), the North Holland region (the Netherlands), the Stockholm region (Sweden), and in all of Denmark.
Results
The average annual incidence of SCD in the 4 registries ranged from 36.8 per 100,000 (95% CI: 23.5-50.1 per 100,000) to 39.7 per 100,000 (95% CI: 32.6-46.8 per 100,000). When extrapolating to each European country and accounting for age and sex, this yields to 249,538 SCD cases per year (95% CI: 155,377-343,719 SCD cases per year). The average annual incidence of OHCA in the 4 registries ranged from 47.8 per 100,000 (95% CI: 21.2-74.4 per 100,000) to 57.9 per 100,000 (95% CI: 19.6-96.3 per 100,000), corresponding to 343,496 OHCA cases per year (95% CI: 216,472-464,922 OHCA cases per year) in the European Union. Incidence rates of SCD and OHCA increased with age and were systematically higher in men compared with women.
Conclusions
By combining data from 4 large, population-based registries with at least 5 years of data collection, this study provided an estimate of the incidence of SCD and OHCA in the European Union.

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

J Am Coll Cardiol: 10 May 2022; 79:1818-1827
Jean-Philippe E, Lerner I, Valentin E, Folke F, ... Jouven X, ESCAPE-NET Investigators
J Am Coll Cardiol: 10 May 2022; 79:1818-1827 | PMID: 35512862
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Abstract

Guidelines for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes: JACC Guideline Comparison.

Kelsey MD, Nelson AJ, Green JB, Granger CB, ... McGuire DK, Pagidipati NJ
Cardiovascular disease is a leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus. These high-risk patients benefit from aggressive risk factor management, with blood pressure and low-density lipoprotein-cholesterol treatment, glycemic control, kidney protection, and lifestyle intervention. There are several recommendation and guideline documents across cardiology, endocrinology, nephrology, and general medicine professional societies from the United States and Europe with recommendations for cardiovascular risk reduction in patients with type 2 diabetes mellitus. Although there are some noteworthy differences, particularly in risk stratification, low-density lipoprotein-cholesterol and blood pressure treatment targets, and the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, overall there is considerable alignment across recommendations from different professional societies.

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

J Am Coll Cardiol: 10 May 2022; 79:1849-1857
Kelsey MD, Nelson AJ, Green JB, Granger CB, ... McGuire DK, Pagidipati NJ
J Am Coll Cardiol: 10 May 2022; 79:1849-1857 | PMID: 35512864
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Abstract

Venous Tone and Stressed Blood Volume in Heart Failure: JACC Review Topic of the Week.

Fudim M, Kaye DM, Borlaug BA, Shah SJ, ... Sunagawa K, Burkhoff D
A number of pathologic processes contribute to the elevation in cardiac filling pressures in heart failure (HF), including myocardial dysfunction and primary volume overload. In this review, we discuss the important role of the venous system and the concepts of stressed blood volume and unstressed blood volume. We review how regulation of venous tone modifies the distribution of blood between these 2 functional compartments, the physical distribution of blood between the pulmonary and systemic circulations, and how these relate to the hemodynamic abnormalities observed in HF. Finally, we review recently applied methods for estimating stressed blood volume and how they are being applied to the results of clinical studies to provide new insights into resting and exercise hemodynamics and therapeutics for HF.

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

J Am Coll Cardiol: 10 May 2022; 79:1858-1869
Fudim M, Kaye DM, Borlaug BA, Shah SJ, ... Sunagawa K, Burkhoff D
J Am Coll Cardiol: 10 May 2022; 79:1858-1869 | PMID: 35512865
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Abstract

Survival Following Alcohol Septal Ablation or Septal Myectomy for Patients With Obstructive Hypertrophic Cardiomyopathy.

Cui H, Schaff HV, Wang S, Lahr BD, ... Ommen SR, Maron MS
Background
There is little information regarding long-term mortality comparing the 2 most common procedures for septal reduction for obstructive hypertrophic cardiomyopathy (HCM), alcohol septal ablation (ASA), and septal myectomy.
Objectives
This study sought to compare the long-term mortality of patients with obstructive HCM following septal myectomy or ASA.
Methods
We evaluated outcomes of 3,859 patients who underwent ASA or septal myectomy in 3 specialized HCM centers. All-cause mortality was the primary endpoint of the study.
Results
In the study cohort, 585 (15.2%) patients underwent ASA, and 3,274 (84.8%) underwent septal myectomy. Patients undergoing ASA were significantly older (median age: 63.0 years [IQR: 52.7-72.8 years] vs 53.7 years [IQR: 44.9-62.8 years]; P < 0.001) and had smaller septal thickness (19.0 mm [IQR: 17.0-22.0 mm] vs 20.0 mm [IQR: 17.0-23.0 mm]; P = 0.007). Patients undergoing ASA also had more comorbidities, including renal failure, diabetes, hypertension, and coronary artery disease. There were 4 (0.7%) early deaths in the ASA group and 9 (0.3%) in the myectomy group. Over a median follow-up of 6.4 years (IQR: 3.6-10.2 years), the 10-year all-cause mortality rate was 26.1% in the ASA group and 8.2% in the myectomy group. After adjustment for age, sex, and comorbidities, the mortality remained greater in patients having septal reduction by ASA (HR: 1.68; 95% CI: 1.29-2.19; P < 0.001).
Conclusions
In patients with obstructive hypertrophic cardiomyopathy, ASA is associated with increased long-term all-cause mortality compared with septal myectomy. This impact on survival is independent of other known factors but may be influenced by unmeasured confounding patient characteristics.

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

J Am Coll Cardiol: 03 May 2022; 79:1647-1655
Cui H, Schaff HV, Wang S, Lahr BD, ... Ommen SR, Maron MS
J Am Coll Cardiol: 03 May 2022; 79:1647-1655 | PMID: 35483751
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Abstract

Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction.

Gaba P, Bhatt DL, Steg PG, Miller M, ... Ballantyne CM, REDUCE-IT Investigators
Background
REDUCE-IT was a double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in the primary endpoint, including death from cardiovascular (CV) causes. The specific impact of IPE among patients with prior myocardial infarction (MI) was unknown.
Objectives
Our goal was to examine the benefit of IPE on ischemic events among patients with prior MI in REDUCE-IT.
Methods
We performed post hoc analyses of patients with prior MI. The primary endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke.
Results
A total of 3,693 patients had a history of prior MI. The primary endpoint was reduced from 26.1% to 20.2% with IPE vs placebo; HR: 0.74 (95% CI: 0.65-0.85; P = 0.00001). The key secondary endpoint was reduced from 18.0% to 13.3%; HR: 0.71 (95% CI: 0.61-0.84; P = 0.00006). There was also a significant 35% relative risk reduction in total ischemic events (P = 0.0000001), a 34% reduction in MI (P = 0.00009), a 30% reduction in CV death (P = 0.01), and a 20% lower rate of all-cause mortality (P = 0.054), although there was a slight increase in atrial fibrillation. Sudden cardiac death and cardiac arrest were also significantly reduced by 40% and 56%, respectively.
Conclusions
Patients with a history of prior MI in REDUCE-IT treated with IPE demonstrated large and significant relative and absolute risk reductions in ischemic events, including CV death. (A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. [REDUCE-IT]; NCT01492361).

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

J Am Coll Cardiol: 03 May 2022; 79:1660-1671
Gaba P, Bhatt DL, Steg PG, Miller M, ... Ballantyne CM, REDUCE-IT Investigators
J Am Coll Cardiol: 03 May 2022; 79:1660-1671 | PMID: 35483753
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Abstract

Cardiovascular Implications of the 2021 KDIGO Blood Pressure Guideline for Adults With Chronic Kidney Disease.

Lee HH, Lee H, Townsend RR, Kim DW, Park S, Kim HC
Background
The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends a systolic blood pressure (BP) target of <120 mm Hg for nondialysis chronic kidney disease (CKD).
Objectives
We sought to examine the potential implications of the 2021 KDIGO BP target, compared with the 2012 KDIGO and 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP targets, as related to cardiovascular disease (CVD) outcomes.
Methods
From the cross-sectional Korea National Health and Nutrition Examination Survey (KNHANES) and longitudinal National Health Insurance Service (NHIS) data, adults with nondialysis CKD were identified and categorized into 4 groups based on concordance/discordance between guidelines: 1) above both targets; 2) above 2021 KDIGO only; 3) above 2012 KDIGO or 2017 ACC/AHA only; and 4) controlled within both targets. We determined the nationally representative proportion and CVD risk of each group.
Results
In KNHANES (n = 1,939), 50.2% had BP above both 2021 and 2012 KDIGO targets, 15.9% above the 2021 KDIGO target only, 3.5% above the 2012 KDIGO target only, and 30.4% controlled within both targets. In NHIS (n = 412,167; median follow-up: 10.0 years), multivariable-adjusted HRs for CVD events were 1.52 (95% CI: 1.47-1.58) among participants with BP above both targets, 1.28 (95% CI: 1.24-1.32) among those with BP above 2021 KDIGO only, and 1.07 (95% CI: 0.61-1.89) among those with BP above 2012 KDIGO only, compared to those with BP controlled within both targets. Results were similar for comparison between 2021 KDIGO and 2017 ACC/AHA BP targets.
Conclusions
New candidates for BP-lowering treatment per the 2021 KDIGO guideline account for a substantial proportion of the total CKD population and bear significantly high CVD risk.

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

J Am Coll Cardiol: 03 May 2022; 79:1675-1686
Lee HH, Lee H, Townsend RR, Kim DW, Park S, Kim HC
J Am Coll Cardiol: 03 May 2022; 79:1675-1686 | PMID: 35483755
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Abstract

Systematic Review of Physical Activity Trajectories and Mortality in Patients With Coronary Artery Disease.

Gonzalez-Jaramillo N, Wilhelm M, Arango-Rivas AM, Gonzalez-Jaramillo V, ... Franco OH, Bano A
Background
The role of lifestyle physical activity (PA) trajectories in the mortality risk of patients with coronary heart disease (CHD) remains unclear.
Objectives
The purpose of this study was to determine the association of longitudinal PA trajectories with all-cause and cardiovascular disease (CVD) mortality in patients with CHD.
Methods
Longitudinal cohorts reporting the association of PA trajectories with mortality in patients with CHD were identified in April 2021 by searching 5 databases without language restrictions. Published HRs and 95% CIs were pooled using random effects models and bias assessed by Egger regression.
Results
A total of 9 prospective cohorts included 33,576 patients. The mean age was 62.5 years. The maximum follow-up was 15.7 years. All of the studies assessed PA through validated questionnaires, and mortality was well documented. Changes in PA defined 4 nominal PA trajectories. Compared with always-inactive patients, the risk of all-cause mortality was 50% lower in those who remained active (HR: 0.50; 95% CI: 0.39-0.63); 45% lower in those who were inactive but became active (HR: 0.55; 95% CI: 0.44-0.7); and 20% lower in those who were active but became inactive (HR: 0.80; 95% CI: 0.64-0.99). Similar results were observed for CVD mortality, except for the category of decreased activity (HR: 0.91; 95% CI: 0.67-1.24). The overall risk of bias was low. No evidence of publication bias was found. Multiple sensitivity analyses provided consistent results.
Conclusions
This study illustrates how patients with CHD may benefit by preserving or adopting an active lifestyle. The observation that the benefits of past activity can be weakened or lost if PA is not maintained may be confounded by disease progression.

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

J Am Coll Cardiol: 03 May 2022; 79:1690-1700
Gonzalez-Jaramillo N, Wilhelm M, Arango-Rivas AM, Gonzalez-Jaramillo V, ... Franco OH, Bano A
J Am Coll Cardiol: 03 May 2022; 79:1690-1700 | PMID: 35483757
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Abstract

The National Cardiovascular Data Registry Data Quality Program 2020: JACC State-of-the-Art Review.

Malenka DJ, Bhatt DL, Bradley SM, Shahian DM, ... Roe M, Masoudi FA
The National Cardiovascular Data Registry is a group of registries maintained by the American College of Cardiology Foundation. These registries are used by a diverse constituency to improve the quality and outcomes of cardiovascular care, to assess the safety and effectiveness of new therapies, and for research. To achieve these goals, registry data must be complete and reliable. In this article, we review the process of National Cardiovascular Data Registry data collection, assess data completeness and integrity, and report on the current state of the data. Registry data are complete. Accuracy is very good but variable, and there is room for improvement. Knowledge of the quality of data is essential to ensuring its appropriate use.

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

J Am Coll Cardiol: 03 May 2022; 79:1704-1712
Malenka DJ, Bhatt DL, Bradley SM, Shahian DM, ... Roe M, Masoudi FA
J Am Coll Cardiol: 03 May 2022; 79:1704-1712 | PMID: 35483759
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Abstract

Complicated Carotid Artery Plaques and Risk of Recurrent Ischemic Stroke or TIA.

Kopczak A, Schindler A, Sepp D, Bayer-Karpinska A, ... Saam T, Dichgans M
Background
Complicated nonstenosing carotid artery plaques (CAPs) are an under-recognized cause of stroke.
Objectives
The purpose of this study was to determine whether complicated CAP ipsilateral to acute ischemic anterior circulation stroke (icCAP) are associated with recurrent ischemic stroke or transient ischemic attack (TIA).
Methods
The CAPIAS (Carotid Plaque Imaging in Acute Stroke) multicenter study prospectively recruited patients with ischemic stroke restricted to the territory of a single carotid artery. Complicated (AHA-lesion type VI) CAP were defined by multisequence, contrast-enhanced carotid magnetic resonance imaging obtained within 10 days from stroke onset. Recurrent events were assessed after 3, 12, 24, and 36 months. The primary outcome was recurrent ischemic stroke or TIA.
Results
Among 196 patients enrolled, 104 patients had cryptogenic stroke and nonstenosing CAP. During a mean follow-up of 30 months, recurrent ischemic stroke or TIA occurred in 21 patients. Recurrent events were significantly more frequent in patients with icCAP than in patients without icCAP, both in the overall cohort (incidence rate [3-year interval]: 9.50 vs 3.61 per 100 patient-years; P = 0.025, log-rank test) and in patients with cryptogenic stroke (10.92 vs 1.82 per 100 patient-years; P = 0.003). The results were driven by ipsilateral events. A ruptured fibrous cap (HR: 4.91; 95% CI: 1.31-18.45; P = 0.018) and intraplaque hemorrhage (HR: 4.37; 95% CI: 1.20-15.97; P = 0.026) were associated with a significantly increased risk of recurrent events in patients with cryptogenic stroke.
Conclusions
Complicated CAP ipsilateral to acute ischemic anterior circulation stroke are associated with an increased risk of recurrent ischemic stroke or TIA. Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933).

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

J Am Coll Cardiol: 27 Apr 2022; epub ahead of print
Kopczak A, Schindler A, Sepp D, Bayer-Karpinska A, ... Saam T, Dichgans M
J Am Coll Cardiol: 27 Apr 2022; epub ahead of print | PMID: 35523659
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Abstract

Association of Left Atrial Structure and Function With Heart Failure in Older Adults.

Inciardi RM, Claggett B, Minamisawa M, Shin SH, ... Chen LY, Solomon SD
Background
Limited data exist to characterize novel measures of left atrial (LA) structure and function in older adults without prevalent heart failure (HF).
Objectives
The aim was to assess reference range of LA measures, their associations with N-terminal pro-B-type natriuretic-peptide (NT-proBNP) and the related risk for incident HF or death.
Methods
We analyzed LA structure (LA maximal [LAViMax] and minimal volume indexed by body surface area) and function (LA emptying fraction, LA reservoir, conduit, and contraction strain) in 4,901 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 75 ± 5 years, 40% male, and 19% Black) without prevalent HF. We assessed sex-specific 10th and 90th percentile ARIC-based reference limits in 301 participants free of prevalent cardiovascular disease, and related LA measures to NT-proBNP and incident HF or death (median follow-up of 5.5 years) in the whole ARIC cohort.
Results
Approximately 20% of the overall population had LA abnormalities according to the ARIC-based reference limit. Each LA measure was associated with NT-proBNP and, except for LAViMax, with incident HF or death after multivariable adjustment (including left ventricular function and NT-proBNP). Results were consistent in participants with normal LAViMax (P for interaction > 0.05). LA measures were prognostic for both incident HF with preserved ejection fraction or death and incident HF with reduced ejection fraction or death. When added to HF risk factors and NT-proBNP (baseline C-statistics = 0.74) all LA measures, except for LAViMax, significantly enhanced the prognostic accuracy.
Conclusions
Novel measures of LA structure and function, but not standard assessment by LAViMax, are associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP.

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

J Am Coll Cardiol: 26 Apr 2022; 79:1549-1561
Inciardi RM, Claggett B, Minamisawa M, Shin SH, ... Chen LY, Solomon SD
J Am Coll Cardiol: 26 Apr 2022; 79:1549-1561 | PMID: 35450571
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Abstract

Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy.

Dybro AM, Rasmussen TB, Nielsen RR, Ladefoged BT, ... Jensen MK, Poulsen SH
Background
The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood.
Objectives
This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM.
Methods
This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest.
Results
No treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008).
Conclusions
In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).

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

J Am Coll Cardiol: 26 Apr 2022; 79:1565-1575
Dybro AM, Rasmussen TB, Nielsen RR, Ladefoged BT, ... Jensen MK, Poulsen SH
J Am Coll Cardiol: 26 Apr 2022; 79:1565-1575 | PMID: 35450573
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Abstract

Elevated Lipoprotein(a) and Risk of Atrial Fibrillation: An Observational and Mendelian Randomization Study.

Mohammadi-Shemirani P, Chong M, Narula S, Perrot N, ... Pigeyre M, Paré G
Background
Atrial fibrillation (AF) is a cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality. However, preventative therapies are needed with ancillary benefits on its cardiovascular comorbidities. Lipoprotein(a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), which itself increases AF risk, but it remains unknown whether Lp(a) is a causal mediator of AF independent of ASCVD.
Objectives
This study investigated the role of Lp(a) in AF and whether it is independent of ASCVD.
Methods
Measured and genetically predicted Lp(a) levels were tested for association with 20,432 cases of incident AF in the UK Biobank (N = 435,579). Mendelian randomization analyses were performed by using summary-level data for AF from publicly available genome-wide association studies (N = 1,145,375).
Results
In the UK Biobank, each 50 nmol/L (23 mg/dL) increase in Lp(a) was associated with an increased risk of incident AF using measured Lp(a) (HR: 1.03; 95% CI: 1.02-1.04 ; P = 1.65 × 10-8) and genetically predicted Lp(a) (OR: 1.03; 95% CI: 1.02-1.05; P = 1.33 × 10-5). Mendelian randomization analyses using independent data replicated the effect (OR: 1.04 per 50 nmol/L Lp[a] increase; 95% CI: 1.03-1.05 per 50 nmol/L Lp[a] increase; P = 9.23 × 10-10). There was no evidence of risk-conferring effect from low-density lipoprotein cholesterol or triglycerides, and only 39% (95% CI: 27%-73%) of Lp(a) risk was mediated through ASCVD, suggesting that Lp(a) partly influences AF independent of its known effects on ASCVD.
Conclusions
Our findings implicate Lp(a) as a potential causal mediator in the development of AF which show that the effects of Lp(a) extend across myocardial tissues. Ongoing clinical trials for Lp(a)-lowering therapies should evaluate effects on AF prevention.

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

J Am Coll Cardiol: 26 Apr 2022; 79:1579-1590
Mohammadi-Shemirani P, Chong M, Narula S, Perrot N, ... Pigeyre M, Paré G
J Am Coll Cardiol: 26 Apr 2022; 79:1579-1590 | PMID: 35450575
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Abstract

Infertility and Risk of Heart Failure in the Women\'s Health Initiative.

Lau ES, Wang D, Roberts M, Taylor CN, ... Eaton CB, Ho JE
Background
There is growing recognition that reproductive factors are associated with increased risk of future cardiovascular disease. Infertility has been less well studied, although emerging data support its association with increased risk of cardiovascular disease. Whether infertility is associated with future risk of heart failure (HF) is not known.
Objectives
This study sought to examine the development of HF and HF subtypes in women with and without history of infertility.
Methods
We followed postmenopausal women from the Women\'s Health Initiative prospectively for the development of HF. Infertility was self-reported at study baseline. Multivariable cause-specific Cox models were used to evaluate the association of infertility with incident overall HF and HF subtypes (heart failure with preserved ejection fraction [HFpEF]: left ventricular ejection fraction of ≥50% vs heart failure with reduced ejection fraction [HFrEF]: left ventricular ejection fraction of <50%]).
Results
Among 38,528 postmenopausal women (mean age: 63 ± 7 years), 5,399 (14%) participants reported a history of infertility. Over a median follow-up of 15 years, 2,373 developed incident HF, including 807 with HFrEF and 1,133 with HFpEF. Infertility was independently associated with future risk of overall HF (HR: 1.16; 95% CI: 1.04-1.30; P = 0.006). Notably, when examining HF subtypes, infertility was associated with future risk of HFpEF (HR: 1.27; 95% CI: 1.09-1.48; P = 0.002) but not HFrEF (HR: 0.97; 95% CI: 0.80-1.18).
Conclusions
Infertility was significantly associated with incident HF. This was driven by increased risk of HFpEF, but not HFrEF, and appeared independent of traditional cardiovascular risk factors and other infertility-related conditions. Future research should investigate mechanisms that underlie the link between infertility and HFpEF.

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

J Am Coll Cardiol: 26 Apr 2022; 79:1594-1603
Lau ES, Wang D, Roberts M, Taylor CN, ... Eaton CB, Ho JE
J Am Coll Cardiol: 26 Apr 2022; 79:1594-1603 | PMID: 35450577
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Abstract

Origins and Evolution of Extracorporeal Circulation: JACC Historical Breakthroughs in Perspective.

Holman WL, Timpa J, Kirklin JK
Midway through the 20th century, direct open-heart operations were not yet a reality, awaiting safe methods to support the cardiopulmonary circulation during cardiac surgery. The scientific advancements collectively leading to safe cardiopulmonary bypass are considered some of the most impactful advances of modern medicine. Stimulated by the work of physiologists and engineers in the late 19th century, primitive pump and oxygenator designs were the forerunners of major work by DeBakey and others in roller pump design and by Gibbon in oxygenator development. Following Gibbon\'s historic successful closure of an atrial septal defect in 1953 with his heart-lung machine, it was left to Lillehei and Kirklin to first successfully repair large series of cardiac malformations. The history leading to these historic events and the subsequent evolution of cardiopulmonary bypass machines for short- and longer-term support is filled with engineering and surgical brilliance, daring innovations, and serendipity.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 26 Apr 2022; 79:1606-1622
Holman WL, Timpa J, Kirklin JK
J Am Coll Cardiol: 26 Apr 2022; 79:1606-1622 | PMID: 35450579
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Abstract

Nutrition Assessment and Dietary Interventions in Heart Failure: JACC Review Topic of the Week.

Driggin E, Cohen LP, Gallagher D, Karmally W, ... Carbone S, Maurer MS
Despite the high prevalence of nutrition disorders in patients with heart failure (HF), major HF guidelines lack specific nutrition recommendations. Because of the lack of standardized definitions and assessment tools to quantify nutritional status, nutrition disorders are often missed in patients with HF. Additionally, a wide range of dietary interventions and overall dietary patterns have been studied in this population. The resulting evidence of benefit is, however, conflicting, making it challenging to determine which strategies are the most beneficial. In this document, we review the available nutritional status assessment tools for patients with HF. In addition, we appraise the current evidence for dietary interventions in HF, including sodium restriction, obesity, malnutrition, dietary patterns, and specific macronutrient and micronutrient supplementation. Furthermore, we discuss the feasibility and challenges associated with the implementation of multimodal nutrition interventions and delineate potential solutions to facilitate addressing nutrition in patients with HF.

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

J Am Coll Cardiol: 26 Apr 2022; 79:1623-1635
Driggin E, Cohen LP, Gallagher D, Karmally W, ... Carbone S, Maurer MS
J Am Coll Cardiol: 26 Apr 2022; 79:1623-1635 | PMID: 35450580
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Abstract

Long-Term Cardiovascular Outcomes After Bariatric Surgery in the Medicare Population.

Mentias A, Aminian A, Youssef D, Pandey A, ... Nissen SE, Desai MY
Background
The long-term effect of bariatric surgery on cardiovascular outcomes in the elderly population is not well studied.
Objectives
The aim of this study was to evaluate the association between bariatric surgery and long-term cardiovascular outcomes in the Medicare population.
Methods
Medicare beneficiaries who underwent bariatric surgery from 2013 to 2019 were matched to a control group of patients with obesity with a 1:1 exact matching based on age, sex, body mass index, and propensity score matching on 87 clinical variables. The study outcomes included all-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke. An instrumental variable analysis was performed as a sensitivity analysis.
Results
The study cohort included 189,770 patients (94,885 matched patients in each group). By study design, the 2 groups had similar age (mean: 62.33 ± 10.62 years), sex (70% female), and degree of obesity (mean body mass index: 44.7 ± 7.3 kg/m2) and were well balanced on all clinical variables. After a median follow-up of 4.0 years (IQR: 2.4-5.7 years), bariatric surgery was associated with a lower risk of mortality (9.2 vs 14.7 per 1,000 person-years; HR: 0.63; 95% CI: 0.60-0.66), new-onset HF (HR: 0.46; 95% CI: 0.44-0.49), MI (HR: 0.63; 95% CI: 0.59-0.68), and stroke (HR: 0.71; 95%: CI: 0.65-0.79) (P < 0.001). The benefit of bariatric surgery was evident in patients who were 65 years and older. Using instrumental variable analysis, bariatric surgery was associated with a lower risk of mortality, HF, and MI.
Conclusions
Among Medicare beneficiaries with obesity, bariatric surgery is associated with lower risk of mortality, new-onset HF, and MI.

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

J Am Coll Cardiol: 19 Apr 2022; 79:1429-1437
Mentias A, Aminian A, Youssef D, Pandey A, ... Nissen SE, Desai MY
J Am Coll Cardiol: 19 Apr 2022; 79:1429-1437 | PMID: 35422238
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Abstract

Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia.

Arenal Á, Ávila P, Jiménez-Candil J, Tercedor L, ... Fernández-Avilés FJ, Berruezo A
Background
In patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD), catheter ablation and antiarrhythmic drugs (AADs) reduce ICD shocks, but the most effective approach remains uncertain.
Objectives
This trial compares the efficacy and safety of catheter ablation vs AAD as first-line therapy in ICD patients with symptomatic ventricular tachycardias (VTs).
Methods
The SURVIVE-VT (Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia) is a prospective, multicenter, randomized trial including patients with ischemic cardiomyopathy and appropriated ICD shock. Patients were 1:1 randomized to complete endocardial substrate-based catheter ablation or antiarrhythmic therapy (amiodarone + beta-blockers, amiodarone alone, or sotalol ± beta-blockers). The primary outcome was a composite of cardiovascular death, appropriate ICD shock, unplanned hospitalization for worsening heart failure, or severe treatment-related complications.
Results
In this trial, 144 patients (median age, 70 years; 96% male) were randomized to catheter ablation (71 patients) or AAD (73 patients). After 24 months, the primary outcome occurred in 28.2% of patients in the ablation group and 46.6% of those in the AAD group (hazard ratio [HR]: 0.52; 95% CI: 0.30-0.90; P = 0.021). This difference was driven by a significant reduction in severe treatment-related complications (9.9% vs 28.8%, HR: 0.30; 95% CI: 0.13-0.71; P = 0.006). Eight patients were hospitalized for heart failure in the ablation group and 13 in the AAD group (HR: 0.56; 95% CI: 0.23-1.35; P = 0.198). There was no difference in cardiac mortality (HR: 0.93; 95% CI: 0.19-4.61; P = 0.929).
Conclusions
In ICD patients with ischemic cardiomyopathy and symptomatic VT, catheter ablation reduced the composite endpoint of cardiovascular death, appropriate ICD shock, hospitalization due to heart failure, or severe treatment-related complications compared to AAD. (Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia [SURVIVE-VT]: NCT03734562).

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

J Am Coll Cardiol: 19 Apr 2022; 79:1441-1453
Arenal Á, Ávila P, Jiménez-Candil J, Tercedor L, ... Fernández-Avilés FJ, Berruezo A
J Am Coll Cardiol: 19 Apr 2022; 79:1441-1453 | PMID: 35422240
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Abstract

External Validation of the FREEDOM Score for Individualized Decision Making Between CABG and PCI.

Takahashi K, Serruys PW, Fuster V, Farkouh ME, ... BEST, and FREEDOM Trial investigators
Background
Although randomized trials have established that coronary artery bypass grafting (CABG) is, on average, the most effective revascularization strategy compared with percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease (MVD), individual patients differ in many characteristics that can affect the benefits and harms of treatment. The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus) score was developed to predict different outcomes with CABG vs PCI on the basis of 8 patient characteristics and the smoking-treatment interaction.
Objectives
This study aimed to assess the ability of the 5-year major adverse cardiovascular event (MACE) model to predict treatment benefit of CABG vs PCI in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials.
Methods
This study identified 702 patients with diabetes and MVD to mirror the FREEDOM participants. Discrimination was assessed by C-index, and calibration was assessed by calibration plots in the PCI and CABG arms, respectively. The ability of the FREEDOM score to predict treatment benefit of CABG vs PCI was assessed.
Results
Overall, CABG was associated with a lower rate of 5-year MACE compared with PCI (12.4% vs 20.3%; log-rank P = 0.021) irrespective of a history of smoking (Pinteraction = 0.975). Both discrimination and calibration were helpful in the PCI arm (C-index: 0.69; slope: 0.96, intercept: -0.24), but moderate in the CABG arm (C-index: 0.61; slope: 0.61; intercept: -0.53). The FREEDOM score showed some heterogeneity of treatment benefit.
Conclusions
The FREEDOM score could identify some heterogeneity of treatment benefit of CABG vs PCI for 5-year MACE. Until further prospective validations are performed, these results should be taken into consideration when using the FREEDOM score in patients with diabetes and MVD. (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972) (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease [BEST]; NCT00997828) (Future Revascularization Evaluation in Patients with Diabetes Mellitus [FREEDOM]; NCT00086450).

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

J Am Coll Cardiol: 19 Apr 2022; 79:1458-1473
Takahashi K, Serruys PW, Fuster V, Farkouh ME, ... BEST, and FREEDOM Trial investigators
J Am Coll Cardiol: 19 Apr 2022; 79:1458-1473 | PMID: 35422242
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Abstract

Percutaneous Pulmonary Angioplasty for Patients With Takayasu Arteritis and Pulmonary Hypertension.

Zhou YP, Wei YP, Yang YJ, Xu XQ, ... Jiang X, Jing ZC
Background
Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to Takayasu arteritis-associated pulmonary hypertension (TA-PH), another chronic obstructive pulmonary vascular disease, remains unclear.
Objectives
This study sought to investigate the efficacy and safety of PTPA for TA-PH.
Methods
Between January 1, 2016, and December 31, 2019, a total of 50 patients with TA-PH who completed the PTPA procedure (the PTPA group) and 21 patients who refused the PTPA procedure (the non-PTPA group) were prospectively enrolled in this cohort study. The primary outcome was all-cause mortality. The safety outcomes included PTPA procedure-related complications.
Results
Baseline characteristics and medical therapies were similar between the PTPA group and the non-PTPA group. During a mean follow-up time of 37 ± 14 months, deaths occurred in 3 patients (6.0%) in the PTPA group and 6 patients (28.6%) in the non-PTPA group, contributing to the 3-year survival rate of 93.7% in the PTPA group and 76.2% in the non-PTPA group (P = 0.0096 for log-rank test). The Cox regression model showed that PTPA was associated with a significantly reduced hazard of all-cause mortality in TA-PH patients (HR: 0.18; 95% CI: 0.05-0.73; P = 0.017). No periprocedural death occurred. Severe complications requiring noninvasive positive pressure ventilation occurred in only 1 of 150 total sessions (0.7%).
Conclusions
PTPA tended to be associated with a reduced risk of all-cause mortality with acceptable safety profiles and seemed to be a promising therapeutic option for TA-PH patients.

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

J Am Coll Cardiol: 19 Apr 2022; 79:1477-1488
Zhou YP, Wei YP, Yang YJ, Xu XQ, ... Jiang X, Jing ZC
J Am Coll Cardiol: 19 Apr 2022; 79:1477-1488 | PMID: 35422244
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Abstract

Sex Differences in Cardiovascular Consequences of Hypertension, Obesity, and Diabetes: JACC Focus Seminar 4/7.

Regensteiner JG, Reusch JEB
It has long been recognized that there are significant differences between the sexes affecting prevalence, incidence, and severity over a broad range of diseases. Until the early 1990s, the limited research conducted on women\'s health focused primarily on diseases affecting fertility and reproduction, and women were excluded from most clinical trials. For these reasons, the prevention, diagnosis, and treatment of serious chronic diseases such as cardiovascular disease in women continue to be based primarily on findings in men, and sex-specific clinical guidelines are mostly lacking. Hypertension, obesity, and diabetes, interrelated risk factors for cardiovascular disease, differ by sex in terms of prevalence and adverse effects as well as by genetics and biology. Research is needed to understand sex differences in hypertension, obesity, and diabetes to optimally inform sex-specific prevention, diagnosis, and treatment strategies for women and men. In this way, sex-specific clinical guidelines can be developed where warranted.

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

J Am Coll Cardiol: 19 Apr 2022; 79:1492-1505
Regensteiner JG, Reusch JEB
J Am Coll Cardiol: 19 Apr 2022; 79:1492-1505 | PMID: 35422246
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Abstract

Sex-Related Factors in Valvular Heart Disease: JACC Focus Seminar 5/7.

Hahn RT, Clavel MA, Mascherbauer J, Mick SL, Asgar AW, Douglas PS
Numerous sex-based differences are observed across the spectrum of valvular heart disease, starting with pathophysiology and progression of disease, moving on to compensation and comorbidities (both cardiovascular such as coronary artery disease and noncardiovascular such as frailty), assessment of severity and hemodynamics including timing of intervention, and procedural risks/benefits and outcomes. The aortic valve is perhaps best understood with sex differences in both pathologic changes and response to volume and pressure overload, yet large gaps in our understanding still exist. Studies of other valve diseases have focused on differences in prevalence, presentation, and outcomes for surgical or transcatheter therapies. Defining sex-specific responses to valvular heart disease may improve disease recognition, define treatment strategies, and improve outcomes.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 19 Apr 2022; 79:1506-1518
Hahn RT, Clavel MA, Mascherbauer J, Mick SL, Asgar AW, Douglas PS
J Am Coll Cardiol: 19 Apr 2022; 79:1506-1518 | PMID: 35422247
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Abstract

Sex-Specific Considerations in Drug and Device Therapy of Cardiac Arrhythmias: JACC Focus Seminar 6/7.

Amuthan R, Curtis AB
Sex and gender are important factors influencing the epidemiology and outcomes of cardiovascular care in various cardiac arrhythmias. Observed sex-related differences are influenced by the effects of both biologically determined sex and culturally defined gender. Under-representation of women in clinical trials and incomplete understanding of the mechanisms behind sex differences have led to inadequate evidence to guide effective sex-specific treatment. This lack of information has contributed to disparities in clinical care. In this review, we examine the effect of sex and gender on the clinical presentation and outcomes with drug and device therapy in various arrhythmias, while acknowledging the paucity of data on the effect of gender. We evaluate the implications of sex on the clinical management of arrhythmias covered by guideline documents, highlight recent data that warrant consideration for additional sex-specific recommendations, and illustrate knowledge gaps that require further study.

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

J Am Coll Cardiol: 19 Apr 2022; 79:1519-1529
Amuthan R, Curtis AB
J Am Coll Cardiol: 19 Apr 2022; 79:1519-1529 | PMID: 35422248
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Abstract

Sex-Based Differences in Heart Failure: JACC Focus Seminar 7/7.

Khan SS, Beach LB, Yancy CW
Sex-based differences exist in risk, symptoms, and management of heart failure (HF). Women have a higher incidence of HF with preserved ejection fraction compared with men. This may be partially caused by the cardiovascular effects of estrogen and sex-specific risk factors (eg, adverse pregnancy outcomes, premature menopause). Key gaps exist in understanding of gender-based differences in HF, which is a distinctly different concept than sex-based differences. Although evidence-based therapies for HF are available, only limited data address sex-specific efficacy, and no data address gender-based efficacy. Persistent shortcomings in representation of women and gender minority participants in clinical trials limit an actionable database. A comprehensive roadmap to close the sex/gender-based gap in HF includes the following: 1) sex/gender-specific personalized prevention; 2) sex/gender-neutral implementation of evidence-based therapies; and 3) sex/gender-appropriate policy-level initiatives to spur research assessing sex/gender-specific causes of HF; enhance sex/gender-specific subgroup reporting; and promote community engagement of these important patient cohorts.

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

J Am Coll Cardiol: 19 Apr 2022; 79:1530-1541
Khan SS, Beach LB, Yancy CW
J Am Coll Cardiol: 19 Apr 2022; 79:1530-1541 | PMID: 35422249
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Abstract

Association of Cumulative Blood Pressure With Cognitive Decline, Dementia, and Mortality.

Li C, Zhu Y, Ma Y, Hua R, Zhong B, Xie W
Background
Elevated blood pressure (BP) has been linked to impaired cognition and dementia in older adults. However, few studies have accounted for long-term cumulative BP exposure.
Objectives
The aim of this study was to test whether long-term cumulative BP was independently associated with subsequent cognitive decline, incident dementia, and all-cause mortality among cognitively healthy adults.
Methods
This study used data from the HRS (Health and Retirement Study) and ELSA (English Longitudinal Study of Ageing). Cumulative BP was calculated as the area under the curve using measurements from wave 0 (1998-1999) to wave 4 (2008-2009) in ELSA and wave 8 (2006-2007) to wave 10 (2010-2011) in the HRS. Outcomes included cognitive decline, incident dementia, and all-cause mortality.
Results
A total of 7,566 and 9,294 participants from ELSA and the HRS were included (44.8% and 40.2% men and median age 62.0 years [IQR: 55.0-70.0 years] and 65.0 years [IQR: 58.0-72.0 years], respectively). The median follow-up duration was 8.0 years (IQR: 4.0-8.0 years) and 8.0 years (IQR: 6.0-8.0 years), respectively. Elevated cumulative systolic BP and pulse pressure were independently associated with accelerated cognitive decline (P < 0.001 for both), elevated dementia risk (P < 0.001 for both), and all-cause mortality (P < 0.001 for both), while a significant inverse association was observed for diastolic BP. Strong dose-response relationships were identified, with similar results for the 2 cohorts.
Conclusions
Long-term cumulative BP was associated with subsequent cognitive decline, dementia risk, and all-cause mortality in cognitively healthy adults aged ≥50 years. Efforts are required to control long-term systolic BP and pulse pressure and to maintain adequate diastolic BP.

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

J Am Coll Cardiol: 12 Apr 2022; 79:1321-1335
Li C, Zhu Y, Ma Y, Hua R, Zhong B, Xie W
J Am Coll Cardiol: 12 Apr 2022; 79:1321-1335 | PMID: 35393012
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Abstract

Late Balloon Valvuloplasty for Transcatheter Heart Valve Dysfunction.

Akodad M, Blanke P, Chuang MA, Duchscherer J, ... Ye J, Webb JG
Background
Transcatheter heart valve (THV) dysfunction with an elevated gradient or paravalvular leak (PVL) may be documented late after THV implantation. Medical management, paravalvular plugs, redo THV replacement, or surgical valve replacement may be considered. However, late balloon dilatation is rarely utilized because of concerns about safety or lack of efficacy.
Objectives
We aimed to evaluate the safety and efficacy of late dilatation in the management of THV dysfunction.
Methods
All patients who underwent late dilatation for symptomatic THV dysfunction at 2 institutions between 2016 and 2021 were identified. Baseline, procedural characteristics, and clinical and echocardiographic outcomes were documented. THV frame expansion was assessed by multislice computed tomography before and after late dilatation.
Results
Late dilatation was performed in 30 patients a median of 4.6 months (IQR: 2.3-11.0 months) after THV implantation in the aortic (n = 25; 83.3%), mitral (n = 2; 6.7%), tricuspid (n = 2; 6.7%) and pulmonary (n = 1; 3.3%) position. THV underexpansion was documented at baseline, and frame expansion substantially improved after late dilatation. The mean transvalvular gradient fell in all patients. For aortic THVs specifically, mean transaortic gradient fell from 25.4 ± 13.9 mm Hg to 10.8 ± 4.1 mm Hg; P < 0.001. PVL was reduced to ≤mild in all 11 patients with a previous >mild PVL. Embolic events, stroke, annular injury, and bioprosthetic leaflet injury were not observed. Symptomatic benefit was durable at 19.6 months (IQR: 14.8-36.1 months) follow-up.
Conclusions
Balloon dilatation late after THV implantation appears feasible and safe in appropriately selected patients and may result in THV frame expansion resulting in improvements in hemodynamic performance and PVL.

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

J Am Coll Cardiol: 12 Apr 2022; 79:1340-1351
Akodad M, Blanke P, Chuang MA, Duchscherer J, ... Ye J, Webb JG
J Am Coll Cardiol: 12 Apr 2022; 79:1340-1351 | PMID: 35393014
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Abstract

Prevalence and Prognostic Implications of Left Ventricular Systolic Dysfunction in Adults With Congenital Heart Disease.

Egbe AC, Miranda WR, Pellikka PA, DeSimone CV, Connolly HM
Background
Although the prevalence and prognostic implications of left ventricular systolic dysfunction (LVSD), and the effect of cardiac therapies on LVSD are well described in patients with acquired heart disease, such data are sparse in adults with congenital heart disease (CHD).
Objectives
The purpose of this study was to determine the prevalence, risk factors, and prognostic implications of LVSD, and the effect of cardiac therapies (guideline-directed medical therapy [GDMT] and cardiac resynchronization therapy [CRT]) on LVSD in adults with CHD.
Methods
This was a retrospective study of adults with CHD with systemic LV (2003-2019). LVSD was defined as left ventricular ejection fraction (LVEF) <52%/<54% (men/women). Cardiovascular event was defined as heart failure hospitalization, heart transplant, and cardiovascular death.
Results
Of 4,358 patients, 554 (12%) had LVSD, and the prevalence of LVSD was higher in right-sided lesions compared with left-sided lesions (15% vs 10%; P < 0.001). Cardiovascular events occurred in 312 (7%) patients. LVEF was independently associated with cardiovascular events (HR: 0.95; 95% CI: 0.93-0.97; P = 0.009). Of 544 patients with LVSD, 311 received GDMT and 48 patients received CRT. LVEF increased by 6% (95% CI: 2%-10%) and 11% (95% CI: 8%-14%), and N-terminal pro-hormone brain natriuretic peptide decreased by 151 pg/mL (95% CI: 62-289 pg/mL) and 201 pg/mL (95% CI: 119-321 pg/mL) in patients who received GDMT and CRT, respectively.
Conclusions
LVSD was present in 12% of adults with CHD, was more common in patients with right-sided lesions, and was associated with cardiovascular events. GDMT and CRT were associated with improvement in LVEF. These results provide a foundation for clinical trials to rigorously test the benefits of these therapies in CHD patients.

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

J Am Coll Cardiol: 12 Apr 2022; 79:1356-1365
Egbe AC, Miranda WR, Pellikka PA, DeSimone CV, Connolly HM
J Am Coll Cardiol: 12 Apr 2022; 79:1356-1365 | PMID: 35393016
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Abstract

Measurement of Midregional Pro-Atrial Natriuretic Peptide to Discover Atrial Fibrillation in Patients With Ischemic Stroke.

Schweizer J, Arnold M, König IR, Bicvic A, ... von Eckardstein A, Katan M
Background
Midregional pro-atrial natriuretic peptide (MR-proANP) is a promising biomarker to differentiate the underlying etiology of acute ischemic stroke (AIS).
Objectives
This study aimed to determine the role of MR-proANP for classification as cardioembolic (CE) stroke, identification of newly diagnosed atrial fibrillation (NDAF), and risk assessment for major adverse cardiovascular events (MACE).
Methods
This study measured MR-proANP prospectively collected within 24 hours after symptom-onset in patients with AIS from the multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study. Primary outcomes were CE stroke etiology and NDAF after prolonged cardiac monitoring, as well as a composite outcome of MACE (recurrent cerebrovascular events, myocardial infarction, or cardiovascular death) within 1 year. Logistic/Poisson and subproportional hazard regression were applied to evaluate the association between MR-proANP levels and outcomes. Additionally, a model for prediction of NDAF was derived and validated as a decision tool for immediate clinical application.
Results
Between October 1, 2014, and October 31, 2017, this study recruited 1,759 patients. Log10MR-proANP levels were associated with CE stroke (OR: 7.96; 95% CI: 4.82-13.14; risk ratio: 3.12; 95% CI: 2.23-4.37), as well as NDAF (OR: 35.3; 95% CI: 17.58-71.03; risk ratio: 11.47; 95% CI: 6.74-19.53), and MACE (subdistributional HR: 2.02; 95% CI: 1.32-3.08) during follow-up. The model to predict NDAF including only age and MR-proANP levels had a good discriminatory capacity with an area under the curve of 0.81 (95% CI: 0.76-0.86), was well calibrated (calibration in the large: -0.086; calibration slope 1.053), and yielded higher net-benefit compared with validated scores to predict NDAF (AS5F score, CHA2DS2-VASc [Congestive Heart Failure, Hypertension, Age ≥65 or ≥75, Diabetes, Prior Cardioembolic Event, (female) Sex, or Vascular Disease] score).
Conclusions
MR-proANP is a valid biomarker to determine risk of NDAF and MACE in patients with AIS and can be used as a decision tool to identify patients for prolonged cardiac monitoring. (Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL study [BIOSIGNAL]; NCT02274727).

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

J Am Coll Cardiol: 12 Apr 2022; 79:1369-1381
Schweizer J, Arnold M, König IR, Bicvic A, ... von Eckardstein A, Katan M
J Am Coll Cardiol: 12 Apr 2022; 79:1369-1381 | PMID: 35393018
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Abstract

Sex as a Biological Variable in Cardiovascular Diseases: JACC Focus Seminar 1/7.

Clayton JA, Gaugh MD
Sex and gender influence all aspects of cardiovascular health and disease-including epidemiology, pathophysiology, diagnosis, clinical manifestation, disease progression, and response to treatment-in complex and interrelated ways. Sex-based and gender-based differences have been identified in risk and presentation of cardiovascular diseases (CVDs); however, failure to address sex and gender as key variables in CVD research and reporting and limited understanding of differences have contributed to disparities in risk assessment, prevention, diagnosis, treatment, and outcomes. Improved consideration of both sex and gender in all phases of the biomedical research continuum, along with educational and training curricula focused on the role of sex and gender in CVD, are needed to provide targeted therapies and improve cardiovascular health outcomes for all.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 12 Apr 2022; 79:1388-1397
Clayton JA, Gaugh MD
J Am Coll Cardiol: 12 Apr 2022; 79:1388-1397 | PMID: 35393021
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Impact:
Abstract

Sex-Specific Considerations in the Presentation, Diagnosis, and Management of Ischemic Heart Disease: JACC Focus Seminar 2/7.

Solola Nussbaum S, Henry S, Yong CM, Daugherty SL, Mehran R, Poppas A
There are sex-related differences in the epidemiology, presentation, diagnostic testing, and management of ischemic heart disease in women compared with men. The adjusted morbidity and mortality are persistently higher, particularly in younger women and Blacks. Women have more angina but less obstructive coronary artery disease, which affects delays in presentation and diagnosis and testing accuracy. The nonbiological factors play a significant role in access to care, ischemic heart disease management, and guideline adherence. Future research focus includes sex-specific outcomes, characterization of the biological differences, and implementation science around quality of clinical care.

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

J Am Coll Cardiol: 12 Apr 2022; 79:1398-1406
Solola Nussbaum S, Henry S, Yong CM, Daugherty SL, Mehran R, Poppas A
J Am Coll Cardiol: 12 Apr 2022; 79:1398-1406 | PMID: 35393022
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Abstract

Sex-Related Outcomes of Medical, Percutaneous, and Surgical Interventions for Coronary Artery Disease: JACC Focus Seminar 3/7.

Gaudino M, Di Franco A, Cao D, Giustino G, ... Dangas GD, Mehran R
Biological and sociocultural differences between men and women are complex and likely account for most of the variations in the epidemiology and treatment outcomes of coronary artery disease (CAD) between the 2 sexes. Worse outcomes in women have been described following both conservative and invasive treatments of CAD. For example, increased levels of residual platelet reactivity during treatment with antiplatelet drugs, higher rates of adverse cardiovascular outcomes following percutaneous coronary revascularization, and higher operative and long-term mortality after coronary bypass surgery have been reported in women compared with in men. Despite the growing recognition of sex-specific determinants of outcomes, representation of women in clinical studies remains low and sex-specific management strategies are generally not provided in guidelines. This review summarizes the current evidence on sex-related differences in patients with CAD, focusing on the differential outcomes following medical therapy, percutaneous coronary interventions, and coronary artery bypass surgery.

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

J Am Coll Cardiol: 12 Apr 2022; 79:1407-1425
Gaudino M, Di Franco A, Cao D, Giustino G, ... Dangas GD, Mehran R
J Am Coll Cardiol: 12 Apr 2022; 79:1407-1425 | PMID: 35393023
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Impact:
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

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

Effects of Experimental Sleep Restriction on Energy Intake, Energy Expenditure, and Visceral Obesity.

Covassin N, Singh P, McCrady-Spitzer SK, St Louis EK, ... Levine JA, Somers VK
Background
Although the consequences of sleep deficiency for obesity risk are increasingly apparent, experimental evidence is limited and there are no studies on body fat distribution.
Objectives
The purpose of this study was to investigate the effects of experimentally-induced sleep curtailment in the setting of free access to food on energy intake, energy expenditure, and regional body composition.
Methods
Twelve healthy, nonobese individuals (9 males, age range 19 to 39 years) completed a randomized, controlled, crossover, 21-day inpatient study comprising 4 days of acclimation, 14 days of experimental sleep restriction (4 hour sleep opportunity) or control sleep (9 hour sleep opportunity), and a 3-day recovery segment. Repeated measures of energy intake, energy expenditure, body weight, body composition, fat distribution and circulating biomarkers were acquired.
Results
With sleep restriction vs control, participants consumed more calories (P = 0.015), increasing protein (P = 0.050) and fat intake (P = 0.046). Energy expenditure was unchanged (all P > 0.16). Participants gained significantly more weight when exposed to experimental sleep restriction than during control sleep (P = 0.008). While changes in total body fat did not differ between conditions (P = 0.710), total abdominal fat increased only during sleep restriction (P = 0.011), with significant increases evident in both subcutaneous and visceral abdominal fat depots (P = 0.047 and P = 0.042, respectively).
Conclusions
Sleep restriction combined with ad libitum food promotes excess energy intake without varying energy expenditure. Weight gain and particularly central accumulation of fat indicate that sleep loss predisposes to abdominal visceral obesity. (Sleep Restriction and Obesity; NCT01580761).

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

J Am Coll Cardiol: 05 Apr 2022; 79:1254-1265
Covassin N, Singh P, McCrady-Spitzer SK, St Louis EK, ... Levine JA, Somers VK
J Am Coll Cardiol: 05 Apr 2022; 79:1254-1265 | PMID: 35361348
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Impact:
Abstract

Prognostic Impact of Mildly Impaired Renal Function in Patients Undergoing Multivessel Coronary Revascularization.

Kim TO, Kang DY, Ahn JM, Kim SO, ... Park DW, Asan Medical Center–Multivessel Revascularization Registry Investigators
Background
The long-term prognostic impact of mildly decreased renal function in patients undergoing coronary revascularization is still unknown.
Objectives
The goal of this study was to investigate the long-term prognostic impact of mildly decreased renal function and comparative outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in such a risk group of patients.
Methods
From the Asan Medical Center-Multivessel Revascularization registry, 10,354 eligible patients who underwent coronary revascularization were classified into 3 groups (stage I [n = 3,735]: normal renal function; stage II [n = 5,122]: mild dysfunction; and stage III [n = 1,497]: moderate dysfunction) according to estimated glomerular filtration rate. The primary outcome was the composite of death, spontaneous myocardial infarction, or stroke. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics.
Results
After propensity matching, the risk for primary composite outcome was not different between the stage I and the stage II group (HR: 1.12; 95% CI: 0.97-1.30). However, the risk of the primary outcome was significantly higher in the stage III group than in the stage I group (HR: 1.50; 95% CI: 1.22-1.84). The relative effect of PCI vs CABG for the primary outcome was similar in the matched cohort of each renal function group of stages I, II, and III.
Conclusions
In patients with multivessel disease after revascularization by PCI or CABG, the presence of mildly decreased renal function was not significantly associated with an increased risk of the primary composite outcome and mortality. Comparative outcomes after PCI and CABG were similar in the borderline-risk group. (Asan Medical Center-Multivessel Revascularization registry; NCT02039752).

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

J Am Coll Cardiol: 05 Apr 2022; 79:1270-1284
Kim TO, Kang DY, Ahn JM, Kim SO, ... Park DW, Asan Medical Center–Multivessel Revascularization Registry Investigators
J Am Coll Cardiol: 05 Apr 2022; 79:1270-1284 | PMID: 35361350
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Impact:
Abstract

Critical Comparison of Documents From Scientific Societies on Cardiac Amyloidosis: JACC State-of-the-Art Review.

Rapezzi C, Aimo A, Serenelli M, Barison A, ... Garcia-Pavia P, Emdin M
Over the last year, 5 national or international scientific societies have issued documents regarding cardiac amyloidosis (CA) to highlight the emerging clinical science, raise awareness, and facilitate diagnosis and management of CA. These documents provide useful guidance for clinicians managing patients with CA, and all include: 1) an algorithm to establish a diagnosis; 2) an emphasis on noninvasive diagnosis with the combined use of bone scintigraphy and the exclusion of a monoclonal protein; and 3) indications for novel disease-modifying therapies for symptomatic CA, either with or without peripheral neuropathy. Nonetheless, the documents diverge on specific details of diagnosis, risk stratification, and treatment. Highlighting the similarities and differences of the documents by the 5 scientific societies with respect to diagnosis, risk stratification, and treatment offers useful insight into the knowledge gaps and unmet needs in the management of CA. An analysis of these documents, therefore, highlights \"gray zones\" requiring further investigation.

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

J Am Coll Cardiol: 05 Apr 2022; 79:1288-1303
Rapezzi C, Aimo A, Serenelli M, Barison A, ... Garcia-Pavia P, Emdin M
J Am Coll Cardiol: 05 Apr 2022; 79:1288-1303 | PMID: 35361352
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Abstract

Comparison of American and European Guidelines for Primary Prevention of Cardiovascular Disease: JACC Guideline Comparison.

Fegers-Wustrow I, Gianos E, Halle M, Yang E
This review compares the primary prevention recommendations of the recent 2021 European Society of Cardiology (ESC) and 2019 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on cardiovascular disease (CVD) prevention. Although the 2019 ACC/AHA guideline represents its inaugural version, the ESC guideline is an update to its 2016 statement. Both guidelines address prevention using a holistic approach and agree on the importance of lifestyle optimization and intensified risk factor management. Cardiovascular (CV) risk assessment tools differ, reflecting the unique populations being screened as well as philosophical differences to their approach. Conventional risk factors are used to estimate CV risk, but each guideline acknowledges the role of risk modifiers to refine risk calculation. The ESC guideline recognizes the importance of nonclassical risk factors, including environmental issues, that impact CV health at the population level and calls for legislative action at the local, regional, and national levels.

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

J Am Coll Cardiol: 05 Apr 2022; 79:1304-1313
Fegers-Wustrow I, Gianos E, Halle M, Yang E
J Am Coll Cardiol: 05 Apr 2022; 79:1304-1313 | PMID: 35361353
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Abstract

Fulminant Myocarditis Following SARS-CoV-2 Infection: JACC Patient Care Pathways.

Rajpal S, Kahwash R, Tong MS, Paschke K, ... Gluckman TJ, Fuster V
A 60-year-old woman with a past medical history of asthma presented with fulminant myocarditis 9 days after testing positive for SARS-CoV-2 and 16 days after developing symptoms consistent with COVID-19. Her hospital course was complicated by the need for veno-arterial extracorporeal membrane oxygenation, ventricular arrhythmias, and pseudomonas bacteremia. She ultimately recovered and was discharged to home with normal left ventricular systolic function. Thereafter, she developed symptomatic ventricular tachycardia, for which she received an implantable cardioverter defibrillator and antiarrhythmic drug therapy.

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

J Am Coll Cardiol: 29 Mar 2022; epub ahead of print
Rajpal S, Kahwash R, Tong MS, Paschke K, ... Gluckman TJ, Fuster V
J Am Coll Cardiol: 29 Mar 2022; epub ahead of print | PMID: 35364210
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Impact:
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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Impact:
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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Impact:
Abstract

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Writing Committee Members, Heidenreich PA, Bozkurt B, Aguilar D, ... Vest AR, Yancy CW
Aim
The \"2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure\" replaces the \"2013 ACCF/AHA Guideline for the Management of Heart Failure\" and the \"2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.\" The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.
Methods
A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021.
Structure
Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients\' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

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

J Am Coll Cardiol: 24 Mar 2022; epub ahead of print
Writing Committee Members, Heidenreich PA, Bozkurt B, Aguilar D, ... Vest AR, Yancy CW
J Am Coll Cardiol: 24 Mar 2022; epub ahead of print | PMID: 35379503
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Impact:
Abstract

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Writing Committee Members, Heidenreich PA, Bozkurt B, Aguilar D, ... Vest AR, Yancy CW
Aim
The \"2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure\" replaces the \"2013 ACCF/AHA Guideline for the Management of Heart Failure\" and the \"2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.\" The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.
Methods
A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021.
Structure
Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients\' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

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

J Am Coll Cardiol: 24 Mar 2022; epub ahead of print
Writing Committee Members, Heidenreich PA, Bozkurt B, Aguilar D, ... Vest AR, Yancy CW
J Am Coll Cardiol: 24 Mar 2022; epub ahead of print | PMID: 35379504
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Impact:
Abstract

Effect of Pelacarsen on Lipoprotein(a) Cholesterol and Corrected Low-Density Lipoprotein Cholesterol.

Yeang C, Karwatowska-Prokopczuk E, Su F, Dinh B, ... Witztum JL, Tsimikas S
Background
Laboratory methods that report low-density lipoprotein cholesterol (LDL-C) include both LDL-C and lipoprotein(a) cholesterol [Lp(a)-C] content.
Objectives
The purpose of this study was to assess the effect of pelacarsen on directly measured Lp(a)-C and LDL-C corrected for its Lp(a)-C content.
Methods
The authors evaluated subjects with a history of cardiovascular disease and elevated Lp(a) randomized to 5 groups of cumulative monthly doses of 20-80 mg pelacarsen vs placebo. Direct Lp(a)-C was measured on isolated Lp(a) using LPA4-magnetic beads directed to apolipoprotein(a). LDL-C was reported as: 1) LDL-C as reported by the clinical laboratory; 2) LDL-Ccorr = laboratory-reported LDL-C - direct Lp(a)-C; and 3) LDL-CcorrDahlén = laboratory LDL-C - [Lp(a) mass × 0.30] estimated by the Dahlén formula.
Results
The baseline median Lp(a)-C values in the groups ranged from 11.9 to 15.6 mg/dL. Compared with placebo, pelacarsen resulted in dose-dependent decreases in Lp(a)-C (2% vs -29% to -67%; P = 0.001-<0.0001). Baseline laboratory-reported mean LDL-C ranged from 68.5 to 89.5 mg/dL, whereas LDL-Ccorr ranged from 55 to 74 mg/dL. Pelacarsen resulted in mean percent/absolute changes of -2% to -19%/-0.7 to -8.0 mg/dL (P = 0.95-0.05) in LDL-Ccorr, -7% to -26%/-5.4 to -9.4 mg/dL (P = 0.44-<0.0001) in laboratory-reported LDL-C, and 3.1% to 28.3%/0.1 to 9.5 mg/dL (P = 0.006-0.50) increases in LDL-CcorrDahlén. Total apoB declined by 3%-16% (P = 0.40-<0.0001), but non-Lp(a) apoB was not significantly changed.
Conclusions
Pelacarsen significantly lowers direct Lp(a)-C and has neutral to mild lowering of LDL-Ccorr. In patients with elevated Lp(a), LDL-Ccorr provides a more accurate reflection of changes in LDL-C than either laboratory-reported LDL-C or the Dahlén formula.

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

J Am Coll Cardiol: 22 Mar 2022; 79:1035-1046
Yeang C, Karwatowska-Prokopczuk E, Su F, Dinh B, ... Witztum JL, Tsimikas S
J Am Coll Cardiol: 22 Mar 2022; 79:1035-1046 | PMID: 35300814
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Impact:
Abstract

Electronic Alerts to Improve Heart Failure Therapy in Outpatient Practice: A Cluster Randomized Trial.

Ghazi L, Yamamoto Y, Riello RJ, Coronel-Moreno C, ... Desai NR, Ahmad T
Background
Use of GDMT is under-prescribed in patients with HFrEF.
Objectives
To examine whether targeted and tailored EHR alerts recommending GDMT in eligible patients with HFrEF improves utilization.
Methods
PROMPT-HF was a pragmatic, EHR-based, cluster-randomized comparative effectiveness trial. 100 providers caring for patients with HFrEF were randomized to either an alert or usual care. The alert notified providers of individualized GDMT recommendations along with patient characteristics. The primary outcome was an increase in the number of GDMT classes prescribed at 30 days post-randomization. Providers were surveyed on knowledge of guidelines and user experience.
Results
We enrolled 1,310 ambulatory HFrEF patients April-October 2021. Median age was 72 years; 31% were female; 18% were black; median LVEF was 32%. At baseline, 84% were receiving β-blockers, 71% RAASi, 29% MRA, and 11% SGLTi. The primary outcome occurred in 176/685 (26%) participants in the alert arm versus 117/625 (19%) in the usual care arm, increasing GDMT class prescription by >40% after alert exposure [adjusted RR: 1.41 (1.03, 1.93); P=0.03]. The number of patients needed to alert to result in an increase in addition of GDMT class was 14. 79% of alerted providers agreed that the alert was effective at enabling improved prescription of medical therapy for HF.
Conclusions
A real-time, targeted, and tailored EHR-based alerting system for outpatients with HFrEF led to significantly higher rates of GDMT at 30 days when compared with usual care. This low-cost intervention can be rapidly integrated into clinical care and accelerate adoption of high-value therapies in heart failure.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 19 Mar 2022; epub ahead of print
Ghazi L, Yamamoto Y, Riello RJ, Coronel-Moreno C, ... Desai NR, Ahmad T
J Am Coll Cardiol: 19 Mar 2022; epub ahead of print | PMID: 35385798
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Impact:
Abstract

Left Ventricular Thrombus Following Acute Myocardial Infarction: JACC State-of-the-Art Review.

Camaj A, Fuster V, Giustino G, Bienstock SW, ... Dweck MR, Goldman ME
The incidence of left ventricular (LV) thrombus following acute myocardial infarction has markedly declined in recent decades caused by advancements in reperfusion and antithrombotic therapies. Despite this, embolic events remain the most feared complication of LV thrombus necessitating systemic anticoagulation. Mechanistically, LV thrombus development depends on Virchow\'s triad (ie, endothelial injury from myocardial infarction, blood stasis from LV dysfunction, and hypercoagulability triggered by inflammation, with each of these elements representing potential therapeutic targets). Diagnostic modalities include transthoracic echocardiography with or without ultrasound-enhancing agents and cardiac magnetic resonance. Most LV thrombi develop within the first 2 weeks post-acute myocardial infarction, and the role of surveillance imaging appears limited. Vitamin K antagonists remain the mainstay of therapy because the efficacy of direct oral anticoagulants is less well established. Only meager data support the routine use of prophylactic anticoagulation, even in high-risk patients.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 14 Mar 2022; 79:1010-1022
Camaj A, Fuster V, Giustino G, Bienstock SW, ... Dweck MR, Goldman ME
J Am Coll Cardiol: 14 Mar 2022; 79:1010-1022 | PMID: 35272796
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Impact:
Abstract

Key Questions About Familial Hypercholesterolemia: JACC Review Topic of the Week.

Sniderman AD, Glavinovic T, Thanassoulis G
Familial hypercholesterolemia (FH) is characterized as a monogenic, autosomal dominant disorder, producing severe hypercholesterolemia within families due to causal variants within genes regulating the low-density lipoprotein receptor pathway. Demonstration of a causal variant is widely accepted as evidence of substantially higher cardiovascular risk. However, recent large-scale population studies challenge this characterization of FH, which appears to account for only a minor portion of those with severe hypercholesterolemia. Moreover, a substantial portion of FH variant positive patients do not have marked hypercholesterolemia. These discordances raise doubt as to how FH should be defined and how the concentration of low-density lipoprotein in plasma is regulated in individuals with and without FH. Moreover, review of the evidence suggests the impact of an FH causal variant on cardiovascular risk may be less than previously accepted and that all patients with severe hypercholesterolemia should be prioritized for therapy and family screening.

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

J Am Coll Cardiol: 14 Mar 2022; 79:1023-1031
Sniderman AD, Glavinovic T, Thanassoulis G
J Am Coll Cardiol: 14 Mar 2022; 79:1023-1031 | PMID: 35272797
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Impact:
Abstract

Restoring Sinus Rhythm Reverses Cardiac Remodeling and Reduces Valvular Regurgitation in Patients With Atrial Fibrillation.

Soulat-Dufour L, Lang S, Addetia K, Ederhy S, ... Lang RM, Cohen A
Background
Cardiac chamber remodeling in atrial fibrillation (AF) reflects the progression of cardiac rhythm and may affect functional regurgitation.
Objectives
The purpose of this study was to explore the 3-dimensional echocardiographic variables of cardiac cavity remodeling and the impact on functional regurgitation in patients with AF with/without sinus rhythm restoration at 12 months.
Methods
A total of 117 consecutive patients hospitalized for AF were examined using serial 3-dimensional transthoracic echocardiography at admission, at 6 months, and at 12 months (337 examinations).
Results
During follow-up, 47 patients with active restoration of sinus rhythm (SR) (through cardioversion and/or ablation) had a decrease in all atrial indexed volumes (Vi), end-systolic (ES) right ventricular (RV) Vi, an increase in end-diastolic (ED) left ventricular Vi, and an improvement in 4-chambers function (P < 0.05). Patients with absence/failure of restoration of SR (n = 39) had an increase in ED left atrial Vi and ED/ES RV Vi without modification of 4-chambers function, except for a decrease in left atrial emptying fraction (P < 0.05). Patients with spontaneous restoration of SR (n = 31) had no changes in Vi or function. The authors found an improvement vs baseline in severity of functional regurgitation in patients with active restoration of SR (tricuspid and mitral regurgitation) and in spontaneous restoration of SR (tricuspid regurgitation) (P < 0.05). In multivariable analysis, right atrial and/or left atrial reverse remodeling exclusively correlated with intervention (cardioversion and/or ablation) during 12-month follow-up.
Conclusions
Management of AF should focus on restoration of SR to induce anatomical (all atrial Vi, ES RV Vi) and/or functional (4 chambers) cardiac cavity reverse remodeling and reduce severity of functional regurgitation. (Thromboembolic and Bleeding Risk Stratification in Patients With Non-valvular Atrial Fibrillation [FASTRHAC]; NCT02741349).

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

J Am Coll Cardiol: 14 Mar 2022; 79:951-961
Soulat-Dufour L, Lang S, Addetia K, Ederhy S, ... Lang RM, Cohen A
J Am Coll Cardiol: 14 Mar 2022; 79:951-961 | PMID: 35272799
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Abstract

5-Year Outcomes of PCI Guided by Measurement of Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve.

Götberg M, Berntorp K, Rylance R, Christiansen EH, ... Erlinge D, Fröbert O
Background
Instantaneous wave-free ratio (iFR) is a coronary physiology index used to assess the severity of coronary artery stenosis to guide revascularization. iFR has previously demonstrated noninferior short-term outcome compared to fractional flow reserve (FFR), but data on longer-term outcome have been lacking.
Objectives
The purpose of this study was to investigate the prespecified 5-year follow-up of the primary composite outcome of all-cause mortality, myocardial infarction, and unplanned revascularization of the iFR-SWEDEHEART trial comparing iFR vs FFR in patients with chronic and acute coronary syndromes.
Methods
iFR-SWEDEHEART was a multicenter, controlled, open-label, registry-based randomized clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2,037 patients were randomized to undergo revascularization guided by iFR or FFR.
Results
No patients were lost to follow-up. At 5 years, the rate of the primary composite endpoint was 21.5% in the iFR group and 19.9% in the FFR group (HR: 1.09; 95% CI: 0.90-1.33). The rates of all-cause death (9.4% vs 7.9%; HR: 1.20; 95% CI: 0.89-1.62), nonfatal myocardial infarction (5.7% vs 5.8%; HR: 1.00; 95% CI: 0.70-1.44), and unplanned revascularization (11.6% vs 11.3%; HR: 1.02; 95% CI: 0.79-1.32) were also not different between the 2 groups. The outcomes were consistent across prespecified subgroups.
Conclusions
In patients with chronic or acute coronary syndromes, an iFR-guided revascularization strategy was associated with no difference in the 5-year composite outcome of death, myocardial infarction, and unplanned revascularization compared with an FFR-guided revascularization strategy. (Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome [iFR SWEDEHEART]; NCT02166736).

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

J Am Coll Cardiol: 14 Mar 2022; 79:965-974
Götberg M, Berntorp K, Rylance R, Christiansen EH, ... Erlinge D, Fröbert O
J Am Coll Cardiol: 14 Mar 2022; 79:965-974 | PMID: 35272801
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Impact:
Abstract

Thrombolysis or Surgery in Patients With Obstructive Mechanical Valve Thrombosis: The Multicenter HATTUSHA Study.

Özkan M, Gündüz S, Güner A, Kalçık M, ... Onan B, Koçoğulları CU
Background
Prosthetic valve thrombosis (PVT) is one of the life-threatening complications of prosthetic heart valve replacement. Due to the lack of randomized controlled trials, the optimal treatment of PVT remains controversial between thrombolytic therapy (TT) and surgery.
Objectives
This study aimed to prospectively evaluate the outcomes of TT and surgery as the first-line treatment strategy in patients with obstructive PVT.
Methods
A total of 158 obstructive PVT patients (women: 103 [65.2%]; median age 49 years [IQR: 39-60 years]) were enrolled in this multicenter observational prospective study. TT was performed using slow (6 hours) and/or ultraslow (25 hours) infusion of low-dose tissue plasminogen activator (t-PA) (25 mg) mostly in repeated sessions. The primary endpoint of the study was 3-month mortality following TT or surgery.
Results
The initial management strategy was TT in 83 (52.5%) patients and surgery in 75 (47.5%) cases. The success rate of TT was 90.4% with a median t-PA dose of 59 mg (IQR: 37.5-100 mg). The incidences of outcomes in surgery and TT groups were as follows: minor complications (29 [38.7%] and 7 [8.4%], respectively), major complications (31 [41.3%] and 5 [6%], respectively), and the 3-month mortality rate (14 [18.7%] and 2 [2.4%], respectively).
Conclusions
Low-dose and slow/ultraslow infusion of t-PA were associated with low complications and mortality and high success rates and should be considered as a viable treatment in patients with obstructive PVT.

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

J Am Coll Cardiol: 14 Mar 2022; 79:977-989
Özkan M, Gündüz S, Güner A, Kalçık M, ... Onan B, Koçoğulları CU
J Am Coll Cardiol: 14 Mar 2022; 79:977-989 | PMID: 35272803
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Impact:
Abstract

Improved Outcomes Following the Ross Procedure Compared With Bioprosthetic Aortic Valve Replacement.

Mazine A, David TE, Stoklosa K, Chung J, Lafreniere-Roula M, Ouzounian M
Background
The ideal aortic valve substitute for young and middle-aged adults remains elusive.
Objectives
This study sought to compare the long-term outcomes of patients undergoing the Ross procedure and those receiving bioprosthetic aortic valve replacements (AVRs).
Methods
Consecutive patients aged 16-60 years who underwent a Ross procedure or surgical bioprosthetic AVR at the Toronto General Hospital between 1990 and 2014 were identified. Propensity score matching was used to account for differences in baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes included valve reintervention, valve deterioration, endocarditis, thromboembolic events, and permanent pacemaker implantation.
Results
Propensity score matching yielded 108 pairs of patients. The median age was 41 years (IQR: 34-47 years). Baseline characteristics were similar between the matched groups. There was no operative mortality in either group. Mean follow-up was 14.5 ± 7.2 years. All-cause mortality was lower following the Ross procedure (HR: 0.35; 95% CI: 0.14-0.90; P = 0.028). Using death as a competing risk, the Ross procedure was associated with lower rates of reintervention (HR: 0.21; 95% CI: 0.10-0.41; P < 0.001), valve deterioration (HR: 0.25; 95% CI: 0.14-0.45; P < 0.001), thromboembolic events (HR: 0.15; 95% CI: 0.05-0.50; P = 0.002), and permanent pacemaker implantation (HR: 0.22; 95% CI: 0.07-0.64; P = 0.006).
Conclusions
In this propensity-matched study, the Ross procedure was associated with better long-term survival and freedom from adverse valve-related events compared with bioprosthetic AVR. In specialized centers with sufficient expertise, the Ross procedure should be considered the primary option for young and middle-aged adults undergoing AVR.

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

J Am Coll Cardiol: 14 Mar 2022; 79:993-1005
Mazine A, David TE, Stoklosa K, Chung J, Lafreniere-Roula M, Ouzounian M
J Am Coll Cardiol: 14 Mar 2022; 79:993-1005 | PMID: 35272805
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Impact:
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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Impact:
Abstract

Variability in Coronary Artery Disease Testing for Patients With New-Onset Heart Failure.

Zheng J, Heidenreich PA, Kohsaka S, Fearon WF, Sandhu AT
Background
Coronary artery disease (CAD) is the most common cause of new-onset heart failure (HF). Although guidelines recommend ischemic evaluation in this population, testing has historically been underutilized.
Objectives
This study aimed to identify contemporary trends in CAD testing for patients with new-onset HF, particularly after publication of the STICHES (Surgical Treatment for Ischemic Heart Failure Extension Study), and to characterize geographic and clinician-level variability in testing patterns.
Methods
We determined the proportion of patients with incident HF who received CAD testing from 2004 to 2019 using an administrative claims database covering commercial insurance and Medicare. We identified demographic and clinical predictors of CAD testing during the 90 days before and after initial diagnosis. Patients were grouped by their county of residence to assess national variation. Patients were then linked to their primary care physician and/or cardiologist to evaluate variation across clinicians.
Results
Among 558,322 patients with new-onset HF, 34.8% underwent CAD testing and 9.3% underwent revascularization. After multivariable adjustment, patients who underwent CAD testing were more likely to be younger, male, diagnosed in an acute care setting, and have systolic dysfunction or recent cardiogenic shock. Incidence of CAD testing remained flat without significant change post-STICHES. Covariate-adjusted testing rates varied from 20% to 45% across counties. The likelihood of testing was higher among patients co-managed by a cardiologist (adjusted OR: 5.12; 95% CI: 4.98-5.27) but varied substantially across cardiologists (IQR: 50.9%-62.4%).
Conclusions
Most patients with new-onset HF across inpatient and outpatient settings did not receive timely testing for CAD. Substantial variability in testing persists across regions and clinicians.

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

J Am Coll Cardiol: 07 Mar 2022; 79:849-860
Zheng J, Heidenreich PA, Kohsaka S, Fearon WF, Sandhu AT
J Am Coll Cardiol: 07 Mar 2022; 79:849-860 | PMID: 35241218
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Abstract

Trends in Utilization of Aortic Valve Replacement for Severe Aortic Stenosis.

Li SX, Patel NK, Flannery LD, Selberg A, ... Turchin A, Elmariah S
Background
Despite the rapid growth of aortic valve replacement (AVR) for aortic stenosis (AS), limited data suggest symptomatic severe AS remains undertreated.
Objectives
This study sought to investigate temporal trends in AVR utilization among patients with a clinical indication for AVR.
Methods
Patients with severe AS (aortic valve area <1 cm2) on transthoracic echocardiograms from 2000 to 2017 at 2 large academic medical centers were classified based on clinical guideline indications for AVR and divided into 4 AS subgroups: high gradient with normal left ventricular ejection fraction (LVEF) (HG-NEF), high gradient with low LVEF (HG-LEF), low gradient with normal LVEF (LG-NEF), and low gradient with low LVEF (LG-LEF). Utilization of AVR was examined and predictors identified.
Results
Of 10,795 patients, 6,150 (57%) had an indication or potential indication for AVR, of whom 2,977 (48%) received AVR. The frequency of AVR varied by AS subtype with LG groups less likely to receive an AVR (HG-NEF: 70%, HG-LEF: 53%, LG-NEF: 32%, LG-LEF: 38%, P < 0.001). AVR volumes grew over the 18-year study period but were paralleled by comparable growth in the number of patients with an indication for AVR. In patients with a Class I indication, younger age, coronary artery disease, smoking history, higher hematocrit, outpatient index transthoracic echocardiogram, and LVEF ≥0.5 were independently associated with an increased likelihood of receiving an AVR. AVR was associated with improved survival in each AS-subgroup.
Conclusions
Over an 18-year period, the proportion of patients with an indication for AVR who did not receive AVR has remained substantial despite the rapid growth of AVR volumes.

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

J Am Coll Cardiol: 07 Mar 2022; 79:864-877
Li SX, Patel NK, Flannery LD, Selberg A, ... Turchin A, Elmariah S
J Am Coll Cardiol: 07 Mar 2022; 79:864-877 | PMID: 35241220
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Impact:
Abstract

2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

Forrest JK, Deeb GM, Yakubov SJ, Rovin JD, ... Huang J, Reardon MJ
Background
The Evolut Low Risk Trial (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients) showed that transcatheter aortic valve replacement (TAVR) with a supra-annular, self-expanding valve was noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke at 2 years. This finding was based on a Bayesian analysis performed after 850 patients had reached 1 year of follow-up.
Objectives
The goal of this study was to report the full 2-year clinical and echocardiographic outcomes for patients enrolled in the Evolut Low Risk Trial.
Methods
A total of 1,414 low-surgical risk patients with severe aortic stenosis were randomized to receive TAVR or surgical AVR. An independent clinical events committee adjudicated adverse events, and a central echocardiographic core laboratory assessed hemodynamic endpoints.
Results
An attempted implant was performed in 730 TAVR and 684 surgical patients from March 2016 to May 2019. The Kaplan-Meier rates for the complete 2-year primary endpoint of death or disabling stroke were 4.3% in the TAVR group and 6.3% in the surgery group (P = 0.084). These rates were comparable to the interim Bayesian rates of 5.3% with TAVR and 6.7% with surgery (difference: -1.4%; 95% Bayesian credible interval: -4.9% to 2.1%). All-cause mortality rates were 3.5% vs 4.4% (P = 0.366), and disabling stroke rates were 1.5% vs 2.7% (P = 0.119), respectively. Between years 1 and 2, there was no convergence of the primary outcome curves.
Conclusions
The complete 2-year follow-up from the Evolut Low Risk Trial found that TAVR is noninferior to surgery for the primary endpoint of all-cause mortality or disabling stroke, with event rates that were slightly better than those predicted by using the Bayesian analysis. (Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients [Evolut Low Risk Trial]; NCT02701283).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 07 Mar 2022; 79:882-896
Forrest JK, Deeb GM, Yakubov SJ, Rovin JD, ... Huang J, Reardon MJ
J Am Coll Cardiol: 07 Mar 2022; 79:882-896 | PMID: 35241222
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Impact:
Abstract

Recovery With Temporary Mechanical Circulatory Support While Waitlisted for Heart Transplantation.

Topkara VK, Sayer GT, Clerkin KJ, Wever-Pinzon O, ... Uriel N, Drakos SG
Background
The 2018 U.S. heart allocation system offers an accelerated pathway for heart transplantation to the most urgent patients.
Objectives
This study sought to determine whether the new allocation system resulted in lower likelihood of candidate recovery.
Methods
Adult patients waitlisted for heart transplantation with temporary mechanical circulatory support at the time of initial listing between 2010 and 2020 in the United Network for Organ Sharing registry were included. Competing events of heart transplantation, waitlist death or delisting for deteriorating condition, and delisting for improved condition (candidate recovery) were analyzed in the new vs old heart allocation system.
Results
A total of 688 patients were waitlisted with venoarterial extracorporeal membrane oxygenation or a surgical nondischargeable biventricular assist device (status 1 or old 1A). Overall, 2,237 patients were waitlisted with an intra-aortic balloon pump, a percutaneous left ventricular assist device (LVAD), or a surgical nondischargeable LVAD (status 2 or old 1A). Patients waitlisted with venoarterial extracorporeal membrane oxygenation or a nondischargeable biventricular assist device had significantly shorter median waitlist times (5 vs 31 days), higher incidence for cardiac transplantation (81.5% vs 43.0%), and lower incidence of candidate recovery (1.5% vs 7.9%) in the new vs old heart allocation system (all P < 0.05). Patients waitlisted with an intra-aortic balloon pump or percutaneous or a nondischargeable LVAD also had significantly shorter median waitlist times (8 vs 35 days), higher incidence of transplantation (88.9% vs 64.9%), and lower incidence of candidate recovery (0.2% vs 1.6%) in the new vs old heart allocation system (all P < 0.05).
Conclusions
Current practice of the new allocation system may not offer select temporary mechanical circulatory support patients the opportunity and adequate time to recover to the point of waitlist removal. Further research will determine which patients would benefit from urgent transplantation vs recovery strategy.

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

J Am Coll Cardiol: 07 Mar 2022; 79:900-913
Topkara VK, Sayer GT, Clerkin KJ, Wever-Pinzon O, ... Uriel N, Drakos SG
J Am Coll Cardiol: 07 Mar 2022; 79:900-913 | PMID: 35241224
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Impact:
Abstract

Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk.

Mehta A, Vasquez N, Ayers CR, Patel J, ... Blaha MJ, Joshi PH
Background
Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination.
Objectives
This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk.
Methods
Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models.
Results
Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.
Conclusions
Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.

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

J Am Coll Cardiol: 28 Feb 2022; 79:757-768
Mehta A, Vasquez N, Ayers CR, Patel J, ... Blaha MJ, Joshi PH
J Am Coll Cardiol: 28 Feb 2022; 79:757-768 | PMID: 35210030
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Impact:
Abstract

Surgical Treatment of Patients With Infective Endocarditis After Transcatheter Aortic Valve Implantation.

Mangner N, Val DD, Abdel-Wahab M, Crusius L, ... Linke A, Rodés-Cabau J
Background
The optimal treatment of patients developing infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is uncertain.
Objectives
The goal of this study was to investigate the clinical characteristics and outcomes of patients with TAVI-IE treated with cardiac surgery and antibiotics (IE-CS) compared with patients treated with antibiotics alone (IE-AB).
Methods
Crude and inverse probability of treatment weighting analyses were applied for the treatment effect of cardiac surgery vs medical therapy on 1-year all-cause mortality in patients with definite TAVI-IE. The study used data from the Infectious Endocarditis after TAVI International Registry.
Results
Among 584 patients, 111 patients (19%) were treated with IE-CS and 473 patients (81%) with IE-AB. Compared with IE-AB, IE-CS was not associated with a lower in-hospital mortality (HRunadj: 0.85; 95% CI: 0.58-1.25) and 1-year all-cause mortality (HRunadj: 0.88; 95% CI: 0.64-1.22) in the crude cohort. After adjusting for selection and immortal time bias, IE-CS compared with IE-AB was also not associated with lower mortality rates for in-hospital mortality (HRadj: 0.92; 95% CI: 0.80-1.05) and 1-year all-cause mortality (HRadj: 0.95; 95% CI: 0.84-1.07). Results remained similar when patients with and without TAVI prosthesis involvement were analyzed separately. Predictors for in-hospital and 1-year all-cause mortality included logistic EuroSCORE I, Staphylococcus aureus, acute renal failure, persistent bacteremia, and septic shock.
Conclusions
In this registry, the majority of patients with TAVI-IE were treated with antibiotics alone. Cardiac surgery was not associated with an improved all-cause in-hospital or 1-year mortality. The high mortality of patients with TAVI-IE was strongly linked to patients\' characteristics, pathogen, and IE-related complications.

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

J Am Coll Cardiol: 28 Feb 2022; 79:772-785
Mangner N, Val DD, Abdel-Wahab M, Crusius L, ... Linke A, Rodés-Cabau J
J Am Coll Cardiol: 28 Feb 2022; 79:772-785 | PMID: 35210032
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Impact:
Abstract

Managing Atherosclerotic Cardiovascular Risk in Young Adults: JACC State-of-the-Art Review.

Stone NJ, Smith SC, Orringer CE, Rigotti NA, ... Pencina MJ, Grundy SM
There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians identify and address high-risk conditions in the 20- to 39-year age range (young adults). These include tobacco use, elevated blood pressure/hypertension, family history of premature ASCVD, primary severe hypercholesterolemia such as familial hypercholesterolemia, diabetes with diabetes-specific risk-enhancing factors, or the presence of multiple other risk-enhancing factors, including in females, a history of pre-eclampsia or menopause under age 40. The authors update current thinking on lipid risk factors such as triglycerides, non-high-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein (a) that are useful in understanding an individual\'s long-term ASCVD risk. The authors review emerging strategies, such as coronary artery calcium and polygenic risk scores in this age group, that have potential clinical utility, but whose best use remains uncertain. Finally, the authors discuss both the obstacles and opportunities for addressing prevention in early adulthood.

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

J Am Coll Cardiol: 28 Feb 2022; 79:819-836
Stone NJ, Smith SC, Orringer CE, Rigotti NA, ... Pencina MJ, Grundy SM
J Am Coll Cardiol: 28 Feb 2022; 79:819-836 | PMID: 35210038
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Impact:
Abstract

Clinical Outcomes in Patients With Delayed Hospitalization for Non-ST-Segment Elevation Myocardial Infarction.

Cha JJ, Bae S, Park DW, Park JH, ... Jeong MH, Ahn TH
Background
Recently, the number of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) has reduced, whereas increased mortality was reported. A plausible explanation for increased mortality was prehospital delay because of patients\' reticence of their symptoms.
Objectives
The purpose of this study was to investigate the association between prehospital delay and clinical outcomes in patients with NSTEMI
Methods:
Among 13,104 patients from the Korea-Acute-Myocardial-Infarction-Registry-National Institutes of Health, the authors evaluated 6,544 patients with NSTEMI. Study patients were categorized into 2 groups according to symptom-to-door (StD) time (<24 or ≥24 hours). The primary outcome was 3-year all-cause mortality, and the secondary outcome was 3-year composite of all-cause mortality, recurrent MI, and hospitalization for heart failure.
Results
Overall, 1,827 (27.9%) patients were classified into the StD time ≥24 hours group. The StD time ≥24 hours group had higher all-cause mortality (17.0% vs 10.5%; P < 0.001) and incidence of secondary outcomes (23.3% vs 15.7%; P < 0.001) than the StD time <24 hours group. The higher all-cause mortality in the StD time ≥24 hours group was observed consistently in the subgroup analysis regarding age, sex, atypical chest pain, dyspnea, Q-wave in electrocardiogram, use of emergency medical services, hypertension, diabetes mellitus, chronic kidney disease, left ventricle dysfunction, TIMI (Thrombolysis In Myocardial Infarction) flow, and the GRACE risk score. In the multivariable analysis, independent predictors of prehospital delay were the elderly, women, nonspecific symptoms such as atypical chest pain or dyspnea, diabetes, and no use of emergency medical services.
Conclusions
Prehospital delay is associated with an increased risk of 3-year all-cause mortality in patients with NSTEMI. (iCReaT Study No. C110016).

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

J Am Coll Cardiol: 28 Feb 2022; 79:311-323
Cha JJ, Bae S, Park DW, Park JH, ... Jeong MH, Ahn TH
J Am Coll Cardiol: 28 Feb 2022; 79:311-323 | PMID: 35086652
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Impact:
Abstract

Criteria for Iron Deficiency in Patients With Heart Failure.

Masini G, Graham FJ, Pellicori P, Cleland JGF, ... Inciardi RM, Clark AL
Background
Guidelines on heart failure (HF) define iron deficiency (ID) as a serum ferritin <100 ng/mL or, when 100-299 ng/mL, a transferrin saturation (TSAT) <20%. Inflammation (common in HF) may hinder interpretation of serum ferritin.
Objectives
This study sought to investigate how different definitions of ID affect its prevalence and relationship to prognosis in ambulatory patients with chronic HF.
Methods
Prevalence, relationship with patients\' characteristics, and outcomes of various ID definitions were evaluated among patients with HF referred to a regional clinic (Hull LifeLab) from 2001 to 2019.
Results
Of 4,422 patients with HF (median age 75 years [range: 68-82 years], 60% men, 32% with reduced left ventricular ejection fraction), 46% had TSAT <20%, 48% had serum iron ≤13 μmol/L, 57% had serum ferritin <100 ng/mL, and 68% fulfilled current guideline criteria for ID, of whom 35% had a TSAT >20%. Irrespective of definition, ID was more common in women and those with more severe symptoms, anemia, or preserved ejection fraction. TSAT <20% and serum iron ≤13 μmol/L, but not guideline criteria, were associated with higher 5-year mortality (HR: 1.27; 95% CI: 1.14-1.43; P < 0.001; and HR: 1.37; 95% CI: 1.22-1.54; P < 0.001, respectively). Serum ferritin <100 ng/mL tended to be associated with lower mortality (HR: 0.91; 95% CI: 0.81-1.01; P = 0.09).
Conclusions
Different definitions of ID provide discordant results for prevalence and prognosis. Definitions lacking specificity may attenuate the benefits of intravenous iron observed in trials while definitions lacking sensitivity may exclude patients who should receive intravenous iron. Prespecified subgroup analyses of ongoing randomized trials should address this issue.

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

J Am Coll Cardiol: 28 Feb 2022; 79:341-351
Masini G, Graham FJ, Pellicori P, Cleland JGF, ... Inciardi RM, Clark AL
J Am Coll Cardiol: 28 Feb 2022; 79:341-351 | PMID: 35086656
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Impact:
Abstract

Race- and Gender-Based Differences in Cardiac Structure and Function and Risk of Heart Failure.

Chandra A, Skali H, Claggett B, Solomon SD, ... Chang PP, Shah AM
Background
Although heart failure (HF) risk and cardiac structure/function reportedly differ according to race and gender, limited data exist in late life when risk of HF is highest.
Objectives
The goal of this study was to evaluate race/gender-based differences in HF risk factors, cardiac structure/function, and incident HF in late life.
Methods
This analysis included 5,149 HF-free participants from ARIC (Atherosclerosis Risk In Communities), a prospective epidemiologic cohort study, who attended visit 5 (2011-2013) and underwent echocardiography. Participants were subsequently followed up for a median 5.5 years for incident HF/death.
Results
Patients\' mean age was 75 ± 5 years, 59% were women, and 20% were Black. Male gender and Black race were associated with lower mean left ventricular ejection fraction. Black race was also associated with greater left ventricular wall thickness and concentricity, differences that persisted after adjusting for cardiovascular comorbidities. After adjusting for cardiovascular comorbidities, men were at higher risk for HF and heart failure with reduced ejection fraction (HFrEF) in Black participants compared with White participants (HF: HR of 2.36 [95% CI: 1.37-4.08] vs 1.16 [95% CI: 0.89-1.51], interaction P = 0.016; HFrEF: HR of 3.70 [95% CI: 1.72-7.95] vs 1.55 [95% CI: 1.01-2.37] respectively, interaction P = 0.039). Black race was associated with a higher incidence of HF overall and HFrEF in men only (HF: 1.65 [95% CI: 1.07-2.53] vs 0.76 [95% CI: 0.49-1.17]; HFrEF: HR of 2.55 [95% CI: 1.46-4.44] vs 0.91 [95% CI: 0.46-1.83]). No race/gender-based differences were observed in risk of incident heart failure with preserved ejection fraction.
Conclusions
Among older persons free of HF, men and Black participants exhibit worse systolic performance and are at heightened risk for HFrEF, whereas the risk of heart failure with preserved ejection fraction is similar across gender and race groups.

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

J Am Coll Cardiol: 28 Feb 2022; 79:355-368
Chandra A, Skali H, Claggett B, Solomon SD, ... Chang PP, Shah AM
J Am Coll Cardiol: 28 Feb 2022; 79:355-368 | PMID: 35086658
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Abstract

Repeat Measures of Lipoprotein(a) Molar Concentration and Cardiovascular Risk.

Trinder M, Paruchuri K, Haidermota S, Bernardo R, ... Januzzi J, Natarajan P
Background
When indicated, guidelines recommend measurement of lipoprotein(a) for cardiovascular risk assessment. However, temporal variability in lipoprotein(a) is not well understood, and it is unclear if repeat testing may help refine risk prediction of coronary artery disease (CAD).
Objectives
The authors examined the stability of repeat lipoprotein(a) measurements and the association between instability in lipoprotein(a) molar concentration with incident CAD.
Methods
The authors assessed the correlation between baseline and first follow-up measurements of lipoprotein(a) in the UK Biobank (n = 16,017 unrelated individuals). The association between change in lipoprotein(a) molar concentration and incident CAD was assessed among 15,432 participants using Cox proportional hazards models.
Results
Baseline and follow-up lipoprotein(a) molar concentration were significantly correlated over a median of 4.42 years (IQR: 3.69-4.93 years; Spearman rho = 0.96; P < 0.0001). The correlation between baseline and follow-up lipoprotein(a) molar concentration were stable across time between measurements of <3 (rho = 0.96), 3-4 (rho = 0.97), 4-5 (rho = 0.96), and >5 years (rho = 0.96). Although there were negligible-to-modest associations between statin use and changes in lipoprotein(a) molar concentration, statin usage was associated with a significant increase in lipoprotein(a) among individuals with baseline levels ≥70 nmol/L. Follow-up lipoprotein(a) molar concentration was significantly associated with risk of incident CAD (HR per 120 nmol/L: 1.32 [95% CI: 1.16-1.50]; P = 0.0002). However, the delta between follow-up and baseline lipoprotein(a) molar concentration was not significantly associated with incident CAD independent of follow-up lipoprotein(a) (P = 0.98).
Conclusions
These findings suggest that, in the absence of therapies substantially altering lipoprotein(a), a single accurate measurement of lipoprotein(a) molar concentration is an efficient method to inform CAD risk.

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

J Am Coll Cardiol: 21 Feb 2022; 79:617-628
Trinder M, Paruchuri K, Haidermota S, Bernardo R, ... Januzzi J, Natarajan P
J Am Coll Cardiol: 21 Feb 2022; 79:617-628 | PMID: 35177190
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Abstract

Splenic Marginal Zone B Lymphocytes Regulate Cardiac Remodeling After Acute Myocardial Infarction in Mice.

Sun Y, Pinto C, Camus S, Duval V, ... Mallat Z, Silvestre JS
Background
Mature B lymphocytes alter the recovery of cardiac function after acute myocardial infarction (MI) in mice. Follicular B cells and marginal zone B (MZB) cells are spatially distinct mature B-cell populations in the spleen, and they exert specific functional properties. microRNA-21 (miR21)/hypoxia-inducible factor-α (HIF-α)-related pathways have been shown to govern B-cell functions.
Objectives
The goal of this study was to unravel the distinct role of MZB cells and that of endogenous activation of miR21/HIF-α signaling in MZB cells during post-ischemic injury.
Methods
Acute MI was induced in mice by permanent ligation of the left anterior descending coronary artery. Cardiac function and remodeling were assessed by using echocardiography and immunohistochemistry. To determine the specific role of MZB cells, the study used mice with B-cell lineage-specific conditional deletion of Notch signaling, which leads to selection deficiency of MZB cells. To evaluate the role of the HIF-1α isoform, mice were generated with MZB-cell lineage-specific conditional deletion of Hif1a.
Results
Acute MI prompted an miR21-dependent increase in HIF-1α, particularly in splenic MZB cells. MZB cell deficiency and MZB cell-specific deletion of miR21 or Hif1a improved cardiac function after acute MI. miR21/HIF-1α signaling in MZB cells was required for Toll-like receptor dependent expression of the monocyte chemoattractant protein CCL7, leading to increased mobilization of inflammatory monocytes to the ischemic myocardium and to adverse post-ischemic cardiac remodeling.
Conclusions
This work reveals a novel function for the miR21/HIF-1α pathway in splenic MZB cells with potential major implications for the modulation of cardiac function after acute MI.

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

J Am Coll Cardiol: 21 Feb 2022; 79:632-647
Sun Y, Pinto C, Camus S, Duval V, ... Mallat Z, Silvestre JS
J Am Coll Cardiol: 21 Feb 2022; 79:632-647 | PMID: 35177192
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Abstract

Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial.

Senior R, Reynolds HR, Min JK, Berman DS, ... Hochman JS, ISCHEMIA Research Group
Background
Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined.
Objectives
The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters.
Methods
This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters.
Results
Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684).
Conclusions
In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

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

J Am Coll Cardiol: 21 Feb 2022; 79:651-661
Senior R, Reynolds HR, Min JK, Berman DS, ... Hochman JS, ISCHEMIA Research Group
J Am Coll Cardiol: 21 Feb 2022; 79:651-661 | PMID: 35177194
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Abstract

Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation.

Leyva F, Zegard A, Okafor O, Foley P, ... Prasad SK, Qiu T
Background
Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias.
Objectives
The purpose of this study was to determine whether presence of myocardial fibrosis on visual assessment (MFVA) and gray zone fibrosis (GZF) mass predicts sudden cardiac death (SCD) and ventricular fibrillation/sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation.
Methods
In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of SCD and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation.
Results
Among 700 patients (age 68.0 ± 12.0 years), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over median 6.93 years (IQR: 5.82-9.32 years). MFVA predicted SCD (HR: 26.3; 95% CI: 3.7-3,337; negative predictive value: 100%). In competing risk analyses, MFVA also predicted the arrhythmic endpoint (subdistribution HR: 19.9; 95% CI: 6.4-61.9; negative predictive value: 98.6%). Compared with no MFVA, a GZF mass measured with the 5SD method (GZF5SD) >17 g was associated with highest risk of SCD (HR: 44.6; 95% CI: 6.12-5,685) and the arrhythmic endpoint (subdistribution HR: 30.3; 95% CI: 9.6-95.8). Adding GZF5SD mass to MFVA led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint.
Conclusions
In CIED recipients, MFVA excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF5SD mass added predictive value in relation to SCD and the arrhythmic endpoint.

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

J Am Coll Cardiol: 21 Feb 2022; 79:665-678
Leyva F, Zegard A, Okafor O, Foley P, ... Prasad SK, Qiu T
J Am Coll Cardiol: 21 Feb 2022; 79:665-678 | PMID: 35177196
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Abstract

Autonomic Neuromodulation for Atrial Fibrillation Following Cardiac Surgery: JACC Review Topic of the Week.

Zafeiropoulos S, Doundoulakis I, Farmakis IT, Miyara S, ... Stavrakis S, Zanos S
Autonomic neuromodulation therapies (ANMTs) (ie, ganglionated plexus ablation, epicardial injections for temporary neurotoxicity, low-level vagus nerve stimulation [LL-VNS], stellate ganglion block, baroreceptor stimulation, spinal cord stimulation, and renal nerve denervation) constitute an emerging therapeutic approach for arrhythmias. Very little is known about ANMTs\' preventive potential for postoperative atrial fibrillation (POAF) after cardiac surgery. The purpose of this review is to summarize and critically appraise the currently available evidence. Herein, the authors conducted a systematic review of 922 articles that yielded 7 randomized controlled trials. In the meta-analysis, ANMTs reduced POAF incidence (OR: 0.37; 95% CI: 0.25 to 0.55) and burden (mean difference [MD]: -3.51 hours; 95% CI: -6.64 to -0.38 hours), length of stay (MD: -0.82 days; 95% CI: -1.59 to -0.04 days), and interleukin-6 (MD: -79.92 pg/mL; 95% CI: -151.12 to -8.33 pg/mL), mainly attributed to LL-VNS and epicardial injections. Moving forward, these findings establish a base for future larger and comparative trials with ANMTs, to optimize and expand their use.

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

J Am Coll Cardiol: 21 Feb 2022; 79:682-694
Zafeiropoulos S, Doundoulakis I, Farmakis IT, Miyara S, ... Stavrakis S, Zanos S
J Am Coll Cardiol: 21 Feb 2022; 79:682-694 | PMID: 35177198
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This program is still in alpha version.