Journal: J Am Coll Cardiol

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<div><h4>Uptitrating Treatment After Heart Failure Hospitalization Across the Spectrum of Left Ventricular Ejection Fraction.</h4><i>Pagnesi M, Metra M, Cohen-Solal A, Edwards C, ... Mebazaa A, Davison B</i><br /><b>Background</b><br />Acute heart failure (AHF) is associated with a poor prognosis regardless of left ventricular ejection fraction (LVEF). STRONG-HF showed the efficacy and safety of a strategy of rapid uptitration of oral treatment for heart failure (HF) and close follow-up (high-intensity care), compared with usual care, in patients recently hospitalized for AHF and enrolled independently from their LVEF.<br /><b>Objectives</b><br />In this study, we sought to assess the impact of baseline LVEF on the effects of high-intensity care vs usual care in STRONG-HF.<br /><b>Methods</b><br />The STRONG-HF trial enrolled patients hospitalized for AHF with any LVEF and not treated with full doses of renin-angiotensin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. High-intensity care with uptitration of oral medications was performed independently from LVEF. The primary endpoint was the composite of HF rehospitalization or all-cause death at day 180.<br /><b>Results</b><br />Among the 1,078 patients randomized, 731 (68%) had LVEF ≤40% and 347 (32%) had LVEF >40%. The treatment benefit of high-intensity care vs usual care on the primary endpoint was consistent across the whole LVEF spectrum (interaction P with LVEF as a continuous variable = 0.372). Mean difference in the EQ-5D visual analog scale change from baseline to day 90 between treatment arms was slightly greater at higher LVEF values, but with no interaction between LVEF as a continuous variable and the treatment strategy (interaction P = 0.358). Serious adverse events were also independent from LVEF.<br /><b>Conclusions</b><br />Rapid uptitration of oral medications for HF and close follow-up reduce 180-day death and HF rehospitalization after AHF hospitalization independently from LVEF. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-ProBNP Testing, of Heart Failure Therapies [STRONG-HF]; NCT03412201).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 06 Jun 2023; 81:2131-2144</small></div>
Pagnesi M, Metra M, Cohen-Solal A, Edwards C, ... Mebazaa A, Davison B
J Am Coll Cardiol: 06 Jun 2023; 81:2131-2144 | PMID: 37257948
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<div><h4>Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation.</h4><i>Lewis MJ, Reardon LC, Aboulhosn J, Haeffele C, ... Krasuski RA, Rosenbaum M</i><br /><b>Background</b><br />The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown.<br /><b>Objectives</b><br />The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients.<br /><b>Methods</b><br />We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses.<br /><b>Results</b><br />A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]).<br /><b>Conclusions</b><br />Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Jun 2023; 81:2149-2160</small></div>
Lewis MJ, Reardon LC, Aboulhosn J, Haeffele C, ... Krasuski RA, Rosenbaum M
J Am Coll Cardiol: 06 Jun 2023; 81:2149-2160 | PMID: 37257950
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<div><h4>Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation.</h4><i>Lewis MJ, Reardon LC, Aboulhosn J, Haeffele C, ... Krasuski RA, Rosenbaum M</i><br /><b>Background</b><br />An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited.<br /><b>Objectives</b><br />The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population.<br /><b>Methods</b><br />A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of \"failing\" Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, \"failing Fontan\" diagnosis by treating cardiologist, or admission for heart failure.<br /><b>Results</b><br />A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade.<br /><b>Conclusions</b><br />In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Jun 2023; 81:2161-2171</small></div>
Lewis MJ, Reardon LC, Aboulhosn J, Haeffele C, ... Krasuski RA, Rosenbaum M
J Am Coll Cardiol: 06 Jun 2023; 81:2161-2171 | PMID: 37257951
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<div><h4>Normative Echocardiographic Left Ventricular Parameters and Reference Intervals in Infants.</h4><i>Vøgg ROB, Sillesen AS, Wohlfahrt J, Pihl C, ... Boyd HA, Bundgaard H</i><br /><b>Background</b><br />In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges.<br /><b>Objectives</b><br />Normative reference intervals and z-scores for 2-dimensional echocardiographic measurements of LV structure and function based on a large group of healthy newborns were developed.<br /><b>Methods</b><br />The study population included 13,454 healthy newborns from the Copenhagen Baby Heart Study who were born at term to healthy mothers, had an echocardiogram performed within 30 days of birth, and did not have congenital heart disease. To develop normative reference intervals, this study modeled 10 LV parameters as a function of body surface area through joint modeling of 4 statistical components.<br /><b>Results</b><br />Infants in the study population (48.5% were female) had a median body surface area of 0.23 m<sup>2</sup> (IQR: 0.22-0.25 m<sup>2</sup>) and median age of 12.0 days (IQR: 8.0-15.0 days) at examination. All normative reference intervals performed well in both sexes without stratification on infant sex. In contrast, creation of separate reference models for infants examined at <7 days of age and those examined at 7-30 days of age was necessary to optimize the performance of the reference intervals.<br /><b>Conclusions</b><br />This study provides normative reference intervals and z-scores for 10 clinical, widely used echocardiographic measures of LV structure and function based on a large cohort of newborns. These results provide highly needed reference material for clinical application by pediatric cardiologists.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Jun 2023; 81:2175-2185</small></div>
Vøgg ROB, Sillesen AS, Wohlfahrt J, Pihl C, ... Boyd HA, Bundgaard H
J Am Coll Cardiol: 06 Jun 2023; 81:2175-2185 | PMID: 37257953
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<div><h4>Multidisciplinary Critical Care Management of Electrical Storm: JACC State-of-the-Art Review.</h4><i>Jentzer JC, Noseworthy PA, Kashou AH, May AM, ... Solomon MA, American College of Cardiology Critical Care Cardiology and Electrophysiology Sections</i><br /><AbstractText>Electrical storm (ES) reflects life-threatening cardiac electrical instability with 3 or more ventricular arrhythmia episodes within 24 hours. Identification of underlying arrhythmogenic cardiac substrate and reversible triggers is essential, as is interrogation and programming of an implantable cardioverter-defibrillator, if present. Medical management includes antiarrhythmic drugs, beta-adrenergic blockade, sedation, and hemodynamic support. The initial intensity of these interventions should be matched to the severity of ES using a stepped-care algorithm involving escalating treatments for higher-risk presentations or recurrent ventricular arrhythmias. Many patients with ES are considered for catheter ablation, which may require the use of temporary mechanical circulatory support. Outcomes after ES are poor, including frequent ES recurrences and deaths caused by progressive heart failure and other cardiac causes. A multidisciplinary collaborative approach to the management of ES is crucial, and evaluation for heart transplantation or palliative care is often appropriate, even for patients who survive the initial episode.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Jun 2023; 81:2189-2206</small></div>
Jentzer JC, Noseworthy PA, Kashou AH, May AM, ... Solomon MA, American College of Cardiology Critical Care Cardiology and Electrophysiology Sections
J Am Coll Cardiol: 06 Jun 2023; 81:2189-2206 | PMID: 37257955
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<div><h4>Screening for Dilated Cardiomyopathy in At-Risk First-Degree Relatives.</h4><i>Ni H, Jordan E, Kinnamon DD, Cao J, ... Hershberger RE, DCM Precision Medicine Study of the DCM Consortium</i><br /><b>Background</b><br />Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD).<br /><b>Objectives</b><br />This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients.<br /><b>Methods</b><br />Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results.<br /><b>Results</b><br />A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM.<br /><b>Conclusions</b><br />Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 May 2023; 81:2059-2071</small></div>
Ni H, Jordan E, Kinnamon DD, Cao J, ... Hershberger RE, DCM Precision Medicine Study of the DCM Consortium
J Am Coll Cardiol: 30 May 2023; 81:2059-2071 | PMID: 37225358
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<div><h4>Improved Outcomes After Pulmonary Valve Replacement in Repaired Tetralogy of Fallot.</h4><i>Bokma JP, Geva T, Sleeper LA, Lee JH, ... Mulder BJM, Valente AM</i><br /><b>Background</b><br />The impact of pulmonary valve replacement (PVR) on major adverse clinical outcomes in patients with repaired tetralogy of Fallot (rTOF) is unknown.<br /><b>Objectives</b><br />The purpose of this study was to determine whether PVR is associated with improved survival and freedom from sustained ventricular tachycardia (VT) in rTOF.<br /><b>Methods</b><br />A PVR propensity score was created to adjust for baseline differences between PVR and non-PVR patients enrolled in INDICATOR (International Multicenter TOF Registry). The primary outcome was time to the earliest occurrence of death or sustained VT. PVR and non-PVR patients were matched 1:1 on PVR propensity score (matched cohort) and in the full cohort, modeling was performed with propensity score as a covariate adjustment.<br /><b>Results</b><br />Among 1,143 patients with rTOF (age 27 ± 14 years, 47% PVR, follow-up 8.3 ± 5.2 years), the primary outcome occurred in 82. The adjusted HR for the primary outcome for PVR vs no-PVR (matched cohort n = 524) was 0.41 (95% CI: 0.21-0.81; multivariable model P = 0.010). Full cohort analysis revealed similar results. Subgroup analysis suggested beneficial effects in patients with advanced right ventricular (RV) dilatation (interaction P = 0.046; full cohort). In patients with RV end-systolic volume index >80 mL/m<sup>2</sup>, PVR was associated with a lower primary outcome risk (HR: 0.32; 95% CI: 0.16-0.62; P < 0.001). There was no association between PVR and the primary outcome in patients with RV end-systolic volume index ≤80 mL/m<sup>2</sup> (HR: 0.86; 95% CI: 0.38-1.92; P = 0.70).<br /><b>Conclusions</b><br />Compared with rTOF patients who did not receive PVR, propensity score-matched individuals receiving PVR had lower risk of a composite endpoint of death or sustained VT.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 May 2023; 81:2075-2085</small></div>
Bokma JP, Geva T, Sleeper LA, Lee JH, ... Mulder BJM, Valente AM
J Am Coll Cardiol: 30 May 2023; 81:2075-2085 | PMID: 37225360
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<div><h4>Procedure-Related Complications of Catheter Ablation for Atrial Fibrillation.</h4><i>Benali K, Khairy P, Hammache N, Petzl A, ... Andrade JG, Macle L</i><br /><b>Background</b><br />Catheter ablation of atrial fibrillation (AF) is a commonly performed procedure. However, it is associated with potentially significant complications. Reported procedure-related complication rates are highly variable, depending in part on study design.<br /><b>Objectives</b><br />The purpose of this systematic review and pooled analysis was to determine the rate of procedure-related complications associated with catheter ablation of AF using data from randomized control trials and to assess temporal trends.<br /><b>Methods</b><br />MEDLINE and EMBASE databases were searched from January 2013 to September 2022 for randomized control trials that included patients undergoing a first ablation procedure of AF using either radiofrequency or cryoballoon (PROSPERO, CRD42022370273).<br /><b>Results</b><br />A total of 1,468 references were retrieved, of which 89 studies met inclusion criteria. A total of 15,701 patients were included in the current analysis. Overall and severe procedure-related complication rates were 4.51% (95% CI: 3.76%-5.32%) and 2.44% (95% CI: 1.98%-2.93%), respectively. Vascular complications were the most frequent type of complication (1.31%). The next most common complications were pericardial effusion/tamponade (0.78%) and stroke/transient ischemic attack (0.17%). The procedure-related complication rate during the most recent 5-year period of publication was significantly lower than during the earlier 5-year period (3.77% vs 5.31%; P = 0.043). The pooled mortality rate was stable over the 2 time periods (0.06% vs 0.05%; P = 0.892). There was no significant difference in complication rate according to pattern of AF, ablation modality, or ablation strategies beyond pulmonary vein isolation.<br /><b>Conclusions</b><br />Procedure-related complications and mortality rates associated with catheter ablation of AF are low and have declined in the past decade.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 May 2023; 81:2089-2099</small></div>
Benali K, Khairy P, Hammache N, Petzl A, ... Andrade JG, Macle L
J Am Coll Cardiol: 30 May 2023; 81:2089-2099 | PMID: 37225362
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<div><h4>The Inflation Reduction Act and Out-of-Pocket Drug Costs for Medicare Beneficiaries With Cardiovascular Disease.</h4><i>Kazi DS, DeJong C, Chen R, Wadhera RK, Tseng CW</i><br /><b>Background</b><br />High out-of-pocket costs can impede access to guideline-directed cardiovascular drugs. The 2022 Inflation Reduction Act (IRA) will eliminate catastrophic coinsurance and cap annual out-of-pocket costs for Medicare Part D patients by 2025.<br /><b>Objectives</b><br />This study sought to estimate the IRA\'s impact on out-of-pocket costs for Part D beneficiaries with cardiovascular disease.<br /><b>Methods</b><br />The investigators chose 4 cardiovascular conditions that frequently require high-cost guideline-recommended drugs: severe hypercholesterolemia; heart failure with reduced ejection fraction (HFrEF); HFrEF with atrial fibrillation (AF); and cardiac transthyretin amyloidosis. This study included 4,137 Part D plans nationwide and compared projected annual out-of-pocket drug costs for each condition in 2022 (baseline), 2023 (rollout), 2024 (5% catastrophic coinsurance eliminated), and 2025 ($2,000 cap on out-of-pocket costs).<br /><b>Results</b><br />In 2022, mean projected annual out-of-pocket costs were $1,629 for severe hypercholesterolemia, $2,758 for HFrEF, $3,259 for HFrEF with AF, and $14,978 for amyloidosis. In 2023, the initial IRA rollout will not significantly change out-of-pocket costs for the 4 conditions. In 2024, elimination of 5% catastrophic coinsurance will lower out-of-pocket costs for the 2 costliest conditions: HFrEF with AF ($2,855, 12% reduction) and amyloidosis ($3,468, 77% reduction). By 2025, the $2,000 cap will lower out-of-pocket costs for all 4 conditions to $1,491 for hypercholesterolemia (8% reduction), $1,954 for HFrEF (29% reduction), $2,000 for HFrEF with AF (39% reduction), and $2,000 for cardiac transthyretin amyloidosis (87% reduction).<br /><b>Conclusions</b><br />The IRA will reduce Medicare beneficiaries\' out-of-pocket drug costs for the selected cardiovascular conditions by 8% to 87%. Future studies should assess the IRA\'s impact on adherence to guideline-directed cardiovascular therapies and health outcomes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 May 2023; 81:2103-2111</small></div>
Kazi DS, DeJong C, Chen R, Wadhera RK, Tseng CW
J Am Coll Cardiol: 30 May 2023; 81:2103-2111 | PMID: 37225364
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<div><h4>Management of Mechanical Prosthetic Heart Valve Thrombosis: JACC Review Topic of the Week.</h4><i>Soria Jiménez CE, Papolos AI, Kenigsberg BB, Ben-Dor I, ... Cohen JE, Rogers T</i><br /><AbstractText>Mechanical prosthetic heart valves, though more durable than bioprostheses, are more thrombogenic and require lifelong anticoagulation. Mechanical valve dysfunction can be caused by 4 main phenomena: 1) thrombosis; 2) fibrotic pannus ingrowth; 3) degeneration; and 4) endocarditis. Mechanical valve thrombosis (MVT) is a known complication with clinical presentation ranging from incidental imaging finding to cardiogenic shock. Thus, a high index of suspicion and expedited evaluation are essential. Multimodality imaging, including echocardiography, cine-fluoroscopy, and computed tomography, is commonly used to diagnose MVT and follow treatment response. Although surgery is oftentimes required for obstructive MVT, other guideline-recommended therapies include parenteral anticoagulation and thrombolysis. Transcatheter manipulation of stuck mechanical valve leaflet is another treatment option for those with contraindications to thrombolytic therapy or prohibitive surgical risk or as a bridge to surgery. The optimal strategy depends on degree of valve obstruction and the patient\'s comorbidities and hemodynamic status on presentation.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 May 2023; 81:2115-2127</small></div>
Soria Jiménez CE, Papolos AI, Kenigsberg BB, Ben-Dor I, ... Cohen JE, Rogers T
J Am Coll Cardiol: 30 May 2023; 81:2115-2127 | PMID: 37225366
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<div><h4>Hemodynamic Assessment in Takotsubo Syndrome.</h4><i>Stiermaier T, Reil JC, Sequeira V, Rawish E, ... Reil GH, Eitel I</i><br /><b>Background</b><br />Takotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology.<br /><b>Objectives</b><br />This study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms.<br /><b>Methods</b><br />Left ventricular (LV) pressure-volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases.<br /><b>Results</b><br />TTS was associated with impaired LV contractility (end-systolic elastance 1.74 mm Hg/mL vs 2.35 mm Hg/mL [P = 0.024]; maximal rate of change in systolic pressure over time 1,533 mm Hg/s vs 1,763 mm Hg/s [P = 0.031]; end-systolic volume at a pressure of 150 mm Hg, 77.3 mL vs 46.4 mL [P = 0.002]); and a shortened systolic period (286 ms vs 343 ms [P < 0.001]). In response, the pressure-volume diagram was shifted rightward with significantly increased LV end-diastolic (P = 0.031) and end-systolic (P < 0.001) volumes, which preserved LV stroke volume (P = 0.370) despite a lower LV ejection fraction (P < 0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant 69.5 ms vs 45.9 ms [P < 0.001]; minimal rate of change in diastolic pressure -1,457 mm Hg/s vs -2,192 mm Hg/s [P < 0.001]), whereas diastolic stiffness (1/compliance) was not affected during TTS (end-diastolic volume at a pressure of 15 mm Hg, 96.7 mL vs 109.0 mL [P = 0.942]). Mechanical efficiency was significantly reduced in TTS (P < 0.001) considering reduced stroke work (P = 0.001), increased potential energy (P = 0.036), and a similar total pressure-volume area compared with that of control subjects (P = 0.357).<br /><b>Conclusions</b><br />TTS is characterized by reduced cardiac contractility, a shortened systolic period, inefficient energetics, and prolonged active relaxation but unaltered diastolic passive stiffness. These findings may suggest decreased phosphorylation of myofilament proteins, which represents a potential therapeutic target in TTS. (Optimized Characterization of Takotsubo Syndrome by Obtaining Pressure Volume Loops [OCTOPUS]; NCT03726528).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 23 May 2023; 81:1979-1991</small></div>
Stiermaier T, Reil JC, Sequeira V, Rawish E, ... Reil GH, Eitel I
J Am Coll Cardiol: 23 May 2023; 81:1979-1991 | PMID: 37197841
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<div><h4>Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease.</h4><i>Gumuser ED, Schuermans A, Cho SMJ, Sporn ZA, ... Natarajan P, Honigberg MC</i><br /><b>Background</b><br />Clonal hematopoiesis of indeterminate potential (CHIP)-the age-related clonal expansion of blood stem cells with leukemia-associated mutations-is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear.<br /><b>Objectives</b><br />This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD.<br /><b>Methods</b><br />Individuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression.<br /><b>Results</b><br />Of 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001).<br /><b>Conclusions</b><br />CHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 23 May 2023; 81:1996-2009</small></div>
Gumuser ED, Schuermans A, Cho SMJ, Sporn ZA, ... Natarajan P, Honigberg MC
J Am Coll Cardiol: 23 May 2023; 81:1996-2009 | PMID: 37197843
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<div><h4>Natriuretic Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload.</h4><i>Verbrugge FH, Martens P, Dauw J, Nijst P, ... Dupont M, Mullens W</i><br /><b>Background</b><br />Acetazolamide facilitates decongestion in acute decompensated heart failure (ADHF).<br /><b>Objectives</b><br />This study sought to investigate the effect of acetazolamide on natriuresis in ADHF and its relationship with outcomes.<br /><b>Methods</b><br />Patients from the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial with complete data on urine output and urine sodium concentration (UNa) were analyzed. Predictors of natriuresis and its relationship with the main trial endpoints were evaluated.<br /><b>Results</b><br />This analysis included 462 of 519 patients (89%) from the ADVOR trial. During 2 days after randomization, UNa was 92 ± 25 mmol/L on average, and total natriuresis was 425 ± 234 mmol. Allocation to acetazolamide strongly and independently predicted natriuresis with a 16 mmol/L (19%) increase in UNa and 115 mmol (32%) greater total natriuresis. Higher systolic blood pressure, better renal function, higher serum sodium levels, and male sex also independently predicted both a higher UNa and greater total natriuresis. A stronger natriuretic response was associated with faster and more complete relief of signs of volume overload, and this effect was already significant on the first morning of assessment (P = 0.022). A significant interaction was observed between the effect of allocation to acetazolamide and UNa on decongestion (P = 0.007). Stronger natriuresis with better decongestion translated into a shorter hospital stay (P < 0.001). After multivariable adjustments, every 10 mmol/L UNa increase was independently associated with a lower risk of all-cause death or heart failure readmission (HR: 0.92; 95% CI: 0.85-0.99).<br /><b>Conclusions</b><br />Increased natriuresis is strongly related to successful decongestion with acetazolamide in ADHF. UNa may be an attractive measure of effective decongestion for future trials. (Acetazolamide in Decompensated Heart Failure with Volume Overload [ADVOR]; NCT03505788).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 23 May 2023; 81:2013-2024</small></div>
Verbrugge FH, Martens P, Dauw J, Nijst P, ... Dupont M, Mullens W
J Am Coll Cardiol: 23 May 2023; 81:2013-2024 | PMID: 37197845
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<div><h4>Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in U.S. Adults.</h4><i>McEvoy JW, Tang O, Wang D, Ndumele CE, ... Christenson RH, Selvin E</i><br /><b>Background</b><br />Myocardial injury is currently defined as a cardiac troponin above the sex-specific 99th percentile of a healthy reference population (upper reference limit [URL]).<br /><b>Objectives</b><br />The purpose of this study was to estimate high-sensitivity (hs) troponin URLs in a representative sample of the U.S. adult population; overall and by sex, race/ethnicity, and age group.<br /><b>Methods</b><br />Among adults participating in the 1999-2004 National Health and Nutrition Examination Survey (NHANES), we measured hs-troponin T using 1 assay (Roche) and hs-troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy reference subgroup, we estimated 99th percentile URLs for each assay using the recommended nonparametric method.<br /><b>Results</b><br />Of 12,545 participants, 2,746 met criteria for the healthy subgroup (mean age 37 years, 50% men). The NHANES 99th percentile URL for hs-troponin T (19 ng/L) matched the manufacturer-reported URL (19 ng/L). NHANES URLs were 13 ng/L (95% CI: 10-15 ng/L) for Abbott hs-troponin I (manufacturer: 28 ng/L), 5 ng/L (95% CI: 4-7 ng/L) for Ortho hs-troponin I (manufacturer: 11 ng/L), and 37 ng/L (95% CI: 27-66 ng/L) for Siemens hs-troponin I (manufacturer: 46.5 ng/L). There were significant differences in URLs by sex, but none by race/ethnicity. Furthermore, the 99th percentile URLs for all 4 hs-troponin assays were statistically significantly lower in healthy adults aged <40 years compared with healthy adults ≥60 years (all P < 0.001 by rank sum testing).<br /><b>Conclusions</b><br />We found URLs for hs-troponin I assays that were substantially lower than currently listed 99th percentile URLs. There were significant differences in hs-troponin T and I URLs by sex and by age group in healthy U.S. adults but none by race/ethnicity.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 23 May 2023; 81:2028-2039</small></div>
McEvoy JW, Tang O, Wang D, Ndumele CE, ... Christenson RH, Selvin E
J Am Coll Cardiol: 23 May 2023; 81:2028-2039 | PMID: 37197846
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<div><h4>Financial Toxicity of Medical Management of Heart Failure: JACC Review Topic of the Week.</h4><i>Sukumar S, Wasfy JH, Januzzi JL, Peppercorn J, Chino F, Warraich HJ</i><br /><AbstractText>Optimal medical management of heart failure (HF) improves quality of life, decreases mortality, and decreases hospitalizations. Cost may contribute to suboptimal adherence to HF medications, especially angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors. Patients\' experiences with HF medication cost include financial burden, financial strain, and financial toxicity. Although there has been research studying financial toxicity in patients with some chronic diseases, there are no validated tools for measuring financial toxicity of HF, and very few data on the subjective experiences of patients with HF and financial toxicity. Strategies to decrease HF-associated financial toxicity include making systemic changes to minimize cost sharing, optimizing shared decision-making, implementing policies to lower drug costs, broadening insurance coverage, and using financial navigation services and discount programs. Clinicians may also improve patient financial wellness through various strategies in routine clinical care. Future research is needed to study financial toxicity and associated patient experiences for HF.</AbstractText><br /><br />Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 23 May 2023; 81:2043-2055</small></div>
Sukumar S, Wasfy JH, Januzzi JL, Peppercorn J, Chino F, Warraich HJ
J Am Coll Cardiol: 23 May 2023; 81:2043-2055 | PMID: 37197848
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<div><h4>Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories.</h4><i>Butler J, Packer M, Siddiqi TJ, Böhm M, ... Anker SD, Zannad F</i><br /><b>Background</b><br />Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction.<br /><b>Objectives</b><br />The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively).<br /><b>Methods</b><br />A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively.<br /><b>Results</b><br />In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very-high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved.<br /><b>Conclusions</b><br />The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 May 2023; 81:1902-1914</small></div>
Butler J, Packer M, Siddiqi TJ, Böhm M, ... Anker SD, Zannad F
J Am Coll Cardiol: 16 May 2023; 81:1902-1914 | PMID: 37164523
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<div><h4>Biomarkers of Thrombotic Status Predict Spontaneous Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction.</h4><i>Kanji R, Gue YX, Memtsas V, Spencer NH, Gorog DA</i><br /><b>Background</b><br />Spontaneous reperfusion, seen in ∼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related artery, with or without ST-segment resolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown.<br /><b>Objectives</b><br />The authors sought to relate spontaneous reperfusion to the thrombotic profile.<br /><b>Methods</b><br />In a prospective study, blood from STEMI patients (n = 801) was tested pre-PCI to assess in vitro, point-of-care, occlusion times (OT) and endogenous lysis times (LT). Spontaneous reperfusion was defined as infarct-related artery Thrombolysis In Myocardial Infarction flow grade 3 before PCI. Patients were followed for major cardiovascular events (death, myocardial infarction, or stroke).<br /><b>Results</b><br />Spontaneous reperfusion was associated with a longer OT (435 seconds vs 366 seconds; P < 0.001) and a shorter LT (1,257 seconds vs 1,616 seconds; P < 0.001), lower troponin, and better left ventricular function. LT was superior to OT for predicting spontaneous reperfusion (area under the curve for LT: 0.707; 95% CI: 0.661-0.753; area under the curve for OT: 0.629; 95% CI: 0.581-0.677). Among patients with spontaneous reperfusion, those with complete, vs partial ST-segment resolution, had a longer OT (P = 0.002) and a shorter LT (P < 0.001). Spontaneous reperfusion was unrelated to clinical characteristics or pain-to-angiography times. Over 4 years, patients with spontaneous reperfusion experienced fewer major adverse cardiovascular events than those without (4.1% vs 10.6%; P = 0.013), especially in those with both spontaneous reperfusion and complete ST-segment resolution (1.5% vs 10.1%; P = 0.029).<br /><b>Conclusions</b><br />We demonstrate a novel hematological signature in STEMI patients with spontaneous reperfusion, namely, decreased platelet reactivity and faster endogenous fibrinolysis, relating to smaller infarcts and improved survival. This finding indicates a role for modulating thrombotic status early after STEMI onset, to facilitate spontaneous reperfusion and improve outcomes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 May 2023; 81:1918-1932</small></div>
Kanji R, Gue YX, Memtsas V, Spencer NH, Gorog DA
J Am Coll Cardiol: 16 May 2023; 81:1918-1932 | PMID: 37164525
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<div><h4>Patient-Reported Outcomes After Tetralogy of Fallot Repair.</h4><i>Kovacs AH, Lebovic G, Raptis S, Blais S, ... Farkouh ME, Wald RM</i><br /><b>Background</b><br />Comprehensive assessment of tetralogy of Fallot (TOF) outcomes extends beyond morbidity and mortality to incorporate patient-reported outcomes (PROs), including quality of life (QOL) and health status (HS).<br /><b>Objectives</b><br />This study explored PROs in adolescents and adults with TOF and delineated variables associated with PROs.<br /><b>Methods</b><br />This was a cross-sectional observational study within a larger prospective registry of adolescents and adults with repaired TOF and moderate or greater pulmonary regurgitation from North America, Europe, and Asia. Participants completed PROs, including a QOL linear analogue scale (QOL-LAS) and an HS visual analogue scale (HS-VAS). Scores were classified according to age cohorts: <18, 18 to 25, 26 to 40, and >40 years.<br /><b>Results</b><br />The study included 607 patients (46.3% female; median age 28.5 years). Median QOL-LAS scores (0-100) were similar across age cohorts (85, 80, 80, 80; P = 0.056). Median HS-VAS scores (0-100) were lowest for the oldest cohort (77) compared with the 3 younger cohorts (85, 80, 80) (P = 0.004). With advancing age, there were increased reports of poor mobility (P < 0.001) and pain or discomfort (P = 0.004); problems in these dimensions were reported by 19.1% and 37.2% of patients aged >40 years, respectively. Of factors associated with superior PROs on multivariable regression modeling (ie, being White, being nonsyndromic, having employment, and having better left ventricular function; P < 0.05), asymptomatic status (functional class I) was the variable associated with the greatest number of QOL and HS measures (P < 0.001).<br /><b>Conclusions</b><br />Strategies to improve TOF outcomes should consider PROs alongside conventional clinical variables. Factors associated with poorer PROs represent opportunities to intervene to improve the lives of patients with TOF.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 May 2023; 81:1937-1950</small></div>
Kovacs AH, Lebovic G, Raptis S, Blais S, ... Farkouh ME, Wald RM
J Am Coll Cardiol: 16 May 2023; 81:1937-1950 | PMID: 37164527
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<div><h4>Multimodality Imaging of Right Heart Function: JACC Scientific Statement.</h4><i>Hahn RT, Lerakis S, Delgado V, Addetia K, ... Pinney S, Friedberg MK</i><br /><AbstractText>Right ventricular (RV) size and function assessed by multimodality imaging are associated with outcomes in a variety of cardiovascular diseases. Understanding RV anatomy and physiology is essential in appreciating the strengths and weaknesses of current imaging methods and gives these measurements greater context. The adaptation of the right ventricle to different types and severity of stress, particularly over time, is specific to the cardiovascular disease process. Multimodality imaging parameters, which determine outcomes, reflect the ability to image the initial and longitudinal RV response to stress. This paper will review the standard and novel imaging methods for assessing RV function and the impact of these parameters on outcomes in specific disease states.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 May 2023; 81:1954-1973</small></div>
Hahn RT, Lerakis S, Delgado V, Addetia K, ... Pinney S, Friedberg MK
J Am Coll Cardiol: 16 May 2023; 81:1954-1973 | PMID: 37164529
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<div><h4>Right Ventricular Function and Coupling to Pulmonary Circulation in Heart Failure with Preserved Ejection Fraction: The PARAGON-HF Trial.</h4><i>Inciardi RM, Abanda M, Shah A, Cikes M, ... McMurray JJV, Solomon SD</i><br /><b>Background</b><br />Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction(HFpEF).<br /><b>Objectives</b><br />To assess the clinical implications of RV function, the association with N-terminal pro-B-type-natriuretic-peptide (NT-proBNP) and the risk for adverse events among HFpEF patients.<br /><b>Methods</b><br />We analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (RVFWLS/PASP ratio) in 528 patients (mean age 74±8 years, 56%female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline NT-proBNP and with total HF hospitalizations and cardiovascular (CV) death were assessed, after accounting for confounders.<br /><b>Results</b><br />Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion (TAPSE) and RV fractional area change, more than half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating NT-proBNP. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and CV deaths. Both absolute RVFWLS (hazard ratio(HR):1.39; 95%confidence interval(95%CI):1.05-1.83;p-value=0.018) and RVFWLS/PASP ratio (HR:1.43;95%CI:1.13-1.80;p-value=0.002) were significantly associated with the composite outcome. Treatment effect of Sacubitril/Valsartan was not modified by measures of RV function.<br /><b>Conclusion</b><br />Worsening RV function and its ratio to pulmonary pressure, is common and significantly associated with an increased risk of HF hospitalizations and CV death in patients with HFpEF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 15 May 2023; epub ahead of print</small></div>
Inciardi RM, Abanda M, Shah A, Cikes M, ... McMurray JJV, Solomon SD
J Am Coll Cardiol: 15 May 2023; epub ahead of print | PMID: 37225045
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<div><h4>Short-term Outcomes of Tricuspid Edge-to-Edge Repair in Clinical Practice.</h4><i>Lurz P, Besler C, Schmitz T, Bekeredjian R, ... Lapp H, Donal E</i><br /><b>Background</b><br />Severe tricuspid regurgitation (TR) is known to be associated with substantial morbidity and mortality.<br /><b>Objectives</b><br />To study the acute outcomes of subjects treated by tricuspid transcatheter edge-to-edge repair with the TriClip system in a contemporary, real-world setting.<br /><b>Methods</b><br />The bRIGHT post-approval study is a prospective, single-arm, open-label, multicenter, post-market registry conducted at 26 sites in Europe. Echocardiographic assessment was performed at a core laboratory.<br /><b>Results</b><br />Enrolled subjects were elderly (79 ± 7 years) with significant comorbidities. Eighty-eight percent had baseline massive or torrential TR and 80% percent of subjects were in NYHA class III or IV. Successful device implantation occurred in 99% of subjects and TR was reduced to ≤moderate at 30 days in 77%. Associated significant improvements in NYHA class (20% to 79% I/II, p < 0.0001) and KCCQ score (19 ± 23 points improvement, p < 0.0001) were observed at 30 days. With baseline TR grade removed as a variable, smaller RAV and smaller tethering distance at baseline were independent predictors of TR reduction to ≤ moderate at discharge (OR:0.679, CI: [0.537, 0.858], p = 0.0012; OR: 0.722, CI: [0.564, 0.924], p=0.0097). Fourteen (2.5%) subjects experienced a major adverse event at 30 days.<br /><b>Conclusions</b><br />Transcatheter tricuspid valve repair was found to be safe and effective in treating significant TR in a diverse, real-world population.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 13 May 2023; epub ahead of print</small></div>
Lurz P, Besler C, Schmitz T, Bekeredjian R, ... Lapp H, Donal E
J Am Coll Cardiol: 13 May 2023; epub ahead of print | PMID: 37207923
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<div><h4>Five-Year Clinical Outcomes After Coronary Bioresorbable Scaffolds and Drug-Eluting Stents: The ABSORB IV Randomized Trial.</h4><i>Stone GW, Kereiakes DJ, Gori T, Metzger DC, ... Ellis SG, ABSORB IV Investigators</i><br /><b>Background</b><br />Bioresorbable vascular scaffolds (BVS) were designed to improve late event-free survival compared with metallic drug-eluting stents. However, initial trials demonstrated worse early outcomes with BVS, in part due to suboptimal technique. In the large-scale, blinded ABSORB IV trial, polymeric everolimus-eluting BVS implanted with improved technique demonstrated non-inferior 1-year outcomes compared with cobalt chromium everolimus-eluting stents (CoCr-EES).<br /><b>Objectives</b><br />To evaluate the long-term outcomes from the ABSORB IV trial.<br /><b>Methods</b><br />We randomized 2,604 patients at 147 sites with stable or acute coronary syndromes to BVS with improved technique vs. CoCr-EES. Patients, clinical assessors and event adjudicators were blinded to randomization. Five-year follow-up was completed.<br /><b>Results</b><br />Target lesion failure (TLF) at 5 years occurred in 216 patients (17.5%) assigned to BVS and 180 patients (14.5%) assigned to CoCr-EES (P=0.03). Device thrombosis within 5 years occurred in 21 (1.7%) BVS and 13 (1.1%) CoCr-EES patients (P=0.15). Event rates were slightly greater with BVS than CoCr-EES through 3-year follow-up and similar between 3-5 years. Angina, also centrally adjudicated, recurred within 5 years in 659 patients (cumulative rate 53.0%) assigned to BVS and 674 patients (53.3%) assigned to CoCr-EES (P=0.63).<br /><b>Conclusions</b><br />In this large-scale, blinded randomized trial, despite improved implantation technique the absolute 5-year rate of TLF was 3% greater after BVS compared with CoCr-EES. The risk period for increased events was restricted to 3 years, the time point of complete scaffold bioresorption; event rates were similar thereafter. Angina recurrence after intervention was frequent during 5-year follow-up but was comparable with both devices.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 13 May 2023; epub ahead of print</small></div>
Stone GW, Kereiakes DJ, Gori T, Metzger DC, ... Ellis SG, ABSORB IV Investigators
J Am Coll Cardiol: 13 May 2023; epub ahead of print | PMID: 37207924
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<div><h4>Incidence, Treatment, and Outcomes of Symptomatic Device Lead-Related Venous Obstruction.</h4><i>Ferro EG, Kramer DB, Li S, Locke AH, ... Zimetbaum PJ, Secemsky EA</i><br /><b>Background</b><br />The incidence and clinical impact of lead-related venous obstruction (LRVO) among patients with cardiovascular implantable electronic devices (CIEDs) is poorly defined.<br /><b>Objectives</b><br />The objectives of this study were to determine the incidence of symptomatic LRVO after CIED implant; describe patterns in CIED extraction and revascularization; and quantify LRVO-related health care utilization based on each type of intervention.<br /><b>Methods</b><br />LRVO status was defined among Medicare beneficiaries after CIED implant from October 1, 2015, to December 31, 2020. Cumulative incidence functions of LRVO were estimated by Fine-Gray methods. LRVO predictors were identified using Cox regression. Incidence rates for LRVO-related health care visits were calculated with Poisson models.<br /><b>Results</b><br />Among 649,524 patients who underwent CIED implant, 28,214 developed LRVO, with 5.0% cumulative incidence at maximum follow-up of 5.2 years. Independent predictors of LRVO included CIEDs with >1 lead (HR: 1.09; 95% CI: 1.07-1.15), chronic kidney disease (HR: 1.17; 95% CI: 1.14-1.20), and malignancies (HR: 1.23; 95% CI: 1.20-1.27). Most patients with LRVO (85.2%) were managed conservatively. Among 4,186 (14.8%) patients undergoing intervention, 74.0% underwent CIED extraction and 26.0% percutaneous revascularization. Notably, 90% of the patients did not receive another CIED after extraction, with low use (2.2%) of leadless pacemakers. In adjusted models, extraction was associated with significant reductions in LRVO-related health care utilization (adjusted rate ratio: 0.58; 95% CI: 0.52-0.66) compared with conservative management.<br /><b>Conclusions</b><br />In a large nationwide sample, the incidence of LRVO was substantial, affecting 1 of every 20 patients with CIEDs. Device extraction was the most common intervention and was associated with long-term reduction in recurrent health care utilization.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 May 2023; epub ahead of print</small></div>
Ferro EG, Kramer DB, Li S, Locke AH, ... Zimetbaum PJ, Secemsky EA
J Am Coll Cardiol: 12 May 2023; epub ahead of print | PMID: 37204378
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<div><h4>Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure.</h4><i>Mentz RJ, Ward JH, Hernandez AF, Lepage S, ... Braunwald E, PARAGLIDE-HF Investigators</i><br /><b>Background</b><br />U.S. guidelines recommend consideration of sacubitril/valsartan in chronic heart failure (HF) and mildly reduced or preserved ejection fraction (EF). Whether initiation is safe and effective in EF >40% after a worsening heart failure (WHF) event is unknown.<br /><b>Objectives</b><br />PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) assessed sacubitril-valsartan vs valsartan in EF >40% following a recent WHF event.<br /><b>Methods</b><br />PARAGLIDE-HF is a double-blind, randomized controlled trial of sacubitril/valsartan vs valsartan in patients with EF >40% enrolled within 30 days of a WHF event. The primary endpoint was time-averaged proportional change in amino terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: 1) cardiovascular death; 2) HF hospitalizations; 3) urgent HF visits; and 4) change in NT-proBNP.<br /><b>Results</b><br />In 466 patients (233 sacubitril/valsartan; 233 valsartan), time-averaged reduction in the NT-proBNP was greater with sacubitril/valsartan (ratio of change: 0.85; 95% CI: 0.73-0.999; P = 0.049). The hierarchical outcome favored sacubitril/valsartan but was not significant (unmatched win ratio: 1.19; 95% CI: 0.93-1.52; P = 0.16). Sacubitril/valsartan reduced worsening renal function (OR: 0.61; 95% CI: 0.40-0.93) but increased symptomatic hypotension (OR: 1.73; 95% CI: 1.09-2.76). There was evidence of a larger treatment effect in the subgroup with EF ≤60% for NT-proBNP change (0.78; 95% CI: 0.61-0.98) and the hierarchical outcome (win ratio: 1.46; 95% CI: 1.09-1.95).<br /><b>Conclusions</b><br />Among patients with EF >40% stabilized after WHF, sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared with valsartan alone, despite more symptomatic hypotension. (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; NCT03988634).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 May 2023; epub ahead of print</small></div>
Mentz RJ, Ward JH, Hernandez AF, Lepage S, ... Braunwald E, PARAGLIDE-HF Investigators
J Am Coll Cardiol: 11 May 2023; epub ahead of print | PMID: 37212758
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<div><h4>Early Outcomes of Adult Heart Transplantation From COVID-19 Infected Donors.</h4><i>Madan S, Chan MAG, Saeed O, Hemmige V, ... Patel SR, Jorde UP</i><br /><b>Background</b><br />There is a paucity of data on heart transplantation (HT) using COVID-19 donors.<br /><b>Objectives</b><br />This study investigated COVID-19 donor use, donor and recipient characteristics, and early post-HT outcomes.<br /><b>Methods</b><br />Between May 2020 and June 2022, study investigators identified 27,862 donors in the United Network for Organ Sharing, with 60,699 COVID-19 nucleic acid amplification testing (NAT) performed before procurement and with available organ disposition. Donors were considered \"COVID-19 donors\" if they were NAT positive at any time during terminal hospitalization. These donors were subclassified as \"active COVID-19\" (aCOV) donors if they were NAT positive within 2 days of organ procurement, or \"recently resolved COVID-19\" (rrCOV) donors if they were NAT positive initially but became NAT negative before procurement. Donors with NAT-positive status >2 days before procurement were considered aCOV unless there was evidence of a subsequent NAT-negative result ≥48 hours after the last NAT-positive result. HT outcomes were compared.<br /><b>Results</b><br />During the study period, 1,445 \"COVID-19 donors\" (COVID-19 NAT positive) were identified; 1,017 of these were aCOV, and 428 were rrCOV. Overall, 309 HTs used COVID-19 donors, and 239 adult HTs from COVID-19 donors (150 aCOV, 89 rrCOV) met study criteria. Compared with non-COV, COVID-19 donors used for adult HT were younger and mostly male (∼80%). Compared with HTs from non-COV donors, recipients of HTs from aCOV donors had increased mortality at 6 months (Cox HR: 1.74; 95% CI: 1.02-2.96; P = 0.043) and 1 year (Cox HR: 1.98; 95% CI: 1.22-3.22; P = 0.006). Recipients of HTs from rrCOV and non-COV donors had similar 6-month and 1-year mortality. Results were similar in propensity-matched cohorts.<br /><b>Conclusions</b><br />In this early analysis, although HTs from aCOV donors had increased mortality at 6 months and 1 year, HTs from rrCOV donors had survival similar to that seen in recipients of HTs from non-COV donors. Continued evaluation and a more nuanced approach to this donor pool are needed.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 May 2023; epub ahead of print</small></div>
Madan S, Chan MAG, Saeed O, Hemmige V, ... Patel SR, Jorde UP
J Am Coll Cardiol: 11 May 2023; epub ahead of print | PMID: 37204379
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<div><h4>Comparison of Left Bundle-Branch Area Pacing to Biventricular Pacing in Candidates for Resynchronization Therapy.</h4><i>Vijayaraman P, Sharma PS, Cano Ó, Ponnusamy SS, ... Subzposh FA, Ellenbogen KA</i><br /><b>Background</b><br />Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well-established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS or expected frequent ventricular pacing. Left bundle branch area pacing (LBBAP) has recently been shown to be a safe alternative to BVP.<br /><b>Objective</b><br />The aim of this study was to compare the clinical outcomes between BVP and LBBAP among patients undergoing CRT.<br /><b>Methods</b><br />This observational study included patients with LVEF≤35% who underwent BVP or LBBAP for the first time for Class I or II indications for CRT between Jan 2018 to June 2022 at 15 international centers. The primary outcome was the composite endpoint of time to death or heart failure hospitalization (HFH). Secondary outcomes included endpoints of death, HFH, and echocardiographic changes. .<br /><b>Results</b><br />A total of 1778 patients met inclusion criteria: BVP 981, LBBAP 797. The mean age was 69±12 years, female 32%, CAD 48%, and LVEF 27±6%. Paced QRSd in LBBAP was significantly narrower than baseline (128±19 vs 161±28ms, p<0.001) and significantly narrower compared to BVP (144±23ms, p<0.001). Following CRT, LVEF improved from 27±6% to 41±13% (p<0.001) with LBBAP compared to an increase from 27±7% to 37±12% (p<0.001) with BVP with significantly greater change from baseline with LBBAP (13±12% vs 10±12%, p<0.001). On multivariable regression analysis, the primary outcome was significantly reduced with LBBAP compared BVP (20.8% vs 28%; HR 1.495; CI 1.213-1.842; p<0.001).<br /><b>Conclusions</b><br />LBBAP improved clinical outcomes when compared to BVP in patients with CRT indications and may be a reasonable alternative to BVP.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 10 May 2023; epub ahead of print</small></div>
Vijayaraman P, Sharma PS, Cano Ó, Ponnusamy SS, ... Subzposh FA, Ellenbogen KA
J Am Coll Cardiol: 10 May 2023; epub ahead of print | PMID: 37220862
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<div><h4>1-Year Outcomes of Transcatheter Tricuspid Valve Repair.</h4><i>Kodali SK, Hahn RT, Davidson CJ, Narang A, ... Leon MB, Eleid MF</i><br /><b>Background</b><br />Surgical management of isolated tricuspid regurgitation (TR) is associated with high morbidity and mortality, thereby creating a significant need for a lower-risk transcatheter solution.<br /><b>Objectives</b><br />The single-arm, multicenter, prospective CLASP TR (Edwards PASCAL TrAnScatheter Valve RePair System in Tricuspid Regurgitation [CLASP TR] Early Feasibility Study) evaluated 1-year outcomes of the PASCAL transcatheter valve repair system (Edwards Lifesciences) to treat TR.<br /><b>Methods</b><br />Study inclusion required a previous diagnosis of severe or greater TR and persistent symptoms despite medical treatment. An independent core laboratory evaluated echocardiographic results, and a clinical events committee adjudicated major adverse events. The study evaluated primary safety and performance outcomes, with echocardiographic, clinical, and functional endpoints. Study investigators report 1-year all-cause mortality and heart failure hospitalization rates.<br /><b>Results</b><br />Sixty-five patients were enrolled: mean age of 77.4 years; 55.4% female; and 97.0% with severe to torrential TR. At 30 days, cardiovascular mortality was 3.1%, the stroke rate was 1.5%, and no device-related reinterventions were reported. Between 30 days and 1 year, there were an additional 3 cardiovascular deaths (4.8%), 2 strokes (3.2%), and 1 unplanned or emergency reintervention (1.6%). One-year postprocedure, TR severity significantly reduced (P < 0.001), with 31 of 36 (86.0%) patients achieving moderate or less TR; 100% had at least 1 TR grade reduction. Freedom from all-cause mortality and heart failure hospitalization by Kaplan-Meier analyses were 87.9% and 78.5%, respectively. Their New York Heart Association functional class significantly improved (P < 0.001) with 92% in class I or II, 6-minute walk distance increased by 94 m (P = 0.014), and overall Kansas City Cardiomyopathy Questionnaire scores improved by 18 points (P < 0.001).<br /><b>Conclusions</b><br />The PASCAL system demonstrated low complication and high survival rates, with significant and sustained improvements in TR, functional status, and quality of life at 1 year. (Edwards PASCAL TrAnScatheter Valve RePair System in Tricuspid Regurgitation [CLASP TR] Early Feasibility Study [CLASP TR EFS]; NCT03745313).<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 09 May 2023; 81:1766-1776</small></div>
Kodali SK, Hahn RT, Davidson CJ, Narang A, ... Leon MB, Eleid MF
J Am Coll Cardiol: 09 May 2023; 81:1766-1776 | PMID: 37137586
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<div><h4>Lipoprotein(a), Oxidized Phospholipids, and Coronary Artery Disease Severity and Outcomes.</h4><i>Gilliland TC, Liu Y, Mohebi R, Miksenas H, ... Januzzi JL, Natarajan P</i><br /><b>Background</b><br />Lipoprotein(a) (Lp[a]) and oxidized phospholipids (OxPLs) are each independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs predict coronary artery disease (CAD) severity and outcomes in a contemporary, statin-treated cohort is not well established.<br /><b>Objectives</b><br />This study sought to evaluate the relationships between Lp(a) particle concentration and OxPLs associated with apolipoprotein B (OxPL-apoB) or apolipoprotein(a) (OxPL-apo[a]) with angiographic CAD and cardiovascular outcomes.<br /><b>Methods</b><br />Among 1,098 participants referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study, Lp(a), OxPL-apoB, and OxPL-apo(a) were measured. Logistic regression estimated the risk of multivessel coronary stenoses by Lp(a)-related biomarker level. Cox proportional hazards regression estimated the risk of major adverse cardiovascular events (MACEs) (coronary revascularization, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) in follow-up.<br /><b>Results</b><br />Median Lp(a) was 26.45 nmol/L (IQR: 11.39-89.49 nmol/L). Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R ≥0.91 for all pairwise combinations). Lp(a) and OxPL-apoB were associated with multivessel CAD. Odds of multivessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI: 1.03-1.18; P = 0.006), 1.18 (95% CI: 1.03-1.34; P = 0.01), and 1.07 (95% CI: 0.99-1.16; P = 0.07), respectively. All biomarkers were associated with cardiovascular events. HRs for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI: 1.03-1.14; P = 0.001), 1.15 (95% CI: 1.05-1.26; P = 0.004), and 1.07 (95% CI: 1.01-1.14; P = 0.02), respectively.<br /><b>Conclusions</b><br />In patients undergoing coronary angiography, Lp(a) and OxPL-apoB are associated with multivessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident cardiovascular events. (Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 May 2023; 81:1780-1792</small></div>
Gilliland TC, Liu Y, Mohebi R, Miksenas H, ... Januzzi JL, Natarajan P
J Am Coll Cardiol: 09 May 2023; 81:1780-1792 | PMID: 37137588
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<div><h4>Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.</h4><i>Muller SA, Gasperetti A, Bosman LP, Schmidt AF, ... Oerlemans MIFJ, Te Riele ASJM</i><br /><b>Background</b><br />Clinical guidelines recommend regular screening for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.<br /><b>Objective</b><br />Determine predictors and probability of ARVC development over time among at-risk relatives.<br /><b>Methods</b><br />We included 136 relatives (46% male, 25.5 (interquartile range (IQR):15.8-44.4) years) from the Netherlands ACM Registry without definite ARVC by 2010 Task Force Criteria (TFC). Phenotype was ascertained using electrocardiograms, Holter monitoring, and cardiac imaging. Subjects were divided into \"possible ARVC\" (only genetic/familial predisposition) and \"borderline ARVC\" (one minor TFC criterion plus genetic/familial predisposition). We performed Cox regression to determine predictors, and multi-state modeling to assess probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% male, 37.0 (IQR:25.4-50.4) years).<br /><b>Results</b><br />At baseline, 93 (68%) had possible and 43 (32%) borderline ARVC. Follow-up was available for 123 (90%) relatives. After 8.1 (IQR:4.2-11.4) years, 41 (33%) developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (p=0.014) and those 20-30 years old (p=0.002) had higher hazard of developing definite ARVC. Furthermore, borderline ARVC patients had higher probability of developing definite ARVC compared to possible patients (1-year probability: 13% vs. 0.6%; 3-year probability: 35% vs. 5%, p<0.01). External replication showed comparable results (p>0.05).<br /><b>Conclusion</b><br />Symptomatic relatives, those in 20-30 age range and with borderline ARVC have higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 09 May 2023; epub ahead of print</small></div>
Muller SA, Gasperetti A, Bosman LP, Schmidt AF, ... Oerlemans MIFJ, Te Riele ASJM
J Am Coll Cardiol: 09 May 2023; epub ahead of print | PMID: 37210036
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<div><h4>Sex Difference in Outcomes of Acute Myocardial Infarction in Young Patients.</h4><i>Sawano M, Lu Y, Caraballo C, Mahajan S, ... Spertus JA, Krumholz HM</i><br /><b>Background</b><br />Younger women experience worse health status than men after their index episode of acute myocardial infarction (AMI). However, whether women have a higher risk for cardiovascular and noncardiovascular hospitalizations in the year after discharge is unknown.<br /><b>Objectives</b><br />The aim of this study was to determine sex differences in causes and timing of 1-year outcomes after AMI in people aged 18 to 55 years.<br /><b>Methods</b><br />Data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which enrolled young patients with AMI across 103 U.S. hospitals, were used. Sex differences in all-cause and cause-specific hospitalizations were compared by calculating incidence rates ([IRs] per 1,000 person-years) and IR ratios with 95% CIs. We then performed sequential modeling to evaluate the sex difference by calculating subdistribution HRs (SHRs) accounting for deaths.<br /><b>Results</b><br />Among 2,979 patients, at least 1 hospitalization occurred among 905 patients (30.4%) in the year after discharge. The leading causes of hospitalization were coronary related (IR: 171.8 [95% CI: 153.6-192.2] among women vs 117.8 [95% CI: 97.3-142.6] among men), followed by noncardiac hospitalization (IR: 145.8 [95% CI: 129.2-164.5] among women vs 69.6 [95% CI: 54.5-88.9] among men). Furthermore, a sex difference was present for coronary-related hospitalizations (SHR: 1.33; 95% CI: 1.04-1.70; P = 0.02) and noncardiac hospitalizations (SHR: 1.51; 95% CI: 1.13-2.07; P = 0.01).<br /><b>Conclusions</b><br />Young women with AMI experience more adverse outcomes than men in the year after discharge. Coronary-related hospitalizations were most common, but noncardiac hospitalizations showed the most significant sex disparity.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 May 2023; 81:1797-1806</small></div>
Sawano M, Lu Y, Caraballo C, Mahajan S, ... Spertus JA, Krumholz HM
J Am Coll Cardiol: 09 May 2023; 81:1797-1806 | PMID: 37137590
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<div><h4>Heart Failure With Preserved Ejection Fraction: JACC Scientific Statement.</h4><i>Borlaug BA, Sharma K, Shah SJ, Ho JE</i><br /><AbstractText>The incidence and prevalence of heart failure with preserved ejection fraction (HFpEF) continue to rise in tandem with the increasing age and burdens of obesity, sedentariness, and cardiometabolic disorders. Despite recent advances in the understanding of its pathophysiological effects on the heart, lungs, and extracardiac tissues, and introduction of new, easily implemented approaches to diagnosis, HFpEF remains under-recognized in everyday practice. This under-recognition presents an even greater concern given the recent identification of highly effective pharmacologic-based and lifestyle-based treatments that can improve clinical status and reduce morbidity and mortality. HFpEF is a heterogenous syndrome and recent studies have suggested an important role for careful, pathophysiological-based phenotyping to improve patient characterization and to better individualize treatment. In this JACC Scientific Statement, we provide an in-depth and updated examination of the epidemiology, pathophysiology, diagnosis, and treatment of HFpEF.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 May 2023; 81:1810-1834</small></div>
Borlaug BA, Sharma K, Shah SJ, Ho JE
J Am Coll Cardiol: 09 May 2023; 81:1810-1834 | PMID: 37137592
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<div><h4>Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction.</h4><i>Khan KR, Khan OA, Chen C, Liu Y, ... Langer NB, Elmariah S</i><br /><b>Background</b><br />Afterload from moderate aortic stenosis (AS) may contribute to adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF).<br /><b>Objectives</b><br />The authors evaluated clinical outcomes in patients with HFrEF and moderate AS relative to those without AS and with severe AS.<br /><b>Methods</b><br />Patients with HFrEF, defined by left ventricular ejection fraction (LVEF) <50% and no, moderate, or severe AS were retrospectively identified. The primary endpoint, defined as a composite of all-cause mortality and heart failure (HF) hospitalization, was compared across groups and within a propensity score-matched cohort.<br /><b>Results</b><br />We included 9,133 patients with HFrEF, of whom 374 and 362 had moderate and severe AS, respectively. Over a median follow-up time of 3.1 years, the primary outcome occurred in 62.7% of patients with moderate AS vs 45.9% with no AS (P < 0.0001); rates were similar with severe and moderate AS (62.0% vs 62.7%; P = 0.68). Patients with severe AS had a lower incidence of HF hospitalization (36.2% vs 43.6%; P < 0.05) and were more likely to undergo AVR within the follow-up period. Within a propensity score-matched cohort, moderate AS was associated with an increased risk of HF hospitalization and mortality (HR: 1.24; 95% CI: 1.04-1.49; P = 0.01) and fewer days alive outside of the hospital (P < 0.0001). Aortic valve replacement (AVR) was associated with improved survival (HR: 0.60; CI: 0.36-0.99; P < 0.05).<br /><b>Conclusions</b><br />In patients with HFrEF, moderate AS is associated with increased rates of HF hospitalization and mortality. Further investigation is warranted to determine whether AVR in this population improves clinical outcomes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1235-1244</small></div>
Khan KR, Khan OA, Chen C, Liu Y, ... Langer NB, Elmariah S
J Am Coll Cardiol: 04 May 2023; 81:1235-1244 | PMID: 36990542
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<div><h4>Blood Levels of Angiotensinogen and Hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA).</h4><i>Trainor PJ, Brambatti M, Carlisle SM, Mullick AE, ... Tsimikas S, DeFilippis AP</i><br /><b>Background</b><br />Angiotensinogen is the proximal precursor of the angiotensin peptide hormones of the renin-angiotensin-aldosterone system (RAAS). Clinical trials are ongoing targeting angiotensinogen for the treatment of hypertension and heart failure. The epidemiology of angiotensinogen is not well defined, particularly its relationship to ethnicity, sex, and blood pressure (BP)/hypertension.<br /><b>Objectives</b><br />The authors sought to determine the relationship of circulating angiotensinogen levels to ethnicity, sex, BP, incident hypertension, and prevalent hypertension in a modern sex-balanced ethnically diverse cohort.<br /><b>Methods</b><br />Plasma angiotensinogen levels were measured in 5,786 participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Linear, logistic, and Cox proportional hazards models were utilized to examine the associations of angiotensinogen with BP, prevalent hypertension, and incident hypertension, respectively.<br /><b>Results</b><br />Angiotensinogen levels were significantly higher in females than males and differed across self-reported ethnicities with the ordering (from highest to lowest): White, Black, Hispanic, and Chinese adults. Higher levels were associated with higher BP and odds of prevalent hypertension, after adjusting for other risk factors. Equivalent relative differences in angiotensinogen were associated with greater differences in BP in males vs females. In males not taking RAAS-blocking medications, a standard deviation increment in log-angiotensinogen was associated with 2.61 mm Hg higher systolic BP (95% CI: 1.49-3.80), while in females the same increment in angiotensinogen was associated with 0.97 mm Hg higher systolic BP (95% CI: 0.30-1.65).<br /><b>Conclusions</b><br />Significant differences in angiotensinogen levels are present between sexes and ethnicities. A positive association is present between levels and prevalent hypertension and BP, which differs between sexes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1248-1259</small></div>
Trainor PJ, Brambatti M, Carlisle SM, Mullick AE, ... Tsimikas S, DeFilippis AP
J Am Coll Cardiol: 04 May 2023; 81:1248-1259 | PMID: 36990544
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<div><h4>Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation.</h4><i>Ninni S, Dombrowicz D, Kuznetsova T, Vicario R, ... Staels B, Montaigne D</i><br /><b>Background</b><br />On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype.<br /><b>Objectives</b><br />The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery.<br /><b>Methods</b><br />Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes.<br /><b>Results</b><br />The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64<sup>+</sup>CD14<sup>+</sup>CD16<sup>-</sup> circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium.<br /><b>Conclusions</b><br />HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1263-1278</small></div>
Ninni S, Dombrowicz D, Kuznetsova T, Vicario R, ... Staels B, Montaigne D
J Am Coll Cardiol: 04 May 2023; 81:1263-1278 | PMID: 36990546
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<div><h4>Early Lead Extraction for Infected Implanted Cardiac Electronic Devices: JACC Review Topic of the Week.</h4><i>Lakkireddy DR, Segar DS, Sood A, Wu M, ... Piccini JP, Granger CB</i><br /><AbstractText>Infection remains a serious complication associated with the cardiac implantable electronic devices (CIEDs), leading to substantial clinical and economic burden globally. This review assesses the burden of cardiac implantable electronic device infection (CIED-I), evidence for treatment recommendations, barriers to early diagnosis and appropriate therapy, and potential solutions. Multiple clinical practice guidelines recommended complete system and lead removal for CIED-I when appropriate. CIED extraction for infection has been consistently reported with high success, low complication, and very low mortality rates. Complete and early extraction was associated with significantly better clinical and economic outcome compared with no or late extraction. However, significant gaps in knowledge and poor recommendation compliance have been reported. Barriers to optimal management may include diagnostic delay, knowledge gaps, and limited access to expertise. A multipronged approach, including education of all stakeholders, a CIED-I alert system, and improving access to experts, could help bring paradigm shift in the treatment of this serious condition.</AbstractText><br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1283-1295</small></div>
Lakkireddy DR, Segar DS, Sood A, Wu M, ... Piccini JP, Granger CB
J Am Coll Cardiol: 04 May 2023; 81:1283-1295 | PMID: 36990548
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<div><h4>Health Status and Clinical Outcomes in Older Adults With Chronic Coronary Disease: The ISCHEMIA Trial.</h4><i>Nguyen DD, Spertus JA, Alexander KP, Newman JD, ... Hochman JS, ISCHEMIA Research Group</i><br /><b>Background</b><br />Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown.<br /><b>Objectives</b><br />The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial.<br /><b>Methods</b><br />One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure.<br /><b>Results</b><br />Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (P<sub>interaction</sub> = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (P<sub>interaction</sub> = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (P<sub>interaction</sub> = 0.29).<br /><b>Conclusions</b><br />Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 May 2023; 81:1697-1709</small></div>
Nguyen DD, Spertus JA, Alexander KP, Newman JD, ... Hochman JS, ISCHEMIA Research Group
J Am Coll Cardiol: 02 May 2023; 81:1697-1709 | PMID: 37100486
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<div><h4>Low Utilization of Lead Extraction Among Patients With Infective Endocarditis and Implanted Cardiac Electronic Devices.</h4><i>Sciria CT, Kogan EV, Mandler AG, Yeo I, ... Thomas G, Cheung JW</i><br /><b>Background</b><br />Cardiac implantable electronic device (CIED)-associated infections are associated with substantial morbidity, mortality, and costs. Guidelines have cited endocarditis as a Class I indication for transvenous lead removal/extraction (TLE) among patients with CIEDs.<br /><b>Objectives</b><br />The authors sought to study utilization of TLE among hospital admissions with infective endocarditis using a nationally representative database.<br /><b>Methods</b><br />Using the Nationwide Readmissions Database (NRD), 25,303 admissions for patients with CIEDs and endocarditis between 2016 and 2019 were evaluated on the basis of International Classification of Diseases-10th Revision, Clinical-Modification (ICD-10-CM) codes.<br /><b>Results</b><br />Among admissions for patients with CIEDs and endocarditis, 11.5% were managed with TLE. The proportion undergoing TLE increased significantly from 2016 to 2019 (7.6% vs 14.9%; P trend < 0.001). Procedural complications were identified in 2.7%. Index mortality was significantly lower among patients managed with TLE (6.0% vs 9.5%; P < 0.001). Presence of Staphylococcus aureus infection, implantable cardioverter-defibrillator, and large hospital size were independently associated with TLE management. TLE management was less likely with older age, female sex, dementia, and kidney disease. After adjustment for comorbidities, TLE was independently associated with significantly lower odds of mortality (adjusted OR: 0.47; 95% CI: 0.37-0.60 by multivariable logistic regression, and adjusted OR: 0.51; 95% CI: 0.40-0.66 by propensity score matching).<br /><b>Conclusions</b><br />Utilization of lead extraction among patients with CIEDs and endocarditis is low, even in the presence of low rates of procedural complications. Lead extraction management is associated with significantly lower mortality, and its use has trended upward between 2016 and 2019. Barriers to TLE for patients with CIEDs and endocarditis require investigation.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 May 2023; 81:1714-1725</small></div>
Sciria CT, Kogan EV, Mandler AG, Yeo I, ... Thomas G, Cheung JW
J Am Coll Cardiol: 02 May 2023; 81:1714-1725 | PMID: 37100488
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<div><h4>Gut Microbiome-Based Management of Patients With Heart Failure: JACC Review Topic of the Week.</h4><i>Mamic P, Snyder M, Tang WHW</i><br /><AbstractText>Despite therapeutic advances, chronic heart failure (HF) is still associated with significant risk of morbidity and mortality. The course of disease and responses to therapies vary widely among individuals with HF, highlighting the need for precision medicine approaches. Gut microbiome stands to be an important aspect of precision medicine in HF. Exploratory clinical studies have revealed shared patterns of gut microbiome dysregulation in this disease, with mechanistic animal studies providing evidence for active involvement of the gut microbiome in development and pathophysiology of HF. Deeper insights into gut microbiome-host interactions in patients with HF promise to deliver novel disease biomarkers, preventative and therapeutic targets, and improve disease risk stratification. This knowledge may enable a paradigm shift in how we care for patients with HF, and pave the path toward improved clinical outcomes through personalized HF care.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 May 2023; 81:1729-1739</small></div>
Mamic P, Snyder M, Tang WHW
J Am Coll Cardiol: 02 May 2023; 81:1729-1739 | PMID: 37100490
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<div><h4>Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer.</h4><i>Lena A, Wilkenshoff U, Hadzibegovic S, Porthun J, ... Landmesser U, Anker MS</i><br /><b>Background</b><br />Body wasting in patients with cancer can affect the heart.<br /><b>Objectives</b><br />The frequency, extent, and clinical and prognostic importance of cardiac wasting in cancer patients is unknown.<br /><b>Methods</b><br />This study prospectively enrolled 300 patients with mostly advanced, active cancer but without significant cardiovascular disease or infection. These patients were compared with 60 healthy control subjects and 60 patients with chronic heart failure (ejection fraction <40%) of similar age and sex distribution.<br /><b>Results</b><br />Cancer patients presented with lower left ventricular (LV) mass than healthy control subjects or heart failure patients (assessed by transthoracic echocardiography: 177 ± 47 g vs 203 ± 64 g vs 300 ± 71 g, respectively; P < 0.001). LV mass was lowest in cancer patients with cachexia (153 ± 42 g; P < 0.001). Importantly, the presence of low LV mass was independent of previous cardiotoxic anticancer therapy. In 90 cancer patients with a second echocardiogram after 122 ± 71 days, LV mass had declined by 9.3% ± 1.4% (P < 0.001). In cancer patients with cardiac wasting during follow-up, stroke volume decreased (P < 0.001) and resting heart rate increased over time (P = 0.001). During follow-up of on average 16 months, 149 patients died (1-year all-cause mortality 43%; 95% CI: 37%-49%). LV mass and LV mass adjusted for height squared were independent prognostic markers (both P < 0.05). Adjustment of LV mass for body surface area masked the observed survival impact. LV mass below the prognostically relevant cutpoints in cancer was associated with reduced overall functional status and lower physical performance.<br /><b>Conclusions</b><br />Low LV mass is associated with poor functional status and increased all-cause mortality in cancer. These findings provide clinical evidence of cardiac wasting-associated cardiomyopathy in cancer.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 25 Apr 2023; 81:1569-1586</small></div>
Lena A, Wilkenshoff U, Hadzibegovic S, Porthun J, ... Landmesser U, Anker MS
J Am Coll Cardiol: 25 Apr 2023; 81:1569-1586 | PMID: 37076211
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<div><h4>Exercise Capacity, NT-proBNP, and Exercise Hemodynamics in Adults Post-Fontan.</h4><i>Miranda WR, Jain CC, Borlaug BA, Jaffe AS, ... Burchill LJ, Egbe AC</i><br /><b>Background</b><br />Cardiopulmonary exercise testing (CPET) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement are frequently performed in adults post-Fontan, but their correlations with exercise invasive hemodynamics are poorly understood. Moreover, whether exercise cardiac catheterization provides incremental prognostic information is unknown.<br /><b>Objectives</b><br />The authors sought to correlate resting and exercise Fontan pressures (FP) and pulmonary artery wedge pressure (PAWP) with peak oxygen consumption (VO<sub>2</sub>) on CPET, NT-proBNP, and clinical outcomes.<br /><b>Methods</b><br />This was a retrospective cohort of 50 adults (age ≥18 years) post-Fontan undergoing supine exercise venous catheterization between 2018 and 2022.<br /><b>Results</b><br />Median age was 31.5 years (IQR: 23.7-36.5 years). Ventricular ejection fraction was 48.5% ± 13.0%. Exercise FP and PAWP were related to peak VO<sub>2</sub> and ln NT-proBNP levels. Patients with peak VO<sub>2</sub> <50% predicted had higher exercise FP (30.0 ± 6.8 mm Hg vs 19 mm Hg [IQR: 16-24 mm Hg]; P < 0.001) and PAWP (25.9 ± 6.3 mm Hg vs 15.1 ± 7.0 mm Hg; P <0.001) compared with those with more preserved exercise capacity. Exercise FP (30.0 ± 7.1 mm Hg vs 23.2 ± 7.2 mm Hg; P = 0.003) and PAWP (25.1 ± 6.7 mm Hg vs 18.8 ± 7.9 mm Hg; P = 0.006) were higher in those with NT-proBNP levels ≥300 pg/mL. During a follow-up of 0.9 years (IQR: 0.6-2.9 years), exercise FP and PAWP remained independently associated with a composite of death, cardiac transplantation, or hospitalization due to heart failure/refractory arrhythmias after adjusting for confounders.<br /><b>Conclusions</b><br />In adults post-Fontan, resting and exercise FP and PAWP were inversely related to exercise capacity on noninvasive CPET, and exercise hemodynamics were directly related to NT-proBNP levels. Exercise FP and PAWP were independently associated with clinical outcomes and might be more sensitive than resting values to predict clinical outcomes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 25 Apr 2023; 81:1590-1600</small></div>
Miranda WR, Jain CC, Borlaug BA, Jaffe AS, ... Burchill LJ, Egbe AC
J Am Coll Cardiol: 25 Apr 2023; 81:1590-1600 | PMID: 37076213
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<div><h4>Long-Term Health Care Utilization After Cardiac Surgery in Children Covered Under Medicaid.</h4><i>Crook S, Dragan K, Woo JL, Neidell M, ... Anderson BR, New York State CHS-COLOUR</i><br /><b>Background</b><br />Understanding the longitudinal burden of health care expenditures and utilization after pediatric cardiac surgery is needed to counsel families, improve care, and reduce outcome inequities.<br /><b>Objectives</b><br />The purpose of this study was to describe and identify predictors of health care expenditures and utilization for Medicaid-insured pediatric cardiac surgical patients.<br /><b>Methods</b><br />All Medicaid enrolled children age <18 years undergoing cardiac surgery in the New York State CHS-COLOUR database, from 2006 to 2019, were followed in Medicaid claims data through 2019. A matched cohort of children without cardiac surgical disease was identified as comparators. Expenditures and inpatient, primary care, subspecialist, and emergency department utilization were modeled using log-linear and Poisson regression models to assess associations between patient characteristics and outcomes.<br /><b>Results</b><br />In 5,241 New York Medicaid-enrolled children, longitudinal health care expenditures and utilization for cardiac surgical patients exceeded noncardiac surgical comparators (cardiac surgical children: $15,500 ± $62,000 per month in year 1 and $1,600 ± $9,100 per month in year 5 vs noncardiac surgical children: $700 ± $6,600 per month in year 1 and $300 ± $2,200 per month in year 5). Children after cardiac surgery spent 52.9 days in hospitals and doctors\' offices in the first postoperative year and 90.5 days over 5 years. Being Hispanic, compared with non-Hispanic White, was associated with having more emergency department visits, inpatient admissions, and subspecialist visits in years 2 to 5, but fewer primary care visits and greater 5-year mortality.<br /><b>Conclusions</b><br />Children after cardiac surgery have significant longitudinal health care needs, even among those with less severe cardiac disease. Health care utilization differed by race/ethnicity, although mechanisms driving disparities should be investigated further.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 25 Apr 2023; 81:1605-1617</small></div>
Crook S, Dragan K, Woo JL, Neidell M, ... Anderson BR, New York State CHS-COLOUR
J Am Coll Cardiol: 25 Apr 2023; 81:1605-1617 | PMID: 37076215
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<div><h4>Familial Hypercholesterolemia: Challenges for a High-Risk Population: JACC Focus Seminar 1/3.</h4><i>Choi D, Malick WA, Koenig W, Rader DJ, Rosenson RS</i><br /><AbstractText>The availability of statins, ezetimibe, and PCSK9 inhibitors has significantly improved the prognosis of familial hypercholesterolemia (FH). However, a great number of individuals with FH do not achieve guideline-recommended low-density lipoprotein (LDL) cholesterol levels despite maximal lipid-lowering therapy. Novel therapies that lower LDL independent of LDL receptor activity can help mitigate atherosclerotic cardiovascular disease risk in most homozygous FH and many heterozygous FH patients. However, access to novel therapies remains limited for heterozygous FH patients with persistent elevation of LDL cholesterol despite treatment with multiple classes of cholesterol-lowering therapies. Conduction of cardiovascular outcomes clinical trials in patients with FH can be challenging because of difficulty in recruitment and long periods of follow-up. In the future, the use of validated surrogate measures of atherosclerosis may allow for clinical trials with fewer study participants and shorter duration, thereby expediting access to novel treatments for patients with FH.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 25 Apr 2023; 81:1621-1632</small></div>
Choi D, Malick WA, Koenig W, Rader DJ, Rosenson RS
J Am Coll Cardiol: 25 Apr 2023; 81:1621-1632 | PMID: 37076217
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<div><h4>Clinical Trial Design for Lipoprotein(a)-Lowering Therapies: JACC Focus Seminar 2/3.</h4><i>Malick WA, Goonewardena SN, Koenig W, Rosenson RS</i><br /><AbstractText>Lipoprotein(a) [Lp(a)] is a source of residual risk in patients with atherosclerotic cardiovascular disease (ASCVD). Clinical trials of fully human monoclonal antibodies targeting proprotein convertase subtilisin kexin 9 have shown that reductions in Lp(a) concentrations may be a predictor of event reduction with this class of cholesterol-lowering therapy. With the advent of selective therapies targeting Lp(a) such as antisense oligonucleotides, small-interfering RNA-based therapies, and gene editing, lowering of Lp(a) may lead to reduction in ASCVD. The phase 3 Lp(a)HORIZON (Assessing the Impact of Lipoprotein(a) Lowering with TQJ230 on Major Cardiovascular Events in Patients With CVD) outcomes trial is currently testing the effect of pelacarsen, an antisense oligonucleotide, on ASCVD risk. Olpasiran is a small-interfering RNA that is in a phase 3 clinical trial. As these therapies enter clinical trials, challenges in trial design will have to be addressed to optimize patient selection and outcomes.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 25 Apr 2023; 81:1633-1645</small></div>
Malick WA, Goonewardena SN, Koenig W, Rosenson RS
J Am Coll Cardiol: 25 Apr 2023; 81:1633-1645 | PMID: 37076218
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<div><h4>Clinical Trial Design for Triglyceride-Rich Lipoprotein-Lowering Therapies: JACC Focus Seminar 3/3.</h4><i>Malick WA, Waksman O, Do R, Koenig W, ... Stroes ESG, Rosenson RS</i><br /><AbstractText>Triglyceride-rich lipoproteins (TRLs) are a source of residual risk in patients with atherosclerotic cardiovascular disease, and are indirectly correlated with triglyceride (TG) levels. Previous clinical trials studying TG-lowering therapies have either failed to reduce major adverse cardiovascular events or shown no linkage of TG reduction with event reduction, particularly when these agents were tested on a background of statin therapy. Limitations in trial design may explain this lack of efficacy. With the advent of new RNA-silencing therapies in the TG metabolism pathway, there is renewed focus on reducing TRLs for major adverse cardiovascular event reduction. In this context, the pathophysiology of TRLs, pharmacological effects of TRL-lowering therapies, and optimal design of cardiovascular outcomes trials are major considerations.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 25 Apr 2023; 81:1646-1658</small></div>
Malick WA, Waksman O, Do R, Koenig W, ... Stroes ESG, Rosenson RS
J Am Coll Cardiol: 25 Apr 2023; 81:1646-1658 | PMID: 37076219
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<div><h4>Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus.</h4><i>Holt A, Strange JE, Nouhravesh N, Nielsen SK, ... Schou M, Lamberts M</i><br /><b>Background</b><br />Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy.<br /><b>Objectives</b><br />The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM.<br /><b>Methods</b><br />Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported.<br /><b>Results</b><br />Included were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23).<br /><b>Conclusions</b><br />NSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Apr 2023; 81:1459-1470</small></div>
Holt A, Strange JE, Nouhravesh N, Nielsen SK, ... Schou M, Lamberts M
J Am Coll Cardiol: 18 Apr 2023; 81:1459-1470 | PMID: 37045515
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<div><h4>Impact of Age and Sex on Left Ventricular Remodeling in Patients With Aortic Regurgitation.</h4><i>Akintoye E, Saijo Y, Braghieri L, Badwan O, ... Griffin BP, Popović ZB</i><br /><b>Background</b><br />Current guidelines for aortic regurgitation (AR) recommend the same linear left ventricular (LV) dimension for intervention regardless of age and sex.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the impact of age and sex on the degree of LV remodeling and outcomes.<br /><b>Methods</b><br />We included consecutive patients with severe AR who were serially monitored by echocardiogram between 2010 and 2016. The 2 main endpoints were as follows: 1) LV end-systolic volume indexed to body surface area (LVESVi) and LV end-diastolic volume indexed to body surface area; and 2) adverse events (AE). We evaluated the longitudinal rate of LV remodeling and determined the association between LV volume and AE by age and sex.<br /><b>Results</b><br />A total of 525 adult patients (26% women) with a median echocardiogram follow-up of 2.0 years (IQR: 1.0-3.6 years) were included. At baseline, older patients (age ≥60 years) had smaller LV volumes compared with younger patients (age <60 years), eg, the mean LVESVi was 27.3 mL/m<sup>2</sup> vs 32.3 mL/m<sup>2</sup>, respectively. Similarly, women had smaller LV volumes compared with men (mean LVESVi was 23.3 mL/m<sup>2</sup> vs 32.4 mL/m<sup>2</sup>). On serial evaluation, older patients and women maintained smaller LV volumes compared with younger patients and men, respectively. There were 210 (40%) AE during follow-up. The optimal discriminatory threshold for AE varies by age and sex, eg, the LVESVi threshold was highest for young men (50 mL/m<sup>2</sup>), intermediate for older men (35 mL/m<sup>2</sup>), and lowest for women (27 mL/m<sup>2</sup>).<br /><b>Conclusions</b><br />On serial evaluation, older patients and women with chronic AR maintained smaller LV volumes than younger patients and men, respectively, and develop AE at lower LV volumes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Apr 2023; 81:1474-1487</small></div>
Akintoye E, Saijo Y, Braghieri L, Badwan O, ... Griffin BP, Popović ZB
J Am Coll Cardiol: 18 Apr 2023; 81:1474-1487 | PMID: 37045517
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<div><h4>Out-of-Pocket Drug Costs for Medicare Beneficiaries With Cardiovascular Risk Factors Under the Inflation Reduction Act.</h4><i>Narasimmaraj PR, Oseran A, Tale A, Xu J, ... Yeh RW, Wadhera RK</i><br /><b>Background</b><br />High out-of-pocket prescription drug costs contribute to financial toxicity, medication nonadherence, and adverse cardiovascular (CV) outcomes. Policymakers recently passed the Inflation Reduction Act, which will cap Medicare out-of-pocket drug costs at $2,000/year and expand full low-income subsidies (LIS). It is unclear how these provisions will affect Medicare beneficiaries with CV risk factors and/or conditions.<br /><b>Objectives</b><br />The authors sought to characterize the population of Medicare beneficiaries with CV risk factors/conditions experiencing out-of-pocket prescription drug costs >$2,000/year and estimate their potential savings under the Inflation Reduction Act\'s spending cap; identify sociodemographic characteristics associated with out-of-pocket costs >$2,000/year; and characterize beneficiaries newly eligible for LIS under the Inflation Reduction Act.<br /><b>Methods</b><br />This was a cross-sectional study of Medicare beneficiaries aged ≥65 years with ≥1 CV risk factor/condition from 2016 to 2019.<br /><b>Results</b><br />An annual estimated 34,056,335 ± 855,653 Medicare beneficiaries (mean ± SE) had ≥1 CV risk factor/condition, of whom 1,020,484 ± 77,055 experienced out-of-pocket drug costs >$2,000/year. The likelihood of experiencing out-of-pocket drug costs >$2,000/year was lower among adults ≥75 years vs 65 to 74 years (adjusted OR: 0.67; 95% CI: 0.49-0.93) and for low-income vs higher-income adults. Among beneficiaries currently spending >$2,000/year, estimated median out-of-pocket drug savings would be $855/year and total annual savings $1,723,031,307 ± $91,150,609 under the Inflation Reduction Act. An estimated 1,289,861 beneficiaries would also become newly eligible for LIS.<br /><b>Conclusions</b><br />More than 1 million older adults with CV risk factors and/or conditions spend >$2,000/year out-of-pocket on prescription drugs and will likely benefit from the Inflation Reduction Act\'s cap, with estimated total out-of-pocket savings of $1.7 billion/year, while another 1.3 million will also become newly eligible for LIS.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Apr 2023; 81:1491-1501</small></div>
Narasimmaraj PR, Oseran A, Tale A, Xu J, ... Yeh RW, Wadhera RK
J Am Coll Cardiol: 18 Apr 2023; 81:1491-1501 | PMID: 37045519
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<div><h4>Evolving Science on Cardiovascular Disease Among Hispanic/Latino Adults: JACC International.</h4><i>Pirzada A, Cai J, Heiss G, Sotres-Alvarez D, ... Wassertheil-Smoller S, Daviglus ML</i><br /><AbstractText>The landmark, multicenter HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is the largest, most comprehensive, longitudinal community-based cohort study to date of diverse Hispanic/Latino persons in the United States. The HCHS/SOL aimed to address the dearth of comprehensive data on risk factors for cardiovascular disease (CVD) and other chronic diseases in this population and has expanded considerably in scope since its inception. This paper describes the aims/objectives and data collection of the HCHS/SOL and its ancillary studies to date and highlights the critical and sizable contributions made by the study to understanding the prevalence of and changes in CVD risk/protective factors and the burden of CVD and related chronic conditions among adults of diverse Hispanic/Latino backgrounds. The continued follow-up of this cohort will allow in-depth investigations on cardiovascular and pulmonary outcomes in this population, and data from the ongoing ancillary studies will facilitate generation of new hypotheses and study questions.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Apr 2023; 81:1505-1520</small></div>
Pirzada A, Cai J, Heiss G, Sotres-Alvarez D, ... Wassertheil-Smoller S, Daviglus ML
J Am Coll Cardiol: 18 Apr 2023; 81:1505-1520 | PMID: 37045521
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<div><h4>The Genetic Determinants of Aortic Distention.</h4><i>Pirruccello JP, Rämö JT, Choi SH, Chaffin MD, ... Lindsay ME, Ellinor PT</i><br /><b>Background</b><br />As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous peripheral blood delivery. Systolic distention and diastolic recoil conserve energy and are enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and vascular disease.<br /><b>Objectives</b><br />In this study, we sought to discover epidemiologic correlates and genetic determinants of aortic distensibility and strain.<br /><b>Methods</b><br />We trained a deep learning model to quantify thoracic aortic area throughout the cardiac cycle from cardiac magnetic resonance images and calculated aortic distensibility and strain in 42,342 UK Biobank participants.<br /><b>Results</b><br />Descending aortic distensibility was inversely associated with future incidence of cardiovascular diseases, such as stroke (HR: 0.59 per SD; P = 0.00031). The heritabilities of aortic distensibility and strain were 22% to 25% and 30% to 33%, respectively. Common variant analyses identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were not significantly associated with thoracic aortic diameter. Nearby genes were involved in elastogenesis and atherosclerosis. Aortic strain and distensibility polygenic scores had modest effect sizes for predicting cardiovascular outcomes (delaying or accelerating disease onset by 2%-18% per SD change in scores) and remained statistically significant predictors after accounting for aortic diameter polygenic scores.<br /><b>Conclusions</b><br />Genetic determinants of aortic function influence risk for stroke and coronary artery disease and may lead to novel targets for medical intervention.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 Apr 2023; 81:1320-1335</small></div>
Pirruccello JP, Rämö JT, Choi SH, Chaffin MD, ... Lindsay ME, Ellinor PT
J Am Coll Cardiol: 11 Apr 2023; 81:1320-1335 | PMID: 37019578
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<div><h4>Combination Moderate-Intensity Statin and Ezetimibe Therapy for Elderly Patients With Atherosclerosis.</h4><i>Lee SH, Lee YJ, Heo JH, Hur SH, ... Jang Y, Kim JS</i><br /><b>Background</b><br />The routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events.<br /><b>Objectives</b><br />We evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD).<br /><b>Methods</b><br />In this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke.<br /><b>Results</b><br />Among the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159).<br /><b>Conclusions</b><br />Moderate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 Apr 2023; 81:1339-1349</small></div>
Lee SH, Lee YJ, Heo JH, Hur SH, ... Jang Y, Kim JS
J Am Coll Cardiol: 11 Apr 2023; 81:1339-1349 | PMID: 37019580
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<div><h4>Prolonged Moderate-Intensity Exercise Does Not Increase Muscle Injury Markers in Symptomatic or Asymptomatic Statin Users.</h4><i>Allard NAE, Janssen L, Lagerwaard B, Nuijten MAH, ... Timmers S, Hopman MTE</i><br /><b>Background</b><br />Statin use may exacerbate exercise-induced skeletal muscle injury caused by reduced coenzyme Q10 (CoQ10) levels, which are postulated to produce mitochondrial dysfunction.<br /><b>Objectives</b><br />We determined the effect of prolonged moderate-intensity exercise on markers of muscle injury in statin users with and without statin-associated muscle symptoms. We also examined the association between leukocyte CoQ10 levels and muscle markers, muscle performance, and reported muscle symptoms.<br /><b>Methods</b><br />Symptomatic (n = 35; age 62 ± 7 years) and asymptomatic statin users (n = 34; age 66 ± 7 years) and control subjects (n = 31; age 66 ± 5 years) walked 30, 40, or 50 km/d for 4 consecutive days. Muscle injury markers (lactate dehydrogenase, creatine kinase, myoglobin, cardiac troponin I, and N-terminal pro-brain natriuretic peptide), muscle performance, and reported muscle symptoms were assessed at baseline and after exercise. Leukocyte CoQ10 was measured at baseline.<br /><b>Results</b><br />All muscle injury markers were comparable at baseline (P > 0.05) and increased following exercise (P < 0.001), with no differences in the magnitude of exercise-induced elevations among groups (P > 0.05). Muscle pain scores were higher at baseline in symptomatic statin users (P < 0.001) and increased similarly in all groups following exercise (P < 0.001). Muscle relaxation time increased more in symptomatic statin users than in control subjects following exercise (P = 0.035). CoQ10 levels did not differ among symptomatic (2.3 nmol/U; IQR: 1.8-2.9 nmol/U), asymptomatic statin users (2.1 nmol/U; IQR: 1.8-2.5 nmol/U), and control subjects (2.1 nmol/U; IQR: 1.8-2.3 nmol/U; P = 0.20), and did not relate to muscle injury markers, fatigue resistance, or reported muscle symptoms.<br /><b>Conclusions</b><br />Statin use and the presence of statin-associated muscle symptoms does not exacerbate exercise-induced muscle injury after moderate exercise. Muscle injury markers were not related to leukocyte CoQ10 levels. (Exercise-induced Muscle Damage in Statin Users; NCT05011643).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 Apr 2023; 81:1353-1364</small></div>
Allard NAE, Janssen L, Lagerwaard B, Nuijten MAH, ... Timmers S, Hopman MTE
J Am Coll Cardiol: 11 Apr 2023; 81:1353-1364 | PMID: 37019582
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<div><h4>Assessing and Addressing Social Determinants of Cardiovascular Health: JACC State-of-the-Art Review.</h4><i>Brandt EJ, Tobb K, Cambron JC, Ferdinand K, ... Lundberg G, Watson K</i><br /><AbstractText>Social determinants of health (SDOH) are the social conditions in which people are born, live, and work. SDOH offers a more inclusive view of how environment, geographic location, neighborhoods, access to health care, nutrition, socioeconomics, and so on are critical in cardiovascular morbidity and mortality. SDOH will continue to increase in relevance and integration of patient management, thus, applying the information herein to clinical and health systems will become increasingly commonplace. This state-of-the-art review covers the 5 domains of SDOH, including economic stability, education, health care access and quality, social and community context, and neighborhood and built environment. Recognizing and addressing SDOH is an important step toward achieving equity in cardiovascular care. We discuss each SDOH within the context of cardiovascular disease, how they can be assessed by clinicians and within health care systems, and key strategies for clinicians and health care systems to address these SDOH. Summaries of these tools and key strategies are provided.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 Apr 2023; 81:1368-1385</small></div>
Brandt EJ, Tobb K, Cambron JC, Ferdinand K, ... Lundberg G, Watson K
J Am Coll Cardiol: 11 Apr 2023; 81:1368-1385 | PMID: 37019584
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<div><h4>Abnormal Conduction-Induced Cardiomyopathy: JACC Review Topic of the Week.</h4><i>Huizar JF, Kaszala K, Tan A, Koneru J, ... Kron J, Ellenbogen KA</i><br /><AbstractText>Nonischemic cardiomyopathies are a frequent occurrence. The understanding of the mechanism(s) and triggers of these cardiomyopathies have led to improvement and even recovery of left ventricular function. Although chronic right ventricular pacing-induced cardiomyopathy has been recognized for many years, left bundle branch block and pre-excitation have been recently identified as potential reversible causes of cardiomyopathy. These cardiomyopathies share a similar abnormal ventricular propagation that can be recognized by a wide QRS duration with left bundle branch block pattern; thus, we coined the term abnormal conduction-induced cardiomyopathies. Such abnormal propagation results in an abnormal contractility that can only be recognized by cardiac imaging as ventricular dyssynchrony. Appropriate diagnosis and treatment will not only lead to improved left ventricular ejection fraction and functional class, but may also reduce morbidity and mortality. This review presents an update of the mechanisms, prevalence, incidence, and risk factors, as well as their diagnosis and management, while highlighting current gaps of knowledge.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Mar 2023; 81:1192-1200</small></div>
Huizar JF, Kaszala K, Tan A, Koneru J, ... Kron J, Ellenbogen KA
J Am Coll Cardiol: 28 Mar 2023; 81:1192-1200 | PMID: 36948737
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<div><h4>Changes in Cardiorespiratory Fitness and Survival in Patients With or Without Cardiovascular Disease.</h4><i>Kokkinos P, Faselis C, Samuel IBH, Lavie CJ, ... Heimal M, Myers J</i><br /><b>Background</b><br />The association between cardiorespiratory fitness (CRF) and mortality risk is based mostly on 1 CRF assessment. The impact of CRF change on mortality risk is not well-defined.<br /><b>Objectives</b><br />This study sought to evaluate changes in CRF and all-cause mortality.<br /><b>Methods</b><br />We assessed 93,060 participants aged 30-95 years (mean 61.3 ± 9.8 years). All completed 2 symptom-limited exercise treadmill tests, 1 or more years apart (mean 5.8 ± 3.7 years) with no evidence of overt cardiovascular disease. Participants were assigned to age-specific fitness quartiles based on peak METS achieved on the baseline exercise treadmill test. Additionally, each CRF quartile was stratified based on CRF changes (increase, decrease, no change) observed on the final exercise treadmill test. Multivariable Cox models were used to estimate HRs and 95% CIs for all-cause mortality.<br /><b>Results</b><br />During a median follow-up of 6.3 years (IQR: 3.7-9.9 years), 18,302 participants died with an average yearly mortality rate of 27.6 events per 1,000 person-years. In general, changes in CRF ≥1.0 MET were associated with inverse and proportionate changes in mortality risk regardless of baseline CRF status. For example, a decline in CRF of >2.0 METS was associated with a 74% increase in risk (HR: 1.74; 95% CI: 1.59-1.91) for low-fit individuals with CVD, and 69% increase (HR: 1.69; 95% CI: 1.45-1.96) for those without CVD.<br /><b>Conclusions</b><br />Changes in CRF reflected inverse and proportional changes in mortality risk for those with and without CVD. The impact of relatively small CRF changes on mortality risk has considerable clinical and public health significance.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 28 Mar 2023; 81:1137-1147</small></div>
Kokkinos P, Faselis C, Samuel IBH, Lavie CJ, ... Heimal M, Myers J
J Am Coll Cardiol: 28 Mar 2023; 81:1137-1147 | PMID: 36948729
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<div><h4>Association of Incident Cardiovascular Disease With Time Course and Cumulative Exposure to Multiple Risk Factors.</h4><i>Domanski MJ, Wu CO, Tian X, Hasan AA, ... Lloyd-Jones DM, Fuster V</i><br /><b>Background</b><br />The quantitative relationship of incident cardiovascular disease (CVD) to lifetime cumulative risk factor exposure is not well understood.<br /><b>Objectives</b><br />Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we examined the quantitative associations of cumulative exposure over time to multiple, simultaneously operating risk factors with CVD incidence and the incidence of its components.<br /><b>Methods</b><br />Regression models were developed quantifying the influence of the time course and severity of multiple CVD risk factors, operating simultaneously, on risk of incident CVD. The outcomes were incident CVD and the incidence of its components: coronary heart disease, stroke, and congestive heart failure.<br /><b>Results</b><br />Our study included 4,958 asymptomatic adults enrolled in CARDIA from 1985 to 1986 (ages 18 to 30 years) who were followed for 30 years. Risk of incident CVD depends on the time course and severity of a series of independent risk factors, the impact of which is mediated by their effects on individual CVD components after age 40 years. Cumulative exposure (AUC vs time) to low-density lipoprotein cholesterol and triglycerides was independently associated with risk of incident CVD. Of the blood pressure variables, areas under the mean arterial pressure vs time curve and the pulse pressure vs time curve were strongly and independently associated with incident CVD risk.<br /><b>Conclusions</b><br />The quantitative description of the link between risk factors and CVD informs the construction of individualized CVD mitigation strategies, design of primary prevention trials, and assessment of public health impact of risk factor-based interventions.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 28 Mar 2023; 81:1151-1161</small></div>
Domanski MJ, Wu CO, Tian X, Hasan AA, ... Lloyd-Jones DM, Fuster V
J Am Coll Cardiol: 28 Mar 2023; 81:1151-1161 | PMID: 36948731
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<div><h4>Influence of Culprit Lesion Intervention on Outcomes in Infarct-Related Cardiogenic Shock With Cardiac Arrest.</h4><i>Zeymer U, Alushi B, Noc M, Mamas MA, ... Lauten A, Thiele H</i><br /><b>Background</b><br />Cardiac arrest (CA) is common in patients with infarct-related cardiogenic shock (CS).<br /><b>Objectives</b><br />The goal of this study was to identify the characteristics and outcomes of culprit lesion percutaneous coronary intervention (PCI) of patients with infarct-related CS stratified according to CA in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) randomized trial and registry.<br /><b>Methods</b><br />Patients with CS with and without CA from the CULPRIT-SHOCK study were analyzed. All-cause death or severe renal failure leading to renal replacement therapy within 30 days and 1-year death were assessed.<br /><b>Results</b><br />Among 1,015 patients, 550 (54.2%) had CA. Patients with CA were younger, more frequently male, had lower rates of peripheral artery disease, a glomerular filtration rate <30 mL/min, and left main disease, and they presented more often with clinical signs of impaired organ perfusion. The composite of all-cause death or severe renal failure within 30 days occurred in 51.2% of patients with CA vs 48.5% in non-CA patients (P = 0.39) and 1-year death in 53.8% vs 50.4% (P = 0.29), respectively. In a multivariate analysis, CA was an independent predictor of 1-year mortality (HR: 1.27; 95% CI: 1.01-1.59). In the randomized trial, culprit lesion-only PCI was superior to immediate multivessel PCI in patients both with and without CA (P for interaction = 0.6).<br /><b>Conclusions</b><br />More than 50% of patients with infarct-related CS had CA. These patients with CA were younger and had fewer comorbidities, but CA was an independent predictor of 1-year mortality. Culprit lesion-only PCI is the preferred strategy, both in patients with and without CA. (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Mar 2023; 81:1165-1176</small></div>
Zeymer U, Alushi B, Noc M, Mamas MA, ... Lauten A, Thiele H
J Am Coll Cardiol: 28 Mar 2023; 81:1165-1176 | PMID: 36948733
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<div><h4>Representation of Women and Minority Faculty and Fellows in Academic Pediatric Cardiology Training Programs.</h4><i>Balasubramanian S, Pasquali SK, Cousino MK, Lowery RE, ... Romano JC, Owens ST</i><br /><b>Background</b><br />Studies have shown that diverse care teams optimize patient outcomes. Describing the current representation of women and minorities has been a critical step in improving diversity across several fields.<br /><b>Objectives</b><br />To address the lack of data specific to pediatric cardiology, the authors conducted a national survey.<br /><b>Methods</b><br />U.S. academic pediatric cardiology programs with fellowship training programs were surveyed. Division directors were invited (July 2021 to September 2021) to complete an e-survey of program composition. Underrepresented minorities in medicine (URMM) were characterized using standard definitions. Descriptive analyses at the hospital, faculty, and fellow level were performed.<br /><b>Results</b><br />Altogether, 52 of 61 programs (85%) completed the survey, representing 1,570 total faculty and 438 fellows, with a wide range in program size (7-109 faculty, 1-32 fellows). Although women comprise approximately 60% of faculty in pediatrics overall, they made up 55% of fellows and 45% of faculty in pediatric cardiology. Representation of women in leadership roles was notably less, including 39% of clinical subspecialty directors, 25% of endowed chairs, and 16% of division directors. URMM comprise approximately 35% of the U.S. population; however, they made up only 14% of pediatric cardiology fellows and 10% of faculty, with very few in leadership roles.<br /><b>Conclusions</b><br />These national data suggest a \"leaky pipeline\" for women in pediatric cardiology and very limited presence of URRM overall. Our findings can inform efforts to elucidate underlying mechanisms for persistent disparity and reduce barriers to improving diversity in the field.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Mar 2023; 81:1181-1188</small></div>
Balasubramanian S, Pasquali SK, Cousino MK, Lowery RE, ... Romano JC, Owens ST
J Am Coll Cardiol: 28 Mar 2023; 81:1181-1188 | PMID: 36948735
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<div><h4>Sudden Cardiac Death Among Adolescents in the United Kingdom.</h4><i>Finocchiaro G, Radaelli D, D\'Errico S, Papadakis M, ... Westaby J, Sheppard MN</i><br /><b>Background</b><br />Causes and precipitating factors of sudden cardiac death (SCD) in adolescents are poorly understood.<br /><b>Objectives</b><br />The authors sought to investigate the etiologies of SCD and their association with physical activity in a large cohort of adolescents.<br /><b>Methods</b><br />Between 1994 and June 2022, 7,675 cases of SCD were consecutively referred to our national cardiac pathology center; 756 (10%) were adolescents. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners.<br /><b>Results</b><br />A structurally normal heart, indicative of sudden arrhythmic death syndrome was the most common autopsy finding (n = 474; 63%). Myocardial diseases were detected in 163 cases (22%), including arrhythmogenic cardiomyopathy (n = 36; 5%), hypertrophic cardiomyopathy (n = 31; 4%), idiopathic left ventricular hypertrophy (n = 31; 4%), and myocarditis (n = 30; 4%). Coronary artery anomalies were identified in 17 cases (2%). Decedents were competitive athletes in 128 cases (17%), and 159 decedents (21%) died during exercise. Arrhythmogenic cardiomyopathy was diagnosed in 8% of athletes compared with 4% of nonathletes (P = 0.05); coronary artery anomalies were significantly more common in athletes (9% vs 1%; P < 0.001), as well as commotio cordis (5% compared with 1% in nonathletes; P = 0.001). The 3 main comorbidities were asthma (n = 58; 8%), epilepsy (n = 44; 6%), and obesity (n = 40; 5%).<br /><b>Conclusions</b><br />Sudden arrhythmic death syndrome and myocardial diseases are the most common conditions diagnosed at autopsy in adolescent victims of SCD. Among causes of SCD, arrhythmogenic cardiomyopathy, coronary artery anomalies, and commotio cordis are more common in young athletes than in similar age sedentary individuals.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Mar 2023; 81:1007-1017</small></div>
Finocchiaro G, Radaelli D, D'Errico S, Papadakis M, ... Westaby J, Sheppard MN
J Am Coll Cardiol: 21 Mar 2023; 81:1007-1017 | PMID: 36922085
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<div><h4>Incidence of Cardiac Arrest During Sports Among Women in the European Union.</h4><i>Weizman O, Empana JP, Blom M, Tan HL, ... Jouven X, ESCAPE-NET Investigators</i><br /><b>Background</b><br />Women represent a growing proportion of sports participants. Still, few original data regarding sudden cardiac arrest during sports (Sr-SCA) in women are available.<br /><b>Objectives</b><br />The authors sought to assess the incidence, characteristics, and outcomes of women presenting with Sr-SCA.<br /><b>Methods</b><br />Data were analyzed from 3 population-based European registries (ESCAPE-NET 2020 Horizon Program) that prospectively and exhaustively collect every case of SCA: SDEC (Paris-Sudden Death Expertise Center), ARREST (AmsteRdam REsuscitation Studies), and SRCR (Swedish Register for Cardiopulmonary Resuscitation). Sr-SCA was defined as SCA during or ≤1 hour after cessation of sports activity.<br /><b>Results</b><br />Of 34,826 SCA between 2006 and 2017, 760 Sr-SCA (2.2%) were identified, including 54 in women. The average annual incidence of Sr-SCA in women in the 3 registries ranged from 0.10 per million (95% CI: 0.01-0.71 per million) to 0.38 per million (95% CI: 0.14-1.04 per million). Overall, the average annual incidence rate of Sr-SCA in women was 0.19 per million (95% CI: 0.14-0.24 per million), >10-fold lower compared with men (2.63 per million [95% CI: 2.45-2.83 per million]; P < 0.0001). When extrapolating to the total European population and accounting for age and sex, this yields 98 cases per year (95% CI: 72-123 cases per year) in women and 1,350 cases per year (95% CI: 1,256-1,451 cases per year) in men. Subject characteristics and circumstances of occurrence were similar in women vs men. Bystander response, time to defibrillation, and survival rate at hospital admission (58.8% vs 58.5%; P = 0.99) and 30 days did not differ significantly between women and men.<br /><b>Conclusions</b><br />These findings emphasize the dramatically lower risk of Sr-SCA in women compared with men, despite similar subject characteristics. This should be considered in designing preparticipation screening strategies in the future.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Mar 2023; 81:1021-1031</small></div>
Weizman O, Empana JP, Blom M, Tan HL, ... Jouven X, ESCAPE-NET Investigators
J Am Coll Cardiol: 21 Mar 2023; 81:1021-1031 | PMID: 36922087
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<div><h4>Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy.</h4><i>Lynch A, Tatangelo M, Ahuja S, Steve Fan CP, ... Weintraub RG, Mital S</i><br /><b>Background</b><br />Genetic defects in the RAS/mitogen-activated protein kinase pathway are an important cause of hypertrophic cardiomyopathy (RAS-HCM). Unlike primary HCM (P-HCM), the risk of sudden cardiac death (SCD) and long-term survival in RAS-HCM are poorly understood.<br /><b>Objectives</b><br />The study\'s objective was to compare transplant-free survival, incidence of SCD, and implantable cardioverter-defibrillator (ICD) use between RAS-HCM and P-HCM patients.<br /><b>Methods</b><br />In an international, 21-center cohort study, we analyzed phenotype-positive pediatric RAS-HCM (n = 188) and P-HCM (n = 567) patients. The between-group differences in cumulative incidence of all outcomes from first evaluation were compared using Gray\'s tests, and age-related hazard of all-cause mortality was determined.<br /><b>Results</b><br />RAS-HCM patients had a lower median age at diagnosis compared to P-HCM (0.9 years [IQR: 0.2-5.0 years] vs 9.8 years [IQR: 2.0-13.9 years], respectively) (P < 0.001). The 10-year cumulative incidence of SCD from first evaluation was not different between RAS-HCM and P-HCM (4.7% vs 4.2%, respectively; P = 0.59). The 10-year cumulative incidence of nonarrhythmic deaths or transplant was higher in RAS-HCM compared with P-HCM (11.0% vs 5.4%, respectively; P = 0.011). The 10-year cumulative incidence of ICD insertions, however, was 5-fold lower in RAS-HCM compared with P-HCM (6.9% vs 36.6%; P < 0.001). Nonarrhythmic deaths occurred primarily in infancy and SCD primarily in adolescence.<br /><b>Conclusions</b><br />RAS-HCM was associated with a higher incidence of nonarrhythmic death or transplant but similar incidence of SCD as P-HCM. However, ICDs were used less frequently in RAS-HCM compared to P-HCM. In addition to monitoring for heart failure and timely consideration of advanced heart failure therapies, better risk stratification is needed to guide ICD practices in RAS-HCM.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Mar 2023; 81:1035-1045</small></div>
Lynch A, Tatangelo M, Ahuja S, Steve Fan CP, ... Weintraub RG, Mital S
J Am Coll Cardiol: 21 Mar 2023; 81:1035-1045 | PMID: 36922089
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<div><h4>Geographic Variation in Access to Cardiac Rehabilitation.</h4><i>Duncan MS, Robbins NN, Wernke SA, Greevy RA, ... Freiberg MS, Bachmann JM</i><br /><b>Background</b><br />There is marked geographic variation in cardiac rehabilitation (CR) initiation, ranging from 10% to 40% of eligible patients at the state level. The potential causes of this variation, such as patient access to CR centers, are not well studied.<br /><b>Objectives</b><br />The authors sought to determine how access to CR centers affects CR initiation in Medicare beneficiaries.<br /><b>Methods</b><br />The authors used Medicare files to identify CR-eligible Medicare beneficiaries and calculate CR initiation rates at the hospital referral region (HRR) level. We used linear regression to evaluate the percent variation in CR initiation accounted for by CR access across HRRs. We then employed geospatial hotspot analysis to identify CR deserts, or counties in which patient load per CR center is disproportionately high.<br /><b>Results</b><br />A total of 1,133,657 Medicare beneficiaries were eligible for CR from 2014 to 2017, of whom 263,310 (23%) initiated CR. The West North Central Census Division had the highest adjusted CR initiation rate (35.4%) and the highest density of CR programs (6.58 per 1,000 CR-eligible Medicare beneficiaries). Density of CR programs accounted for 21.2% of geographic variation in CR initiation at the HRR level. A total of 40 largely urban counties comprising 14% of the United States population age ≥65 years had disproportionately low CR access and were identified as CR deserts.<br /><b>Conclusions</b><br />A substantial proportion of geographic variation in CR initiation was related to access to CR programs, with a significant amount of the U.S. population living in CR deserts. These data invite further study on interventions to increase CR access.<br /><br />Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 21 Mar 2023; 81:1049-1060</small></div>
Duncan MS, Robbins NN, Wernke SA, Greevy RA, ... Freiberg MS, Bachmann JM
J Am Coll Cardiol: 21 Mar 2023; 81:1049-1060 | PMID: 36922091
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<div><h4>Nonthrombogenic Roles of the Left Atrial Appendage: JACC Review Topic of the Week.</h4><i>Alkhouli M, Di Biase L, Natale A, Rihal CS, ... Lakkireddy D, Friedman PA</i><br /><AbstractText>The atrial appendage (LAA) is a well-established source of cardioembolism in patients with atrial fibrillation. Therefore, research involving the LAA has largely focused on its thrombogenic attribute and the utility of its exclusion in stroke prevention. However, recent studies have highlighted several novel functions of the LAA that may have important therapeutic implications. In this paper, we provide a concise overview of the LAA anatomy and summarize the emerging data on its nonthrombogenic roles.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Mar 2023; 81:1063-1075</small></div>
Alkhouli M, Di Biase L, Natale A, Rihal CS, ... Lakkireddy D, Friedman PA
J Am Coll Cardiol: 21 Mar 2023; 81:1063-1075 | PMID: 36922093
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<div><h4>Sex Differences in Epidemiology, Care, and Outcomes in Patients With Acute Chest Pain.</h4><i>Dawson LP, Nehme E, Nehme Z, Davis E, ... Smith K, Stub D</i><br /><b>Background</b><br />Discrepancies in cardiovascular care for women are well described, but few data assess the entire patient journey for chest pain care.<br /><b>Objectives</b><br />This study aimed to assess sex differences in epidemiology and care pathways from emergency medical services (EMS) contact through to clinical outcomes following discharge.<br /><b>Methods</b><br />This is a state-wide population-based cohort study including consecutive adult patients attended by EMS for acute undifferentiated chest pain in Victoria, Australia (January 1, 2015, to June 30, 2019). EMS clinical data were individually linked to emergency and hospital administrative datasets, and mortality data and differences in care quality and outcomes were assessed using multivariable analyses.<br /><b>Results</b><br />In 256,901 EMS attendances for chest pain, 129,096 attendances (50.3%) were women, and mean age was 61.6 years. Age-standardized incidence rates were marginally higher for women compared with men (1,191 vs 1,135 per 100,000 person-years). In multivariable models, women were less likely to receive guideline-directed care across most care measures including transport to hospital, prehospital aspirin or analgesia administration, 12-lead electrocardiogram, intravenous cannula insertion, and off-load from EMS or review by emergency department clinicians within target times. Similarly, women with acute coronary syndrome were less likely to undergo angiography or be admitted to a cardiac or intensive care unit. Thirty-day and long-term mortality was higher for women diagnosed with ST-segment elevation myocardial infarction, but lower overall.<br /><b>Conclusions</b><br />Substantial differences in care are present across the spectrum of acute chest pain management from first contact through to hospital discharge. Women have higher mortality for STEMI, but better outcomes for other etiologies of chest pain compared with men.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; 81:933-945</small></div>
Dawson LP, Nehme E, Nehme Z, Davis E, ... Smith K, Stub D
J Am Coll Cardiol: 14 Mar 2023; 81:933-945 | PMID: 36889871
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<div><h4>Predicting Malignant Ventricular Arrhythmias Using Real-Time Remote Monitoring.</h4><i>Ginder C, Li J, Halperin JL, Akar JG, ... Chattopadhyay I, Upadhyay GA</i><br /><b>Background</b><br />Although implantable cardioverter-defibrillator (ICD) therapies are associated with increased morbidity and mortality, the prediction of malignant ventricular arrhythmias has remained elusive.<br /><b>Objectives</b><br />The purpose of this study was to evaluate whether daily remote-monitoring data may predict appropriate ICD therapies for ventricular tachycardia or ventricular fibrillation.<br /><b>Methods</b><br />This was a post hoc analysis of IMPACT (Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices), a multicenter, randomized, controlled trial of 2,718 patients evaluating atrial tachyarrhythmias and anticoagulation for patients with heart failure and ICD or cardiac resynchronization therapy with defibrillator devices. All device therapies were adjudicated as either appropriate (to treat ventricular tachycardia or ventricular fibrillation) or inappropriate (all others). Remote monitoring data in the 30 days before device therapy were utilized to develop separate multivariable logistic regression and neural network models to predict appropriate device therapies.<br /><b>Results</b><br />A total of 59,807 device transmissions were available for 2,413 patients (age 64 ± 11 years, 26% women, 64% ICD). Appropriate device therapies (141 shocks, 10 antitachycardia pacing) were delivered to 151 patients. Logistic regression identified shock lead impedance and ventricular ectopy as significantly associated with increased risk of appropriate device therapy (sensitivity 39%, specificity 91%, AUC: 0.72). Neural network modeling yielded significantly better (P < 0.01 for comparison) predictive performance (sensitivity 54%, specificity 96%, AUC: 0.90), and also identified patterns of change in atrial lead impedance, mean heart rate, and patient activity as predictors of appropriate therapies.<br /><b>Conclusions</b><br />Daily remote monitoring data may be utilized to predict malignant ventricular arrhythmias in the 30 days before device therapies. Neural networks complement and enhance conventional approaches to risk stratification.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; 81:949-961</small></div>
Ginder C, Li J, Halperin JL, Akar JG, ... Chattopadhyay I, Upadhyay GA
J Am Coll Cardiol: 14 Mar 2023; 81:949-961 | PMID: 36889873
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<div><h4>Effect of Prosthesis-Patient Mismatch on Long-Term Clinical Outcomes After Bioprosthetic Aortic Valve Replacement.</h4><i>Dismorr M, Glaser N, Franco-Cereceda A, Sartipy U</i><br /><b>Background</b><br />Prosthesis-patient mismatch (PPM) is common following surgical aortic valve replacement (SAVR).<br /><b>Objectives</b><br />The purpose of this study was to quantify the impact of PPM on all-cause mortality, heart failure hospitalization, and reintervention following bioprosthetic SAVR.<br /><b>Methods</b><br />This observational nationwide cohort study from SWEDEHEART (Swedish Web system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies) and other national registers included all patients who underwent primary bioprosthetic SAVR in Sweden from 2003 to 2018. PPM was defined according to the Valve Academic Research Consortium 3 criteria. Outcomes were all-cause mortality, heart failure hospitalization, and aortic valve reintervention. Regression standardization was used to account for intergroup differences and to estimate cumulative incidence differences.<br /><b>Results</b><br />We included 16,423 patients (no PPM: 7,377 [45%]; moderate PPM: 8,502 [52%]; and severe PPM: 544 [3%]). After regression standardization, the cumulative incidence of all-cause mortality at 10 years was 43% (95% CI: 24%-44%) in the no PPM group compared with 45% (95% CI: 43%-46%) and 48% (95% CI: 44%-51%) in the moderate and severe PPM groups, respectively. The survival difference at 10 years was 4.6% (95% CI: 0.7%-8.5%) and 1.7% (95% CI: 0.1%-3.3%) in no vs severe PPM and no vs moderate PPM, respectively. The difference in heart failure hospitalization at 10 years was 6.0% (95% CI: 2.2%-9.7%) in severe vs no PPM. There was no difference in aortic valve reintervention in patients with or without PPM.<br /><b>Conclusions</b><br />Increasing grades of PPM were associated with long-term mortality, and severe PPM was associated with increased heart failure. Moderate PPM was common, but the clinical significance may be negligible because the absolute risk differences in clinical outcomes were small.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; 81:964-975</small></div>
Dismorr M, Glaser N, Franco-Cereceda A, Sartipy U
J Am Coll Cardiol: 14 Mar 2023; 81:964-975 | PMID: 36889875
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<div><h4>Prevalence and Complications of Aberrant Subclavian Artery in Patients With Heritable and Nonheritable Arteriopathies.</h4><i>Giuliani L, Di Toro A, Urtis M, Narula N, ... Cameron D, Arbustini E</i><br /><b>Background</b><br />An aberrant subclavian artery (ASA) (or lusoria) is the most common congenital anomaly of the aortic arch (0.5%-2.2%; female-to-male ratio 2:1 to 3:1). ASA can become aneurysmal and result in dissection, involving Kommerell\'s diverticulum when present and the aorta. Data of its significance in genetic arteriopathies are not available.<br /><b>Objectives</b><br />The purpose of this study was to assess the prevalence and complications of ASA in gene-positive and -negative nonatherosclerotic arteriopathies.<br /><b>Materials</b><br />The series includes 1,418 consecutive patients with gene-positive (n = 854) and gene-negative arteriopathies (n = 564) diagnosed as part of institutional work-up for nonatherosclerotic syndromic and nonsyndromic arteriopathies. Comprehensive evaluation includes genetic counseling, next-generation sequencing multigene testing, cardiovascular and multidisciplinary assessment, and whole-body computed tomography angiography.<br /><b>Results</b><br />ASA was found in 34 of 1,418 cases (2.4%), with a similar prevalence in gene-positive (n = 21 of 854, 2.5%) and gene-negative (n = 13 of 564, 2.3%) arteriopathies. Of the former 21 patients, 14 had Marfan syndrome, 5 had Loeys-Dietz syndrome, 1 had type-IV Ehlers-Danlos syndrome, and 1 had periventricular heterotopia type 1. ASA did not segregate with genetic defects. Dissection occurred in 5 of 21 patients with genetic arteriopathies (23.8%; 2 Marfan syndrome and 3 Loeys-Dietz syndrome), all with associated Kommerell\'s diverticulum. No dissections occurred in gene-negative patients. At baseline, none of the 5 patients with ASA dissection fulfilled criteria for elective repair according to guidelines.<br /><b>Conclusions</b><br />The risk of complications of ASA is higher in patients with genetic arteriopathies and is difficult to predict. In these diseases, imaging of the supra-aortic trunks should enter baseline investigations. Determination of precise indications for repair can prevent unexpected acute events such as those described.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; 81:979-991</small></div>
Giuliani L, Di Toro A, Urtis M, Narula N, ... Cameron D, Arbustini E
J Am Coll Cardiol: 14 Mar 2023; 81:979-991 | PMID: 36889877
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<div><h4>Designing Biocompatible Tissue Engineered Heart Valves In Situ: JACC Review Topic of the Week.</h4><i>Cordoves EM, Vunjak-Novakovic G, Kalfa DM</i><br /><AbstractText>Valvular heart disease is a globally prevalent cause of morbidity and mortality, with both congenital and acquired clinical presentations. Tissue engineered heart valves (TEHVs) have the potential to radically shift the treatment landscape for valvular disease by functioning as life-long valve replacements that overcome the current limitations of bioprosthetic and mechanical valves. TEHVs are envisioned to meet these goals by functioning as bioinstructive scaffolds that guide the in situ generation of autologous valves capable of growth, repair, and remodeling within the patient. Despite their promise, clinical translation of in situ TEHVs has proven challenging largely because of the unpredictable and patient-specific nature of the TEHV and host interaction following implantation. In light of this challenge, we propose a framework for the development and clinical translation of biocompatible TEHVs, wherein the native valvular environment actively informs the valve\'s design parameters and sets the benchmarks by which it is functionally evaluated.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; 81:994-1003</small></div>
Cordoves EM, Vunjak-Novakovic G, Kalfa DM
J Am Coll Cardiol: 14 Mar 2023; 81:994-1003 | PMID: 36889879
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<div><h4>Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.</h4><i>Sachdev V, Sharma K, Keteyian SJ, Alcain CF, ... Council on Arteriosclerosis, Thrombosis and Vascular Biology; and American College of Cardiology</i><br /><AbstractText>Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; epub ahead of print</small></div>
Sachdev V, Sharma K, Keteyian SJ, Alcain CF, ... Council on Arteriosclerosis, Thrombosis and Vascular Biology; and American College of Cardiology
J Am Coll Cardiol: 14 Mar 2023; epub ahead of print | PMID: 36958952
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Abstract
<div><h4>Identification of High-Risk Coronary Lesions by 3-Vessel Optical Coherence Tomography.</h4><i>Jiang S, Fang C, Xu X, Xing L, ... Dai J, Yu B</i><br /><b>Background</b><br />Optical coherence tomography (OCT) may provide a method for detecting histologically defined high-risk plaques in vivo.<br /><b>Objectives</b><br />The authors aimed to investigate the prognostic value of OCT for identifying patients and lesions that are at risk for adverse cardiac events.<br /><b>Methods</b><br />Between January 2017 and May 2019, OCT of all the 3 main epicardial arteries was performed in 883 patients with acute myocardial infarction (MI) who were referred for primary percutaneous coronary intervention. The primary endpoint was the composite of cardiac death, nonculprit lesion-related nonfatal MI, and unplanned coronary revascularization. Patients were followed for up to 4 years (median 3.3 years).<br /><b>Results</b><br />The 4-year cumulative rate of the primary endpoint was 7.2%. In patient-level analysis, thin-cap fibroatheroma (TCFA) (adjusted HR: 3.05; 95% CI: 1.67-5.57) and minimal lumen area (MLA) <3.5 mm<sup>2</sup> (adjusted HR: 3.71; 95% CI: 1.22-11.34) were independent predictors of the primary endpoint. In lesion-level analysis, nonculprit lesions responsible for subsequent events were not angiographically severe at baseline (mean diameter stenosis 43.8% ± 13.4%). TCFA (adjusted HR: 8.15; 95% CI: 3.67-18.07) and MLA <3.5 mm<sup>2</sup> (adjusted HR: 4.33; 95% CI: 1.81-10.38) were predictive of events arising from each specific lesion. TCFAs with an MLA <3.5 mm<sup>2</sup> carried a higher risk and were sufficient for identifying patients at risk for the composite of cardiac death and nonculprit lesion-related nonfatal MI.<br /><b>Conclusions</b><br />OCT imaging of angiographically nonobstructive territories in patients with acute MI can aid in identifying patients and lesions at increased risk for adverse cardiac events.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 Mar 2023; epub ahead of print</small></div>
Jiang S, Fang C, Xu X, Xing L, ... Dai J, Yu B
J Am Coll Cardiol: 11 Mar 2023; epub ahead of print | PMID: 36925409
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Abstract
<div><h4>Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure.</h4><i>Perin EC, Borow KM, Henry TD, Mendelsohn FO, ... Itescu S, Greenberg B</i><br /><b>Background</b><br />Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF).<br /><b>Objectives</b><br />This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF.<br /><b>Methods</b><br />This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity.<br /><b>Results</b><br />The primary endpoint was similar between treatment groups (HR: 1.17; 95% CI: 0.81-1.69; P = 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR: 0.42; 95% CI: 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR: 0.72; 95% CI: 0.51-1.03) in the analysis population (n = 537), and by 75% (HR: 0.25; 95% CI: 0.09-0.66) and 38% (HR: 0.62; 95% CI: 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mg/L).<br /><b>Conclusions</b><br />The primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Mar 2023; 81:849-863</small></div>
Perin EC, Borow KM, Henry TD, Mendelsohn FO, ... Itescu S, Greenberg B
J Am Coll Cardiol: 07 Mar 2023; 81:849-863 | PMID: 36858705
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<div><h4>Initial Findings From the National Cardiovascular Data Registry of Atrial Fibrillation Ablation Procedures.</h4><i>Hsu JC, Darden D, Du C, Marine JE, ... Akar J, Kowey PR</i><br /><b>Background</b><br />The National Cardiovascular Data Registry (NCDR) AFib Ablation Registry was created to assess real-world prevalence, demographic characteristics, procedural management, and outcomes of patients undergoing atrial fibrillation (AF) ablation procedures.<br /><b>Objectives</b><br />The goal of this study was to characterize the patient, hospital, and physician characteristics and in-hospital outcomes related to AF ablation in the first 5 years of the registry.<br /><b>Methods</b><br />This paper describes the AFib Ablation Registry structure and governance, outcome assessment processes, data quality, and data collection processes. The characteristics of the patient population, hospitals, and in-hospital outcomes are also described.<br /><b>Results</b><br />A total of 76,219 patients were included in the registry between January 2016 and December 2020 (mean age 65.5 ± 10.3 years, 65.2% male, 55.8% paroxysmal AF, mean CHA<sub>2</sub>DS<sub>2</sub>-VASc score 2.7 ± 1.6) treated by 708 physicians in 162 hospitals. Successful isolation of all pulmonary veins was achieved in 92.4% of patients. The prevalence of any complication during procedural admission was 2.50% and major complication was 0.9%, including significant bradycardia in 0.47%, heart failure in 0.47%, and pericardial effusion requiring intervention in 0.44%. Hospitalization >1 day occurred in 11.8% of patients, and in-hospital death was rare (n = 41 [0.05%]).<br /><b>Conclusions</b><br />The NCDR AFib Ablation Registry is the largest multicenter, prospective cohort study of patients undergoing catheter ablation worldwide. Results in the first 5 years showed that successful pulmonary vein isolation is achieved in the majority of patients, with a low rate of complications. Future studies from the registry will assess practice trends, evaluate treatment patterns associated with different patient outcomes, and support development of evidence-based guidelines.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Mar 2023; 81:867-878</small></div>
Hsu JC, Darden D, Du C, Marine JE, ... Akar J, Kowey PR
J Am Coll Cardiol: 07 Mar 2023; 81:867-878 | PMID: 36858707
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<div><h4>Association Between Shock Etiology and 5-Year Outcomes After Venoarterial Extracorporeal Membrane Oxygenation.</h4><i>Danial P, Olivier ME, Bréchot N, Ponnaiah M, ... Leprince P, Lebreton G</i><br /><b>Background</b><br />Outcomes of patients requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO) vary greatly by etiology, but large studies that incorporate the spectrum of shock supported with ECMO are rare.<br /><b>Objectives</b><br />The purpose of this study was to describe the etiology-related outcome of patients with shock supported with peripheral VA-ECMO.<br /><b>Methods</b><br />All consecutive adults with peripheral VA-ECMO between January 2015 and August 2018 at Pitié-Salpêtrière Hospital (Paris, France) were included in this retrospective observational study. The indication for VA-ECMO was cardiogenic shock. Rates of hospital death and neurological, renal, and pulmonary complications were evaluated according to etiology.<br /><b>Results</b><br />Among 1,253 patients, hospital and 5-year survival rates were, respectively, 73.3% and 57.3% for primary graft failure, 58.6% and 54.0% for drug overdose, 53.2% and 45.3% for dilated cardiomyopathy, 51.6% and 50.0% for arrhythmic storm, 46.8% and 38.3% for massive pulmonary embolism, 44.4% and 42.4% for sepsis-induced cardiogenic shock, 37.9% and 32.9% for fulminant myocarditis, 37.3% and 31.5% for acute myocardial infarction, 34.6% and 33.3% for postcardiotomy excluding primary graft failure, 25.7% and 22.8% for other/unknown etiology, and 11.1% and 0.0% for refractory vasoplegia shock. Renal failure requiring hemodialysis developed in 50.0%, neurological complications in 16.0%, and hydrostatic pulmonary edema in 9.0%.<br /><b>Conclusions</b><br />Although the outcome differs depending on etiology, this difference is related more to the severity of the situation associated with the cause rather than the cause of the shock per se. Survival to 5 years varied by cause, which may reflect the natural course of the chronic disease and illustrates the need for long-term follow-up.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Mar 2023; 81:897-909</small></div>
Danial P, Olivier ME, Bréchot N, Ponnaiah M, ... Leprince P, Lebreton G
J Am Coll Cardiol: 07 Mar 2023; 81:897-909 | PMID: 36858709
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<div><h4>Pericoronary Adipose Tissue as a Marker of Cardiovascular Risk: JACC Review Topic of the Week.</h4><i>Tan N, Dey D, Marwick TH, Nerlekar N</i><br /><AbstractText>Vascular inflammation is a key driver in atherosclerotic progression and plaque rupture. Recent evidence has shown that coronary computed tomography provides a noninvasive method of quantifying coronary inflammation by mapping changes in pericoronary adipose tissue (PCAT) radiodensity, which are associated with cardiovascular diseases. However, there are significant knowledge gaps in the performance and measurement of PCAT that complicate its interpretation. In this review the authors aim to summarize the role of PCAT in cardiac imaging and explore the clinical implications and applicability as a novel biomarker of cardiovascular risk, as well as to discuss its limitations and potential pitfalls.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Mar 2023; 81:913-923</small></div>
Tan N, Dey D, Marwick TH, Nerlekar N
J Am Coll Cardiol: 07 Mar 2023; 81:913-923 | PMID: 36858711
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<div><h4>Effect of Dapagliflozin on Health Status in Patients With Preserved or Mildly Reduced Ejection Fraction.</h4><i>Kosiborod MN, Bhatt AS, Claggett BL, Vaduganathan M, ... McMurray JJV, Solomon SD</i><br /><b>Background</b><br />Patients with heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) experience a high burden of symptoms, physical limitations, and poor quality of life; improving health status is a key goal of management.<br /><b>Objectives</b><br />In a prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, we examine effects of dapagliflozin on health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ).<br /><b>Methods</b><br />The DELIVER trial randomized patients with symptomatic HFmrEF/HFpEF to dapagliflozin 10 mg or placebo. KCCQ was evaluated at randomization, 1, 4, and 8 months; KCCQ Total Symptom Score (TSS) was a key secondary endpoint. Patients were stratified by KCCQ-TSS tertiles; Cox models examined effects of dapagliflozin on clinical outcomes. We evaluated the effects of dapagliflozin on KCCQ-TSS, Physical Limitations (PLS), Clinical Summary (CSS), and Overall Summary (OSS) domains. Responder analyses compared proportions of dapagliflozin vs placebo-treated patients with clinically meaningful changes in KCCQ.<br /><b>Results</b><br />A total of 5,795 patients had baseline KCCQ (median KCCQ-TSS 72.9). The effects of dapagliflozin on reducing cardiovascular death/worsening HF appeared more pronounced in patients with greater baseline symptom burden (lowest-to-highest KCCQ-TSS tertile: HR: 0.70 [95% CI: 0.58-0.84]; 0.81 [95% CI: 0.65-1.01]; 1.07 [95% CI: 0.83-1.37]; P<sub>interaction</sub> = 0.026). Dapagliflozin improved KCCQ-TSS, -PLS, -CSS, and -OSS at 8 months (2.4, 1.9, 2.3, and 2.1 points higher vs placebo; P < 0.001 for all). Dapagliflozin-treated patients experienced improvements in KCCQ-TSS regardless of EF (P<sub>interaction</sub> = 0.85). Fewer dapagliflozin-treated patients had deterioration, and more had improvements in all KCCQ domains at 8 months.<br /><b>Conclusions</b><br />The clinical benefits of dapagliflozin in HFmrEF/HFpEF appear especially pronounced in those with greater baseline symptom impairment. Dapagliflozin improved all KCCQ domains and the proportion of patients experiencing clinically meaningful changes in health status. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Mar 2023; 81:460-473</small></div>
Kosiborod MN, Bhatt AS, Claggett BL, Vaduganathan M, ... McMurray JJV, Solomon SD
J Am Coll Cardiol: 07 Mar 2023; 81:460-473 | PMID: 36526515
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<div><h4>Association of Cardiac Remodeling with Aortic Regurgitation Outcomes: The AR Consortium of the SCMR Registry.</h4><i>Malahfji M, Crudo V, Kaolawanich Y, Nguyen DT, ... Kim R, Shah DJ</i><br /><b>Background</b><br />Quantitative cardiac magnetic resonance (CMR) outcome studies in aortic regurgitation (AR) are few. It is unclear if volume measurements are beneficial over diameters.<br /><b>Objectives</b><br />To evaluate the association of CMR quantitative thresholds and outcomes in AR patients.<br /><b>Methods</b><br />in a multicenter study, asymptomatic patients with moderate or severe AR on CMR with preserved LV ejection fraction (LVEF) were evaluated. Primary outcome was development of symptoms or decrease in LVEF to <50%, guideline indications for surgery based on LV dimensions, or death under medical management. Secondary outcome was the same excluding surgery for remodeling indications. We excluded patients who underwent surgery within 30 days of CMR. ROC analyses for the association with outcome were performed.<br /><b>Results</b><br />We studied 458 patients, median age 60 (IQR 46-70) years. During a median follow-up of 2.4 years (IQR 0.9, 5.3), 133 events occurred. Optimal thresholds were regurgitant volume of 47 ml and regurgitant fraction of 43%, indexed LV end-systolic (iLVES) volume of 43 ml/m<sup>2,</sup> iLVED volume of 109 ml/m<sup>2</sup>, and iLVES diameter of 2 cm/m<sup>2</sup>. In multivariable regression analysis, iLVES volume ≥43 ml/m<sup>2</sup> (HR 2.53 (1.75, 3.66), P<0.001) and and iLVED volume ≥ 109 ml/m<sup>2</sup> were independently associated with the outcomes and provided additional discrimination improvement over iLVES diameter, whereas iLVES diameter was independently associated with the primary outcome but not the secondary outcome.<br /><b>Conclusion</b><br />In asymptomatic AR patients with preserved LVEF, CMR findings can be used to guide management. CMR based LV end-systolic volume assessment performed favorably compared to LV diameters.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 03 Mar 2023; epub ahead of print</small></div>
Malahfji M, Crudo V, Kaolawanich Y, Nguyen DT, ... Kim R, Shah DJ
J Am Coll Cardiol: 03 Mar 2023; epub ahead of print | PMID: 36882135
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This program is still in alpha version.