Journal: J Am Coll Cardiol

Sorted by: date / impact
Abstract

Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy.

Wang Y, Zhu H, Hou X, Wang Z, ... Zou J, LBBP-RESYNC Investigators
Background
Left bundle branch pacing (LBBP) is the most rapidly growing conduction system pacing technique that is capable of correcting intrinsic left bundle branch block (LBBB). As such, it is potentially an optimal alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP).
Objectives
The authors sought to compare the efficacy of LBBP-CRT with BiVP-CRT in patients with heart failure and reduced left ventricular ejection fraction (LVEF).
Methods
This is a prospective, randomized trial of patients with nonischemic cardiomyopathy and LBBB with 6-month preplanned follow-up. Crossovers were allowed if LBBP or BiVP were unsuccessful. The primary endpoint was the difference in LVEF improvement between 2 groups. The secondary endpoints included changes in echocardiographic measurements, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, 6-minute walk distance, QRS duration, and CRT response.
Results
The study included 40 consecutive patients (20 males, mean age 63.7 years, LVEF 29.7% ± 5.6%). Crossovers occurred in 10% of LBBP-CRT and 20% of BiVP-CRT. All patients completed follow-up. Intention-to-treat analysis showed significantly higher LVEF improvement at 6 months after LBBP-CRT than BiVP-CRT (mean difference: 5.6%; 95% CI: 0.3-10.9; P = 0.039). LBBP-CRT also appeared to have greater reductions in left ventricular end-systolic volume (-24.97 mL; 95% CI: -49.58 to -0.36 mL) and NT-proBNP (-1,071.80 pg/mL; 95% CI: -2,099.40 to -44.20 pg/mL), and comparable changes in New York Heart Association functional class, 6-minute walk distance, QRS duration, and rates of CRT response compared with BiVP-CRT.
Conclusions
LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in heart failure patients with nonischemic cardiomyopathy and LBBB. (Left Bundle Branch Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy [LBBP-RESYNC]; NCT04110431).

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

J Am Coll Cardiol: 27 Sep 2022; 80:1205-1216
Wang Y, Zhu H, Hou X, Wang Z, ... Zou J, LBBP-RESYNC Investigators
J Am Coll Cardiol: 27 Sep 2022; 80:1205-1216 | PMID: 36137670
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Abstract

Abbreviated Antiplatelet Therapy After Coronary Stenting in Patients With Myocardial Infarction at High Bleeding Risk.

Smits PC, Frigoli E, Vranckx P, Ozaki Y, ... Valgimigli M, MASTER DAPT Investigators
Background
The optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear.
Objectives
The objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction.
Methods
In the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies. Randomization was stratified by acute or recent myocardial infarction at index procedure. Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes events (NACE); major adverse cardiac and cerebral events (MACCE); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding.
Results
NACE and MACCE did not differ with abbreviated vs nonabbreviated APT regimens in patients with an acute or recent myocardial infarction (n = 1,780; HR: 0.83; 95% CI: 0.61-1.12 and HR: 0.86; 95% CI: 0.62-1.19, respectively) or without an acute or recent myocardial infarction (n = 2,799; HR: 1.03; 95% CI: 0.77-1.38 and HR: 1.13; 95% CI: 0.80-1.59; Pinteraction = 0.31 and 0.25, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding was significantly reduced in patients with or without an acute or recent myocardial infarction (HR: 0.65; 95% CI: 0.46-0.91 and HR: 0.71; 95% CI: 0.54-0.92; Pinteraction = 0.72) with abbreviated APT.
Conclusions
A 1-month DAPT strategy in patients with HBR presenting with an acute or recent myocardial infarction results in similar NACE and MACCE rates and reduces bleedings compared with a nonabbreviated DAPT strategy. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

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

J Am Coll Cardiol: 27 Sep 2022; 80:1220-1237
Smits PC, Frigoli E, Vranckx P, Ozaki Y, ... Valgimigli M, MASTER DAPT Investigators
J Am Coll Cardiol: 27 Sep 2022; 80:1220-1237 | PMID: 36137672
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Abstract

Determinants of Drug-Coated Balloon Failure in Patients Undergoing Femoropopliteal Arterial Intervention.

Krishnan P, Farhan S, Schneider P, Kamran H, ... Laird J, Zeller T
Background
Drug-coated balloons (DCB) are frequently used to treat femoropopliteal artery disease. However, patency loss occurs in ≥10% of patients within 12 months posttreatment with poor understanding of the underlying mechanisms.
Objectives
The authors sought to investigate the determinants of DCB failure in femoropopliteal disease.
Methods
Data from randomized clinical trials (IN.PACT SFA, MDT-2113 SFA Japan) and 2 prespecified imaging cohorts of the IN.PACT Global Clinical Study were included. Influential procedural characteristics were evaluated by an independent angiographic core laboratory. The primary endpoint was DCB failure (patency loss during follow-up). Additional endpoints were binary restenosis and clinically driven target lesion revascularization. Multivariable analyses evaluated the clinical, anatomical, and procedural predictors of DCB failure.
Results
Included were 557 participants with single lesions and 12-month core laboratory-adjudicated duplex ultrasonography. Key clinical characteristics were as follows: mean age 68.8 years, 67.5% male, 87.6% with hypertension, 76.9% with hyperlipidemia, 40.5% with diabetes mellitus, 90.5% in Rutherford Classification Category (RCC) 2 to 3, and 9.5% in RCC 4 to 5. Average length and reference vessel diameter (RVD) were 16.37 cm and 4.66 mm, respectively; 49.7% of lesions were totally occluded. In multivariable analysis, only residual stenosis >30% was associated with patency loss, whereas residual stenosis >30% and smaller preprocedure RVD were associated with increased binary restenosis risk. RCC >3 and residual stenosis >30% were associated with increased 12-month clinically driven target lesion revascularization risk.
Conclusions
Patency loss after DCB treatment was influenced by procedural and clinical factors. Residual stenosis >30%, smaller preprocedure RVD, and higher RCC may be considered predictors of increased risk of DCB failure and its components in femoropopliteal artery disease. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA]; NCT01947478; IN.PACT Global Clinical Study; NCT01609296).

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

J Am Coll Cardiol: 27 Sep 2022; 80:1241-1250
Krishnan P, Farhan S, Schneider P, Kamran H, ... Laird J, Zeller T
J Am Coll Cardiol: 27 Sep 2022; 80:1241-1250 | PMID: 36137674
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Abstract

Coronary Intervention Guided by Quantitative Flow Ratio vs Angiography in Patients With or Without Diabetes.

Jin Z, Xu B, Yang X, Jia R, ... Stone GW, FAVOR III China Study Group
Background
The clinical utility of the quantitative flow ratio (QFR), a novel angiography-based index for the functional assessment of coronary stenoses, has recently been demonstrated in patients undergoing percutaneous coronary intervention (PCI).
Objectives
This study aimed to ascertain whether the beneficial outcomes of QFR guidance for lesion selection during PCI is affected by diabetes status.
Methods
This substudy from the FAVOR III China trial, in which diabetes was one of the prespecified factors for stratified randomization, compared clinical outcomes of QFR-guided vs angiography-guided PCI lesion selection according to the presence of diabetes. The primary endpoint was the 1-year risk of major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization).
Results
Among 3,825 patients enrolled, 1,295 (33.9%) had diabetes, 347 (26.8%) of whom were treated with insulin. Baseline characteristics were well balanced between treatment arms in both diabetic and nondiabetic patients. Compared with standard angiography-based lesion selection, the QFR-guided strategy consistently reduced the risk of 1-year MACE in both diabetic patients (6.2% vs 9.6%; HR: 0.64; 95% CI: 0.43-0.95) and nondiabetic patients (5.6% vs 8.3%; HR: 0.66; 95% CI: 0.49-0.89) (Pinteraction = 0.88). Among patients in whom PCI was deferred after QFR, the risk of 1-year MACE was similar in patients with and without diabetes (4.5% vs 6.2%; P = 0.51).
Conclusions
A QFR-guided lesion selection strategy improves PCI outcomes compared with standard angiography guidance in patients both with and without diabetes. (The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease [FAVOR III China Study]; NCT03656848).

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

J Am Coll Cardiol: 27 Sep 2022; 80:1254-1264
Jin Z, Xu B, Yang X, Jia R, ... Stone GW, FAVOR III China Study Group
J Am Coll Cardiol: 27 Sep 2022; 80:1254-1264 | PMID: 36137676
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Abstract

Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy.

Escobar-Lopez L, Ochoa JP, Royuela A, Verdonschot JAJ, ... Merlo M, Garcia-Pavia P
Background
Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption.
Objectives
This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD.
Methods
Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries.
Results
A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78).
Conclusions
The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.

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

J Am Coll Cardiol: 20 Sep 2022; 80:1115-1126
Escobar-Lopez L, Ochoa JP, Royuela A, Verdonschot JAJ, ... Merlo M, Garcia-Pavia P
J Am Coll Cardiol: 20 Sep 2022; 80:1115-1126 | PMID: 36109106
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Abstract

Cumulative Systolic Blood Pressure Load and Cardiovascular Risk in Patients With Diabetes.

Wang N, Harris K, Hamet P, Harrap S, ... Chalmers J, Rodgers A
Background
Standard measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time.
Objectives
The purpose of this study was to assess the association between cumulative systolic blood pressure (SBP) load and risk of cardiovascular events in patients with type 2 diabetes.
Methods
A post hoc analysis of patients with type 2 diabetes followed by the ADVANCE-ON (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation - Observational Study). Cumulative SBP load was defined as the area under curve for SBP values ≥130 mm Hg divided by the area under curve for all measured SBP values over a 24-month exposure period. HRs for the association between cumulative SBP load with major cardiovascular events and death were estimated using Cox models.
Results
Over a median 7.6 years of follow-up, 1,469 major cardiovascular events, 1,615 deaths, and 660 cardiovascular deaths were observed in 9,338 participants. Each 1-SD increase in cumulative SBP load was associated with a 14% increase in major cardiovascular events (HR: 1.14; 95% CI: 1.09-1.20), 13% increase in all-cause mortality (HR: 1.13; 95% CI: 1.13-1.18), and 21% increase in cardiovascular death (HR: 1.21; 95% CI: 1.13-1.29). For the prediction of cardiovascular events and death, cumulative SBP load outperformed mean SBP, time-below-target SBP, and visit-to-visit SBP variability in terms of Akaike information criterion and net reclassification indexes.
Conclusions
Cumulative SBP load may provide better prediction of major cardiovascular events compared with traditional BP measures among patients with type 2 diabetes. These findings reinforce the importance of both the magnitude and duration of exposure to elevated SBP in assessing cardiovascular risk. (Action in Diabetes and Vascular Disease Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study [ADVANCE-ON]; NCT00949286).

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

J Am Coll Cardiol: 20 Sep 2022; 80:1147-1155
Wang N, Harris K, Hamet P, Harrap S, ... Chalmers J, Rodgers A
J Am Coll Cardiol: 20 Sep 2022; 80:1147-1155 | PMID: 36109108
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Abstract

Clinical Predictors of Recurrent Supraventricular Tachycardia in Infancy.

Moore JA, Stephens SB, Kertesz NJ, Evans DL, ... Morris SA, Miyake CY
Background
Data regarding recurrence risk among infants with supraventricular tachycardia (SVT) are limited.
Objectives
The purpose of this study was to determine incidence and factors associated with SVT recurrence.
Methods
This was a retrospective single-center study (1984-2020) with prospective phone follow-up of infants with structurally normal hearts diagnosed at age ≤1 year with re-entrant SVT. Primary outcome was first SVT recurrence after hospital discharge. Classification and regression tree analysis was performed to determine a risk algorithm.
Results
Among 460 infants (62% male), 87% were diagnosed at ≤60 days of age (median 13 days; IQR: 1-31 days). During a median follow-up of 5.2 years (IQR: 1.8-11.2 years), 33% had recurrence. On multivariable analysis, factors associated with recurrence included: fetal or late (>60 days) diagnosis (HR: 1.90; 95% CI: 1.26-2.86; and HR: 1.73; 95% CI: 1.07-2.77, respectively), Wolff-Parkinson-White (WPW) syndrome (HR: 2.46; 95% CI: 1.75-3.45), and need for multi-antiarrhythmic or second-line therapy (HR: 2.08; 95% CI: 1.45-2.99). Based on the classification and regression tree analysis, WPW incurred the highest risk. Among those without WPW, age at diagnosis was the most important factor predicting risk. Fetal or late diagnosis incurred higher risk, and if multi-antiarrhythmic or second-line therapy was also required, risk nearly doubled. Infants without WPW, who were diagnosed early (0-60 days), and who were discharged on propranolol were at lowest recurrence risk.
Conclusions
Infants with SVT are most likely to be diagnosed at ≤60 days and be male. Risk factors for recurrence (occurred in 33%), present at time of diagnosis, include WPW, fetal or late diagnosis, and multi-antiarrhythmic or second-line therapy. Infants with early diagnosis, without WPW, and discharged on first-line monotherapy are at lowest recurrence risk.

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

J Am Coll Cardiol: 20 Sep 2022; 80:1159-1172
Moore JA, Stephens SB, Kertesz NJ, Evans DL, ... Morris SA, Miyake CY
J Am Coll Cardiol: 20 Sep 2022; 80:1159-1172 | PMID: 36109110
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Abstract

Transcatheter Edge-to-Edge Repair in Patients with Severe Mitral Regurgitation and Cardiogenic Shock: TVT Registry Analysis.

Simard T, Vemulapalli S, Jung RG, Vekstein A, ... Hibbert B, Alkhouli M
Background
Data on the efficacy of transcatheter edge-to-edge repair (TEER) in patients with cardiogenic shock (CS) are limited.
Objectives
We investigated the characteristics and outcomes of consecutive patients with significant MR and CS who underwent TEER.
Methods
The STS/ACC/TVT Registry was assessed from November 22, 2013, to December 31, 2021. CS was defined as [i] CS, [ii] inotrope-use or [iii] mechanical circulatory support prior to TEER. Device success was defined as MR reduction of >1 grade and a final MR grade<2+. The primary outcome was the impact of device success on 1-year mortality or heart failure (HF) re-admissions. Cox proportional hazards model were used to report the risk-adjusted association between device success and 1-year outcomes.
Results
A total of 3,797 patients met the inclusion criteria. Mean age was 73.0±11.9 and 59.5% were male. Mean STS-score (MV repair) was 14.9±15.3. MR etiology was degenerative (53.4%) and functional (27.5%). Device success was achieved in 3,249(85.6%) patients given successful achievement of [i] final MR grade <2+(88.2%) and [ii] MR reduction >1 absolute grade(91.4%). At one-year after TEER, device success was associated with significantly lower all-cause mortality (34.6% vs.55.5%, adjusted-HR 0.49,95%CI 0.41-0.59,p<0.001), and a composite of mortality or HF admissions (29.6% vs. 45.2%, adjusted HR 0.51,95%CI 0.42-0.62,p<0.001).
Conclusion
Successful MR reduction is achievable in most patients with CS and is associated with significantly lower mortality and HF hospitalization at 1-year. Randomized trials assessing TEER in CS are needed to establish this potential therapeutic approach.
Condensed abstract
We examined the role of transcatheter edge-to-edge repair (TEER) in patients with cardiogenic shock and mitral regurgitation (MR). We identified 3,797 patients with cardiogenic shock who underwent TEER between 2013-2021 in the STS/ACC/TVT registry. Mean age was 73.0±11.9 and 59.5% were males. Mean STS was 14.9±15.3. Device success (defined as MR reduction of >1 grade and a final MR <2+) was achieved in 3,249 patients (85.6%). At one-year, device success was associated with lower all-cause mortality (34.6% vs.55.5%,adjusted-HR 0.49,95%CI 0.41-0.58, p<0.001), and a composite of mortality and HF admissions (29.6% vs. 45.2%, adjusted HR 0.51,95%CI 0.42-0.62, p<0.001).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 13 Sep 2022; epub ahead of print
Simard T, Vemulapalli S, Jung RG, Vekstein A, ... Hibbert B, Alkhouli M
J Am Coll Cardiol: 13 Sep 2022; epub ahead of print | PMID: 36126766
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Abstract

Clinical Outcomes in Patients With Dilated Cardiomyopathy and Ventricular Tachycardia.

Zeppenfeld K, Wijnmaalen AP, Ebert M, Baldinger SH, ... Hindricks G, Stevenson WG
Background
Recurrent ventricular tachycardia (VT) due to dilated cardiomyopathy (DCM) is difficult to treat, and long-term outcome data are limited.
Objectives
The aim of this study was to identify predictors of mortality or heart transplantation (HTx) and VT recurrence.
Methods
Consecutive patients with DCM accepted for radiofrequency catheter ablation (RFCA) of VT at 9 centers were prospectively enrolled and followed.
Results
Of 281 consecutive patients (mean age 60 ± 13 years, 85% men, mean left ventricular ejection fraction [LVEF] 36% ± 12%), 35% had VT storm, 20% had incessant VT, and amiodarone was unsuccessful in 68%. During follow-up of 21 months (IQR: 6-30 months), 67 patients (24%) died or underwent HTx, and 138 (49%) had VT recurrence (45 within 30 days, defined as early); the 4-year rate of VT recurrence or mortality or HTx was 70%. Independent predictors of mortality or HTx were early VT recurrence (HR: 2.92; 95% CI: 1.37-6.21; P < 0.01), amiodarone at discharge (HR: 3.23; 95% CI: 1.43-7.33; P < 0.01), renal dysfunction (HR: 1.92; 95% CI: 1.01-3.64; P = 0.046), and LVEF (HR: 1.36; 95% CI: 1.0-1.84; P = 0.052). LVEF ≤32% identified patients at risk for mortality or HTx (area under the curve: 0.75). Mortality or HTx per 100 person-years was 40.4 events after early, compared with 14.2 events after later VT recurrence and 8.5 events with no VT recurrence after RFCA (P < 0.01 for both). Patients with early recurrence and LVEFs ≤32% had a 1-year rate of mortality or HTx of 55%. VT recurrence was predicted by prior implantable cardioverter-defibrillator shocks, basal anteroseptal VT origin, and procedural failure but not LVEF.
Conclusions
Patients with DCM needing RFCA for VT are a high-risk group. Following RFCA, approximately one-half remain free of VT recurrence. Early VT recurrence with LVEF ≤32% identifies those at very high risk for mortality or HTx, and screening for mechanical support or HTx should be considered. Late VT recurrence after RFCA does not predict worse outcome.

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

J Am Coll Cardiol: 13 Sep 2022; 80:1045-1056
Zeppenfeld K, Wijnmaalen AP, Ebert M, Baldinger SH, ... Hindricks G, Stevenson WG
J Am Coll Cardiol: 13 Sep 2022; 80:1045-1056 | PMID: 36075673
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Abstract

Outcomes of Repair of Congenital Aortic Valve Lesions Using Autologous Pericardium vs Porcine Intestinal Submucosa.

Sengupta A, Beroukhim R, Baird CW, Del Nido PJ, ... Sanders SP, Nathan M
Background
Outcomes following congenital aortic valve (AoV) repair are plagued by progressive dysfunction of currently available leaflet substitute materials.
Objectives
We compared the long-term outcomes of congenital AoV repair using porcine intestinal submucosa vs autologous pericardium (AP).
Methods
This was a single-center retrospective review of all patients who underwent congenital AoV repair with either porcine intestinal submucosa or AP from October 2009 to March 2013. The primary outcome was postdischarge (late) unplanned AoV reintervention. Secondary outcomes included number of late AoV reinterventions and a composite of at least moderate aortic regurgitation or stenosis at latest follow-up or before the first reintervention. Associations between leaflet repair material and outcomes were assessed using multivariable regression models, adjusting for prespecified patient-related and operative variables.
Results
Of 26 porcine intestinal submucosa and 49 AP patients who met entry criteria, the median age was 11.0 years (IQR: 4.7-16.6 years). At a median follow-up of 8.5 years (IQR: 4.4-9.6 years), 17 (65.4%) porcine intestinal submucosa and 22 (44.9%) AP patients underwent at least 1 AoV reintervention. On multivariable analysis, porcine intestinal submucosa use was significantly associated with unplanned AoV reintervention (HR: 4.6; 95% CI: 2.2-9.8; P < 0.001), number of postdischarge AoV reinterventions (incidence rate ratio: 1.7; 95% CI: 1.0-2.9; P = 0.037), and at least moderate aortic regurgitation or stenosis at latest follow-up or before the first reintervention (OR: 5.0; 95% CI: 1.2-21.0; P = 0.027).
Conclusions
Aortic valvuloplasty with porcine intestinal submucosa is associated with earlier time to reintervention compared with autologous pericardium. The search for the ideal AoV leaflet repair material continues.

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

J Am Coll Cardiol: 13 Sep 2022; 80:1060-1068
Sengupta A, Beroukhim R, Baird CW, Del Nido PJ, ... Sanders SP, Nathan M
J Am Coll Cardiol: 13 Sep 2022; 80:1060-1068 | PMID: 36075675
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Abstract

Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease.

Hecht S, Butcher SC, Pio SM, Kong WKF, ... Bax JJ, Pibarot P
Background
The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied.
Objectives
The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction.
Methods
We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes.
Results
The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group).
Conclusions
In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD.

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

J Am Coll Cardiol: 13 Sep 2022; 80:1071-1084
Hecht S, Butcher SC, Pio SM, Kong WKF, ... Bax JJ, Pibarot P
J Am Coll Cardiol: 13 Sep 2022; 80:1071-1084 | PMID: 36075677
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Abstract

Exercise for Primary and Secondary Prevention of Cardiovascular Disease: JACC Focus Seminar 1/4.

Tucker WJ, Fegers-Wustrow I, Halle M, Haykowsky MJ, Chung EH, Kovacic JC
Regular exercise that meets or exceeds the current physical activity guidelines is associated with a reduced risk of cardiovascular disease (CVD) and mortality. Therefore, exercise training plays an important role in primary and secondary prevention of CVD. In this part 1 of a 4-part focus seminar series, we highlight the mechanisms and physiological adaptations responsible for the cardioprotective effects of exercise. This includes an increase in cardiorespiratory fitness secondary to cardiac, vascular, and skeletal muscle adaptations and an improvement in traditional and nontraditional CVD risk factors by exercise training. This extends to the role of exercise and its prescription in patients with CVDs (eg, coronary artery disease, chronic heart failure, peripheral artery disease, or atrial fibrillation) with special focus on the optimal mode, dosage, duration, and intensity of exercise to reduce CVD risk and improve clinical outcomes in these patients.

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

J Am Coll Cardiol: 13 Sep 2022; 80:1091-1106
Tucker WJ, Fegers-Wustrow I, Halle M, Haykowsky MJ, Chung EH, Kovacic JC
J Am Coll Cardiol: 13 Sep 2022; 80:1091-1106 | PMID: 36075680
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Abstract

Ischemic Heart Disease in Young Women: JACC Review Topic of the Week.

Minissian MB, Mehta PK, Hayes SN, Park K, ... Piazza G, Pepine CJ
The Cardiovascular Disease in Women Committee of the American College of Cardiology convened a working group to develop a consensus regarding the continuing rise of mortality rates in young women aged 35 to 54 years. Heart disease mortality rates in young women continue to increase. Young women have increased mortality secondary to ischemic heart disease (IHD) compared with comparably aged men and similar mortality to that observed among older women. The authors reviewed the published evidence, including observational and mechanistic/translational data, and identified knowledge gaps pertaining to young women. This paper provides clinicians with pragmatic, evidence-based management strategies for young women at risk for IHD. Next-step research opportunities are outlined. This report presents highlights of the working group review and a summary of suggested research directions to advance the IHD field in the next decade.

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

J Am Coll Cardiol: 06 Sep 2022; 80:1014-1022
Minissian MB, Mehta PK, Hayes SN, Park K, ... Piazza G, Pepine CJ
J Am Coll Cardiol: 06 Sep 2022; 80:1014-1022 | PMID: 36049799
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Abstract

Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries.

Broberg CS, van Dissel A, Minnier J, Aboulhosn J, ... Kutty S, Opotowsky AR
Background
For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes.
Objectives
The authors aimed to determine factors associated with survival in a large cohort of such individuals.
Methods
This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS).
Results
From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography.
Conclusions
For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.

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

J Am Coll Cardiol: 06 Sep 2022; 80:951-963
Broberg CS, van Dissel A, Minnier J, Aboulhosn J, ... Kutty S, Opotowsky AR
J Am Coll Cardiol: 06 Sep 2022; 80:951-963 | PMID: 36049802
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Abstract

Screening for Cardiac Amyloidosis 5 to 15 Years After Surgery for Bilateral Carpal Tunnel Syndrome.

Westin O, Fosbøl EL, Maurer MS, Leicht BP, ... Johannesen HH, Gustafsson F
Background
Bilateral carpal tunnel syndrome (CTS) is a common extracardiac manifestation of amyloidosis and usually predates overt cardiac amyloidosis (CA) by several years. Screening studies on patients undergoing CTS surgery have shown a low yield of CA (2.0%), but high prevalence of amyloid in the carpal ligament. The proportion of patients with amyloid in the carpal ligament who later develop CA is unknown.
Objectives
The authors sought to investigate the prevalence of undiagnosed CA 5 to 15 years after surgery for bilateral CTS.
Methods
Using national registries, the authors identified subjects aged 60 to 85 years with prior CTS surgery, where the first procedure on the second wrist was performed 5 to 15 years earlier. Invitations to participate in the study were sent by mail. Per international recommendations, the initial cardiac evaluation included echocardiography, 99mtechnetium-pyrophosphate scintigraphy, and assessment of monoclonal proteins in serum and urine.
Results
A total of 250 subjects (35.7% of those invited) participated in the study. The median age was 70.4 years, and 50% were female. CA was diagnosed in 12 patients (4.8%; 95% CI: 2.5%-8.2%), and all cases were wild-type transthyretin amyloidosis (ATTRwt). The prevalence of ATTRwt in men was 8.8% (95% CI: 4.5%-15.2%; n = 11), and 21.2% (95% CI: 11.1%-34.7%) in male subjects ≥70 years with a BMI <30 kg/m2. All but 2 patients diagnosed with ATTRwt were in the lowest disease severity score (Mayo score).
Conclusions
Screening for CA in patients with prior surgery for bilateral CTS finds approximately 5% with early-stage transthyretin CA. The clinical yield was higher (>1 in 5) when focusing on nonobese men ≥70 years, showing potential for systematic screening.

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

J Am Coll Cardiol: 06 Sep 2022; 80:967-977
Westin O, Fosbøl EL, Maurer MS, Leicht BP, ... Johannesen HH, Gustafsson F
J Am Coll Cardiol: 06 Sep 2022; 80:967-977 | PMID: 36049804
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Abstract

Validated Model for Prediction of Adverse Cardiac Outcome in Patients With Fabry Disease.

Orsborne C, Bradley J, Bonnett LJ, Pleva LA, ... Miller CA, Reid AB
Background
The cardiac manifestations of Fabry disease are the leading cause of death, but risk stratification remains inadequate. Identifying patients who are at risk of adverse cardiac outcome may facilitate more evidence-based treatment guidance. Contemporary cardiovascular cardiac magnetic resonance biomarkers have become widely adopted, but their prognostic value remains unclear.
Objectives
The objective of this study was to develop, internally validate, and evaluate the performance of, a prognostic model, including contemporary deep phenotyping, which can be used to generate individual risk estimates for adverse cardiac outcome in patients with Fabry disease.
Methods
This longitudinal prospective cohort study consisted of 200 consecutive patients with Fabry disease undergoing clinical cardiac magnetic resonance. Median follow-up was 4.5 years (IQR: 2.7-6.3 years). Prognostic models were developed using Cox proportional hazards modeling. Outcome was a composite of adverse cardiac events. Model performance was evaluated. A risk calculator, which provides 5-year estimated risk of adverse cardiac outcome for individual patients, including men and women, was generated.
Results
The highest performing, internally validated, parsimonious multivariable model included age, native myocardial T1 dispersion (SD of per voxel myocardial T1 relaxation times), and indexed left ventricular mass. Median optimism-adjusted c-statistic across 5 imputed model development data sets was 0.77 (95% CI: 0.70-0.84). Model calibration was excellent across the full risk profile.
Conclusions
This study developed and internally validated a risk prediction model that accurately predicts 5-year risk of adverse cardiac outcome for individual patients with Fabry disease, including men and women, which could easily be integrated into clinical care. External validation is warranted.

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

J Am Coll Cardiol: 06 Sep 2022; 80:982-994
Orsborne C, Bradley J, Bonnett LJ, Pleva LA, ... Miller CA, Reid AB
J Am Coll Cardiol: 06 Sep 2022; 80:982-994 | PMID: 36049806
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Abstract

Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

Stamatelopoulos K, Mueller-Hennessen M, Georgiopoulos G, Lopez-Ayala P, ... Giannitsis E, Stellos K
Background
Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are at high residual risk for long-term cardiovascular (CV) mortality. Cathepsin S (CTSS) is a lysosomal cysteine protease with elastolytic and collagenolytic activity that has been involved in atherosclerotic plaque rupture.
Objectives
The purpose of this study was to determine the following: 1) the prognostic value of circulating CTSS measured at patient admission for long-term mortality in NSTE-ACS; and 2) its additive value over the GRACE (Global Registry of Acute Coronary Events) risk score.
Methods
This was a single-center cohort study, consecutively recruiting patients with adjudicated NSTE-ACS (n = 1,112) from the emergency department of an academic hospital. CTSS was measured in serum using enzyme-linked immunosorbent assay. All-cause mortality at 8 years was the primary endpoint. CV death was the secondary endpoint.
Results
In total, 367 (33.0%) deaths were recorded. CTSS was associated with increased risk of all-cause mortality (HR for highest vs lowest quarter of CTSS: 1.89; 95% CI: 1.34-2.66; P < 0.001) and CV death (HR: 2.58; 95% CI: 1.15-5.77; P = 0.021) after adjusting for traditional CV risk factors, high-sensitivity C-reactive protein, left ventricular ejection fraction, high-sensitivity troponin-T, revascularization and index diagnosis (unstable angina/ non-ST-segment elevation myocardial infarction). When CTSS was added to the GRACE score, it conferred significant discrimination and reclassification value for all-cause mortality (Delta Harrell\'s C: 0.03; 95% CI: 0.012-0.047; P = 0.001; and net reclassification improvement = 0.202; P = 0.003) and CV death (AUC: 0.056; 95% CI: 0.017-0.095; P = 0.005; and net reclassification improvement = 0.390; P = 0.001) even after additionally considering high-sensitivity troponin-T and left ventricular ejection fraction.
Conclusions
Circulating CTSS is a predictor of long-term mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score.

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

J Am Coll Cardiol: 06 Sep 2022; 80:998-1010
Stamatelopoulos K, Mueller-Hennessen M, Georgiopoulos G, Lopez-Ayala P, ... Giannitsis E, Stellos K
J Am Coll Cardiol: 06 Sep 2022; 80:998-1010 | PMID: 36049808
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Abstract

Comparative Risks of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease.

Regalado ES, Morris SA, Braverman AC, Hostetler EM, ... Jondeau G, Milewicz DM
Background
Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.
Objectives
This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.
Methods
A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, and location of recruitment.
Results
Significant differences in aortic event risk were identified among the smooth muscle contraction genes (ACTA2, MYLK, and PRKG1; P = 0.002) and among the genes for Loeys-Dietz syndrome, which encode proteins in the transforming growth factor (TGF)-β pathway (SMAD3, TGFB2, TGFBR1, and TGFBR2;P < 0.0001). Cumulative incidence of type A aortic dissection was higher than elective aneurysm surgery in patients with variants in ACTA2, MYLK, PRKG1, and SMAD3; in contrast, patients with TGFBR2 variants had lower cumulative incidence of type A aortic dissection than elective aneurysm surgery. Cumulative incidence of type B aortic dissection was higher for ACTA2, PRKG1, and TGFBR2 than other genes. After adjusting for proband status, sex, and recruitment location, specific variants in ACTA2 and TGFBR2 were associated with substantially higher risk of aortic event with childhood onset.
Conclusions
Gene- and variant-specific data on aortic events in individuals with HTAD support personalized aortic surveillance and clinical management.

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

J Am Coll Cardiol: 30 Aug 2022; 80:857-869
Regalado ES, Morris SA, Braverman AC, Hostetler EM, ... Jondeau G, Milewicz DM
J Am Coll Cardiol: 30 Aug 2022; 80:857-869 | PMID: 36007983
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Abstract

Polygenic Risk Score Predicts Sudden Death in Patients With Coronary Disease and Preserved Systolic Function.

Sandhu RK, Dron JS, Liu Y, Moorthy MV, ... Khera AV, Albert CM
Background
A familial predisposition to sudden and/or arrhythmic death (SAD) in the setting of coronary artery disease (CAD) exists; however, the genetic basis is poorly understood.
Objectives
The purpose of this study was to determine whether a genome-wide polygenic score for coronary artery disease (GPSCAD) might have utility in SAD risk stratification in CAD patients without severe systolic dysfunction.
Methods
A previously validated GPSCAD was generated utilizing genome-wide genotyping in 4,698 PRE-DETERMINE participants of European ancestry with CAD and left ventricular ejection fraction >30%-35%. The population was dichotomized according to top GPSCAD decile as defined by the general population, and absolute, proportional, and relative risks for SAD and non-SAD were estimated using competing risk analyses.
Results
Over a median follow-up of 8.0 years, participants in the top GPSCAD decile were at elevated absolute SAD risk (8.0%; 95% CI: 5.1%-12.4% vs 4.8%; 95% CI: 3.3%-7.0%; P = 0.005) and proportional SAD risk (29% vs 16%; P = 0.0003) compared with the remainder. After controlling for left ventricular ejection fraction, clinical factors, and electrocardiogram parameters, the top GPSCAD decile was associated with SAD (subdistribution HR: 1.77; 95% CI: 1.23-2.54; P = 0.002) but not non-SAD (subdistribution HR: 1.00; 95% CI: 0.80-1.25; P = 0.98) (P for Δ = 0.003). The addition of the top GPSCAD decile to the multivariable model significantly improved net reclassification indexes (NRIs) (continuous NRI: 14.0%; P = 0.024; and categorical NRI: 6.6%; P = 0.005) but not the C-index (difference in C-index: 0.007; P = 0.143).
Conclusions
Among CAD patients without severe systolic dysfunction, high GPSCAD specifically predicted SAD and enriched for both absolute and proportional SAD risk, identifying a population who might benefit from defibrillator therapy.

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

J Am Coll Cardiol: 30 Aug 2022; 80:873-883
Sandhu RK, Dron JS, Liu Y, Moorthy MV, ... Khera AV, Albert CM
J Am Coll Cardiol: 30 Aug 2022; 80:873-883 | PMID: 36007985
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Abstract

Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial.

Fagundes A, Morrow DA, Oyama K, Furtado RHM, ... Sabatine MS, Bergmark BA
Background
Biomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood.
Objectives
We examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures.
Methods
FOURIER was a randomized trial of the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro-B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL).
Results
When patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HRadj: 1.57 [95% CI: 1.38-1.78]; high score: HRadj: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HRadj: 1.33 [95% CI: 1.06-1.67]; high score: HRadj: 2.07 [95% CI: 1.52-2.83]) and its components (Ptrend <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each).
Conclusions
A biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk coronary anatomy at the time of revascularization. These findings provide insight into the relationships between cardiovascular biomarkers, coronary anatomical complexity, and incident clinical events. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633).

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

J Am Coll Cardiol: 30 Aug 2022; 80:887-897
Fagundes A, Morrow DA, Oyama K, Furtado RHM, ... Sabatine MS, Bergmark BA
J Am Coll Cardiol: 30 Aug 2022; 80:887-897 | PMID: 36007987
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Abstract

Impact and Modifiers of Ventricular Pacing in Patients With Single Ventricle Circulation.

Chubb H, Bulic A, Mah D, Moore JP, ... McElhinney DB, Dubin AM
Background
Palliation of the single ventricle (SV) circulation is associated with a burden of lifelong complications. Previous studies have identified that the need for a permanent ventricular pacing system (PPMv) may be associated with additional adverse long-term outcomes.
Objectives
The goal of this study was to quantify the attributable risk of PPMv in patients with SV, and to identify modifiable risk factors.
Methods
This international study was sponsored by the Pediatric and Congenital Electrophysiology Society. Centers contributed baseline and longitudinal data for functionally SV patients with PPMv. Enrollment was at implantation. Controls were matched 1:1 to PPMv subjects by ventricular morphology and sex, identified within center, and enrolled at matched age. Primary outcome was transplantation or death.
Results
In total, 236 PPMv subjects and 213 matched controls were identified (22 centers, 9 countries). Median age at enrollment was 5.3 years (quartiles: 1.5-13.2 years), follow-up 6.9 years (3.4-11.6 years). Median percent ventricular pacing (Vp) was 90.8% (25th-75th percentile: 4.3%-100%) in the PPMv cohort. Across 213 matched pairs, multivariable HR for death/transplant associated with PPMv was 3.8 (95% CI 1.9-7.6; P < 0.001). Within the PPMv population, higher Vp (HR: 1.009 per %; P = 0.009), higher QRS z-score (HR: 1.19; P = 0.009) and nonapical lead position (HR: 2.17; P = 0.042) were all associated with death/transplantation.
Conclusions
PPMv in patients with SV is associated with increased risk of heart transplantation and death, despite controlling for increased associated morbidity of the PPMv cohort. Increased Vp, higher QRS z-score, and nonapical ventricular lead position are all associated with higher risk of adverse outcome and may be modifiable risk factors.

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

J Am Coll Cardiol: 30 Aug 2022; 80:902-914
Chubb H, Bulic A, Mah D, Moore JP, ... McElhinney DB, Dubin AM
J Am Coll Cardiol: 30 Aug 2022; 80:902-914 | PMID: 36007989
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Abstract

Severe Mental Illness and Cardiovascular Disease: JACC State-of-the-Art Review.

Goldfarb M, De Hert M, Detraux J, Di Palo K, ... Piña I, Ringen PA
People with severe mental illness, consisting of schizophrenia, bipolar disorder, and major depression, have a high burden of modifiable cardiovascular risk behaviors and conditions and have a cardiovascular mortality rate twice that of the general population. People with acute and chronic cardiovascular disease are at a higher risk of developing mental health symptoms and disease. There is emerging evidence for shared etiological factors between severe mental illness and cardiovascular disease that includes biological, genetic, and behavioral mechanisms. This state-of-the art review will describe the relationship between severe mental illness and cardiovascular disease, explore the factors that lead to poor cardiovascular outcomes in people with severe mental illness, propose strategies to improve the cardiovascular health of people with severe mental illness, and present areas for future research focus.

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

J Am Coll Cardiol: 30 Aug 2022; 80:918-933
Goldfarb M, De Hert M, Detraux J, Di Palo K, ... Piña I, Ringen PA
J Am Coll Cardiol: 30 Aug 2022; 80:918-933 | PMID: 36007991
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Abstract

Ancestry, Lipoprotein(a), and Cardiovascular Risk Thresholds: JACC Review Topic of the Week.

Tsimikas S, Marcovina SM
This study reviews ancestral differences in the genetics of the LPA gene, risk categories of elevated lipoprotein(a) [Lp(a)] as defined by guidelines, ancestry-specific Lp(a) risk, absolute and proportional risk, predictive value of risk thresholds among different ancestries, and differences between laboratory vs clinical accuracy in Lp(a) assays. For clinical decision-making, the preponderance of evidence suggests that the predictive value of Lp(a) does not vary sufficiently to mandate the use of ancestry-specific risk thresholds. This paper interprets the literature on Lp(a) and ancestral risk to support: 1) clinicians on understanding cardiovascular disease risk in different ancestral groups; 2) trialists for the design of clinical trials to ensure adequate ancestral diversity to support broad conclusions of drug effects; 3) regulators in the evaluation of the design and interpretation of results of Lp(a)-lowering trials with different Lp(a) inclusion thresholds; and 4) clinical laboratories to measure Lp(a) by assays that discriminate risk thresholds appropriately.

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

J Am Coll Cardiol: 30 Aug 2022; 80:934-946
Tsimikas S, Marcovina SM
J Am Coll Cardiol: 30 Aug 2022; 80:934-946 | PMID: 36007992
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Abstract

The Athlete\'s Heart-Challenges and Controversies: JACC Focus Seminar 4/4.

La Gerche A, Wasfy MM, Brosnan MJ, Claessen G, ... Baggish AL, Kovacic JC
Regular exercise promotes structural, functional, and electrical remodeling of the heart, often referred to as the \"athlete\'s heart,\" with intense endurance sports being associated with the greatest degree of cardiac remodeling. However, the extremes of exercise-induced cardiac remodeling are potentially associated with uncommon side effects. Atrial fibrillation is more common among endurance athletes and there is speculation that other arrhythmias may also be more prevalent. It is yet to be determined whether this arrhythmic susceptibility is a result of extreme exercise remodeling, genetic predisposition, or other factors. Gender may have the greatest influence on the cardiac response to exercise, but there has been far too little research directed at understanding differences in the sportsman\'s vs sportswoman\'s heart. Here in part 4 of a 4-part seminar series, the controversies and ambiguities regarding the athlete\'s heart, and in particular, its arrhythmic predisposition, genetic, and gender influences are reviewed in depth.

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

J Am Coll Cardiol: 30 Aug 2022; epub ahead of print
La Gerche A, Wasfy MM, Brosnan MJ, Claessen G, ... Baggish AL, Kovacic JC
J Am Coll Cardiol: 30 Aug 2022; epub ahead of print | PMID: 36075838
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Abstract

Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction.

Butt JH, Dewan P, Jhund PS, Anand IS, ... Solomon SD, McMurray JJV
Background
Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk-benefit profile is perceived to be less favorable than in nonfrail patients.
Objectives
This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.
Methods
Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death.
Results
A frailty index (FI) was calculable in 4,795 patients. In total, 45.2% had class 1 frailty (FI ≤0.210, not frail), 43.5% had class 2 frailty (FI 0.211-0.310, more frail), and 11.4% had class 3 frailty (FI ≥0.311, most frail). There was a graded relationship between FI class and the primary endpoint, with a significantly higher risk associated with greater frailty (class 1: reference; class 2 rate ratio: 2.19 [95% CI: 1.85-2.60]; class 3 rate ratio: 3.29 [95% CI: 2.65-4.09]). The effect of sacubitril/valsartan vs valsartan on the primary endpoint from lowest to highest FI class (as a rate ratio) was: 0.98 [95% CI: 0.76-1.27], 0.92 [95% CI: 0.76-1.12], and 0.69 [95% CI: 0.51-0.95]), respectively (Pinteraction = 0.23). When FI was examined as a continuous variable, the interaction with treatment was significant for the primary outcome (Pinteraction = 0.002) and total heart failure hospitalizations (Pinteraction < 0.001), with those most frail deriving greater benefit.
Conclusions
Frailty was common in heart failure with preserved ejection fraction and associated with worse outcomes. Compared with valsartan, sacubitril/valsartan seemed to show a greater reduction in the primary endpoint with increasing frailty, although this was not significant when FI was examined as a categorical variable. (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

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

J Am Coll Cardiol: 26 Aug 2022; epub ahead of print
Butt JH, Dewan P, Jhund PS, Anand IS, ... Solomon SD, McMurray JJV
J Am Coll Cardiol: 26 Aug 2022; epub ahead of print | PMID: 36050227
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Abstract

Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction.

Cunningham JW, Vaduganathan M, Claggett BL, Kulac IJ, ... McMurray JJV, Solomon SD
Background
Patients recently hospitalized for heart failure (HF) are at high risk for rehospitalization and death.
Objectives
The purpose of this study was to investigate clinical outcomes and response to dapagliflozin in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF) who were enrolled during or following hospitalization.
Methods
The DELIVER (Dapagliflozin Evaluation to Improve the LIVES of Patients With PReserved Ejection Fraction Heart Failure) trial randomized patients with HF and LVEF >40% to dapagliflozin or placebo. DELIVER permitted randomization during or shortly after hospitalization for HF in clinically stable patients off intravenous HF therapies. This prespecified analysis investigated whether recent HF hospitalization modified risk of clinical events or response to dapagliflozin. The primary outcome was worsening HF event or cardiovascular death.
Results
Of 6,263 patients in DELIVER, 654 (10.4%) were randomized during HF hospitalization or within 30 days of discharge. Recent HF hospitalization was associated with greater risk of the primary outcome after multivariable adjustment (HR: 1.88; 95% CI: 1.60-2.21; P < 0.001). Dapagliflozin reduced the primary outcome by 22% in recently hospitalized patients (HR: 0.78; 95% CI: 0.60-1.03) and 18% in patients without recent hospitalization (HR: 0.82; 95% CI: 0.72-0.94; Pinteraction = 0.71). Rates of adverse events, including volume depletion, diabetic ketoacidosis, or renal events, were similar with dapagliflozin and placebo in recently hospitalized patients.
Conclusions
Dapagliflozin safely reduced risk of worsening HF or cardiovascular death similarly in patients with and without history of recent HF hospitalization. Starting dapagliflozin during or shortly after HF hospitalization in patients with mildly reduced or preserved LVEF appears safe and effective. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

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

J Am Coll Cardiol: 26 Aug 2022; epub ahead of print
Cunningham JW, Vaduganathan M, Claggett BL, Kulac IJ, ... McMurray JJV, Solomon SD
J Am Coll Cardiol: 26 Aug 2022; epub ahead of print | PMID: 36041912
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Abstract

Air Pollution and Coronary Vasomotor Disorders in Patients with Myocardial Ischemia and Non-Obstructive Coronary Arteries.

Camilli M, Russo M, Rinaldi R, Caffè A, ... Crea F, Montone RA
Background
Coronary vasomotor abnormalities are important causes of myocardial ischemia in patients with non-obstructive coronary artery disease (NOCAD). However, the role of air pollution in determining coronary vasomotor disorders has never been investigated.
Objectives
We aimed to evaluate the association between long-term exposure to particulate matter 2.5 (PM2.5) and 10 (PM10), and coronary vasomotor disorders in NOCAD patients.
Methods
Patients with myocardial ischemia and NOCAD undergoing coronary angiography and intracoronary provocation test with acetylcholine (ACh) were prospectively studied. Both patients with chronic myocardial ischemia (INOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA) were enrolled. Based on each case\'s home address, exposure to PM2.5 and PM10 was assessed.
Results
We included 287 patients (median age 62.0 years [52.0-70.0], 149 [51.9%] males): 161 (56.1%) INOCA and 126 (43.9%) MINOCA. One hundred seventy-six patients (61.3%) had positive provocation test. Exposure to PM2.5 and PM10 was higher in patients with a positive provocation test (p<0.001). At multivariate logistic regression analysis, PM2.5 and PM10 were independent predictors of a positive provocation test (p=0.001 and p=0.029, respectively). Interestingly, among these patients, PM2.5 and PM10 were both independent predictors of MINOCA (p<0.001 and p=0.001, respectively) as clinical presentation, while PM2.5 was independently associated with the occurrence of epicardial spasm as opposed to microvascular spasm (p=0.001).
Conclusions
Higher exposure to PM2.5 and PM10 in patients with myocardial ischemia and NOCAD is associated with coronary vasomotor abnormalities. In particular, PM2.5 is an independent risk factor for the occurrence of epicardial spasm and MINOCA as clinical presentation.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 25 Aug 2022; epub ahead of print
Camilli M, Russo M, Rinaldi R, Caffè A, ... Crea F, Montone RA
J Am Coll Cardiol: 25 Aug 2022; epub ahead of print | PMID: 36049556
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Abstract

Heart Failure With Preserved Ejection Fraction as an Exercise Deficiency Syndrome: JACC Focus Seminar 2/4.

La Gerche A, Howden EJ, Haykowsky MJ, Lewis GD, Levine BD, Kovacic JC
Across differing spectrums of cardiac function and cardiac pathologies, there are strong associations between measures of cardiorespiratory fitness and burden of symptoms, quality of life, and prognosis. In this part 2 of a 4-part series, we contend that there is a strong association among physical activity, cardiorespiratory fitness, and cardiac function. We argue that a chronic lack of exercise is a major risk factor for heart failure with preserved ejection fraction in some patients. In support of this hypothesis, increasing physical activity is associated with greater cardiac mass, greater stroke volumes, greater cardiac output and peak oxygen consumption, and fewer clinical events. Conversely, physical inactivity results in cardiac atrophy, reduced output, reduced chamber size, and decreased ability to augment cardiac performance with exercise. Moreover, physical inactivity is a strong predictor of heart failure risk and death. In sum, exercise deficiency should be considered part of the broad heart failure with preserved ejection fraction phenotype.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 24 Aug 2022; epub ahead of print
La Gerche A, Howden EJ, Haykowsky MJ, Lewis GD, Levine BD, Kovacic JC
J Am Coll Cardiol: 24 Aug 2022; epub ahead of print | PMID: 36075837
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Abstract

Randomized Trial of Early mTOR Inhibition in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Stähli BE, Klingenberg R, Heg D, Branca M, ... Lüscher TF, Ruschitzka F
Background
Early inflammation following acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) affects myocardial infarct (MI) size and left ventricular remodeling. The mammalian target of rapamycin (mTOR) is involved in the enhanced inflammatory response and its inhibition has exerted beneficial effects on MI size in preclinical models of acute MI.
Objectives
The Controlled Level EVERolimus in Acute Coronary Syndromes trial (CLEVER-ACS) evaluated the effects of targeting inflammation by mTOR inhibition in patients with STEMI undergoing PCI.
Methods
CLEVER-ACS was a randomized, multicenter, international, double-blind, placebo-controlled trial. A total of 150 patients with STEMI undergoing PCI were randomly assigned to oral everolimus (days 1-3: 7.5 mg qd, days 4-5: 5.0 mg qd) or placebo for 5 days. The primary endpoint was the change in myocardial infarct size, the secondary endpoint the change in microvascular obstruction (MVO) from baseline (12 hours - 5 days after PCI) to 30 days as assessed by cardiac magnetic resonance imaging (CMR).
Results
The changes in MI size from baseline to 30 days, the primary endpoint, were -14.2 (95% CI -17.4 to -11.1) g and -12.3 (95% CI -16.0 to -8.7) g in the everolimus and placebo groups (p=0.99). Corresponding changes in MVO were -4.8 (-6.7 to -2.9) g and -6.3 (-8.7 to -4.0) g in the everolimus and placebo groups (p=0.14). Adverse events did not differ between the study groups.
Conclusions
Among STEMI patients undergoing PCI, early mTOR inhibition with everolimus did not reduce MI size or MVO at 30 days.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 24 Aug 2022; epub ahead of print
Stähli BE, Klingenberg R, Heg D, Branca M, ... Lüscher TF, Ruschitzka F
J Am Coll Cardiol: 24 Aug 2022; epub ahead of print | PMID: 36049557
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Abstract

Estimated Event-Free Survival Benefits with Dapagliflozin in HF with Mildly Reduced or Preserved Ejection Fraction.

Vaduganathan M, Claggett BL, Jhund P, de Boer RA, ... McMurray JJV, Solomon SD
Background
Recent guidelines support consideration of sodium glucose co-transporter(SGLT)-2 inhibitors in the long-term management of heart failure (HF) with mildly reduced or preserved ejection fraction. Patients and clinicians may be interested in the expected lifetime benefits of SGLT-2 inhibitors.
Objectives
To estimate event-free survival gains from long-term use of dapagliflozin in patients with HF with mildly reduced or preserved ejection fraction overall and in clinically relevant subgroups.
Methods
In this pre-specified analysis of DELIVER, we applied validated nonparametric age-based methods to extrapolate potential gains in survival free from the primary endpoint (cardiovascular death or worsening HF event) from long-term use of dapagliflozin. Eligible participants had symptomatic HF, LVEF>40%, elevated natriuretic peptide levels, and structural heart disease. For every year between age 55 and 85, we estimated event-free survival using age at randomization rather than time from randomization as the time horizon. Residual lifespan free from primary endpoint was estimated based on area under the survival curve in each arm.
Results
Among 6,263 participants, mean survival free from the primary endpoint for a 65-year-old participant was 12.1 (95%CI 11.0 to 13.2) years with dapagliflozin and 9.7 (95%CI 8.8 to 10.7) years with placebo, representing a 2.3 (95%CI 0.9 to 3.8) year event-free survival gain(P=0.002). Treatment gains in survival free from the primary endpoint ranged from 2.0 (95%CI -0.6 to 4.6) years in a 55-year-old to 1.2 (95%CI -0.1 to 2.4) years in a 75-year-old. Mean event-free survival was greater with dapagliflozin than with placebo across all 14 subgroups.
Conclusions
Treatment with dapagliflozin is projected to extend event-free survival by up to 2-2.5 years among middle age and older individuals with HF with mildly reduced, preserved, or improved ejection fraction.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 24 Aug 2022; epub ahead of print
Vaduganathan M, Claggett BL, Jhund P, de Boer RA, ... McMurray JJV, Solomon SD
J Am Coll Cardiol: 24 Aug 2022; epub ahead of print | PMID: 36041669
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Abstract

The Association of Socioeconomic Status With Hypertension in 76 Low- and Middle-Income Countries.

Kirschbaum TK, Sudharsanan N, Manne-Goehler J, De Neve JW, ... Jaacks LM, Geldsetzer P
Background
Effective equity-focused health policy for hypertension in low- and middle-income countries (LMICs) requires an understanding of the condition\'s current socioeconomic gradients and how these are likely to change in the future as countries develop economically.
Objectives
This cross-sectional study aimed to determine how hypertension prevalence in LMICs varies by individuals\' education and household wealth, and how these socioeconomic gradients in hypertension prevalence are associated with a country\'s gross domestic product (GDP) per capita.
Methods
We pooled nationally representative household survey data from 76 LMICs. We disaggregated hypertension prevalence by education and household wealth quintile, and used regression analyses to adjust for age and sex.
Results
We included 1,211,386 participants in the analysis. Pooling across all countries, hypertension prevalence tended to be similar between education groups and household wealth quintiles. The only world region with a clear positive association of hypertension with education or household wealth quintile was Southeast Asia. Countries with a lower GDP per capita had, on average, a more positive association of hypertension with education and household wealth quintile than countries with a higher GDP per capita, especially in rural areas and among men.
Conclusions
Differences in hypertension prevalence between socioeconomic groups were generally small, with even the least educated and least wealthy groups having a substantial hypertension prevalence. Our cross-sectional interaction analyses of GDP per capita with the socioeconomic gradients of hypertension suggest that hypertension may increasingly affect adults in the lowest socioeconomic groups as LMICs develop economically.

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

J Am Coll Cardiol: 23 Aug 2022; 80:804-817
Kirschbaum TK, Sudharsanan N, Manne-Goehler J, De Neve JW, ... Jaacks LM, Geldsetzer P
J Am Coll Cardiol: 23 Aug 2022; 80:804-817 | PMID: 35981824
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Abstract

Repair of Abdominal Aortic Aneurysms: JACC Focus Seminar, Part 1.

Hensley SE, Upchurch GR
Abdominal aortic aneurysms (AAAs), defined by an aortic diameter >3 cm, affect >1 million people in the United States. Risk factors for AAA include male sex, family history of AAA, smoking, Caucasian ethnicity, and age. Patients with known AAA should undergo regular surveillance via ultrasonography. Medical management, including smoking cessation and blood pressure management, is recommended for asymptomatic patients who do not meet the threshold for intervention. Repair options include endovascular aortic repair and open surgical repair, with good outcomes in long-term follow-up. Men with AAA >5.5 cm and women with AAA >5.0 cm in general should undergo elective repair. Medical management, including smoking cessation and blood pressure management, is recommended for asymptomatic patients who do not meet the threshold for intervention.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 23 Aug 2022; 80:821-831
Hensley SE, Upchurch GR
J Am Coll Cardiol: 23 Aug 2022; 80:821-831 | PMID: 35981826
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Abstract

Inflammatory Diseases of the Aorta: JACC Focus Seminar, Part 2.

Kadian-Dodov D, Seo P, Robson PM, Fayad ZA, Olin JW
Inflammatory aortitis is most often caused by large vessel vasculitis (LVV), including giant cell arteritis, Takayasu\'s arteritis, immunoglobulin G4-related aortitis, and isolated aortitis. There are distinct differences in the clinical presentation, imaging findings, and natural history of LVV that are important for the cardiovascular provider to know. If possible, histopathologic specimens should be obtained to aide in accurate diagnosis and management of LVV. In most cases, corticosteroids are utilized in the acute phase, with the addition of steroid-sparing agents to achieve disease remission while sparing corticosteroid toxic effects. Endovascular and surgical procedures have been described with success but should be delayed until disease control is achieved whenever possible. Long-term management should include regular follow-up with rheumatology and surveillance imaging for sequelae of LVV.

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

J Am Coll Cardiol: 23 Aug 2022; 80:832-844
Kadian-Dodov D, Seo P, Robson PM, Fayad ZA, Olin JW
J Am Coll Cardiol: 23 Aug 2022; 80:832-844 | PMID: 35981827
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Abstract

Thoracoabdominal Aortic Disease and Repair: JACC Focus Seminar, Part 3.

Ouzounian M, Tadros RO, Svensson LG, Lyden SP, Oderich GS, Coselli JS
Thoracoabdominal aortic disease is a rare but life-threatening condition that requires expert multidisciplinary collaborative management. Intervention is indicated in patients with symptomatic aneurysms or when an aneurysm reaches a certain threshold of diameter or rate of expansion. The strategies for spinal cord and end-organ protection have evolved over several decades, resulting in improved outcomes after repair. Open repair, although invasive, provides definitive and durable repair. Endovascular approaches are rapidly evolving, and the results with fenestrated and branched endografts are promising. Both open repair and endovascular repair require highly specialized expertise, and outcomes are best when repair is undertaken in an elective setting by a dedicated team. Patients with degenerative thoracoabdominal aortic aneurysms and chronic dissections should be followed up closely and referred for elective repair when indicated.

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

J Am Coll Cardiol: 23 Aug 2022; 80:845-856
Ouzounian M, Tadros RO, Svensson LG, Lyden SP, Oderich GS, Coselli JS
J Am Coll Cardiol: 23 Aug 2022; 80:845-856 | PMID: 35981828
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Abstract

Association of Medication Adherence With Health Outcomes in the ISCHEMIA Trial.

Garcia RA, Spertus JA, Benton MC, Jones PG, ... Maron DJ, ISCHEMIA Research Group
Background
The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes.
Objectives
The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management.
Methods
Self-reported medication-taking behavior was assessed at randomization with a modified 4-item Morisky-Green-Levine Adherence Scale, and participants were classified as adherent or nonadherent. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ-7) summary score (SS), which ranges from 0 to 100 (higher score = better). The association of adherence with outcomes was evaluated using Bayesian proportional odds models, including an interaction by study arm (conservative vs invasive).
Results
Among 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. Nonadherent participants had worse baseline SAQ-7 SS in both conservative (72.9 ± 19.3 vs 75.6 ± 18.4) and invasive (71.0 ± 19.8 vs 74.2 ± 18.7) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 SS in both treatment groups (mean difference in SAQ-7 SS with conservative treatment = 1.6 [95% credible interval: 0.3-2.9] vs with invasive management = 1.9 [95% credible interval: 0.8-3.1]), with no interaction by treatment.
Conclusions
More than 1 in 4 participants reported medication nonadherence, which was associated with worse health status in both conservative and invasive treatment strategies at baseline and 12 months. Strategies to improve medication adherence are needed to improve health status outcomes in CCD, regardless of treatment strategy. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

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

J Am Coll Cardiol: 23 Aug 2022; 80:755-765
Garcia RA, Spertus JA, Benton MC, Jones PG, ... Maron DJ, ISCHEMIA Research Group
J Am Coll Cardiol: 23 Aug 2022; 80:755-765 | PMID: 35981820
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Abstract

Impact of Medication Nonadherence in a Clinical Trial of Dual Antiplatelet Therapy.

Valgimigli M, Frigoli E, Vranckx P, Ozaki Y, ... Heg D, MASTER DAPT Investigators
Background
Nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials.
Objectives
The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial.
Methods
At 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3.
Results
In total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation.
Conclusions
In the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

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

J Am Coll Cardiol: 23 Aug 2022; 80:766-778
Valgimigli M, Frigoli E, Vranckx P, Ozaki Y, ... Heg D, MASTER DAPT Investigators
J Am Coll Cardiol: 23 Aug 2022; 80:766-778 | PMID: 35981821
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Abstract

Athletic Activity for Patients With Hypertrophic Cardiomyopathy and Other Inherited Cardiovascular Diseases: JACC Focus Seminar 3/4.

Semsarian C, Gray B, Haugaa KH, Lampert R, Sharma S, Kovacic JC
As explored throughout this JACC Focus Seminar series, participation in regular exercise offers significant positive benefits for cardiovascular health. However, patients with underlying inherited cardiovascular diseases, such as hypertrophic cardiomyopathy, have historically been restricted from sports participation because of the risk of sudden cardiac death. Over the last decade, new data has challenged this restrictive approach. Today, the notion of individualized, patient-centered shared decision-making is being progressively adopted to guide patients with an inherited cardiovascular disease to decide if they can undertake regular exercise, or even if they can participate in competitive sports. Here in this part 3 of a 4-part seminar series, we focus on these concepts and recent data with respect to exercise and the heart in patients with hypertrophic cardiomyopathy and other inherited cardiovascular diseases, with particular emphasis on participation in recreational and competitive sports for these individuals.

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

J Am Coll Cardiol: 19 Aug 2022; epub ahead of print
Semsarian C, Gray B, Haugaa KH, Lampert R, Sharma S, Kovacic JC
J Am Coll Cardiol: 19 Aug 2022; epub ahead of print | PMID: 36075839
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Abstract

Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Cognitive Function.

Rosoff DB, Bell AS, Jung J, Wagner J, Mavromatis LA, Lohoff FW
Background
Lipid-lowering therapy with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition are effective strategies in reducing cardiovascular disease risk; however, concerns remain about potential long-term adverse neurocognitive effects.
Objectives
This genetics-based study aimed to evaluate the relationships of long-term PCSK9 inhibition and statin use on neurocognitive outcomes.
Methods
We extracted single-nucleotide polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and PCSK9 from predominantly European ancestry-based genome-wide association studies summary-level statistics of low-density lipoprotein cholesterol and performed drug-target Mendelian randomization, proxying the potential neurocognitive impact of drug-based PCSK9 and HMGCR inhibition using a range of outcomes to capture the complex facets of cognition and dementia.
Results
Using data from a combined sample of ∼740,000 participants, we observed a neutral cognitive profile related to genetic PCSK9 inhibition, with no significant effects on cognitive performance, memory performance, or cortical surface area. Conversely, we observed several adverse associations for HMGCR inhibition with lowered cognitive performance (beta: -0.082; 95% CI: -0.16 to -0.0080; P = 0.03), reaction time (beta = 0.00064; 95% CI: 0.00030-0.00098; P = 0.0002), and cortical surface area (beta = -0.18; 95% CI: -0.35 to -0.014; P = 0.03). Neither PCSK9 nor HMGCR inhibition impacted biomarkers of Alzheimer\'s disease progression or Lewy body dementia risk. Consistency of findings across Mendelian randomization methods accommodating different assumptions about genetic pleiotropy strengthens causal inference.
Conclusions
Using a wide range of cognitive function and dementia endpoints, we failed to find genetic evidence of an adverse PCSK9-related impact, suggesting a neutral cognitive profile. In contrast, we observed adverse neurocognitive effects related to HMGCR inhibition, which may well be outweighed by the cardiovascular benefits of statin use, but nonetheless may warrant pharmacovigilance.

Published by Elsevier Inc.

J Am Coll Cardiol: 16 Aug 2022; 80:653-662
Rosoff DB, Bell AS, Jung J, Wagner J, Mavromatis LA, Lohoff FW
J Am Coll Cardiol: 16 Aug 2022; 80:653-662 | PMID: 35953131
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Abstract

Prevalence and Prognostic Implications of Discordant Grading and Flow-Gradient Patterns in Moderate Aortic Stenosis.

Stassen J, Ewe SH, Singh GK, Butcher SC, ... Marsan NA, Bax JJ
Background
The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown.
Objectives
The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS.
Methods
Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m2, and LVEF ≥50%); \"paradoxical\" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m2, and LVEF ≥50%) and \"classical\" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality.
Results
Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, \"paradoxical\" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and \"classical\" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality.
Conclusions
Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS.

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

J Am Coll Cardiol: 16 Aug 2022; 80:666-676
Stassen J, Ewe SH, Singh GK, Butcher SC, ... Marsan NA, Bax JJ
J Am Coll Cardiol: 16 Aug 2022; 80:666-676 | PMID: 35953133
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Abstract

Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease.

Hemnes AR, Leopold JA, Radeva MK, Beck GJ, ... Horn EM, PVDOMICS Study Group
Background
PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification.
Objectives
The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort.
Methods
Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death.
Results
A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH.
Conclusions
PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887).

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

J Am Coll Cardiol: 16 Aug 2022; 80:697-718
Hemnes AR, Leopold JA, Radeva MK, Beck GJ, ... Horn EM, PVDOMICS Study Group
J Am Coll Cardiol: 16 Aug 2022; 80:697-718 | PMID: 35953136
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Impact:
Abstract

Management of Patients With Severe Mitral Annular Calcification: JACC State-of-the-Art Review.

Chehab O, Roberts-Thomson R, Bivona A, Gill H, ... Prendergast B, Rajani R
Mitral annular calcification (MAC) is a common and challenging pathologic condition, especially in the context of an aging society. Surgical mitral valve intervention in patients with MAC is difficult, with varying approaches to the calcified annular anatomy, and the advent of transcatheter valve interventions has provided additional treatment options. Advanced imaging provides the foundation for heart team discussions and management decisions concerning individual patients. This review focuses on the prognosis of, preoperative planning for, and management strategies for patients with MAC.

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

J Am Coll Cardiol: 16 Aug 2022; 80:722-738
Chehab O, Roberts-Thomson R, Bivona A, Gill H, ... Prendergast B, Rajani R
J Am Coll Cardiol: 16 Aug 2022; 80:722-738 | PMID: 35953138
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Impact:
Abstract

Mitral Valve Dysfunction in Patients With Annular Calcification: JACC Review Topic of the Week.

Churchill TW, Yucel E, Deferm S, Levine RA, Hung J, Bertrand PB
Mitral annular calcification (MAC) is a common clinical finding and is associated with adverse clinical outcomes, but the clinical impact of MAC-related mitral valve (MV) dysfunction remains underappreciated. Patients with MAC frequently have stenotic, regurgitant, or mixed valvular disease, and this valvular dysfunction is increasingly recognized to be independently associated with worse prognosis. MAC-related MV dysfunction is a distinct pathophysiologic entity, and importantly much of the diagnostic and therapeutic paradigm from published rheumatic MV disease research cannot be applied in this context, leaving important gaps in our knowledge. This review summarizes the current epidemiology, pathophysiology, diagnosis, and classification of MAC-related MV dysfunction and proposes both an integrative definition and an overarching approach to this important and increasingly recognized clinical condition.

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

J Am Coll Cardiol: 16 Aug 2022; 80:739-751
Churchill TW, Yucel E, Deferm S, Levine RA, Hung J, Bertrand PB
J Am Coll Cardiol: 16 Aug 2022; 80:739-751 | PMID: 35953139
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Impact:
Abstract

Dapagliflozin, atrial fibrillation, and heart failure with mildly reduced or preserved ejection fraction in DELIVER.

Butt JH, Kondo T, Jhund PS, Comin-Colet J, ... Solomon SD, McMurray JJ
Background
Atrial fibrillation (AF) is common in heart failure (HF), is associated with worse outcomes, compared to sinus rhythm, and may modify the effects of therapy.
Objectives
We examined the effects of dapagliflozin according to the presence or not of AF in the Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure trial (DELIVER).
Methods
A total of 6,263 patients with HF with NYHA functional class II-IV, LVEF >40%, evidence of structural heart disease, and elevated NT-proBNP levels were randomized to dapagliflozin or placebo. Clinical outcomes, and the effect of dapagliflozin, according to AF status, were examined. The primary outcome was a composite of cardiovascular death or a worsening HF.
Results
Of the 6,261 patients with data on baseline AF, 43.3% had no AF, 18.0% paroxysmal AF, and 38.7% persistent/permanent AF. The risk of the primary endpoint was higher in patients with AF, especially paroxysmal AF, driven by a higher rate of HF hospitalization: no AF, HF hospitalization rate per 100 person-years (95% CI), 4.5 (4.0-5.1); paroxysmal AF 7.5 (6.4-8.7); persistent/permanent AF 6.4 (5.7-7.1) (P<0.001). The benefit of dapagliflozin on the primary outcome was consistent across AF types: no AF, HR (95% CI) 0.89 (0.74-1.08); paroxysmal AF, 0.75 (0.58-0.97); persistent AF, 0.79 (0.66-0.95) [Pinteraction=0.49]. Consistent effects were observed for HF hospitalization, cardiovascular death, all-cause mortality, and improvement in the KCCQ-TSS.
Conclusions
In DELIVER, the beneficial effects of dapagliflozin, compared with placebo, on clinical events and symptoms were consistent, irrespective of type of AF at baseline.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 13 Aug 2022; epub ahead of print
Butt JH, Kondo T, Jhund PS, Comin-Colet J, ... Solomon SD, McMurray JJ
J Am Coll Cardiol: 13 Aug 2022; epub ahead of print | PMID: 36041668
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Abstract

Natural History of MYH7-related Dilated Cardiomyopathy.

de Frutos F, Ochoa JP, Navarro-Peñalver M, Baas A, ... Garcia-Pavia P, European Genetic Cardiomyopathies Initiative Investigators
Background
Variants in MYH7 are responsible for disease in 1-5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described.
Objectives
We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression.
Methods
We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% females, 35.6±19.2 years) recruited from 29 international centers.
Results
At initial evaluation, 106 patients (72.1%) had DCM (LVEF 34.5±11.7%). Median follow-up was 4.5 years (interquartile range: 1.7-8.0) and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years. Thirty-six percent of patients with DCM met imaging criteria for LV non-compaction. During follow-up, 28% showed left ventricular reverse remodeling (LVRR). Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths due to end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia (MVA) rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF≤35%, respectively). ESHF and MVA were significantly lower compared with LMNA-related DCM and similar than in DCM caused by TTN truncating variants.
Conclusions
MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low LVRR, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 11 Aug 2022; epub ahead of print
de Frutos F, Ochoa JP, Navarro-Peñalver M, Baas A, ... Garcia-Pavia P, European Genetic Cardiomyopathies Initiative Investigators
J Am Coll Cardiol: 11 Aug 2022; epub ahead of print | PMID: 36007715
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Impact:
Abstract

Cardiovascular Disease Projections in the United States Based on the 2020 Census Estimates.

Mohebi R, Chen C, Ibrahim NE, McCarthy CP, ... Wasfy JH, Januzzi JL
Background
Understanding trends in cardiovascular (CV) risk factors and CV disease according to age, sex, race, and ethnicity is important for policy planning and public health interventions.
Objectives
The goal of this study was to project the number of people with CV risk factors and disease and further explore sex, race, and ethnical disparities.
Methods
The prevalence of CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) and CV disease (ischemic heart disease, heart failure, myocardial infarction, and stroke) according to age, sex, race, and ethnicity was estimated by using logistic regression models based on 2013-2018 National Health and Nutrition Examination Survey data and further combining them with 2020 U.S. Census projection counts for years 2025-2060.
Results
By the year 2060, compared with the year 2025, the number of people with diabetes mellitus will increase by 39.3% (39.2 million [M] to 54.6M), hypertension by 27.2% (127.8M to 162.5M), dyslipidemia by 27.5% (98.6M to 125.7M), and obesity by 18.3% (106.3M to 125.7M). Concurrently, projected prevalence will similarly increase compared with 2025 for ischemic heart disease by 31.1% (21.9M to 28.7M), heart failure by 33.0% (9.7M to 12.9M), myocardial infarction by 30.1% (12.3M to 16.0M), and stroke by 34.3% (10.8M to 14.5M). Among White individuals, the prevalence of CV risk factors and disease is projected to decrease, whereas significant increases are projected in racial and ethnic minorities.
Conclusions
Large future increases in CV risk factors and CV disease prevalence are projected, disproportionately affecting racial and ethnic minorities. Future health policies and public health efforts should take these results into account to provide quality, affordable, and accessible health care.

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

J Am Coll Cardiol: 09 Aug 2022; 80:565-578
Mohebi R, Chen C, Ibrahim NE, McCarthy CP, ... Wasfy JH, Januzzi JL
J Am Coll Cardiol: 09 Aug 2022; 80:565-578 | PMID: 35926929
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Abstract

Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure.

Ye F, Wang X, Wu S, Ma S, ... Wang J, FIRST Investigators
Background
Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.
Objectives
This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.
Methods
Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.
Results
We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.
Conclusions
The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).

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

J Am Coll Cardiol: 09 Aug 2022; 80:584-594
Ye F, Wang X, Wu S, Ma S, ... Wang J, FIRST Investigators
J Am Coll Cardiol: 09 Aug 2022; 80:584-594 | PMID: 35926931
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Abstract

Cardiorespiratory Fitness and Mortality Risk Across the Spectra of Age, Race, and Sex.

Kokkinos P, Faselis C, Samuel IBH, Pittaras A, ... Zhang J, Myers J
Background
Cardiorespiratory fitness (CRF) is inversely associated with all-cause mortality. However, the association of CRF and mortality risk for different races, women, and elderly individuals has not been fully assessed.
Objectives
The aim of this study was to evaluate the association of CRF and mortality risk across the spectra of age, race, and sex.
Methods
A total of 750,302 U.S. veterans aged 30 to 95 years (mean age 61.3 ± 9.8 years) were studied, including septuagenarians (n = 110,637), octogenarians (n = 26,989), African Americans (n = 142,798), Hispanics (n = 35,197), Native Americans (n = 16,050), and women (n = 45,232). Age- and sex-specific CRF categories (quintiles and 98th percentile) were established objectively on the basis of peak METs achieved during a standardized exercise treadmill test. Multivariable Cox models were used to estimate HRs and 95% CIs for mortality across the CRF categories.
Results
During follow-up (median 10.2 years, 7,803,861 person-years of observation), 174,807 subjects died, averaging 22.4 events per 1,000 person-years. The adjusted association of CRF and mortality risk was inverse and graded across the age spectrum, sex, and race. The lowest mortality risk was observed at approximately 14.0 METs for men (HR: 0.24; 95% CI: 0.23-0.25) and women (HR: 0.23; 95% CI: 0.17-0.29), with no evidence of an increase in risk with extremely high CRF. The risk for least fit individuals (20th percentile) was 4-fold higher (HR: 4.09; 95% CI: 3.90-4.20) compared with extremely fit individuals.
Conclusions
The association of CRF and mortality risk across the age spectrum (including septuagenarians and octogenarians), men, women, and all races was inverse, independent, and graded. No increased risk was observed with extreme fitness. Being unfit carried a greater risk than any of the cardiac risk factors examined.

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

J Am Coll Cardiol: 09 Aug 2022; 80:598-609
Kokkinos P, Faselis C, Samuel IBH, Pittaras A, ... Zhang J, Myers J
J Am Coll Cardiol: 09 Aug 2022; 80:598-609 | PMID: 35926933
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Impact:
Abstract

Deep Learning Electrocardiographic Analysis for Detection of Left-Sided Valvular Heart Disease.

Elias P, Poterucha TJ, Rajaram V, Moller LM, ... Leon MB, Perotte AJ
Background
Valvular heart disease is an important contributor to cardiovascular morbidity and mortality and remains underdiagnosed. Deep learning analysis of electrocardiography (ECG) may be useful in detecting aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR).
Objectives
This study aimed to develop ECG deep learning algorithms to identify moderate or severe AS, AR, and MR alone and in combination.
Methods
A total of 77,163 patients undergoing ECG within 1 year before echocardiography from 2005-2021 were identified and split into train (n = 43,165), validation (n = 12,950), and test sets (n = 21,048; 7.8% with any of AS, AR, or MR). Model performance was assessed using area under the receiver-operating characteristic (AU-ROC) and precision-recall curves. Outside validation was conducted on an independent data set. Test accuracy was modeled using different disease prevalence levels to simulate screening efficacy using the deep learning model.
Results
The deep learning algorithm model accuracy was as follows: AS (AU-ROC: 0.88), AR (AU-ROC: 0.77), MR (AU-ROC: 0.83), and any of AS, AR, or MR (AU-ROC: 0.84; sensitivity 78%, specificity 73%) with similar accuracy in external validation. In screening program modeling, test characteristics were dependent on underlying prevalence and selected sensitivity levels. At a prevalence of 7.8%, the positive and negative predictive values were 20% and 97.6%, respectively.
Conclusions
Deep learning analysis of the ECG can accurately detect AS, AR, and MR in this multicenter cohort and may serve as the basis for the development of a valvular heart disease screening program.

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

J Am Coll Cardiol: 09 Aug 2022; 80:613-626
Elias P, Poterucha TJ, Rajaram V, Moller LM, ... Leon MB, Perotte AJ
J Am Coll Cardiol: 09 Aug 2022; 80:613-626 | PMID: 35926935
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Impact:
Abstract

Impact of the COVID-19 Pandemic on Cardiovascular Health in 2020: JACC State-of-the-Art Review.

Roth GA, Vaduganathan M, Mensah GA
The impact of COVID-19 on the burden of cardiovascular diseases (CVD) during the early pandemic remains unclear. COVID-19 has become one of the leading causes of global mortality, with a disproportionate impact on persons with CVD. Studies of health facility admissions for CVD found significant decreases during the pandemic. Studies of hospital mortality for CVD were more variable. Studies of population-level CVD mortality differed across countries, with most showing decreases, although some revealed increases in deaths. In some countries where large increases in CVD deaths were reported in vital registration systems, misclassification of COVID-19 as CVD may have occurred. Taken together, studies suggest heterogeneous effects of the COVID-19 pandemic on CVD without large increases in CVD mortality in 2020 for a number of countries. Clinical and population science research is needed to examine the ways in which the pandemic has affected CVD burden.

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

J Am Coll Cardiol: 09 Aug 2022; 80:631-640
Roth GA, Vaduganathan M, Mensah GA
J Am Coll Cardiol: 09 Aug 2022; 80:631-640 | PMID: 35926937
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Impact:
Abstract

Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures.

Thornhill MH, Gibson TB, Yoon F, Dayer MJ, ... O\'Gara PT, Baddour LM
Background
Antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) is recommended to prevent infective endocarditis (IE) in those at high IE risk, but there are sparse data supporting a link between IDPs and IE or AP efficacy in IE prevention.
Objectives
The purpose of this study was to investigate any association between IDPs and IE, and the effectiveness of AP in reducing this.
Methods
We performed a case-crossover analysis and cohort study of the association between IDPs and IE, and AP efficacy, in 7,951,972 U.S. subjects with employer-provided Commercial/Medicare-Supplemental coverage.
Results
Time course studies showed that IE was most likely to occur within 4 weeks of an IDP. For those at high IE risk, case-crossover analysis demonstrated a significant temporal association between IE and IDPs in the preceding 4 weeks (OR: 2.00; 95% CI: 1.59-2.52; P = 0.002). This relationship was strongest for dental extractions (OR: 11.08; 95% CI: 7.34-16.74; P < 0.0001) and oral-surgical procedures (OR: 50.77; 95% CI: 20.79-123.98; P < 0.0001). AP was associated with a significant reduction in IE incidence following IDP (OR: 0.49; 95% CI: 0.29-0.85; P = 0.01). The cohort study confirmed the associations between IE and extractions or oral surgical procedures in those at high IE risk and the effect of AP in reducing these associations (extractions: OR: 0.13; 95% CI: 0.03-0.34; P < 0.0001; oral surgical procedures: OR: 0.09; 95% CI: 0.01-0.35; P = 0.002).
Conclusions
We demonstrated a significant temporal association between IDPs (particularly extractions and oral-surgical procedures) and subsequent IE in high-IE-risk individuals, and a significant association between AP use and reduced IE incidence following these procedures. These data support the American Heart Association, and other, recommendations that those at high IE risk should receive AP before IDP.

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

J Am Coll Cardiol: 06 Aug 2022; epub ahead of print
Thornhill MH, Gibson TB, Yoon F, Dayer MJ, ... O'Gara PT, Baddour LM
J Am Coll Cardiol: 06 Aug 2022; epub ahead of print | PMID: 35987887
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Impact:
Abstract

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations.

Whelton PK, Carey RM, Mancia G, Kreutz R, Bundy JD, Williams B
The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Copyright © 2022 American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Aug 2022; epub ahead of print
Whelton PK, Carey RM, Mancia G, Kreutz R, Bundy JD, Williams B
J Am Coll Cardiol: 04 Aug 2022; epub ahead of print | PMID: 35965201
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Abstract

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

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

Copyright © 2022. Published by Elsevier Inc.

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

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

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

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

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

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

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

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

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

Nurse-Provided Lung and Inferior Vena Cava Assessment in Patients With Heart Failure.

Zisis G, Yang Y, Huynh Q, Whitmore K, ... Carrington MJ, Marwick TH
Background
Residual congestion detected using handheld ultrasound may be associated with increased risk of readmission and death after hospitalization for acute decompensated heart failure (ADHF). However, effective application necessitates routine use by nonexperts delivering clinical care.
Objectives
The objective of this study was to determine the ability of heart failure (HF) nurses to deliver a predischarge lung and inferior vena cava (IVC) assessment (LUICA) to predict 90-day outcomes.
Methods
In this multisite, prospective, observational study, HF nurses scanned 240 patients with ADHF (median age: 77 years; 56% men) using a 9-zone LUICA protocol. Obtained images were reviewed by independent nurses who were blinded to clinical characteristics and outcomes. Based on a B-line cut-off of 10, patients were dichotomized as congested (n = 115) or not congested (n = 125).
Results
Congested patients were more likely to have previous cardiac operations, long-standing HF (>6 months), and renal impairment. At 90 days, HF readmission or mortality occurred in 42 congested patients (37%) compared with 18 noncongested patients (14%). Pulmonary congestion increased at 30-day (OR: 3.86; 95% CI: 1.65-8.99; P < 0.01) and 90-day (OR: 3.42; 95% CI: 1.82-6.4; P < 0.01) HF readmission or mortality risk and 90-day mortality (OR: 5.18; 95% CI: 1.44-18.69; P < 0.01). Pulmonary congestion increased the 90-day odds of HF readmission and/or death by 3.3- to 4.2-fold (P < 0.01), independent of demographics, HF characteristics, comorbidities, and event risk score. Over 90 days, days alive out of hospital were fewer (78.3 ± 21.4 days vs 85.5 ± 12.4 days; P < 0.01) in congested patients.
Conclusions
LUICA can be a powerful tool for detection of predischarge residual congestion. HF nurses can obtain images and provide diagnostic reports that are predictive of ADHF outcomes.

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

J Am Coll Cardiol: 02 Aug 2022; 80:513-523
Zisis G, Yang Y, Huynh Q, Whitmore K, ... Carrington MJ, Marwick TH
J Am Coll Cardiol: 02 Aug 2022; 80:513-523 | PMID: 35902175
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Impact:
Abstract

Bioprosthetic Aortic Valve Hemodynamics: Definitions, Outcomes, and Evidence Gaps: JACC State-of-the-Art Review.

Herrmann HC, Pibarot P, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
A virtual workshop was organized by the Heart Valve Collaboratory to identify areas of expert consensus, areas of disagreement, and evidence gaps related to bioprosthetic aortic valve hemodynamics. Impaired functional performance of bioprosthetic aortic valve replacement is associated with adverse patient outcomes; however, this assessment is complicated by the lack of standardization for labelling, definitions, and measurement techniques, both after surgical and transcatheter valve replacement. Echocardiography remains the standard assessment methodology because of its ease of performance, widespread availability, ability to do serial measurements over time, and correlation with outcomes. Management of a high gradient after replacement requires integration of the patient\'s clinical status, physical examination, and multimodality imaging in addition to shared patient decisions regarding treatment options. Future priorities that are underway include efforts to standardize prosthesis sizing and labelling for both surgical and transcatheter valves as well as trials to characterize the consequences of adverse hemodynamics.

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

J Am Coll Cardiol: 02 Aug 2022; 80:527-544
Herrmann HC, Pibarot P, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
J Am Coll Cardiol: 02 Aug 2022; 80:527-544 | PMID: 35902177
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Impact:
Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Criteria for Defining Stages of Cardiogenic Shock Severity.

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

Copyright © 2022. Published by Elsevier Inc.

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

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

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

Copyright © 2022. Published by Elsevier Inc.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

LMNA Variants and Risk of Adult-Onset Cardiac Disease.

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

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

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

Preoperative Atrial Fibrillation and Cardiovascular Outcomes After Noncardiac Surgery.

Prasada S, Desai MY, Saad M, Smilowitz NR, ... Nakhla S, Mentias A
Background
The impact of pre-existing atrial fibrillation (AF) on outcomes after noncardiac surgery is not clear.
Objectives
We aimed to study the impact of AF on the risk of adverse outcomes after noncardiac surgery in a nationwide cohort.
Methods
We identified Medicare beneficiaries admitted for noncardiac surgery from 2015 to 2019 and divided the study cohort into 2 groups: with and without AF. Noncardiac surgery was classified into vascular, thoracic, general, genitourinary, gynecological, orthopedics and neurosurgery, breast, head and neck, and transplant. We used propensity score matching on exact age, sex, race, urgency and type of surgery, revised cardiac risk index (RCRI) and CHA2DS2-VASc score, and tight caliper on other comorbidities. The study outcomes were 30-day mortality, stroke, myocardial infarction, and heart failure. We examined the incremental utility of AF in addition to RCRI to predict adverse events after noncardiac surgery.
Results
The study cohort included 8,635,758 patients who underwent noncardiac surgery (16.4% with AF). Patients with AF were older, more likely to be men, and had higher prevalence of comorbidities. After propensity score matching, AF was associated with higher risk of mortality (OR: 1.31; 95% CI: 1.30-1.32), heart failure (OR: 1.31; 95% CI: 1.30-1.33), and stroke (OR: 1.40; 95% CI: 1.37-1.43) and lower risk of myocardial infarction (OR: 0.81; 95% CI: 0.79-0.82). Results were consistent in subgroup analysis by sex, race, type of surgery, and all strata of RCRI and CHA2DS2-VASc score. AF improved the discriminative ability of RCRI (C-statistic 0.73 to 0.76).
Conclusion
Pre-existing AF is independently associated with postoperative adverse outcomes after NCS.

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

J Am Coll Cardiol: 28 Jun 2022; 79:2471-2485
Prasada S, Desai MY, Saad M, Smilowitz NR, ... Nakhla S, Mentias A
J Am Coll Cardiol: 28 Jun 2022; 79:2471-2485 | PMID: 35738707
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Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Copyright © 2022. Published by Elsevier Inc.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Early Coronary Atherosclerosis in Women With Previous Preeclampsia.

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

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

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