Journal: J Am Heart Assoc

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Abstract

Population Trends in All-Cause Mortality and Cause Specific-Death With Incident Atrial Fibrillation.

Singh SM, Abdel-Qadir H, Pang A, Fang J, ... Wijeysundera HC, Ko DT

Background Limited studies have evaluated population-level temporal trends in mortality and cause of death in patients with contemporary managed atrial fibrillation. This study reports the temporal trends in 1-year overall and cause-specific mortality in patients with incident atrial fibrillation. Methods and results Patients with incident atrial fibrillation presenting to an emergency department or hospitalized in Ontario, Canada, were identified in population-level linked administrative databases that included data on vital statistics and cause of death. Temporal trends in 1-year all-cause and cause-specific mortality was determined for individuals identified between April 1, 2007 (fiscal year [FY] 2007) and March 31, 2016 (FY 2015). The study cohort consisted of 110 302 individuals, 69±15 years of age with a median congestive heart failure, hypertension, age (≥75 years), diabetes mellitus, stroke (2 points), vascular disease, age (≥65 years), sex category (female) score of 2.8. There was no significant decline in the adjusted 1-year all-cause mortality between the first and last years of the study period (adjusted mortality: FY 2007, 8.0%; FY 2015, 7.8%; P for trend=0.68). Noncardiovascular death accounted for 61% of all deaths; the adjusted 1-year noncardiovascular mortality rate rose from 4.5% in FY 2007 to 5.2% in FY 2015 (P for trend=0.007). In contrast, the 1-year cardiovascular mortality rate decreased from 3.5% in FY 2007 to 2.6% in FY 2015 (P for trend=0.01). CONCLUSIONS Overall 1-year all-cause mortality in individuals with incident atrial fibrillation has not improved despite a significant reduction in the rate of cardiovascular death. These findings highlight the importance of recognizing and managing concomitant noncardiovascular conditions in patients with atrial fibrillation.



J Am Heart Assoc: 19 Oct 2020; 9:e016810
Singh SM, Abdel-Qadir H, Pang A, Fang J, ... Wijeysundera HC, Ko DT
J Am Heart Assoc: 19 Oct 2020; 9:e016810 | PMID: 32924719
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Abstract

Association Between Left Ventricular Mechanical Deformation and Myocardial Fibrosis in Nonischemic Cardiomyopathy.

Csecs I, Pashakhanloo F, Paskavitz A, Jang J, ... Manning WJ, Nezafat R

Background In patients with nonischemic cardiomyopathy, nonischemic fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is related to adverse cardiovascular outcomes. However, its relationship with left ventricular (LV) mechanical deformation parameters remains unclear. We sought to investigate the association between LV mechanics and the presence, location, and extent of fibrosis in patients with nonischemic cardiomyopathy. Methods and Results We retrospectively identified 239 patients with nonischemic cardiomyopathy (67% male; 55±14 years) referred for a clinical cardiovascular magnetic resonance. LGE was present in 109 patients (46%), most commonly (n=52; 22%) in the septum. LV deformation parameters did not differentiate between LGE-positive and LGE-negative groups. Global longitudinal, radial, and circumferential strains, twist and torsion showed no association with extent of fibrosis. Patients with septal fibrosis had a more depressed LV ejection fraction (30±12% versus 35±14%; =0.032) and more impaired global circumferential strain (-7.9±3.5% versus -9.7±4.4%; =0.045) and global radial strain (10.7±5.2% versus 13.3±7.7%; =0.023) than patients without septal LGE. Global longitudinal strain was similar in both groups. While patients with septal-only LGE (n=28) and free wall-only LGE (n=32) had similar fibrosis burden, the septal-only LGE group had more impaired LV ejection fraction and global circumferential, longitudinal, and radial strains (all <0.05). Conclusions There is no association between LV mechanical deformation parameters and presence or extent of fibrosis in patients with nonischemic cardiomyopathy. Septal LGE was associated with poor global LV function, more impaired global circumferential and radial strains, and more impaired global strain rates.



J Am Heart Assoc: 01 Oct 2020:e016797; epub ahead of print
Csecs I, Pashakhanloo F, Paskavitz A, Jang J, ... Manning WJ, Nezafat R
J Am Heart Assoc: 01 Oct 2020:e016797; epub ahead of print | PMID: 33006296
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Abstract

Unmasking Arrhythmogenic Hubs of Reentry Driving Persistent Atrial Fibrillation for Patient-Specific Treatment.

Hansen BJ, Zhao J, Helfrich KM, Li N, ... Hummel JD, Fedorov VV

Background Atrial fibrillation (AF) driver mechanisms are obscured to clinical multielectrode mapping approaches that provide partial, surface-only visualization of unstable 3-dimensional atrial conduction. We hypothesized that transient modulation of refractoriness by pharmacologic challenge during multielectrode mapping improves visualization of hidden paths of reentrant AF drivers for targeted ablation. Methods and Results Pharmacologic challenge with adenosine was tested in ex vivo human hearts with a history of AF and cardiac diseases by multielectrode and high-resolution subsurface near-infrared optical mapping, integrated with 3-dimensional structural imaging and heart-specific computational simulations. Adenosine challenge was also studied on acutely terminated AF drivers in 10 patients with persistent AF. Ex vivo, adenosine stabilized reentrant driver paths within arrhythmogenic fibrotic hubs and improved visualization of reentrant paths, previously seen as focal or unstable breakthrough activation pattern, for targeted AF ablation. Computational simulations suggested that shortening of atrial refractoriness by adenosine may (1) improve driver stability by annihilating spatially unstable functional blocks and tightening reentrant circuits around fibrotic substrates, thus unmasking the common reentrant path; and (2) destabilize already stable reentrant drivers along fibrotic substrates by accelerating competing fibrillatory wavelets or secondary drivers. In patients with persistent AF, adenosine challenge unmasked hidden common reentry paths (9/15 AF drivers, 41±26% to 68±25% visualization), but worsened visualization of previously visible reentry paths (6/15, 74±14% to 34±12%). AF driver ablation led to acute termination of AF. Conclusions Our ex vivo to in vivo human translational study suggests that transiently altering atrial refractoriness can stabilize reentrant paths and unmask arrhythmogenic hubs to guide targeted AF driver ablation treatment.



J Am Heart Assoc: 19 Oct 2020; 9:e017789
Hansen BJ, Zhao J, Helfrich KM, Li N, ... Hummel JD, Fedorov VV
J Am Heart Assoc: 19 Oct 2020; 9:e017789 | PMID: 33006292
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Abstract

Computerized Analysis of the Ventricular Fibrillation Waveform Allows Identification of Myocardial Infarction: A Proof-of-Concept Study for Smart Defibrillator Applications in Cardiac Arrest.

Thannhauser J, Nas J, Rebergen DJ, Westra SW, ... Bonnes JL, Brouwer MA

Background In cardiac arrest, computerized analysis of the ventricular fibrillation (VF) waveform provides prognostic information, while its diagnostic potential is subject of study. Animal studies suggest that VF morphology is affected by prior myocardial infarction (MI), and even more by acute MI. This experimental in-human study reports on the discriminative value of VF waveform analysis to identify a prior MI. Outcomes may provide support for in-field studies on acute MI. Methods and Results We conducted a prospective registry of implantable cardioverter defibrillator recipients with defibrillation testing (2010-2014). From 12-lead surface ECG VF recordings, we calculated 10 VF waveform characteristics. First, we studied detection of prior MI with lead II, using one key VF characteristic (amplitude spectrum area [AMSA]). Subsequently, we constructed diagnostic machine learning models: model A, lead II, all VF characteristics; model B, 12-lead, AMSA only; and model C, 12-lead, all VF characteristics. Prior MI was present in 58% (119/206) of patients. The approach using the AMSA of lead II demonstrated a C-statistic of 0.61 (95% CI, 0.54-0.68). Model A performance was not significantly better: 0.66 (95% CI, 0.59-0.73), =0.09 versus AMSA lead II. Model B yielded a higher C-statistic: 0.75 (95% CI, 0.68-0.81), <0.001 versus AMSA lead II. Model C did not improve this further: 0.74 (95% CI, 0.67-0.80), =0.66 versus model B. Conclusions This proof-of-concept study provides the first in-human evidence that MI detection seems feasible using VF waveform analysis. Information from multiple ECG leads rather than from multiple VF characteristics may improve diagnostic accuracy. These results require additional experimental studies and may serve as pilot data for in-field smart defibrillator studies, to try and identify acute MI in the earliest stages of cardiac arrest.



J Am Heart Assoc: 19 Oct 2020; 9:e016727
Thannhauser J, Nas J, Rebergen DJ, Westra SW, ... Bonnes JL, Brouwer MA
J Am Heart Assoc: 19 Oct 2020; 9:e016727 | PMID: 33003984
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Abstract

Femoral Versus Nonfemoral Subclavian/Carotid Arterial Access Route for Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Faroux L, Junquera L, Mohammadi S, Del Val D, ... Delarochellière R, Rodés-Cabau J

Background Some concerns remain regarding the safety of transcarotid and transsubclavian approaches for transcatheter aortic valve replacement. We aimed to compare the risk of 30-day complications and death in transcarotid/transsubclavian versus transfemoral transcatheter aortic valve replacement recipients. Methods and Results Data from 20 studies, including 79 426 patients (16 studies) and 3992 patients (4 studies) for the evaluation of the unadjusted and adjusted impact of the arterial approach were sourced, respectively. The use of a transcarotid/transsubclavian approach was associated with an increased risk of stroke when using unadjusted data (risk ratio [RR], 2.28; 95% CI, 1.90-2.72) as well as adjusted data (odds ratio [OR], 1.53; 95% CI, 1.05-2.22). The pooled results deriving from unadjusted data showed an increased risk of 30-day death (RR, 1.46; 95% CI, 1.22-1.74) and bleeding (RR, 1.53; 95% CI, 1.18-1.97) in patients receiving transcatheter aortic valve replacement through a transcarotid/transsubclavian access (compared with the transfemoral group), but the associations between the arterial access and death (OR, 1.22; 95% CI, 0.89-1.69), bleeding (OR, 1.05; 95% CI, 0.68-1.61) were no longer significant when using adjusted data. No significant effect of the arterial access on vascular complication was observed in unadjusted (RR, 0.84; 95% CI, 0.66-1.06) and adjusted (OR, 0.79; 95% CI, 0.53-1.17) analyses. Conclusions Transcarotid and transsubclavian approaches for transcatheter aortic valve replacement were associated with an increased risk of stroke compared with the transfemoral approach. However, these nonfemoral arterial alternative accesses were not associated with an increased risk of 30-day death, bleeding, or vascular complication when taking into account the confounding factors.



J Am Heart Assoc: 19 Oct 2020; 9:e017460
Faroux L, Junquera L, Mohammadi S, Del Val D, ... Delarochellière R, Rodés-Cabau J
J Am Heart Assoc: 19 Oct 2020; 9:e017460 | PMID: 32990146
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Abstract

Coronary Microvascular Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Artery Disease Is Associated With Elevated Serum Homocysteine Levels.

Ahmad A, Corban MT, Toya T, Sara JD, ... Lerman LO, Lerman A

Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (<40% angiographic stenosis), who underwent CMED evaluation with functional angiography and had serum homocysteine levels measured. Patients were classified as having normal microvascular function versus CMED. Patients in the CMED group (n=743; 52%) had higher mean age (52.1±12.2 versus 50.0±12.4 years; <0.0001), higher body mass index (29.1 [25.0-32.8] versus 27.5 [24.2-32.4]; =0.001), diabetes mellitus (12.5% versus 9.4%; =0.03), and fewer women (63.5% versus 68.7%; =0.04) compared with patients in the normal microvascular function group. However, they had lower rates of smoking history, and mildly lower low-density lipoprotein cholesterol levels. Serum homocysteine levels were significantly higher in patients with CMED, and the highest quartile of serum homocysteine level (>9 µmol/L) was an independent predictor of CMED (odds ratio, 1.34 [95% CI, 1.03-1.75]; =0.03) after adjustment for age; sex; body mass index; chronic kidney disease (CKD); diabetes mellitus; smoking exposure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol and triglycerides; and aspirin, statin, and B vitamin use. Conclusions Patients with CMED have significantly higher levels of serum homocysteine. Elevated serum homocysteine levels were associated with a significantly increased odds of an invasive diagnosis of CMED. The current study supports a potential role for homocysteine for diagnosis and target treatment in the patients with early coronary atherosclerosis.



J Am Heart Assoc: 19 Oct 2020; 9:e017746
Ahmad A, Corban MT, Toya T, Sara JD, ... Lerman LO, Lerman A
J Am Heart Assoc: 19 Oct 2020; 9:e017746 | PMID: 32993421
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Abstract

Association of Health Status Scores With Cardiovascular and Limb Outcomes in Patients With Symptomatic Peripheral Artery Disease: Insights From the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) Trial.

Rymer JA, Mulder H, Smolderen KG, Hiatt WR, ... Jones WS, Patel MR

Background There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events. Methods and Results In an analysis of the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) trial, we examined the characteristics of 13 801 patients by tertile of health status instrument scores collected in the trial (EuroQol 5-Dimensions [EQ-5D], EQ visual analog scale [VAS], and peripheral artery questionnaire). We assessed the association between the baseline health status measurements and major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization procedures during trial follow-up and the association between 12-month health status change scores and subsequent end points during follow-up. There were 13 217 (95%) patients with EQ-5D scores, 13 533 (98%) with VAS scores, and 4431 (32%) with peripheral artery questionnaire scores. Patients in the lowest baseline EQ-5D tertile (0 to <0.69) were more likely to be female with severe claudication compared with the highest tertile (0.79-1.0; <0.01). Patients in the lowest VAS (0-60) and peripheral artery questionnaire (0-49) tertiles had lower ankle-brachial indices compared with the highest tertiles (80-100 and 76-108, respectively; <0.01). There was a significant association between baseline EQ-5D, VAS, and peripheral artery questionnaire scores and adjusted major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization (<0.05). Improved EQ-5D and VAS scores over 12 months were associated with reduced risk of subsequent major adverse cardiovascular events or lower-extremity revascularization (all <0.01). Conclusions Although health status instruments are rarely used in clinical practice, these measures are associated with outcomes, including major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization. Further research is needed to determine the relationship between changes in these instruments, revascularization, and outcomes.



J Am Heart Assoc: 19 Oct 2020; 9:e016573
Rymer JA, Mulder H, Smolderen KG, Hiatt WR, ... Jones WS, Patel MR
J Am Heart Assoc: 19 Oct 2020; 9:e016573 | PMID: 32924754
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Abstract

Mortality in Patients With Right Bundle-Branch Block in the Absence of Cardiovascular Disease.

Gaba P, Pedrotty D, DeSimone CV, Bonikowske AR, Allison TG, Kapa S

Background Right bundle-branch block (RBBB) occurs in 0.2% to 1.3% of people and is considered a benign finding. However, some studies have suggested increased risk of cardiovascular morbidity and mortality. We sought to evaluate risk attributable to incidental RBBB in patients without prior diagnosis of cardiovascular disease (CVD). Methods and Results We reviewed the Mayo Clinic Integrated Stress Center database for exercise stress tests performed from 1993 to 2010. Patients with no known CVD-defined as absence of coronary disease, structural heart disease, heart failure, or cerebrovascular disease-were selected. Only Minnesota residents were included, all of whom had full mortality and outcomes data. There were 22 806 patients without CVD identified; 220 of whom (0.96%) had RBBB, followed for 6 to 23 years (mean 12.4±5.1). There were 8256 women (36.2%), mean age was 52±11 years; and 1837 deaths (8.05%), including 645 cardiovascular-related deaths (2.83%), occurred over follow-up. RBBB was predictive of all-cause (hazard ratio [HR], 1.5; 95% CI, 1.1-2.0; =0.0058) and cardiovascular-related mortality (HR,1.7; 95% CI, 1.1-2.8; =0.0178) after adjusting for age, sex, diabetes mellitus, hypertension, obesity, current and past history of smoking, and use of a heart rate-lowering drug. Patients with RBBB exhibited more hypertension (34.1% versus 23.7%, <0.0003), decreased functional aerobic capacity (82±25% versus 90±24%; <0.0001), slower heart rate recovery (13.5±11.5 versus 17.1±9.4 bpm; <0.0001), and more dyspnea (28.2% versus 22.4%; <0.0399) on exercise testing. Conclusions Patients with RBBB without CVD have increased risk of all-cause mortality, cardiovascular-related mortality, and lower exercise tolerance. These data suggest RBBB may be a marker of early CVD and merit further prospective evaluation.



J Am Heart Assoc: 19 Oct 2020; 9:e017430
Gaba P, Pedrotty D, DeSimone CV, Bonikowske AR, Allison TG, Kapa S
J Am Heart Assoc: 19 Oct 2020; 9:e017430 | PMID: 32924743
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Abstract

Association Between Atazanavir-Induced Hyperbilirubinemia and Cardiovascular Disease in Patients Infected with HIV.

Li M, Chan WW, Zucker SD
Background
Serum bilirubin is inversely associated with cardiovascular risk. Atazanavir, an HIV protease inhibitor that competitively inhibits bilirubin conjugation, provides a unique opportunity to examine whether selectively increasing bilirubin is cardioprotective. We sought to determine whether patients receiving atazanavir manifest a reduced risk of cardiovascular disease compared with those receiving darunavir, an HIV protease inhibitor that does not increase serum bilirubin.
Methods and results
This was a retrospective cohort study of 1020 patients with HIV. The main outcome was time to myocardial infarction or ischemic stroke. Mean follow-up was 6.6±3.4 years, with 516 receiving atazanavir and 504 darunavir. Atazanavir patients exhibited significantly higher serum total bilirubin (1.7 versus 0.4 mg/dL; <0.001) and longer mean time to ischemic event (10.2 versus 9.4 years; <0.001). On Cox regression, atazanavir treatment (hazard ratio [HR], 0.38; 95% CI, 0.21-0.71; =0.002) and serum bilirubin (HR, 0.60; 95% CI, 0.41-0.89; =0.011) were independently associated with a lower risk of an ischemic event. Notably, when atazanavir and bilirubin were included together in the Cox regression model, atazanavir lost significance (HR, 0.55; 95% CI, 0.24-1.29; =0.169) consistent with bilirubin being an intermediate variable on the causal pathway between atazanavir and its effect on cardiovascular disease. Patients on atazanavir also had a significantly lower risk of developing new cardiovascular disease (HR, 0.53; 95% CI, 0.33-0.86; =0.010) and longer mean time to death (12.2 versus 10.8 years; <0.001).
Conclusions
Patients with HIV on atazanavir manifest a decreased risk of cardiovascular disease when compared with those on darunavir, an effect that appears to be mediated by serum bilirubin.



J Am Heart Assoc: 19 Oct 2020; 9:e016310
Li M, Chan WW, Zucker SD
J Am Heart Assoc: 19 Oct 2020; 9:e016310 | PMID: 32930032
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High-Sensitivity Cardiac Troponin I and T Response Following Strenuous Activity is Attenuated by Smokeless Tobacco: NEEDED (North Sea Race Endurance Exercise Study) 2014.

Skranes JB, Kleiven Ø, Aakre KM, Skadberg Ø, ... Omland T, Ørn S

Background Use of snus, a smokeless tobacco product, is increasing in Scandinavia. Strenuous physical activity is associated with an acute increase in high-sensitivity cardiac troponin (swhs-cTn) concentrations. Current smoking is associated with lower hs-cTn, but whether this also holds true for smokeless tobacco and whether tobacco affects the hs-cTn response to exercise remain unknown. Methods and Results We measured hs-cTnI and hs-cTnT concentrations in 914 recreational athletes before and 3 and 24 hours after a 91-km bicycle race. Self-reported snus tobacco habits were reported as noncurrent (n=796) and current (n=118). The association between snus use and change in log-transformed hs-cTnI and hs-cTnT concentrations (ie, the differences between concentrations at baseline and 3 hours and 24 hours ) were assessed by multivariable linear regression analysis. Concentrations of hs-cTn at baseline were lower in current than in noncurrent snus users (hs-cTnI median, 1.7 ng/L; Q1 to Q3: 1.6-2.3 versus 2.0 ng/L; Q1 to Q3: 1.6-3.2 [=0.020]; and hs-cTnT: median, 2.9 ng/L, Q1 to Q3: 2.9-3.5 versus 2.9 ng/L, Q1 to Q3: 2.9-4.3 [=0.021]). In fully adjusted multivariable models, use of snus was associated with lower change in hs-cTn concentrations from baseline to 3 hours (hs-cTnI: -29% [=0.002], hs-cTnT: -18% [=0.010]) and 24 hours (hscTnI: -30% [=0.010], hs-cTnT -19%, [=0.013]). Conclusions Resting hs-cTn concentrations are lower and the exercise-induced cardiac troponin response is attenuated in current users of smokeless tobacco compared with nonusers. Further insight into the pathophysiological processes underlying the attenuated cardiac troponin response to exercise in tobacco users is needed. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02166216.



J Am Heart Assoc: 19 Oct 2020; 9:e017363
Skranes JB, Kleiven Ø, Aakre KM, Skadberg Ø, ... Omland T, Ørn S
J Am Heart Assoc: 19 Oct 2020; 9:e017363 | PMID: 32930023
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Association of Hypertriglyceridemia with All-Cause Mortality and Atherosclerotic Cardiovascular Events in a Low-Risk Italian Population: The TG-REAL Retrospective Cohort Analysis.

Arca M, Veronesi C, D\'Erasmo L, Borghi C, ... Degli Esposti L,

Background Evidence regarding the relationships among high plasma triglycerides (TG), all-cause mortality, and atherosclerotic cardiovascular disease (ASCVD) events in low-to-moderate risk individuals is limited. The aim of this study was to determine whether the presence of high TG levels influences the risk of all-cause mortality and ASCVD events in a population cohort followed in the real-world clinical setting. Methods and Results A retrospective longitudinal cohort analysis using administrative databases of 3 Italian Local Health Units was performed. All individuals with at least one TG measurement between January 1, 2010 and December 31, 2015 were followed through December 2016. Outcome measures included incident ASCVD events and all-cause mortality. Individuals with normal TG levels (<150 mg/dL) were compared with those with high (150-500 mg/dL) and very high TG (>500 mg/dL). 158 042 individuals (142 289 with normal, 15 558 with high, and 195 with very high TG) were considered. In the whole cohort, the overall incidence rates of ASCVD and all-cause mortality were 7.2 and 17.1 per 1000 person-years, respectively. After multivariate adjustment for potential confounders, individuals with high and very high TG showed a significantly increased risk of all-cause mortality (hazard ratio [HR]=1.49 [95% confidence interval (CI) 1.36-1.63], <0.001, and HR=3.08 [95% CI 1.46-6.50], <0.01, respectively) and incident ASCVD events (HR=1.61 [95% CI 1.43-1.82], <0.001, and HR=2.30 [95% CI 1.02-5.18], <0.05, respectively) as compared to those with normal TG. Conclusions Moderate-to-severe elevation of TG is associated with a significantly increased risk of all-cause mortality and ASCVD events in a large cohort of low-to-moderate cardiovascular risk individuals in a real-world clinical setting.



J Am Heart Assoc: 19 Oct 2020; 9:e015801
Arca M, Veronesi C, D'Erasmo L, Borghi C, ... Degli Esposti L,
J Am Heart Assoc: 19 Oct 2020; 9:e015801 | PMID: 32954906
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NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus.

Malachias MVB, Jhund PS, Claggett BL, Wijkman MO, ... McMurray JJV, Pfeffer MA

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the discriminatory ability of risk-prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT-proBNP by itself for death and cardiovascular events in high-risk patients with T2DM. Methods and Results Cox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT-proBNP alone and with NT-proBNP added, using C-statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6-year follow-up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT-proBNP alone was as discriminatory as the base model for predicting death (C-statistic, 0.745 versus 0.744, =0.95) and the cardiovascular composite outcome (C-statistic, 0.723 versus 0.731, =0.37). When NT-proBNP was added, it increased the predictive ability of the base model for death (C-statistic, 0.779 versus 0.744, <0.001) and for cardiovascular composite outcome (C-statistic, 0.763 versus 0.731, <0.001). Conclusions In high-risk patients with T2DM, NT-proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00549757.



J Am Heart Assoc: 19 Oct 2020; 9:e017462
Malachias MVB, Jhund PS, Claggett BL, Wijkman MO, ... McMurray JJV, Pfeffer MA
J Am Heart Assoc: 19 Oct 2020; 9:e017462 | PMID: 32964800
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Severe Aortic Stenosis and Chronic Kidney Disease: Outcomes and Impact of Aortic Valve Replacement.

Bohbot Y, Candellier A, Diouf M, Rusinaru D, ... Vanoverschelde JL, Tribouilloy C

Background The prognostic significance of chronic kidney disease (CKD) in severe aortic stenosis is poorly understood and no studies have yet evaluated the effect of aortic-valve replacement (AVR) versus conservative management on long-term mortality by stage of CKD. Methods and Results We included 4119 patients with severe aortic stenosis. The population was divided into 4 groups according to the baseline estimated glomerular filtration rate: no CKD, mild CKD, moderate CKD, and severe CKD. The 5-year survival rate was 71±1% for patients without CKD, 62±2% for those with mild CKD, 54±3% for those with moderate CKD, and 34±4% for those with severe CKD (<0.001). By multivariable analysis, patients with moderate or severe CKD had a significantly higher risk of all-cause (hazard ratio [HR] [95% CI]=1.36 [1.08-1.71]; =0.009 and HR [95% CI]=2.16 [1.67-2.79]; <0.001, respectively) and cardiovascular mortality (HR [95% CI]=1.39 [1.03-1.88]; =0.031 and HR [95% CI]=1.69 [1.18-2.41]; =0.004, respectively) than patients without CKD. Despite more symptoms, AVR was less frequent in moderate (=0.002) and severe CKD (<0.001). AVR was associated with a marked reduction in all-cause and cardiovascular mortality versus conservative management for each CKD group (all <0.001). The joint-test showed no interaction between AVR and CKD stages (=0.676) indicating a nondifferentialeffect of AVR across stages of CKD. After propensity matching, AVR was still associated with substantially better survival for each CKD stage relative to conservative management (all <0.0017). Conclusions In severe aortic stenosis, moderate and severe CKD are associated with increased mortality and decreased referral to AVR. AVR markedly reduces all-cause and cardiovascular mortality, regardless of the CKD stage. Therefore, CKD should not discourage physicians from considering AVR.



J Am Heart Assoc: 19 Oct 2020; 9:e017190
Bohbot Y, Candellier A, Diouf M, Rusinaru D, ... Vanoverschelde JL, Tribouilloy C
J Am Heart Assoc: 19 Oct 2020; 9:e017190 | PMID: 32964785
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Hyperoxygenation With Cardiopulmonary Resuscitation and Targeted Temperature Management Improves Post-Cardiac Arrest Outcomes in Rats.

Li J, Wang J, Shen Y, Dai C, ... Wu Y, Li Y

Background Oxygen plays a pivotal role in cardiopulmonary resuscitation (CPR) and postresuscitation intervention for cardiac arrest. However, the optimal method to reoxygenate patients has not been determined. This study investigated the effect of timing of hyperoxygenation on neurological outcomes in cardiac arrest/CPR rats treated with targeted temperature management. Methods and Results After induction of ventricular fibrillation, male Sprague-Dawley rats were randomized into 4 groups (n=16/group): (1) normoxic control; (2) O_CPR, ventilated with 100% O during CPR; (3) O_CPR+postresuscitation, ventilated with 100% O during CPR and the first 3 hours of postresuscitation; and (4) O_postresuscitation, ventilated with 100% O during the first 3 hours of postresuscitation. Targeted temperature management was induced immediately after resuscitation and maintained for 3 hours in all animals. Postresuscitation hemodynamics, neurological recovery, and pathological analysis were assessed. Brain tissues of additional rats undergoing the same experimental procedure were harvested for ELISA-based quantification assays of oxidative stress-related biomarkers and compared with the sham-operated rats (n=6/group). We found that postresuscitation mean arterial pressure and quantitative electroencephalogram activity were significantly increased, whereas astroglial protein S100B, degenerated neurons, oxidative stress-related biomarkers, and neurologic deficit scores were significantly reduced in the O_CPR+postresuscitation group compared with the normoxic control group. In addition, 96-hour survival rates were significantly improved in all of the hyperoxygenation groups. Conclusions In this cardiac arrest/CPR rat model, hyperoxygenation coupled with targeted temperature management attenuates ischemia/reperfusion-induced injuries and improves survival rates. The beneficial effects of high-concentration oxygen are timing and duration dependent. Hyperoxygenation commenced with CPR, which improves outcomes when administered during hypothermia.



J Am Heart Assoc: 19 Oct 2020; 9:e016730
Li J, Wang J, Shen Y, Dai C, ... Wu Y, Li Y
J Am Heart Assoc: 19 Oct 2020; 9:e016730 | PMID: 32964774
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Abstract

Food Insecurity Is Associated With Cardiovascular and All-Cause Mortality Among Adults in the United States.

Sun Y, Liu B, Rong S, Du Y, ... Wallace RB, Bao W

Background Food insecurity is a global leading public health challenge that affects not only developing countries but also developed countries, including the United States. About 50 million Americans are food insecure. In this study we examined the associations of the adult food insecurity with all-cause and cardiovascular disease mortality in a nationally representative sample of US adults. Methods and Results We included 27 188 US adults (age ≥40 years of age) who participated in the US National Health and Nutrition Examination Survey from 1999 to 2014. Food insecurity status was assessed using the Food Security Survey Module developed by the US Department of Agriculture. Mortality from all causes and cardovascular disease was ascertained through data linkage to the National Death Index through December 31, 2015. We used multivariable Cox proportional hazards regression with sampling weights to estimate hazard ratios (HRs) and 95% CIs of all-cause and cardiovascular disease mortality, according to food security status. During 205 389 person-years of the period, 5039 deaths occurred, including 1084 cardiovascular disease deaths. After adjustment for age, sex, race/ethnicity, education, income, and dietary and lifestyle factors, participants with very low food security had higher risk of all-cause and cardiovascular disease mortality, with multivariable-adjusted HRs of 1.32 (95% CI, 1.07-1.62), and 1.53 (95% CI, 1.04-2.26), respectively, compared with those with high food security. Conclusions Food insecurity is significantly associated with increased risk of excess death from cardiovascular disease and all causes in US adults.



J Am Heart Assoc: 19 Oct 2020; 9:e014629
Sun Y, Liu B, Rong S, Du Y, ... Wallace RB, Bao W
J Am Heart Assoc: 19 Oct 2020; 9:e014629 | PMID: 32975173
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Abstract

Effect of a Housing Intervention on Selected Cardiovascular Risk Factors Among Homeless Adults With Mental Illness: 24-Month Follow-Up of a Randomized Controlled Trial.

Chum A, Wang R, Nisenbaum R, O\'Campo P, Stergiopoulos V, Hwang S

Background Cardiovascular disease is a leading cause of mortality among people experiencing homelessness. This study investigated whether housing intervention affects cardiovascular disease risk factors among homeless adults with mental illnesses over a 24-month period. Methods and Results We conducted a randomized controlled trial of a Housing First intervention that provided community-based scattered-site housing and support services. Five hundred seventy-five participants were randomized to the intervention (n=301) or treatment as usual (TAU) (n=274). Analyses were performed according to the intention-to-treat principle using generalized estimating equations. There were no differences in change over 24 months between the 2 groups for blood pressure, tobacco, and cocaine/crack use. However, the intervention had an impact on reducing the number of days of alcohol intoxication by 1.58 days compared with TAU (95% CI, -2.88 to -0.27, =0.0018). Over the 24-month period, both the intervention and TAU groups had significant reductions in tobacco and cocaine use. Conclusions The intervention, compared with TAU, did not result in greater improvements in many of the selected cardiovascular risk factors. Since the study took place in a service-rich city with a range of pre-existing supportive services and universal health insurance, the high level of usual services available to the TAU group may have contributed to reductions in their cardiovascular disease risk factors. Further research is needed to develop interventions to reduce risk factors of cardiovascular disease among people experiencing homelessness and mental illness beyond existing treatments. REGISTRATION www.isrctn.comURL: www.isrctn.com. Unique Identifier: ISRCTN42520374.



J Am Heart Assoc: 19 Oct 2020; 9:e016896
Chum A, Wang R, Nisenbaum R, O'Campo P, Stergiopoulos V, Hwang S
J Am Heart Assoc: 19 Oct 2020; 9:e016896 | PMID: 32975159
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Abstract

Carotid Intima-Media Thickness and the Risk of Sudden Cardiac Death: The ARIC Study and the CHS.

Suzuki T, Wang W, Wilsdon A, Butler KR, ... Sotoodehnia N, Mosley TH

Background Sudden cardiac death (SCD) is associated with severe coronary heart disease in the great majority of cases. Whether carotid intima-media thickness (C-IMT), a known surrogate marker of subclinical atherosclerosis, is associated with risk of SCD in a general population remains unknown. The objective of this study was to investigate the association between C-IMT and risk of SCD. Methods and Results We examined a total of 20 862 participants: 15 307 participants of the ARIC (Atherosclerosis Risk in Communities) study and 5555 participants of the CHS (Cardiovascular Health Study). C-IMT and common carotid artery intima-media thickness was measured at baseline by ultrasound. Presence of plaque was judged by trained readers. Over a median of 23.5 years of follow-up, 569 participants had SCD (1.81 cases per 1000 person-years) in the ARIC study. Mean C-IMT and common carotid artery intima-media thickness were associated with risk of SCD after adjustment for traditional risk factors and time-varying adjustors: hazard ratios (HRs) with 95% CIs for fourth versus first quartile were 1.64 (1.15-2.63) and 1.49 (1.05-2.11), respectively. In CHS, 302 participants developed SCD (4.64 cases per 1000 person-years) over 13.1 years. Maximum C-IMT was associated with risk of SCD after adjustment: HR (95% CI) for fourth versus first quartile was 1.75 (1.22-2.51). Presence of plaque was associated with 35% increased risk of SCD: HR (95% CI) of 1.37 (1.13-1.67) in the ARIC study and 1.32 (1.04-1.68) in CHS. Conclusions C-IMT was associated with risk of SCD in 2 biracial community-based cohorts. C-IMT may be used as a marker of SCD risk and potentially to initiate early therapeutic interventions to mitigate the risk.



J Am Heart Assoc: 19 Oct 2020; 9:e016981
Suzuki T, Wang W, Wilsdon A, Butler KR, ... Sotoodehnia N, Mosley TH
J Am Heart Assoc: 19 Oct 2020; 9:e016981 | PMID: 32975158
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Abstract

Association of Changes in Cardiovascular Health Metrics and Risk of Subsequent Cardiovascular Disease and Mortality.

Gaye B, Tajeu GS, Vasan RS, Lassale C, ... Singh-Manoux A, Jouven X

Background The extent to which change in cardiovascular health (CVH) in midlife reduces risk of subsequent cardiovascular disease and mortality is unclear. Methods and Results CVH was computed at 2 ARIC (Atherosclerosis Risk in Communities) study visits in 1987 to 1989 and 1993 to 1995, using 7 metrics (smoking, body mass index, total cholesterol, blood glucose, blood pressure, physical activity, and diet), each classified as poor, intermediate, and ideal. Overall CVH was classified as poor, intermediate, and ideal to correspond to 0 to 2, 3 to 4, and 5 to 7 metrics at ideal levels. There 10 038 participants, aged 44 to 66 years that were eligible. From the first to the second study visit, there was an improvement in overall CVH for 17% of participants and a decrease in CVH for 21% of participants. At both study visits, 28%, 27%, and 6% had poor, intermediate, and ideal overall CVH, respectively. Compared with those with poor CVH at both visits, the risk of cardiovascular disease (hazard ratio [HR], 0.26; 95% CI, 0.20-0.34) and mortality (HR, 0.35; 95% CI, 0.29-0.44) was lowest in those with ideal CVH at both measures. Improvement from poor to intermediate/ideal CVH was also associated with a lower risk of cardiovascular disease (HR, 0.67; 95% CI, 0.59-0.75) and mortality (HR, 0.80; 95% CI, 0.72-0.89). Conclusions Improvement in CVH or stable ideal CVH, compared with those with poor CVH over time, is associated with a lower risk of incident cardiovascular disease and all-cause mortality. The change in smoking status and cholesterol may have accounted for a large part of the observed association.



J Am Heart Assoc: 19 Oct 2020; 9:e017458
Gaye B, Tajeu GS, Vasan RS, Lassale C, ... Singh-Manoux A, Jouven X
J Am Heart Assoc: 19 Oct 2020; 9:e017458 | PMID: 32985301
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Abstract

Sex Differences in Modifiable Risk Factors and Severity of Coronary Artery Disease.

Manfrini O, Yoon J, van der Schaar M, Kedev S, ... Cenko E, Bugiardini R

Background It is still unknown whether traditional risk factors may have a sex-specific impact on coronary artery disease (CAD) burden. Methods and Results We identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries; Clini​calTr​ials.gov, NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between traditional risk factors and severity of CAD and its relationship with 30-day mortality. Relative risk (RR) ratios and 95% CIs were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Estimates were compared by test of interaction on the log scale. Severity of CAD was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD. The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49 (95% CI, 0.41-0.60) and among those with diabetes mellitus was 0.89 (95% CI, 0.62-1.29), with an interaction by diabetes mellitus status of=0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41-0.61) in nonsmokers to 0.75 (95% CI, 0.54-1.03) in current smokers, with an interaction by smoking status of =0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR, 1.75; 95% CI, 1.48-2.07). No sex differences in mortality were observed in patients with nonobstructive CAD. Conclusions Obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01218776.



J Am Heart Assoc: 19 Oct 2020; 9:e017235
Manfrini O, Yoon J, van der Schaar M, Kedev S, ... Cenko E, Bugiardini R
J Am Heart Assoc: 19 Oct 2020; 9:e017235 | PMID: 32981423
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Abstract

Blood Pressure and Outcomes in Patients With Different Etiologies of Intracerebral Hemorrhage: A Multicenter Cohort Study.

Zhang S, Wang Z, Zheng A, Yuan R, ... Wu B, Liu M

Background We aimed to investigate the association between blood pressure (BP) and outcomes in intracerebral hemorrhage (ICH) subtypes with different etiologies. Methods and Results A total of 5656 in-hospital patients with spontaneous ICH were included between January 2012 and December 2016 in a prospective multicenter cohort study. Etiological subtypes of ICH were assigned using SMASH-U (structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined) classification. Elevated systolic BP was defined as ≥140 mm Hg. Hypertension was defined as elevated BP for >1 month before the onset of ICH. The primary outcomes were measured as 1-month survival rate and 3-month mortality. A total of 5380 patients with ICH were analyzed, of whom 4052 (75.3%) had elevated systolic BP on admission and 3015 (56.0%) had hypertension. In multinomial analysis of patients who passed away by 3 months, systolic BP on admission was significantly different in cerebral amyloid angiopathy (<0.001), structural lesion (<0.001), and undetermined subtypes (=0.003), compared with the hypertensive angiopathy subtype. Elevated systolic BP was dose-responsively associated with higher 3-month mortality in hypertensive angiopathy (=0.013) and undetermined (=0.005) subtypes. In cerebral amyloid angiopathy, hypertension history had significant inverse association with 3-month mortality (adjusted odds ratio, 0.37, 95% CI, 0.20-0.65; <0.001). Similarly, adjusted Cox regression indicated decreased risk of 1-month survival rate in the presence of hypertension in patients with cerebral amyloid angiopathy (adjusted hazard ratio, 0.47; 95% CI, 0.24-0.92; =0.027). Conclusions This study suggests that the association between BP and ICH outcomes might specifically depend on its subtypes, and cerebral amyloid angiopathy might be pathologically distinctive from the others. Future studies of individualized BP-lowering strategy are needed to validate our findings.



J Am Heart Assoc: 19 Oct 2020; 9:e016766
Zhang S, Wang Z, Zheng A, Yuan R, ... Wu B, Liu M
J Am Heart Assoc: 19 Oct 2020; 9:e016766 | PMID: 32924756
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Abstract

Effects of Home-Based Cardiac Rehabilitation on Time to Enrollment and Functional Status in Patients With Ischemic Heart Disease.

Schopfer DW, Whooley MA, Allsup K, Pabst M, ... Duvernoy CS, Forman DE

Background Cardiac rehabilitation is an established performance measure for adults with ischemic heart disease, but patient participation is remarkably low. Home-based cardiac rehabilitation (HBCR) may be more practical and feasible, but evidence regarding its efficacy is limited. We sought to compare the effects of HBCR versus facility-based cardiac rehabilitation (FBCR) on functional status in patients with ischemic heart disease. Methods and Results This was a pragmatic trial of 237 selected patients with a recent ischemic heart disease event, who enrolled in HBCR or FBCR between August 2015 and September 2017. The primary outcome was 3-month change in distance completed on a 6-minute walk test. Secondary outcomes included rehospitalization as well as patient-reported physical activity, quality of life, and self-efficacy. Characteristics of the 116 patients enrolled in FBCR and 121 enrolled in HBCR were similar, except the mean time from index event to enrollment was shorter for HBCR (25 versus 77 days; <0.001). As compared with patients undergoing FBCR, those in HBCR achieved greater 3-month gains in 6-minute walk test distance (+95 versus +41 m; <0.001). After adjusting for demographics, comorbid conditions, and indication, the mean change in 6-minute walk test distance remained significantly greater for patients enrolled in HBCR (+101 versus +40 m; <0.001). HBCR participants reported greater improvements in quality of life and physical activity but less improvement in exercise self-efficacy. There were no deaths or cardiovascular hospitalizations. Conclusions Patients enrolled in HBCR achieved greater 3-month functional gains than those enrolled in FBCR. Our data suggest that HBCR may safely derive equivalent benefits in exercise capacity and overall program efficacy in selected patients. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02105246.



J Am Heart Assoc: 19 Oct 2020; 9:e016456
Schopfer DW, Whooley MA, Allsup K, Pabst M, ... Duvernoy CS, Forman DE
J Am Heart Assoc: 19 Oct 2020; 9:e016456 | PMID: 32954885
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Abstract

Time-Varying Depressive Symptoms and Cardiovascular and All-Cause Mortality: Does the Risk Vary by Age or Sex?

Bryant KB, Jannat-Khah DP, Cornelius T, Khodneva Y, ... Safford MM, Moise N

Background Depressive symptoms are associated with mortality. Data regarding moderation of this effect by age and sex are inconsistent, however. We aimed to identify whether age and sex modify the association between depressive symptoms and all-cause and cardiovascular disease (CVD) mortality. Methods and Results The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort of Black and White individuals recruited between 2003 and 2007. Associations between time-varying depressive symptoms (Center for Epidemiologic Studies Depression scale score ≥4 versus <4) and all-cause and CVD mortality were measured using Cox proportional hazard models adjusting for demographic and clinical risk factors. All results were stratified by age or sex and by self-reported health status. Of 29 491 participants, 3253 (11%) had baseline elevated depressive symptoms. Mean age was 65 (9.4) years, with 55.1% of participants female, 41.1% Black, and 46.4% had excellent/very good health. Depressive symptoms were measured at baseline, on average 4.9 (SD, 1.5), then 2.1 (SD, 0.4) years later. Neither age nor sex moderated the association between elevated time-varying depressive symptoms and all-cause or CVD mortality (all-cause: age 45-64 years adjusted hazard ratio [aHR], 1.38; 95% CI, 1.18-1.61 versus age ≥65 years aHR,1.36; 95% CI, 1.23-1.50; =0.05; CVD: age 45-64 years aHR, 1.17; 95% CI, 0.90-1.53 versus age ≥65 years aHR, 1.26; 95% CI, 1.06-1.50; =0.54; all-cause: males aHR, 1.46; 95% CI, 1.29-1.64 versus female aHR, 1.34; 95% CI, 1.19-1.50; =0.35; CVD: male aHR, 1.32; 95% CI, 1.08-1.62 versus female aHR, 1.22; 95% CI, 1.00-1.47; =0.64). Similar results were observed when stratified by self-reported health status. Conclusions Depressive symptoms confer mortality risk regardless of age and sex, including individuals who report excellent/very good health.



J Am Heart Assoc: 19 Oct 2020; 9:e016661
Bryant KB, Jannat-Khah DP, Cornelius T, Khodneva Y, ... Safford MM, Moise N
J Am Heart Assoc: 19 Oct 2020; 9:e016661 | PMID: 32981424
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Abstract

Effect of Deep Hypothermic Circulatory Arrest Versus Moderate Hypothermic Circulatory Arrest in Aortic Arch Surgery on Postoperative Renal Function: A Systematic Review and Meta-Analysis.

Cao L, Guo X, Jia Y, Yang L, Wang H, Yuan S

Background Moderate hypothermic circulatory arrest (MHCA) has been widely used in aortic arch surgery. However, the renal function after MHCA remains controversial. We performed a systematic review and meta-analysis direct comparison of the postoperative renal function of MHCA versus deep hypothermic circulatory arrest (DHCA) in aortic arch surgery. Methods and Results We searched PubMed, Embase, and the Cochrane Library for postoperative renal function after aortic arch surgery with using MHCA and DHCA, published from inception to January 31, 2020. The primary outcome was renal failure. Secondary outcomes were the need for renal therapy and other major postoperative outcomes. The random-effects model was used for all comparisons to pool the estimates. A total of 14 observational studies with 4142 patients were included. Compared with DHCA, MHCA significantly reduced the incidence of renal failure (odds ratio [OR], 0.76; 95% CI, 0.61-0.94; =0.011; I=0.0%) and the need of renal replacement (OR, 0.68; 95% CI, 0.48-0.97; =0.034; I=0.0%). Subgroup analysis showed that when the hypothermic circulatory arrest time was <30 minutes, the incidence of renal failure in MHCA group was significantly lower than that in DHCA group (OR, 0.73; 95% CI, 0.54-0.99; =0.040; I=1.1%), whereas an insignificant difference between 2 groups when hypothermic circulatory arrest time was >30 minutes (OR, 0.76; 95% CI, 0.51-1.13; =0.169; I=17.3%). Conclusions MHCA compared with DHCA reduces the incidence of renal failure and the need for renal replacement. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020169348.



J Am Heart Assoc: 19 Oct 2020; 9:e017939
Cao L, Guo X, Jia Y, Yang L, Wang H, Yuan S
J Am Heart Assoc: 19 Oct 2020; 9:e017939 | PMID: 32990132
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Abstract

Associations of Carotid Intima-Media Thickness and Plaque Heterogeneity With the Risks of Stroke Subtypes and Coronary Artery Disease in the Japanese General Population: The Circulatory Risk in Communities Study.

Shimoda S, Kitamura A, Imano H, Cui R, ... Kiyama M, Iso H

Background Evidence on the associations of carotid intima-media thickness and carotid plaque characteristics with stroke subtypes and coronary artery disease risks in Asians is limited. This study investigated these associations in the Japanese general population. Methods and Results Maximum intima-media thicknesses of both the common carotid artery and internal carotid artery and carotid plaque characteristics were evaluated in 2943 Japanese subjects aged 40 to 75 years without history of cardiovascular disease. Subjects were followed up for a median of 15.1 years. Using a multivariate Cox proportional hazard model, we found that hazard ratios (HRs) and 95% CIs for the highest (≥1.07 mm) versus lowest (≤0.77 mm) quartiles of maximum intima-media thicknesses of the common carotid artery were 1.97 (1.26-3.06) for total stroke, 1.52 (0.67-3.41) for hemorrhagic stroke, 2.45 (1.41-4.27) for ischemic stroke, 3.60 (1.64-7.91) for lacunar infarction, 1.53 (0.69-3.41) for nonlacunar cerebral infarction, 2.68 (1.24-5.76) for coronary artery disease, and 2.11 (1.44-3.12) for cardiovascular disease (similar results were found for maximum intima-media thicknesses of the internal carotid artery). HRs(95% CIs) for heterogeneous plaque versus no plaque were 1.58 (1.09-2.30) for total stroke, 1.25 (0.58-2.70) for hemorrhagic stroke, 1.74 (1.13-2.67) for ischemic stroke, 1.84 (1.03-3.19) for lacunar infarction, 1.58 (0.80-3.11) for nonlacunar cerebral infarction, 2.11 (1.20-3.70) for coronary artery disease, and 1.71 (1.25-2.35) for cardiovascular disease. Conclusions Maximum intima-media thicknesses of the common carotid artery, maximum intima-media thicknesses of the internal carotid artery, and heterogeneous plaque were associated with the risks of stroke, lacunar infarction, coronary artery disease, and cardiovascular disease in Asians.



J Am Heart Assoc: 19 Oct 2020; 9:e017020
Shimoda S, Kitamura A, Imano H, Cui R, ... Kiyama M, Iso H
J Am Heart Assoc: 19 Oct 2020; 9:e017020 | PMID: 32990124
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Abstract

Risk Model for Decline in Activities of Daily Living Among Older Adults Hospitalized With Acute Myocardial Infarction: The SILVER-AMI Study.

Hajduk AM, Dodson JA, Murphy TE, Tsang S, ... Brush JE, Chaudhry SI

Background Functional decline (ie, a decrement in ability to perform everyday activities necessary to live independently) is common after acute myocardial infarction (AMI) and associated with poor long-term outcomes; yet, we do not have a tool to identify older AMI survivors at risk for this important patient-centered outcome. Methods and Results We used data from the prospective SILVER-AMI (Comprehensive Evaluation of Risk Factors in Older Patients With Acute Myocardial Infarction) study of 3041 patients with AMI, aged ≥75 years, recruited from 94 US hospitals. Participants were assessed during hospitalization and at 6 months to collect data on demographics, geriatric impairments, psychosocial factors, and activities of daily living. Clinical variables were abstracted from the medical record. Functional decline was defined as a decrement in ability to independently perform essential activities of daily living (ie, bathing, dressing, transferring, and ambulation) from baseline to 6 months postdischarge. The mean age of the sample was 82±5 years; 57% were men, 90% were White, and 13% reported activity of daily living decline at 6 months postdischarge. The model identified older age, longer hospital stay, mobility impairment during hospitalization, preadmission physical activity, and depression as risk factors for decline. Revascularization during AMI hospitalization and ability to walk a quarter mile before AMI were associated with decreased risk. Model discrimination (c=0.78) and calibration were good. Conclusions We identified a parsimonious model that predicts risk of activity of daily living decline among older patients with AMI. This tool may aid in identifying older patients with AMI who may benefit from restorative therapies to optimize function after AMI.



J Am Heart Assoc: 19 Oct 2020; 9:e015555
Hajduk AM, Dodson JA, Murphy TE, Tsang S, ... Brush JE, Chaudhry SI
J Am Heart Assoc: 19 Oct 2020; 9:e015555 | PMID: 33000681
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Abstract

Relation of Different Fruit and Vegetable Sources With Incident Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Zurbau A, Au-Yeung F, Blanco Mejia S, Khan TA, ... Jenkins DJA, Sievenpiper JL

Background Public health policies reflect concerns that certain fruit sources may not have the intended benefits and that vegetables should be preferred to fruit. We assessed the relation of fruit and vegetable sources with cardiovascular outcomes using a systematic review and meta-analysis of prospective cohort studies. Methods and Results MEDLINE, EMBASE, and Cochrane were searched through June 3, 2019. Two independent reviewers extracted data and assessed study quality (Newcastle-Ottawa Scale). Data were pooled (fixed effects), and heterogeneity (Cochrane-Q and I) and certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. Eighty-one cohorts involving 4 031 896 individuals and 125 112 cardiovascular events were included. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (risk ratio, 0.93 [95% CI, 0.89-0.96]; 0.91 [0.88-0.95]; and 0.94 [0.90-0.97], respectively), coronary heart disease (0.88 [0.83-0.92]; 0.88 [0.84-0.92]; and 0.92 [0.87-0.96], respectively), and stroke (0.82 [0.77-0.88], 0.82 [0.79-0.85]; and 0.88 [0.83-0.93], respectively) incidence. Total fruit and vegetables, fruit, and vegetables were associated with decreased cardiovascular disease (0.89 [0.85-0.93]; 0.88 [0.86-0.91]; and 0.87 [0.85-0.90], respectively), coronary heart disease (0.81 [0.72-0.92]; 0.86 [0.82-0.90]; and 0.86 [0.83-0.89], respectively), and stroke (0.73 [0.65-0.81]; 0.87 [0.84-0.91]; and 0.94 [0.90-0.99], respectively) mortality. There were greater benefits for citrus, 100% fruit juice, and pommes among fruit sources and allium, carrots, cruciferous, and green leafy among vegetable sources. No sources showed an adverse association. The certainty of the evidence was \"very low\" to \"moderate,\" with the highest for total fruit and/or vegetables, pommes fruit, and green leafy vegetables. Conclusions Fruits and vegetables are associated with cardiovascular benefit, with some sources associated with greater benefit and none showing an adverse association. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03394339.



J Am Heart Assoc: 19 Oct 2020; 9:e017728
Zurbau A, Au-Yeung F, Blanco Mejia S, Khan TA, ... Jenkins DJA, Sievenpiper JL
J Am Heart Assoc: 19 Oct 2020; 9:e017728 | PMID: 33000670
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Abstract

Nondietary Cardiovascular Health Metrics With Patient Experience and Loss of Productivity Among US Adults Without Cardiovascular Disease: The Medical Expenditure Panel Survey 2006 to 2015.

Tibuakuu M, Okunrintemi V, Savji N, Stone NJ, ... Blumenthal RS, Michos ED

Background The American Heart Association 2020 Impact Goals aimed to promote population health through emphasis on cardiovascular health (CVH). We examined the association between nondietary CVH metrics and patient-reported outcomes among a nationally representative sample of US adults without cardiovascular disease. Methods and Results We included adults aged ≥18 years who participated in the Medical Expenditure Panel Survey between 2006 and 2015. CVH metrics were scored 1 point for each of the following: not smoking, being physically active, normal body mass index, no hypertension, no diabetes mellitus, and no dyslipidemia, or 0 points if otherwise. Diet was not assessed in Medical Expenditure Panel Survey. Patient-reported outcomes were obtained by telephone survey and included questions pertaining to patient experience and health-related quality of life. Regression models were used to compare patient-reported outcomes based on CVH, adjusting for sociodemographic factors and comorbidities. There were 177 421 Medical Expenditure Panel Survey participants (mean age, 45 [17] years) representing ~187 million US adults without cardiovascular disease. About 12% (~21 million US adults) had poor CVH. Compared with individuals with optimal CVH, those with poor CVH had higher odds of reporting poor patient-provider communication (odds ratio, 1.14; 95% CI, 1.05-1.24), poor healthcare satisfaction (odds ratio, 1.15; 95% CI, 1.08-1.22), poor perception of health (odds ratio, 5.89; 95% CI, 5.35-6.49), at least 2 disability days off work (odds ratio, 1.39; 95% CI, 1.30-1.48), and lower health-related quality of life scores. Conclusions Among US adults without cardiovascular disease, meeting a lower number of ideal CVH metrics is associated with poor patient-reported healthcare experience, poor perception of health, and lower health-related quality of life. Preventive measures aimed at optimizing ideal CVH metrics may improve patient-reported outcomes among this population.



J Am Heart Assoc: 19 Oct 2020; 9:e016744
Tibuakuu M, Okunrintemi V, Savji N, Stone NJ, ... Blumenthal RS, Michos ED
J Am Heart Assoc: 19 Oct 2020; 9:e016744 | PMID: 32998625
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Abstract

Association of Isolated Diastolic Hypertension Based on the Cutoff Value in the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines With Subsequent Cardiovascular Events in the General Population.

Kaneko H, Itoh H, Yotsumoto H, Kiriyama H, ... Yasunaga H, Komuro I

Background The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines lowered the threshold of blood pressure (BP) for hypertension to 130/80 mm Hg. However, the clinical significance of isolated diastolic hypertension (IDH) according to the cutoff value of the 2017 ACC/AHA guidelines was uncertain. Methods and Results We analyzed the claims database of Japan Medical Data Center (a nationwide epidemiological database). We excluded individuals who were aged <20 years, had systolic hypertension, were taking antihypertensive medication, or had prevalent cardiovascular disease, and studied 1 746 493 individuals (mean age, 42.9±10.7 years; 961 097 men [55.0%]). The average observational period was 1107±855 days. Stage 1 IDH, defined as diastolic BP 80 to 89 mm Hg, and stage 2 IDH, defined as diastolic BP ≥90 mm Hg, were found in 230 513 (13.2%) and 16 159 (0.9%) individuals, respectively. Compared with individuals with normal diastolic BP, individuals with stage 1 and stage 2 IDH were older and more likely to be men. Prevalence of classic risk factors was higher in patients with IDH. Kaplan-Meier curves showed that stage 1 and stage 2 IDH were associated with a higher incidence of cardiovascular events, defined as myocardial infarction, angina pectoris, and stroke. Multivariable analysis showed that stage 1 (hazard ratio [HR], 1.17) and stage 2 (HR, 1.28) IDH were independently associated with a higher incidence of cardiovascular events. Subgroup analyses showed that the association of IDH with cardiovascular events was seen irrespective of age and sex. Conclusions The analysis of a nationwide epidemiological database showed that IDH based on the cutoff value in the 2017 ACC/AHA BP guidelines was associated with an elevated risk of subsequent cardiovascular events.



J Am Heart Assoc: 19 Oct 2020; 9:e017963
Kaneko H, Itoh H, Yotsumoto H, Kiriyama H, ... Yasunaga H, Komuro I
J Am Heart Assoc: 19 Oct 2020; 9:e017963 | PMID: 32993440
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Abstract

Trends in Reoperative Coronary Artery Bypass Graft Surgery for Older Adults in the United States, 1998 to 2017.

Mori M, Wang Y, Murugiah K, Khera R, ... Geirsson A, Krumholz HM

Background The likelihood of undergoing reoperative coronary artery bypass graft surgery (CABG) is important for older patients who are considering first-time CABG. Trends in the reoperative CABG for these patients are unknown. Methods and Results We used the Medicare fee-for-service inpatient claims data of adults undergoing isolated first-time CABG between 1998 and 2017. The primary outcome was time to first reoperative CABG within 5 years of discharge from the index surgery, treating death as a competing risk. We fitted a Cox regression to model the likelihood of reoperative CABG as a function of patient baseline characteristics. There were 1 666 875 unique patients undergoing first-time isolated CABG and surviving to hospital discharge. The median (interquartile range) age of patients did not change significantly over time (from 74 [69-78] in 1998 to 73 [69-78] in 2017); the proportion of women decreased from 34.8% to 26.1%. The 5-year rate of reoperative CABG declined from 0.77% (95% CI, 0.72%-0.82%) in 1998 to 0.23% (95% CI, 0.19%-0.28%) in 2013. The annual proportional decline in the 5-year rate of reoperative CABG overall was 6.6% (95% CI, 6.0%-7.1%) nationwide, which did not differ across subgroups, except the non-white non-black race group that had an annual decline of 8.5% (95% CI, 6.2%-10.7%). Conclusions Over a recent 20-year period, the Medicare fee-for-service patients experienced a significant decline in the rate of reoperative CABG. In this cohort of older adults, the rate of declining differed across demographic subgroups.



J Am Heart Assoc: 12 Oct 2020:e016980; epub ahead of print
Mori M, Wang Y, Murugiah K, Khera R, ... Geirsson A, Krumholz HM
J Am Heart Assoc: 12 Oct 2020:e016980; epub ahead of print | PMID: 33045889
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Abstract

Patients With Acute Ischemic Stroke Who Receive Brain Magnetic Resonance Imaging Demonstrate Favorable In-Hospital Outcomes.

Lee H, Yang Y, Liu B, Castro SA, Shi T

Background Use of inpatient brain magnetic resonance imaging (MRI) in patients with acute ischemic stroke is highly institution dependent and has been associated with increased length and cost of hospital stay. We examined whether inpatient brain MRI in patients with acute ischemic stroke is associated with improved clinical outcomes to justify its resource requirements. Methods and Results The National Inpatient Sample database was queried retrospectively to find 94 003 patients who were admitted for acute ischemic stroke and then received inpatient brain MRI between 2012 and 2014. Multivariable regression analysis was performed with respect to a control group to assess for differences in the rates of inpatient mortality and complications, as well as the length and cost of hospital stay based on brain MRI use. Inpatient brain MRI was independently associated with lower rates of inpatient mortality (1.67% versus 3.09%; adjusted odds ratio [OR], 0.60; 95% CI, 0.53-0.68; <0.001), gastrostomy (2.28% versus 2.89%; adjusted OR, 0.82; 95% CI, 0.73-0.93; <0.001), and mechanical ventilation (1.97% versus 2.82%; adjusted OR, 0.68; 95% CI, 0.60-0.77; <0.001). Brain MRI was independently associated with ≈0.32 days (8%) and $1131 (11%) increase in the total length (<0.001) and cost (<0.001) of hospital stay, respectively. Conclusions Inpatient brain MRI in patients with acute ischemic stroke is associated with substantial decrease in the rates of inpatient mortality and complications, at the expense of marginally increased length and cost of hospitalization.



J Am Heart Assoc: 09 Oct 2020:e016987; epub ahead of print
Lee H, Yang Y, Liu B, Castro SA, Shi T
J Am Heart Assoc: 09 Oct 2020:e016987; epub ahead of print | PMID: 33043760
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Abstract

Regulator of G-Protein Signaling 5 Maintains Brain Endothelial Cell Function in Focal Cerebral Ischemia.

Sladojevic N, Yu B, Liao JK

Background Regulator of G-protein signaling 5 (RGS5) is a negative modulator of G-protein-coupled receptors. The role of RGS5 in brain endothelial cells is not known. We hypothesized that RGS5 in brain microvascular endothelial cells may be an important mediator of blood-brain barrier function and stroke severity after focal cerebral ischemia. Methods and Results Using a transient middle cerebral artery occlusion model, we found that mice with global and endothelial-specific deletion ofexhibited larger cerebral infarct size, greater neurological motor deficits, and increased brain edema. In our in vitro models, we observed increased G activity and elevated intracellular Ca levels in brain endothelial cells. Furthermore, the loss of endothelial RGS5 leads to decreased endothelial NO synthase expression and phosphorylation, relocalization of endothelial tight junction proteins, and increased cell permeability. Indeed, RGS5 deficiency leads to increased Rho-associated kinase and myosin light chain kinase activity, which were partially reversed in our in vitro model by pharmacological inhibition of G, metabotropic glutamate receptor 1, and ligand-gated ionotropic glutamate receptor. Conclusions Our findings indicate that endothelial RGS5 plays a novel neuroprotective role in focal cerebral ischemia. Loss of endothelial RGS5 leads to hyperresponsiveness to glutamate signaling pathways, enhanced Rho-associated kinase- and myosin light chain kinase-mediated actin-cytoskeleton reorganization, endothelial dysfunction, tight junction protein relocalization, increased blood-brain barrier permeability, and greater stroke severity. These findings suggest that preservation of endothelial RGS5 may be an important therapeutic strategy for maintaining blood-brain barrier integrity and limiting the severity of ischemic stroke.



J Am Heart Assoc: 14 Sep 2020; 9:e017533
Sladojevic N, Yu B, Liao JK
J Am Heart Assoc: 14 Sep 2020; 9:e017533 | PMID: 32875943
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Abstract

Cardiac Conduction Disorders as Markers of Cardiac Events in Myotonic Dystrophy Type 1.

Itoh H, Hisamatsu T, Tamura T, Segawa K, ... Takahashi MP, Matumura T

Background Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1. Methods and Results This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine-thymine-guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow-up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow-up period of 87 months (Q1-Q3, 37-138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22-15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9-7.19, <0.05) or QRS duration ≥120 ms (HR, 9.41; 95% CI, 2.62-33.77,< 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval <240 ms or QRS duration <120 ms; these cardiac conduction parameters were not related to sudden death. Conclusions Cardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted.



J Am Heart Assoc: 30 Aug 2020; 9:e015709
Itoh H, Hisamatsu T, Tamura T, Segawa K, ... Takahashi MP, Matumura T
J Am Heart Assoc: 30 Aug 2020; 9:e015709 | PMID: 32812471
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Abstract

Factor VII Activating Protease Expression in Human Platelets and Accumulation in Symptomatic Carotid Plaque.

Parahuleva MS, Worsch M, Euler G, Choukeir M, ... Schieffer B, Markus B

Background Factor VII activating protease (FSAP) is of interest as a marker for vascular inflammation and plaque destabilization. The aim of this study was to analyze the expression profile of FSAP in endarterectomy specimens that were taken from patients with asymptomatic and symptomatic carotid atherosclerotic plaques and to compare them with circulating FSAP levels. Methods and Results Plasma FSAP concentration, activity, and mRNA expression were measured in endarterectomy specimens and in monocytes and platelets. Plaque and plasma FSAP levels were higher in symptomatic patients (n=10) than in asymptomatic patients (n=14). Stronger FSAP immunostaining was observed in advanced symptomatic lesions, in intraplaque hemorrhage-related structures, and in lipid-rich areas within the necrotic core. FSAP was also colocalized with monocytes and macrophages (CD11b/CD68-positive cells) and platelets (CD41-positive cells) of the plaques. Moreover, human platelets expressed FSAP in vitro, at both the mRNA and protein levels. Expression is stimulated by thrombin receptor-activating peptide and ADP and reduced by acetylsalicylic acid. Conclusions Plasma FSAP levels were significantly increased in patients with symptomatic carotid stenosis and thus may be involved in plaque development This plaque-associated FSAP may be produced by platelets or macrophages or may be taken up from the circulation. To establish FSAP\'s utility as a circulating or plaque biomarker in patients with symptomatic carotid atherosclerotic plaques, further studies are needed.



J Am Heart Assoc: 30 Aug 2020; 9:e016445
Parahuleva MS, Worsch M, Euler G, Choukeir M, ... Schieffer B, Markus B
J Am Heart Assoc: 30 Aug 2020; 9:e016445 | PMID: 32856552
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Abstract

Time-Dependent Cardiovascular Treatment Benefit Model for Lipid-Lowering Therapies.

Khan I, Peterson ED, Cannon CP, Sedita LE, Edelberg JM, Ray KK

Background With the availability of new lipid-lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time-dependent model from published randomized controlled trials summarizing the relationship between low-density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. Methods and Results A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low-density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time-dependent model had better predictions than cholesterol treatment trialists\' estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ≥2% with intensive treatment with high-intensity statin, ezetimibe, and high-dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high- or moderate-intensity statin alone were achieved in higher-risk populations with 2 to 5 years of treatment, and lower-risk populations with 9 to 11 years of treatment. Conclusions The time-dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid-lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid-lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.



J Am Heart Assoc: 03 Aug 2020; 9:e016506
Khan I, Peterson ED, Cannon CP, Sedita LE, Edelberg JM, Ray KK
J Am Heart Assoc: 03 Aug 2020; 9:e016506 | PMID: 32720582
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Abstract

Outcomes of Reoperative Coronary Artery Bypass Graft Surgery in the United States.

Elbadawi A, Hamed M, Elgendy IY, Omer MA, ... Brilakis E, Jneid H

Background There is a paucity of data on the trends and outcomes of reoperative coronary artery bypass graft (CABG) surgery during the current decade in the United States. Methods and Results We queried the National Inpatient Sample database (2002-2016) for all hospitalizations with isolated CABG procedure. We reported the temporal trends and outcomes of reoperative CABG versus primary CABG procedures. The main outcome was in-hospital mortality. Among 3 212 768 hospitalizations with CABG, 46 820 (1.5%) had reoperative CABG. Over the 15-year study period, there were no changes in the proportion of reoperative CABG (1.8% in 2002 versus 2.2% in 2016, =0.08), and the related in-hospital mortality (3.7% in 2002 versus 2.7% in 2016, =0.97). Reoperative CABG was performed in patients with increasingly higher risk profile. Compared with primary CABG, hospitalizations for reoperative CABG were associated with higher in-hospital mortality (3.2% versus 1.9%, <0.001), cardiac arrest, cardiogenic shock, vascular complications, and respiratory complications. Among hospitalizations for reoperative CABG, the predictors of higher mortality included history of heart failure and chronic kidney disease. Conclusions In this 15-year nationwide analysis, reoperative CABG procedures were increasingly performed in patients with higher risk profile. In-hospital mortality rates were relatively low and did not change during the examined period. Compared with primary CABG, reoperative CABG is associated with higher in-hospital mortality.



J Am Heart Assoc: 03 Aug 2020; 9:e016282
Elbadawi A, Hamed M, Elgendy IY, Omer MA, ... Brilakis E, Jneid H
J Am Heart Assoc: 03 Aug 2020; 9:e016282 | PMID: 32691683
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Abstract

Resource Utilization in the First 2 Years Following Operative Correction for Tetralogy of Fallot: Study Using Data From the Optum\'s De-Identified Clinformatics Data Mart Insurance Claims Database.

O\'Byrne ML, DeCost G, Katcoff H, Savla JJ, ... Faerber JA, Mercer-Rosa L

Background Despite excellent operative survival, correction of tetralogy of Fallot frequently is accompanied by residual lesions that may affect health beyond the incident hospitalization. Measuring resource utilization, specifically cost and length of stay, provides an integrated measure of morbidity not appreciable in traditional outcomes. Methods and Results We conducted a retrospective cohort study, using de-identified commercial insurance claims data, of 269 children who underwent operative correction of tetralogy of Fallot from January 2004 to September 2015 with ≥2 years of continuous follow-up (1) to describe resource utilization for the incident hospitalization and subsequent 2 years, (2) to determine whether prolonged length of stay (>7 days) in the incident hospitalization was associated with increased subsequent resource utilization, and (3) to explore whether there was regional variation in resource utilization with both direct comparisons and multivariable models adjusting for known covariates. Subjects with prolonged incident hospitalization length of stay demonstrated greater resource utilization (total cost as well as counts of outpatient visits, hospitalizations, and catheterizations) after hospital discharge (<0.0001 for each), though the number of subsequent operative and transcatheter interventions were not significantly different. Regional differences were observed in the cost of incident hospitalization as well as subsequent hospitalizations, outpatient visits, and the costs associated with each. Conclusions This study is the first to report short- and medium-term resource utilization following tetralogy of Fallot operative correction. It also demonstrates that prolonged length of stay in the initial hospitalization is associated with increased subsequent resource utilization. This should motivate research to determine whether these differences are because of modifiable factors.



J Am Heart Assoc: 03 Aug 2020; 9:e016581
O'Byrne ML, DeCost G, Katcoff H, Savla JJ, ... Faerber JA, Mercer-Rosa L
J Am Heart Assoc: 03 Aug 2020; 9:e016581 | PMID: 32691679
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Abstract

Association Between the Gut Microbiota and Blood Pressure in a Population Cohort of 6953 Individuals.

Palmu J, Salosensaari A, Havulinna AS, Cheng S, ... Lahti L, Niiranen TJ

Background Several small-scale animal studies have suggested that gut microbiota and blood pressure (BP) are linked. However, results from human studies remain scarce and conflicting. We wanted to elucidate the multivariable-adjusted association between gut metagenome and BP in a large, representative, well-phenotyped population sample. We performed a focused analysis to examine the previously reported inverse associations between sodium intake andabundance and betweenabundance and BP. Methods and Results We studied a population sample of 6953 Finns aged 25 to 74 years (mean age, 49.2±12.9 years; 54.9% women). The participants underwent a health examination, which included BP measurement, stool collection, and 24-hour urine sampling (N=829). Gut microbiota was analyzed using shallow shotgun metagenome sequencing. In age- and sex-adjusted models, the α (within-sample) and β (between-sample) diversities of taxonomic composition were strongly related to BP indexes (<0.001 for most). In multivariable-adjusted models, β diversity was only associated with diastolic BP (=0.032). However, we observed significant, mainly positive, associations between BP indexes and 45 microbial genera (<0.05), of which 27 belong to the phylum . Interestingly, we found mostly negative associations between 19 distinctspecies and BP indexes (<0.05). Of these, greater abundance of the known probioticwas associated with lower mean arterial pressure and lower dietary sodium intake (<0.001 for both). Conclusions Although the associations between overall gut taxonomic composition and BP are weak, individuals with hypertension demonstrate changes in several genera. We demonstrate strong negative associations of certainspecies with sodium intake and BP, highlighting the need for experimental studies.



J Am Heart Assoc: 03 Aug 2020; 9:e016641
Palmu J, Salosensaari A, Havulinna AS, Cheng S, ... Lahti L, Niiranen TJ
J Am Heart Assoc: 03 Aug 2020; 9:e016641 | PMID: 32691653
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Abstract

Predictors of Atrial Fibrillation During Long-Term Implantable Cardiac Monitoring Following Cryptogenic Stroke.

Riordan M, Opaskar A, Yoruk A, Younis A, ... Goldenberg I, Aktas MK

Background Following cryptogenic stroke, guidelines recommend cardiac monitoring for occult atrial fibrillation (AF). We aimed to evaluate predictors of AF during long-term implantable cardiac monitoring. Methods and Results We studied 293 consecutive patients who underwent implantable cardiac monitor implant (Medtronic LINQ) following hospitalization for cryptogenic stroke at the University of Rochester Medical Center from January 2013 to September 2018. Multivariable Cox proportional hazards regression modeling was used to identify predictors of AF during long-term monitoring. At 36 months of follow-up, the cumulative rate of implantable cardiac monitor-detected AF events was 32% in the total study population. Multivariable analysis identified age ≥70 years as the most powerful predictor of the development of AF events during follow-up (hazard ratio, 2.28 [95% CI, 1.39-3.76]; =0.001). Replacing age with the CHADS-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex category) score resulted in a weaker association, for which each 1-point increment in the CHADS-VASC score was associated with an 18% increased risk of developing AF (95% CI, 1.00-1.38; =0.047). Consistent results were shown using Kaplan-Meier analysis by age and by the CHADSVASc score. Conclusions Cryptogenic stroke patients continue to develop AF episodes during 36 months of implantable cardiac monitoring following the index event. Age is the most powerful predictor of occult AF in this population.



J Am Heart Assoc: 03 Aug 2020; 9:e016040
Riordan M, Opaskar A, Yoruk A, Younis A, ... Goldenberg I, Aktas MK
J Am Heart Assoc: 03 Aug 2020; 9:e016040 | PMID: 32689866
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Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Di Minno A, Lupoli R, Calcaterra I, Poggio P, ... Iannuzzo G, Di Minno MND

Background Bempedoic acid (BA) is a novel lipid-lowering drug. We performed a systematic review and meta-analysis on efficacy and safety of BA compared with standard treatment in patients with hypercholesterolemia. Methods and Results Studies were systematically searched in the PubMed, Web of Science, Scopus, and EMBASE databases. Efficacy outcome was represented by percentage changes (mean difference [MD] with pertinent 95% CIs) in total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol, and hs-CRP (high-sensitivity C-reactive protein) in BA patients and controls. Seven studies were included (2767 BA-treated patients and 1469 controls), showing a more significant reduction in low-density lipoprotein cholesterol (MD, -17.5%; 95% CI, -22.9% to -12.0%), total cholesterol (MD, -10.9%; 95% CI, -13.3% to -8.5%), non-high-density lipoprotein cholesterol (MD, -12.3%; 95% CI, -15.3% to -9.20%), apolipoprotein B (MD, -10.6%; 95% CI, -13.2% to -8.02%), and hs-CRP (MD, -13.2%; 95% CI, -16.7% to -9.79%) in BA-treated patients compared with controls. Results were confirmed when separately analyzing studies on patients with high cardiovascular risk, studies on statin-intolerant patients, and studies on patients with hypercholesterolemia on maximally tolerated lipid-lowering therapy. BA-treated subjects reported a higher rate of treatment discontinuation caused by adverse effects, of gout flare, and of increase in uric acid compared with controls. On the other hand, BA-treated patients showed a lower incidence of new-onset diabetes mellitus than controls. Conclusions BA is associated with a significant reduction in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP compared with standard treatment. Documented efficacy is accompanied by an acceptable safety profile.



J Am Heart Assoc: 03 Aug 2020; 9:e016262
Di Minno A, Lupoli R, Calcaterra I, Poggio P, ... Iannuzzo G, Di Minno MND
J Am Heart Assoc: 03 Aug 2020; 9:e016262 | PMID: 32689862
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Abstract

Intracoronary Saline-Induced Hyperemia During Coronary Thermodilution Measurements of Absolute Coronary Blood Flow: An Animal Mechanistic Study.

Adjedj J, Picard F, Collet C, Bruneval P, ... De Bruyne B, Ghaleh B

Background Absolute hyperemic coronary blood flow and microvascular resistances can be measured by continuous thermodilution with a dedicated infusion catheter. We aimed to determine the mechanisms of this hyperemic response in animal. Methods and Results Twenty open chest pigs were instrumented with flow probes on coronary arteries. The following possible mechanisms of saline-induced hyperemia were explored compared with maximal hyperemia achieve with adenosine by testing: (1) various infusion rates; (2) various infusion content and temperature; (3) NO production inhibition with L-arginine methyl ester and endothelial denudation; (4) effects of vibrations generated by rotational atherectomy and of infusion through one end-hole versus side-holes. Saline infusion rates of 5, 10 and 15 mL/min did not reach maximal hyperemia as compared with adenosine. Percentage of coronary blood flow expressed in percent of the coronary blood flow after adenosine were 48±17% at baseline, 57±18% at 5 mL/min, 65±17% at 10 mL/min, 82±26% at 15 mL/min and 107±18% at 20 mL/min. Maximal hyperemia was observed during infusion of both saline at body temperature and glucose 5%, after endothelial denudation, l-arginine methyl ester administration, and after stent implantation. The activation of a Rota burr in the first millimeters of the epicardial artery also induced maximal hyperemia. Maximal hyperemia was achieved by infusion through lateral side-holes but not through an end-hole catheter. Conclusions Infusion of saline at 20 mL/min through a catheter with side holes in the first millimeters of the epicardial artery induces maximal hyperemia. The data indicate that this vasodilation is related neither to the composition/temperature of the indicator nor is it endothelial mediated. It is suggested that it could be elicited by epicardial wall vibrations.



J Am Heart Assoc: 03 Aug 2020; 9:e015793
Adjedj J, Picard F, Collet C, Bruneval P, ... De Bruyne B, Ghaleh B
J Am Heart Assoc: 03 Aug 2020; 9:e015793 | PMID: 32689859
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Abstract

Right-Sided Infective Endocarditis 2020: Challenges and Updates in Diagnosis and Treatment.

Shmueli H, Thomas F, Flint N, Setia G, Janjic A, Siegel RJ

Compared with the extensive data on left-sided infective endocarditis (IE), there is much less published information on the features and management of right-sided IE. Right-sided IE accounts for 5% to 10% of all IE cases, and compared with left-sided IE, it is more often associated with intravenous drug use, intracardiac devices, and central venous catheters, all of which has become more prevalent over the past 20 years. In this manuscript on right-sided IE we provide an up-to-date overview on the epidemiology, etiology, microbiology, potential locations of infection in the right heart, diagnosis, imaging, common complications, management, and prognosis. We present updated information on the treatment of pacemaker and device infections, infected fibrin sheaths that appear to be an easily missed source of infection after central line as well as pacemaker removal. We review current data on the AngioVac percutaneous aspiration device, which can obviate the need for surgery in patients with infected pacemaker leads and fibrin sheaths. We also focused on advanced diagnostic modalities, such as positron emission tomography/computed tomography. All of these are supported by specific case examples with detailed echocardiographic imaging from our experience.



J Am Heart Assoc: 03 Aug 2020; 9:e017293
Shmueli H, Thomas F, Flint N, Setia G, Janjic A, Siegel RJ
J Am Heart Assoc: 03 Aug 2020; 9:e017293 | PMID: 32700630
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Abstract

Possible Link Between the ABO Blood Group of Bioprosthesis Recipients and Specific Types of Structural Degeneration.

Schussler O, Lila N, Grau J, Ruel M, Lecarpentier Y, Carpentier A

Background Pigs/bovines share common antigens with humans: α-Gal, present in all pigs/bovines close to the human B-antigen; and AH-histo-blood-group antigen, identical to human AH-antigen and present only in some animals. We investigate the possible impact of patients\' ABO blood group on bioprosthesis structural valve degeneration (SVD) through calcification/pannus/tears/perforations for patients ≤60 years at implantation. Methods and Results This was a single-center study (Paris, France) that included all degenerative bioprostheses explanted between 1985 and 1998, mostly porcine bioprostheses (Carpentier-Edwards second/third porcine bioprostheses) and some bovine bioprostheses. For the period 1998 to 2014, only porcine bioprostheses with longevity ≥13 years were included (total follow-up ≥29 years). Except for blood groups, important predictive factors for SVD were prospectively collected (age at implantation/longevity/number/site/sex/SVD types) and analyzed using logistic regression. All variables were available for 500 explanted porcine bioprostheses. By multivariate analyses, the A group was associated with an increased risk of: tears (odds ratio[OR], 1.61; =0.026); pannus (OR, 1.5; =0.054), pannus with tears (OR, 1.73; =0.037), and tendency for lower risk of: calcifications (OR, 0.63; =0.087) or isolated calcification (OR, 0.67; =0.17). A-antigen was associated with lower risk of perforations (OR 0.56; =0.087). B-group patients had an increased risk of: perforations (OR, 1.73; =0.043); having a pannus that was calcified (OR, 3.0, =0.025). B-antigen was associated with a propensity for calcifications in general (OR, 1.34; =0.25). Conclusions Patient\'s ABO blood group is associated with specific SVD types. We hypothesize that carbohydrate antigens, which may or may not be common to patient and animal bioprosthetic tissue, will determine a patient\'s specific immunoreactivity with respect to xenograft tissue and thus bioprosthesis outcome in terms of SVD.



J Am Heart Assoc: 03 Aug 2020; 9:e015909
Schussler O, Lila N, Grau J, Ruel M, Lecarpentier Y, Carpentier A
J Am Heart Assoc: 03 Aug 2020; 9:e015909 | PMID: 32698708
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Combining Biomarkers and Imaging for Short-Term Assessment of Cardiovascular Disease Risk in Apparently Healthy Adults.

Gore MO, Ayers CR, Khera A, deFilippi CR, ... Levine BD, de Lemos JA

Background Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. Methods and Results We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5- and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). Conclusions A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.



J Am Heart Assoc: 03 Aug 2020; 9:e015410
Gore MO, Ayers CR, Khera A, deFilippi CR, ... Levine BD, de Lemos JA
J Am Heart Assoc: 03 Aug 2020; 9:e015410 | PMID: 32698652
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Abstract

Life Course Changes in Cardiometabolic Risk Factors Associated With Preterm Delivery: The 30-Year CARDIA Study.

Sun B, Bertolet M, Brooks MM, Hubel CA, ... Gunderson EP, Catov JM

Background Women who deliver preterm infants (<37 weeks) have excess cardiovascular risk; however, it is unclear whether the unfavorable changes in the cardiometabolic profile associated with preterm delivery initiate before, during, or after childbearing. Methods and Results We identified 1306 women (51% Black) with births between baseline (1985-1986) and year 30 in the CARDIA (Coronary Artery Risk Development in Young Adults) study. We compared life course changes in blood pressure, body mass index, waist circumference, and lipids in women with preterm deliveries (n=318) with those with all term deliveries (n=988), using piecewise linear mixed-effects models. Specifically, we evaluated group differences in rates of change before and after the childbearing period and change in level across the childbearing period. After adjusting for the covariates, women with preterm deliveries had a higher change in diastolic blood pressure across the childbearing period than those with all term deliveries (1.59 versus -0.73 mm Hg, <0.01); the rates of change did not differ by group, both prechildbearing and postchildbearing. Women with preterm deliveries had a larger body mass index increase across the childbearing period (1.66 versus 1.22 kg/m, =0.03) compared with those with all term deliveries, followed by a steeper increase after the childbearing period (0.22 versus 0.17 kg/m per year, =0.02). Conclusions Preterm delivery was associated with unfavorable patterns of change in diastolic blood pressure and adiposity that originate during the childbearing years and persist or exacerbate later in life. These adverse changes may contribute to the elevated cardiovascular risk among women with preterm delivery.



J Am Heart Assoc: 03 Aug 2020; 9:e015900
Sun B, Bertolet M, Brooks MM, Hubel CA, ... Gunderson EP, Catov JM
J Am Heart Assoc: 03 Aug 2020; 9:e015900 | PMID: 32696706
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Abstract

Effects of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Beverages on Cardiometabolic Risk Factors, Body Composition, and Sweet Taste Preference: A Randomized Controlled Trial.

Ebbeling CB, Feldman HA, Steltz SK, Quinn NL, Robinson LM, Ludwig DS

Background A 2018 American Heart Association science advisory indicated that, pending further research, artificially sweetened beverages (ASBs) may be an appropriate initial replacement for sugar-sweetened beverages (SSBs) during transition to unsweetened beverages (USBs). Methods and Results We randomly assigned 203 adults (121 males, 82 females; 91.6% retention), who habitually consumed SSBs, to 3 groups and delivered free SSBs, ASBs, or USBs to their homes for 12 months. Outcomes included serum triglyceride to high-density lipoprotein cholesterol ratio (primary), body weight, and sweet taste preference (experimental assessment, 0%-18% sucrose solutions). Change in serum triglyceride to high-density lipoprotein cholesterol ratio was not different between groups. Although overall change in weight also was not different between groups, we found effect modification (=0.006) by central adiposity. Among participants in the highest tertile of baseline trunk fat but not other tertiles, weight gain was greater (=0.002) for the SSB (4.4±1.0 kg, estimate±SE) compared with ASB (0.5±0.9 kg) or USB (-0.2±0.9 kg) group. Both sweetness threshold (-1.0±0.2% m/v; =0.005) and favorite concentration (-2.3±0.4% m/v; <0.0001) decreased in the USB group; neither changed in the SSB group. In the ASB group, sweetness threshold did not change, and favorite concentration decreased (-1.1±0.5% m/v; =0.02). Pairwise comparison between the ASB and USB groups indicated a difference in sweetness threshold (=0.015). Conclusions Replacing SSBs with noncaloric beverages for 12 months did not affect serum triglyceride to high-density lipoprotein cholesterol ratio. Among individuals with central adiposity, replacing SSBs with either ASBs or USBs lowered body weight. However, USBs may have the most favorable effect on sweet taste preference. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT01295671.



J Am Heart Assoc: 03 Aug 2020; 9:e015668
Ebbeling CB, Feldman HA, Steltz SK, Quinn NL, Robinson LM, Ludwig DS
J Am Heart Assoc: 03 Aug 2020; 9:e015668 | PMID: 32696704
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Abstract

Impact of Kidney Function on the Blood Proteome and on Protein Cardiovascular Risk Biomarkers in Patients With Stable Coronary Heart Disease.

Yang J, Brody EN, Murthy AC, Mehler RE, ... Williams SA, Ganz P

Background Chronic kidney disease (CKD) confers increased cardiovascular risk, not fully explained by traditional factors. Proteins regulate biological processes and inform the risk of diseases. Thus, in 938 patients with stable coronary heart disease from the Heart and Soul cohort, we quantified 1054 plasma proteins using modified aptamers (SOMAscan) to: (1) discern how reduced glomerular filtration influences the circulating proteome, (2) learn of the importance of kidney function to the prognostic information contained in recently identified protein cardiovascular risk biomarkers, and (3) identify novel and even unique cardiovascular risk biomarkers among individuals with CKD. Methods and Results Plasma protein levels were correlated to estimated glomerular filtration rate (eGFR) using Spearman-rank correlation coefficients. Cox proportional hazard models were used to estimate the association between individual protein levels and the risk of the cardiovascular outcome (first among myocardial infarction, stroke, heart failure hospitalization, or mortality). Seven hundred and nine (67.3%) plasma proteins correlated with eGFR at <0.05 (ρ 0.06-0.74); 218 (20.7%) proteins correlated with eGFR moderately or strongly (ρ 0.2-0.74). Among the previously identified 196 protein cardiovascular biomarkers, just 87 remained prognostic after correction for eGFR. Among patients with CKD (eGFR <60 mL/min per 1.73 m), we identified 21 protein cardiovascular risk biomarkers of which 8 are unique to CKD. Conclusions CKD broadly alters the composition of the circulating proteome. We describe protein biomarkers capable of predicting cardiovascular risk independently of glomerular filtration, and those that are prognostic of cardiovascular risk specifically in patients with CKD and even unique to patients with CKD.



J Am Heart Assoc: 03 Aug 2020; 9:e016463
Yang J, Brody EN, Murthy AC, Mehler RE, ... Williams SA, Ganz P
J Am Heart Assoc: 03 Aug 2020; 9:e016463 | PMID: 32696702
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Abstract

Treatment With a Marine Oil Supplement Alters Lipid Mediators and Leukocyte Phenotype in Healthy Patients and Those With Peripheral Artery Disease.

Schaller MS, Chen M, Colas RA, Sorrentino TA, ... Dalli J, Conte MS

Background Peripheral artery disease (PAD) is an advanced form of atherosclerosis characterized by chronic inflammation. Resolution of inflammation is a highly coordinated process driven by specialized pro-resolving lipid mediators endogenously derived from omega-3 fatty acids. We investigated the impact of a short-course, oral, enriched marine oil supplement on leukocyte phenotype and biochemical mediators in patients with symptomatic PAD and healthy volunteers. Methods and Results This was a prospective, open-label study of 5-day oral administration of an enriched marine oil supplement, assessing 3 escalating doses in 10 healthy volunteers and 10 patients with PAD. Over the course of the study, there was a significant increase in the plasma level of several lipid mediator families, total specialized pro-resolving lipid mediators, and specialized pro-resolving lipid mediator:prostaglandin ratio. Supplementation was associated with an increase in phagocytic activity of peripheral blood monocytes and neutrophils. Circulating monocyte phenotyping demonstrated reduced expression of multiple proinflammatory markers (cluster of differentiation 18, 163, 54, and 36, and chemokine receptor 2). Similarly, transcriptional profiling of monocyte-derived macrophages displayed polarization toward a reparative phenotype postsupplementation. The most notable cellular and biochemical changes over the study occurred in patients with PAD. There were strong correlations between integrated biochemical measures of lipid mediators (specialized pro-resolving lipid mediators:prostaglandin ratio) and phenotypic changes in circulating leukocytes in both healthy individuals and patients with PAD. Conclusions These data suggest that short-term enriched marine oil supplementation dramatically remodels downstream lipid mediator pathways and induces a less inflammatory and more pro-resolution phenotype in circulating leukocytes and monocyte-derived macrophages. Further studies are required to determine the potential clinical relevance of these findings in patients with PAD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02719665.



J Am Heart Assoc: 03 Aug 2020; 9:e016113
Schaller MS, Chen M, Colas RA, Sorrentino TA, ... Dalli J, Conte MS
J Am Heart Assoc: 03 Aug 2020; 9:e016113 | PMID: 32696697
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Abstract

Impact of Self-Monitoring of Blood Pressure on Processes of Hypertension Care and Long-Term Blood Pressure Control.

Bryant KB, Sheppard JP, Ruiz-Negrón N, Kronish IM, ... McManus RJ, Bellows BK

Background Self-monitoring of blood pressure (SMBP) improves blood pressure (BP) outcomes at 12-months, but information is lacking on how SMBP affects hypertension care processes and longer-term BP outcomes. Methods and Results We pooled individual participant data from 4 randomized clinical trials of SMBP in the United Kingdom (combined n=2590) with varying intensities of support. Multivariable random effects regression was used to estimate the probability of antihypertensive intensification at 12 months for usual care versus SMBP. Using these data, we simulated 5-year BP control rates using a validated mathematical model. Trial participants were mostly older adults (mean age 66.6 years, SD 9.5), male (53.9%), and predominantly white (95.6%); mean baseline BP was 151.8/85.0 mm Hg. Compared with usual care, the likelihood of antihypertensive intensification increased with both SMBP with feedback to patient or provider alone (odds ratio 1.8, 95% CI 1.2-2.6) and with telemonitoring or self-management (3.3, 2.5-4.2). Over 5 years, we estimated 33.4% BP control (<140/90 mm Hg) with usual care (95% uncertainty interval 27.7%-39.4%). One year of SMBP with feedback to patient or provider alone achieved 33.9% (28.3%-40.3%) BP control and SMBP with telemonitoring or self-management 39.0% (33.1%-45.2%) over 5 years. If SMBP interventions and associated BP control processes were extended to 5 years, BP control increased to 52.4% (45.4%-59.8 %) and 72.1% (66.5%-77.6%), respectively. Conclusions One year of SMBP plus telemonitoring or self-management increases the likelihood of antihypertensive intensification and could improve BP control rates at 5 years; continuing SMBP for 5 years could further improve BP control.



J Am Heart Assoc: 03 Aug 2020; 9:e016174
Bryant KB, Sheppard JP, Ruiz-Negrón N, Kronish IM, ... McManus RJ, Bellows BK
J Am Heart Assoc: 03 Aug 2020; 9:e016174 | PMID: 32696695
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Abstract

Dismal Outcomes and High Societal Burden of Mitral Valve Regurgitation in France in the Recent Era: A Nationwide Perspective.

Messika-Zeitoun D, Candolfi P, Vahanian A, Chan V, ... Mesana T, Enriquez-Sarano M

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population-based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In-hospital and 1-year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1-year mortality or all-cause readmission and 1-year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390-615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.



J Am Heart Assoc: 03 Aug 2020; 9:e016086
Messika-Zeitoun D, Candolfi P, Vahanian A, Chan V, ... Mesana T, Enriquez-Sarano M
J Am Heart Assoc: 03 Aug 2020; 9:e016086 | PMID: 32696692
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Abstract

Refractory Hypertension and Risks of Adverse Cardiovascular Events and Mortality in Patients With Resistant Hypertension: A Prospective Cohort Study.

Cardoso CRL, Salles GF

Background The long-term prognosis of refractory hypertension (RfHT), defined as failure to control blood pressure (BP) levels despite an antihypertensive treatment with ≥5 medications including a diuretic and mineraloreceptor antagonist, has never been evaluated. Methods and Results In a prospective cohort study with 1576 patients with resistant hypertension, patients were classified as refractory or nonrefractory based on uncontrolled clinic (or office) and ambulatory BPs during the first 2 years of follow-up. Multivariate Cox analyses examined the associations between the diagnosis of RfHT and the occurrence of total cardiovascular events (CVEs), major adverse CVEs, and cardiovascular and all-cause mortality, after adjustments for other risk factors. In total, 135 patients (8.6%) had RfHT by uncontrolled ambulatory BPs and 167 (10.6%) by uncontrolled clinic BPs. Over a median Follow-Up of 8.9 years, 338 total CVEs occurred (288 major adverse CVEs, including 124 myocardial infarctions, and 96 strokes), and 331 patients died, 196 from cardiovascular causes. The diagnosis of RfHT, using either classification by clinic or ambulatory BPs, was associated with significantly higher risks of major adverse CVEs, cardiovascular mortality, and stroke incidence, with hazard ratios varying from 1.54 to 2.14 in relation to patients with resistant nonrefractory hypertension; however, the classification based on ambulatory BPs was better in identifying higher risk patients than the classification based on clinic BP levels. Conclusions Patients with RfHT, particularly when defined by uncontrolled ambulatory BP levels, had higher risks of major adverse CVEs and mortality in relation to patients with resistant but nonrefractory hypertension, supporting the concept of refractory hypertension as a true extreme phenotype of antihypertensive treatment failure.



J Am Heart Assoc: 30 Aug 2020; 9:e017634
Cardoso CRL, Salles GF
J Am Heart Assoc: 30 Aug 2020; 9:e017634 | PMID: 32851922
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High Mortality Rates Among Patients With Non-Traumatic Intracerebral Hemorrhage and Atrial Fibrillation on Antithrombotic Therapy Are Independent of the Presence of Cerebral Amyloid Angiopathy: Insights From a Population-Based Study.

Ponamgi SP, Ward R, DeSimone CV, English S, ... Asirvatham SJ, Holmes D

Background Intracerebral hemorrhage (ICH) risk is higher in elderly patients with atrial fibrillation on antithrombotic therapy as well as those with cerebral amyloid angiopathy (CAA). We investigated if mortality among patients with atrial fibrillation on antithrombotic therapy presenting with non-traumatic ICH was influenced by underlying CAA. Methods and Results We used the Rochester Epidemiology Project to identify 6045 patients with atrial fibrillation aged >55 years on anticoagulation or antiplatelet therapy from 1995 to 2016. Seventy-four patients in this cohort presented with non-traumatic ICH. Medical records including imaging data were reviewed to identify those with CAA and record baseline variables and outcomes of interest; 38 of our 74 patients (51.4%) (mean age 81.5 years) met Modified Boston Criteria for possible or probable CAA. Twenty-six of 74 patients (35%) died during the first 30 days while 56 of the 74 (76%) patients died by 10 years follow-up after index ICH. Overall mortality was not significantly different between the CAA and non-CAA groups at any point of time during follow-up (=0.89) even amongst patients restarted on anticoagulation +/- antiplatelet (n=19) (=0.46) or those patients restarted only on antiplatelet therapy (n=22) (=0.66). Three of the 41 patients who restarted on antithrombotic therapy had a recurrent ICH; these 3 patients met criteria for possible or probable CAA. Conclusions Although more than half of our patients with atrial fibrillation on antithrombotic therapy and non-traumatic ICH met Modified Boston Criteria for CAA, CAA did not significantly influence the high mortality seen in this cohort.



J Am Heart Assoc: 03 Aug 2020; 9:e016893
Ponamgi SP, Ward R, DeSimone CV, English S, ... Asirvatham SJ, Holmes D
J Am Heart Assoc: 03 Aug 2020; 9:e016893 | PMID: 32715895
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Abstract

Prespecified Risk Criteria Facilitate Adequate Discharge and Long-Term Outcomes After Transfemoral Transcatheter Aortic Valve Implantation.

Spence MS, Baan J, Iacovelli F, Martinelli GL, ... Tamburino C, Barbanti M

Background Despite the availability of guidelines for the performance of transcatheter aortic valve implantation (TAVI), current treatment pathways vary between countries and institutions, which impact on the mean duration of postprocedure hospitalization. Methods and Results This was a prospective, multicenter registry of 502 patients to validate the appropriateness of discharge timing after transfemoral TAVI, using prespecified risk criteria from FAST-TAVI (Feasibility and Safety of Early Discharge After Transfemoral [TF] Transcatheter Aortic Valve Implantation), based on hospital events within 1-year after discharge. The end point-a composite of all-cause mortality, vascular access-related complications, permanent pacemaker implantation, stroke, cardiac rehospitalization, kidney failure, and major bleeding-was reached in 27.0% of patients (95% CI, 23.3-31.2) within 1 year after intervention; 7.5% (95% CI, 5.5-10.2) had in-hospital complications before discharge and 19.6% (95% CI, 16.3-23.4) within 1 year after discharge. Overall mortality within 1 year after discharge was 7.3% and rates of cardiac rehospitalization 13.5%, permanent pacemaker implantation 4.2%, any stroke 1.8%, vascular-access-related complications 0.7%, life-threatening bleeding 0.7%, and kidney failure 0.4%. Composite events within 1 year after discharge were observed in 18.8% and 24.3% of patients with low risk of complications/early (≤3 days) discharge and high risk and discharged late (>3 days) (concordant discharge), respectively. Event rate in patients with discordant discharge was 14.3% with low risk but discharged late and increased to 50.0% in patients with high risk but discharged in ≤3 days. Conclusions The FAST-TAVI risk assessment provides a tool for appropriate, risk-based discharge that was validated with the 1-year event rate after transfemoral TAVI. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02404467.



J Am Heart Assoc: 03 Aug 2020; 9:e016990
Spence MS, Baan J, Iacovelli F, Martinelli GL, ... Tamburino C, Barbanti M
J Am Heart Assoc: 03 Aug 2020; 9:e016990 | PMID: 32715844
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Abstract

Feasibility and Safety of Laparoscopic-Guided Epicardial Access for Ventricular Tachycardia Ablation.

Carmo AAL, Zenobio S, Santos BC, Rocha MOC, Ribeiro ALP

Background The usual approach to epicardial access in patients with Chagas cardiomyopathy and megacolon is surgical access to avoid bowel injury. However, there are concerns regarding its safety in cases of Chagas cardiomyopathy with reports of prolonged mechanical ventilation and high mortality in this clinical setting. The aim of this study was to examine feasibility and complication rates for ventricular tachycardia ablation performed with laparoscopic-guided epicardial access. Methods and Results This single center study examined complication rates of the first 11 cases of ventricular tachycardia ablation in patients with Chagas cardiomyopathy, using laparoscopic guidance to access epicardial space. All 11 patients underwent epicardial VT ablation using laparoscopic-guided epicardial access, and the complication rates were compared with historical medical reports. The main demographic features of our population were age, 63±13 years; men, 82%; and median ejection fraction, 31% (Q1=30% and Q3=46%). All patients were sent for ventricular tachycardia ablation because of medical therapy failure. The reason for laparoscopy was megacolon in 10 patients and massive liver enlargement in 1 patient. Epicardial access was achieved in all patients. Complications included 1 severe cardiogenic shock and 1 phrenic nerve paralysis. No intra-abdominal organ injury occurred; only 1 death, which was caused by progressive heart failure, was reported more than 1 month after the procedure. Conclusions Laparoscopic-guided epicardial access in the setting of ventricular tachycardia ablation and enlarged intra-abdominal organ is a simple alternative to more complex surgical access and can be performed with low complication rates.



J Am Heart Assoc: 03 Aug 2020; 9:e016654
Carmo AAL, Zenobio S, Santos BC, Rocha MOC, Ribeiro ALP
J Am Heart Assoc: 03 Aug 2020; 9:e016654 | PMID: 32715839
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Abstract

Cerebral Small-Vessel Disease and Risk of Incidence of Depression: A Meta-Analysis of Longitudinal Cohort Studies.

Fang Y, Qin T, Liu W, Ran L, ... Pan D, Wang M

Background Results of several longitudinal cohort studies suggested an association between cerebral small-vessel disease and depression. Therefore, we performed a meta-analysis to explore whether cerebral small-vessel disease imparts increased risk for incident depression. Methods and Results We searched prospective cohort studies relevant to the relationship between cerebral small-vessel disease and incident depression published through September 6, 2019, which yielded 16 cohort studies for meta-analysis based on the relative odds ratio (OR) calculated with fixed- and random-effect models. Baseline white matter hyperintensities (WMHs) (pooled OR, 1.37; 95% CI, 1.14-1.65), enlarged perivascular spaces (pooled OR, 1.33; 95% CI, 1.03-1.71), and cerebral atrophy (pooled OR, 2.83; 95% CI, 1.54-5.23) were significant risk factors for incident depression. Presence of deep WMHs (pooled OR, 1.47; 95% CI, 1.05-2.06) was a stronger predictor of depression than were periventricular WMHs (pooled OR, 1.31; 95% CI, 0.93-1.86). What\'s more, the pooled OR increased from 1.20 for the second quartile to 1.96 for the fourth quartile, indicating that higher the WMH severity brings greater risk of incident depression (25th-50th: pooled OR, 1.20; 95% CI, 0.68-2.12; 50th-75th; pooled OR, 1.42; 95% CI, 0.81-2.46; 75th-100th: OR, 1.96; 95% CI, 1.06-3.64). These results were stable to subgroup analysis for age, source of participants, follow-up time, and methods for assessing WMHs and depression. Conclusions Cerebral small-vessel disease features such as WMHs, enlarged perivascular spaces, and cerebral atrophy, especially the severity of WMHs and deep WMHs, are risk factors for incident depression.



J Am Heart Assoc: 03 Aug 2020; 9:e016512
Fang Y, Qin T, Liu W, Ran L, ... Pan D, Wang M
J Am Heart Assoc: 03 Aug 2020; 9:e016512 | PMID: 32715831
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Abstract

Macrophage NCOR1 Deficiency Ameliorates Myocardial Infarction and Neointimal Hyperplasia in Mice.

Du LJ, Sun JY, Zhang WC, Wang YL, ... Auwerx J, Duan SZ

Background NCOR1 (nuclear receptor corepressor 1) is an essential coregulator of gene transcription. It has been shown that NCOR1 in macrophages plays important roles in metabolic regulation. However, the function of macrophage NCOR1 in response to myocardial infarction (MI) or vascular wire injury has not been elucidated. Methods and Results Here, using macrophageknockout mouse in combination with a mouse model of MI, we demonstrated that macrophage NCOR1 deficiency significantly reduced infarct size and improved cardiac function after MI. In addition, macrophage NCOR1 deficiency markedly inhibited neointimal hyperplasia and vascular remodeling in a mouse model of arterial wire injury. Inflammation and macrophage proliferation were substantially attenuated in hearts and arteries of macrophageknockout mice after MI and arterial wire injury, respectively. Cultured primary macrophages from macrophageknockout mice manifested lower expression of inflammatory genes upon stimulation by interleukin-1β, interleukin-6, or lipopolysaccharide, together with much less activation of inflammatory signaling cascades including signal transducer and activator of transcription 1 and nuclear factor-κB. Furthermore, macrophageknockout macrophages were much less proliferative in culture, with inhibited cell cycle progression compared with control cells. Conclusions Collectively, our data have demonstrated that NCOR1 is a critical regulator of macrophage inflammation and proliferation and that deficiency of NCOR1 in macrophages attenuates MI and neointimal hyperplasia. Therefore, macrophage NCOR1 may serve as a potential therapeutic target for MI and restenosis.



J Am Heart Assoc: 03 Aug 2020; 9:e015862
Du LJ, Sun JY, Zhang WC, Wang YL, ... Auwerx J, Duan SZ
J Am Heart Assoc: 03 Aug 2020; 9:e015862 | PMID: 32720575
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Abstract

A Better Predictor of Acute Kidney Injury After Cardiac Surgery: The Largest Area Under the Curve Below the Oxygen Delivery Threshold During Cardiopulmonary Bypass.

Oshita T, Hiraoka A, Nakajima K, Muraki R, ... Yoshitaka H, Sakaguchi T

Background The aim of this study was to compare the predictive accuracy of acute kidney injury (AKI) after cardiac surgery using cardiopulmonary bypass for the largest area under the curve (AUC) below the oxygen delivery (DO) threshold and the cumulative AUC below the DO threshold. Methods and Results From March 2017 to October 2019, 202 patients who had undergone cardiac surgery with cardiopulmonary bypass were enrolled. The perfusion parameters were recorded every 20 seconds, and the DO (10×pump flow index [L/min per m]×[hemoglobin (g/dL)×1.36×arterial oxygen saturation (%)+partial pressure of arterial oxygen (mm Hg)×0.003]) threshold of 300 mL/min per m was considered to define sufficient DO. The nadir DO, the cumulative AUC below the [Formula: see text], and the largest AUC below the [Formula: see text] were used to predict the incidence of AKI. Postoperative AKI was observed in 12.4% of patients (25/202). By multivariable analysis, the largest AUC below the [Formula: see text] ≥880 (odds ratio [OR], 4.9; 95% CI, 1.2-21.5 [=0.022]), preoperative hemoglobin concentration ≤11.6 g/dL (OR, 7.6; 95% CI, 2.0-32.3 [=0.004]), and red blood cell transfusions during cardiopulmonary bypass ≥2 U (OR, 3.3; 95% CI, 1.0-11.1 [=0.041]) were detected as independent risk factors for AKI. Receiver operating curve analysis revealed that the largest AUC below the [Formula: see text] was more accurate to predict postoperative AKI compared with the nadir DO and the cumulative AUC below the [Formula: see text] (differences between areas, 0.0691 [=0.006] and 0.0395 [=0.001]). Conclusions These data suggest that a high AUC below the [Formula: see text] is an important independent risk factor for AKI after cardiopulmonary bypass, which could be considered for risk prediction models of AKI.



J Am Heart Assoc: 03 Aug 2020; 9:e015566
Oshita T, Hiraoka A, Nakajima K, Muraki R, ... Yoshitaka H, Sakaguchi T
J Am Heart Assoc: 03 Aug 2020; 9:e015566 | PMID: 32720572
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Abstract

Population Density Analysis of Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction in Japan.

Yamaji K, Kohsaka S, Inohara T, Numasawa Y, ... Amano T, Ikari Y

Background Despite recent progress in the treatment of ST-segment-elevation myocardial infarction, data on geographic disparities application of the evidence-based therapy remain limited. Methods and Results The J-PCI (Japanese Percutaneous Coronary Intervention) registry is a nationwide registry to assure the quality of delivered care. Between January 2014 and December 2018, 209 521 patients underwent percutaneous coronary intervention for ST-segment-elevation myocardial infarction in 1126 institutions. The patients were divided into tertiles according to the population density (PD) of the percutaneous coronary intervention institution location (low: <951.7/km, n = 69 797; medium: 951.7-4729.7/km, n = 69 750; high: ≥4729.7/km, n = 69 974). Patients treated in high PD administrative districts were younger and more likely to be male. No significant correlation was observed between PD and door-to-balloon time (regression coefficients: 0.036 per 1000 people/km; 95% CI, -0.232 to 0.304;  = 0.79). Patients treated in low-PD areas had higher crude in-hospital mortality rates than those treated in high-PD areas (low: 2.89%; medium: 2.60%; high: 2.38%;  < 0.001); PD and in-hospital mortality had a significantly inverse association, before and after adjusting for baseline characteristics (crude odds ratio [OR], 0.983 per 1000/km; 95% CI, 0.973-0.992;  < 0.001; adjusted OR, 0.980 per 1000/km; 95% CI, 0.964-0.996;  = 0.01, respectively). Higher-PD districts had more operators per institution (low: 6; interquartile range, 3-10; medium: 7; IQR, 3-13; high: 8; IQR, 5-13;  < 0.001), suggesting an inverse association with in-hospital mortality (OR, 0.992; 95% CI, 0.986-0.999;  = 0.03). Conclusions Geographic inequality was observed in in-hospital mortality of patients with ST-segment-elevation myocardial infarction who underwent percutaneous coronary intervention. Variation in the number of operators per institution, rather than traditional quality indicators (eg, door-to-balloon time) might explain the difference in in-hospital mortality.



J Am Heart Assoc: 03 Aug 2020; 9:e016952
Yamaji K, Kohsaka S, Inohara T, Numasawa Y, ... Amano T, Ikari Y
J Am Heart Assoc: 03 Aug 2020; 9:e016952 | PMID: 32720569
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Retraction to: Diversity, Inclusion, and Equity: Evolution of Race and Ethnicity Considerations for the Cardiology Workforce in the United States of America From 1969 to 2019.



For the article \"Diversity, Inclusion, and Equity: Evolution of Race and Ethnicity Considerations for the Cardiology Workforce in the United States of America From 1969 to 2019\" by Norman C. Wang (1), the American Heart Association became aware of serious concerns after publication.The author\'s institution, the University of Pittsburgh Medical Center (UPMC), has notified the Editor-in-Chief that the article contains many misconceptions and misquotes and that together those inaccuracies, misstatements, and selective misreading of source materials strip the paper of its scientific validity.will be publishing a detailed rebuttal. This retraction notice will be updated with a link to the rebuttal when it publishes. The Editor-in-Chief deeply regrets publishing the article and offers his apologies. The American Heart Association and the Editor-in-Chief have determined that the best interest of the public and the research community will be served by issuing this notice of retraction.The author does not agree to the retraction. The Editors and the American Heart Association retract the article from publication in .1. J Am Heart Assoc. 2020;9:e015959. https://doi.org/10.1161/JAHA.120.015959.



J Am Heart Assoc: 05 Aug 2020:e014602; epub ahead of print
J Am Heart Assoc: 05 Aug 2020:e014602; epub ahead of print | PMID: 32757972
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Impact:
Abstract

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From the International Kawasaki Disease Registry.

McCrindle BW, Manlhiot C, Newburger JW, Harahsheh AS, ... Dahdah N,

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CAAscore ≥2.5) was used. Time-to-event analyses were performed using the Kaplan-Meier method and Cox proportional hazard models for risk factor analysis. In patients with CAAscores ≥10, the cumulative incidence of luminal narrowing (>50% of lumen diameter), coronary artery thrombosis, and composite major adverse cardiovascular complications at 10 years was 20±3%, 18±2%, and 14±2%, respectively. No complications were observed in patients with a CAAscore <10. Higher CAAscore and a greater number of coronary artery branches affected were associated with increased risk of all types of complications. At 10 years, normalization of luminal diameter was noted in 99±4% of patients with small (2.5≤<5.0), 92±1% with medium (5.0≤<10), and 57±3% with large CAAs (≥10). CAAs in the left anterior descending and circumflex coronary artery branches were more likely to normalize. Risk factor analysis of coronary artery branch level outcomes was performed with a total of 893 affected branches withscore ≥10 in 440 patients. In multivariable regression models, hazards of luminal narrowing and thrombosis were higher for patients with CAAs of the right coronary artery and left anterior descending branches, those with CAAs that had complex architecture (other than isolated aneurysms), and those with CAAs withscores ≥20. Conclusions For patients with CAA after KD, medium-term risk of complications is confined to those with maximum CAAscores ≥10. Further risk stratification and close follow-up, including advanced imaging, in patients with large CAAs is warranted.



J Am Heart Assoc: 03 Aug 2020; 9:e016440
McCrindle BW, Manlhiot C, Newburger JW, Harahsheh AS, ... Dahdah N,
J Am Heart Assoc: 03 Aug 2020; 9:e016440 | PMID: 32750313
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Abstract

Noninvasive Prediction of Elevated Wedge Pressure in Pulmonary Hypertension Patients Without Clear Signs of Left-Sided Heart Disease: External Validation of the OPTICS Risk Score.

Jansen SMA, Huis In \'t Veld AE, Jacobs W, Grotjohan HP, ... de Man FS, Bogaard HJ

Background Although most newly presenting patients with pulmonary hypertension (PH) have elevated pulmonary artery wedge pressure, identification of so-called postcapillary PH can be challenging. A noninvasive tool predicting elevated pulmonary artery wedge pressure in patients with incident PH may help avoid unnecessary invasive diagnostic procedures. Methods and Results A combination of clinical data, ECG, and echocardiographic parameters was used to refine a previously developed left heart failure risk score in a retrospective cohort of pre- and postcapillary PH patients. This updated score (renamed the OPTICS risk score) was externally validated in a prospective cohort of patients from 12 Dutch nonreferral centers the OPTICS network. Using the updated OPTICS risk score, the presence of postcapillary PH could be predicted on the basis of body mass index ≥30, diabetes mellitus, atrial fibrillation, dyslipidemia, history of valvular surgery, sum of SV1 (deflection in V1 in millimeters) and RV6 (deflection in V6 in millimeters) on ECG, and left atrial dilation. The external validation cohort included 81 postcapillary PH patients and 66 precapillary PH patients. Using a predefined cutoff of >104, the OPTICS score had 100% specificity for postcapillary PH (sensitivity, 22%). In addition, we investigated whether a high probability of heart failure with preserved ejection fraction, assessed by the HFPEF score (obesity, atrial fibrillation, age >60 yrs, ≥2 antihypertensives, E/e\' >9, and pulmonary artery systolic pressure by echo >35 mmHg), similarly predicted the presence of elevated pulmonary artery wedge pressure. High probability of heart failure with preserved ejection fraction (HFPEF score ≥6) was less specific for postcapillary PH. Conclusions In a community setting, the OPTICS risk score can predict elevated pulmonary artery wedge pressure in PH patients without clear signs of left-sided heart disease. The OPTICS risk score may be used to tailor the decision to perform invasive diagnostic testing.



J Am Heart Assoc: 03 Aug 2020; 9:e015992
Jansen SMA, Huis In 't Veld AE, Jacobs W, Grotjohan HP, ... de Man FS, Bogaard HJ
J Am Heart Assoc: 03 Aug 2020; 9:e015992 | PMID: 32750312
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Abstract

Retinal and Renal Microvasculature in Relation to Central Hemodynamics in 11-Year-Old Children Born Preterm or At Term.

Wei FF, Raaijmakers A, Melgarejo JD, Cauwenberghs N, ... Allegaert K, Staessen JA

Background Prematurity disrupts the perinatal maturation of the microvasculature and macrovasculature and confers high risk of vascular dysfunction later in life. No previous studies have investigated the crosstalk between the microvasculature and macrovasculature in childhood. Methods and Results In a case-control study, we enrolled 55 children aged 11 years weighing <1000 g at birth and 71 matched controls (October 2014-November 2015). We derived central blood pressure (BP) wave by applanation tonometry and calculated the forward/backward pulse waves by an automated pressure-based wave separation algorithm. We measured the renal resistive index by pulsed wave Doppler and the central retinal arteriolar equivalent by computer-assisted program software. Compared with controls, patients had higher central systolic BP (101.5 versus 95.2 mm Hg, <0.001) and backward wave amplitude (15.5 versus 14.2 mm Hg, =0.029), and smaller central retinal arteriolar equivalent (163.2 versus 175.4 µm, <0.001). In multivariable analyses, central retinal arteriolar equivalent was smaller with higher values (+1 SD) of central systolic BP (-2.94 µm; 95% CI, -5.18 to -0.70 µm [=0.011]) and forward (-2.57 µm; CI, -4.81 to -0.32 µm [=0.026]) and backward (-3.20 µm; CI, -5.47 to -0.94 µm [=0.006]) wave amplitudes. Greater renal resistive index was associated with higher backward wave amplitude (0.92 mm Hg, =0.036). Conclusions In childhood, prematurity compared with term birth is associated with higher central systolic BP and forward/backward wave amplitudes. Higher renal resistive index likely moves reflection points closer to the heart, thereby explaining the inverse association of central retinal arteriolar equivalent with central systolic BP and backward wave amplitude. These observations highlight the crosstalk between the microcirculation and macrocirculation in children. Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02147457.



J Am Heart Assoc: 03 Aug 2020; 9:e014305
Wei FF, Raaijmakers A, Melgarejo JD, Cauwenberghs N, ... Allegaert K, Staessen JA
J Am Heart Assoc: 03 Aug 2020; 9:e014305 | PMID: 32750311
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Abstract

Associations of Left Ventricular Structure and Function With Blood Pressure in Heart Failure With Preserved Ejection Fraction: Analysis of the TOPCAT Trial.

Wei FF, Xue R, Thijs L, Liang W, ... Dong Y, Liu C

Background Data on the association of systolic and diastolic blood pressure with the structure and function of failing hearts with preserved ejection fraction (EF) are sparse. Methods and Results This analysis included 935 patients with heart failure (49.4% women; mean age, 69.9 years) with preserved EF (≥45%) enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) Trial before initiation of randomized therapy. Left ventricular (LV) structure (dimensions, wall thickness, and mass index), diastolic function (left atrial volume index, transmitral blood flow, and mitral annular velocities), and systolic function (EF and longitudinal strain) were assessed echocardiographically. In multivariable-adjusted analyses, association sizes expressed per 1-SD (14.8-mm Hg) increment in systolic blood pressure were 0.020 cm (=0.003) and 0.018 cm (=0.004) for LV septal and posterior wall thickness, respectively, and 2.42 mg/m (=0.018) for LV mass index. The corresponding associations with diastolic blood pressure were nonsignificant (≥0.067). In similarly adjusted analyses, the association sizes expressed per 1-SD (10.7-mm Hg) increment in diastolic blood pressure were -0.15 for E/A (<0.001), -0.76 for E/e\' (=0.006), and -0.62% for EF (=0.024). These findings were consistent, if models including systolic blood pressure were additionally adjusted for diastolic blood pressure and vice versa, albeit that the relation of EF with diastolic blood pressure weakened (-0.54%; =0.10). Conclusions In diastolic heart failure, LV wall thickness and LV mass index increased with higher systolic blood pressure, but not with higher diastolic blood pressure, whereas functional measures reflecting diastolic LV function decreased with higher diastolic blood pressure, independent of systolic blood pressure. These observations highlight the importance of controlling both systolic and diastolic blood pressure as modifiable risk factors to reduce the risk of LV remodeling and diastolic LV dysfunction.



J Am Heart Assoc: 03 Aug 2020; 9:e016009
Wei FF, Xue R, Thijs L, Liang W, ... Dong Y, Liu C
J Am Heart Assoc: 03 Aug 2020; 9:e016009 | PMID: 32750310
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Abstract

Altered Acylcarnitine Metabolism Is Associated With an Increased Risk of Atrial Fibrillation.

Smith E, Fernandez C, Melander O, Ottosson F

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the pathogenesis is not completely understood. The application of metabolomics could help in discovering new metabolic pathways involved in the development of the disease. Methods and Results We measured 112 baseline fasting metabolites of 3770 participants in the Malmö Diet and Cancer Study; these participants were free of prevalent AF. Incident cases of AF were ascertained through previously validated registers. The associations between baseline levels of metabolites and incident AF were investigated using Cox proportional hazard models. During 23.1 years of follow-up, 650 cases of AF were identified (incidence rate: 8.6 per 1000 person-years). In Cox regression models adjusted for AF risk factors, 7 medium- and long-chain acylcarnitines were associated with higher risk of incident AF (hazard ratio [HR] ranging from 1.09; 95% CI, 1.00-1.18 to 1.14, 95% CI, 1.05-1.24 per 1 SD increment of acylcarnitines). Furthermore, caffeine and acisoga were also associated with an increased risk (HR, 1.17; 95% CI, 1.06-1.28 and 1.08; 95% CI, 1.00-1.18, respectively), while beta carotene was associated with a lower risk (HR, 0.90; 95% CI, 0.82-0.99). Conclusions For the first time, we show associations between altered acylcarnitine metabolism and incident AF independent of traditional AF risk factors in a general population. These findings highlight metabolic alterations that precede AF diagnosis by many years and could provide insight into the pathogenesis of AF. Future studies are needed to replicate our finding in an external cohort as well as to test whether the relationship between acylcarnitines and AF is causal.



J Am Heart Assoc: 19 Oct 2020:e016737; epub ahead of print
Smith E, Fernandez C, Melander O, Ottosson F
J Am Heart Assoc: 19 Oct 2020:e016737; epub ahead of print | PMID: 33076748
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Abstract

Clinical Implications of Hepatic Hemodynamic Evaluation by Abdominal Ultrasonographic Imaging in Patients With Heart Failure.

Yoshihisa A, Ishibashi S, Matsuda M, Yamadera Y, ... Kunii H, Takeishi Y

Background It has been reported that liver stiffness assessed by transient elastography are correlated with right atrial pressure, which is associated with worse outcome in patients with heart failure (HF). We aimed to clarify clinical implications of hepatic hemodynamic evaluation (liver congestion and hypoperfusion) by abdominal ultrasonography in patients with HF. Methods and Results We performed abdominal ultrasonography, right-heart catheterization, and echocardiography, then followed up for cardiac events such as cardiac death or worsening HF in patients with HF. Regarding liver congestion, liver stiffness assessed by shear wave elastography (SWE) of the liver was significantly correlated with right atrial pressure determined by right-heart catheterization (=0.343; <0.01), right atrial end-systolic area, and inferior vena cava diameter determined by echocardiography. Regarding liver hypoperfusion, peak systolic velocity (PSV) of the celiac artery was correlated with cardiac index determined by right-heart catheterization (=0.291; <0.001) and tricuspid annular plane systolic excursion determined by echocardiography. According to the Kaplan-Meier analysis, HF patients with high SWE and low PSV had the highest cardiac event rate (log-rank =0.033). In the Cox proportional hazard analysis, high SWE and low PSV were associated with high cardiac event rate (high SWE: hazard ratio [HR], 2.039; 95% CI, 1.131-4.290; low PSV: HR, 2.211; 95% CI, 1.199-4.449), and the combination of high SWE and low PSV was a predictor of cardiac events (HR, 4.811; 95% CI, 1.562-14.818). Conclusions Intrahepatic congestion and hypoperfusion determined by abdominal ultrasonography (liver SWE and celiac PSV) are associated with adverse prognosis in patients with HF.



J Am Heart Assoc: 03 Aug 2020; 9:e016689
Yoshihisa A, Ishibashi S, Matsuda M, Yamadera Y, ... Kunii H, Takeishi Y
J Am Heart Assoc: 03 Aug 2020; 9:e016689 | PMID: 32750309
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Abstract

Oxidized Low-Density Lipoprotein Induces Macrophage Production of Prothrombotic Microparticles.

Marchini JF, Manica A, Crestani P, Dutzmann J, ... Libby P, Croce K

Background Activated vascular cells produce submicron prothrombotic and proinflammatory microparticle vesicles. Atherosclerotic plaques contain high levels of microparticles. Plasma microparticle levels increase during acute coronary syndromes and the thrombotic consequences of plaque rupture likely involve macrophage-derived microparticles (MΦMPs). The activation pathways that promote MΦMP production remain poorly defined. This study tested the hypothesis that signals implicated in atherogenesis also stimulate MΦMP production. Methods and Results We stimulated human primary MΦs with proinflammatory cytokines and atherogenic lipids, and measured MΦMP production by flow cytometry. Oxidized low-density lipoprotein (oxLDL; 25 µg/mL) induced MΦMP production in a concentration-dependent manner (293% increase; <0.001), and these oxLDL MΦMP stimulatory effects were mediated by CD36. OxLDL stimulation increased MΦMP tissue factor content by 78% (<0.05), and oxLDL-induced MΦMP production correlated with activation of caspase 3/7 signaling pathways. Salvionolic acid B, a CD36 inhibitor and a CD36 inhibitor antibody reduced oxLDL-induced MΦMP by 67% and 60%, respectively. Caspase 3/7 inhibition reduced MΦMP release by 52% (<0.01) and caspase 3/7 activation increased MΦMP production by 208% (<0.01). Mevastatin pretreatment (10 µM) decreased oxLDL-induced caspase 3/7 activation and attenuated oxLDL-stimulated MΦMP production and tissue factor content by 60% (<0.01) and 43% (<0.05), respectively. Conclusions OxLDL induces the production of prothrombotic microparticles in macrophages. This process depends on caspases 3 and 7 and CD36 and is inhibited by mevastatin pretreatment. These findings link atherogenic signaling pathways, inflammation, and plaque thrombogenicity and identify a novel potential mechanism for antithrombotic effects of statins independent of LDL lowering.



J Am Heart Assoc: 03 Aug 2020; 9:e015878
Marchini JF, Manica A, Crestani P, Dutzmann J, ... Libby P, Croce K
J Am Heart Assoc: 03 Aug 2020; 9:e015878 | PMID: 32750308
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Abstract

Elevated Heart Rate and Survival in Children With Dilated Cardiomyopathy: A Multicenter Study From the Pediatric Cardiomyopathy Registry.

Rossano JW, Kantor PF, Shaddy RE, Shi L, ... Depre C, Lipshultz SE

Background In adults with heart failure, elevated heart rate is associated with lower survival. We determined whether an elevated heart rate was associated with an increased risk of death or heart transplant in children with dilated cardiomyopathy. Methods and Results The study is an analysis of the Pediatric Cardiomyopathy Registry and includes baseline data, annual follow-up, and censoring events (transplant or death) in 557 children (51% male, median age 1.8 years) with dilated cardiomyopathy diagnosed between 1994 and 2011. An elevated heart rate was defined as 2 or more SDs above the mean heart rate of children, adjusted for age. The primary outcomes were heart transplant and death. Heart rate was elevated in 192 children (34%), who were older (median age, 2.3 versus 0.9 years; <0.001), more likely to have heart failure symptoms (83% versus 67%; <0.001), had worse ventricular function (median fractional shorteningscore, -9.7 versus -9.1; =0.02), and were more often receiving anticongestive therapies (96% versus 86%; <0.001) than were children with a normal heart rate. Controlling for age, ventricular function, and cardiac medications, an elevated heart rate was independently associated with death (adjusted hazard ratio [HR] 2.6; <0.001) and with death or transplant (adjusted HR 1.5; =0.01). Conclusions In children with dilated cardiomyopathy, elevated heart rate was associated with an increased risk of death and cardiac transplant. Further study is warranted into the association of elevated heart rate and disease severity in children with dilated cardiomyopathy and as a potential target of therapy.



J Am Heart Assoc: 03 Aug 2020; 9:e015916
Rossano JW, Kantor PF, Shaddy RE, Shi L, ... Depre C, Lipshultz SE
J Am Heart Assoc: 03 Aug 2020; 9:e015916 | PMID: 32750307
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Abstract

Determinants of Pericoronary Adipose Tissue Attenuation on Computed Tomography Angiography in Coronary Artery Disease.

Sugiyama T, Kanaji Y, Hoshino M, Yamaguchi M, ... Sasano T, Kakuta T

Background Recent studies have reported the association between pericoronary inflammation assessed by pericoronary adipose tissue attenuation (PCATA) on computed tomography angiography and worse outcomes in patients with coronary artery disease. We investigated the determinants predicting increased PCATA in patients with known or suspected coronary artery disease. Methods and Results A total of 540 patients who underwent computed tomography angiography and invasive coronary angiography were studied. Mean computed tomography attenuation values of PCAT (-190 to -30 Hounsfield units) (PCATA) were assessed at the proximal 40-mm segments of all 3 major coronary arteries by crude analysis. Univariable and multivariable analyses were performed to determine the predictors of increased PCATA surrounding the proximal right coronary artery. Mean right coronary artery-PCATA was -72.22±8.47 Hounsfield units and the average of 3-vessel PCATA was -70.24±6.60 Hounsfield units. Multivariable linear regression analysis revealed that the independent determinants of right coronary artery-PCATA were male (β coefficient=4.965, <0.001), left ventricular mass index (β coefficient=0.040, =0.025), and angiographically significant stenosis (diameter stenosis >50%) (β coefficient=2.418, =0.008). Sex-related determinants were NT-proBNP level (N-terminal pro-B-type natriuretic peptide; β coefficient <0.001, =0.026), Agatston score (β coefficient=-0.002, =0.010), left ventricular mass index (β coefficient=0.041, =0.028), and significant stenosis (β coefficient=4.006, <0.001) in male patients and left ventricular ejection fraction (β coefficient=-0.217, =0.010) and significant stenosis (β coefficient=3.835, =0.023) in female patients. Conclusions Right coronary artery-PCATA was associated with multiple clinical characteristics, established risk factors, and the presence of significant stenosis. Our results suggest that clinically significant factors such as sex, left ventricular hypertrophy, ejection fraction, calcification, and epicardial stenosis should be taken into account in the assessment of pericoronary inflammation using computed tomography angiography.



J Am Heart Assoc: 03 Aug 2020; 9:e016202
Sugiyama T, Kanaji Y, Hoshino M, Yamaguchi M, ... Sasano T, Kakuta T
J Am Heart Assoc: 03 Aug 2020; 9:e016202 | PMID: 32750306
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Abstract

Ischemic Preconditioning Improves Microvascular Endothelial Function in Remote Vasculature by Enhanced Prostacyclin Production.

Rytter N, Carter H, Piil P, Sørensen H, ... Gliemann L, Hellsten Y

Background The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. Methods and results A total of 12 healthy young men and women participated in 2 experimental days in a random counterbalanced order. On one day the participants underwent 4×5 minutes of forearm ischemic preconditioning, and on the other day they completed 4×5 minutes of hand-grip exercise. On both days, catheters were placed in the brachial and femoral artery and vein for infusion of acetylcholine, sodium nitroprusside, and epoprostenol. Vascular conductance was calculated from blood flow measurements with ultrasound Doppler and arterial and venous blood pressures. Ischemic preconditioning enhanced (<0.05) the remote vasodilator response to intra-arterial acetylcholine in the leg at 5 and 90 minutes after application. The enhanced response was associated with a 6-fold increase (<0.05) in femoral venous plasma prostacyclin levels and with a transient increase (<0.05) in arterial plasma levels of brain-derived neurotrophic factor and vascular endothelial growth factor. In contrast, hand-grip exercise did not influence remote microvascular function. CONCLUSIONS These findings demonstrate that ischemic preconditioning of the forearm improves remote microvascular endothelial function and suggest that one of the underlying mechanisms is a humoral-mediated potentiation of prostacyclin formation.



J Am Heart Assoc: 03 Aug 2020; 9:e016017
Rytter N, Carter H, Piil P, Sørensen H, ... Gliemann L, Hellsten Y
J Am Heart Assoc: 03 Aug 2020; 9:e016017 | PMID: 32750305
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Abstract

Left Heart Factors in Embolic Stroke of Undetermined Source in a Multiethnic Asian and North African Cohort.

Kamran S, Singh R, Akhtar N, George P, ... Hamid T, Perkins JD

Background Cardiac features diverge in Asians; however, it is not known how these differences relate to embolic stroke of unknown source (ESUS) in Southeast Asian and Eastern Mediterranean regions. Methods and Results A retrospective analysis of prospectively collected acute ischemic stroke data from 2014 to 2018 was performed. Stroke subtypes were noncardioembolic stroke (large-vessel and small-vessel disease; n=1348), cardioembolic stroke (n=532), and ESUS (n=656). Subtypes were compared by demographic, clinical, and echocardiographic factors. In multivariate logistic regression, patients with ESUS in comparison with noncardioembolic stroke were twice as likely to have left ventricular diastolic dysfunction (=0.001), 3 times the odds of global hypokinesia (=0.001), and >7 times the odds of left ventricular wall motion abnormalities (=0.001). In the second model comparing ESUS with cardioembolic stroke, patients with ESUS were 3 times more likely to have left ventricular wall motion abnormalities (=0.001) and 1.5 times more likely to have left ventricular diastolic dysfunction grade I (=0.009), and 3 times more likely to have left ventricular diastolic dysfunction grades II and III (=0.009), whereas age (=0.001) and left atrial volume index (=0.004) showed an inverse relation with ESUS. ESUS in patients ≥61 years old had higher levels of traditional risk factors such as coronary artery disease, but the coronary artery disease was not significantly different in ESUS age groups (=0.80) despite higher left ventricular wall motion abnormalities (=0.001). Conclusions Patients with ESUS and noncardioembolic stroke were younger than patients with cardioembolic stroke. While a third of the patients with ESUS >45 years old had coronary artery disease, it was unrecognized or underreported in the older ESUS age group (61 years old). In patients with ESUS from Southeast Asia and Eastern Mediterranean regions, left ventricular wall motion abnormalities and left ventricular diastolic dysfunction were related to ESUS.



J Am Heart Assoc: 03 Aug 2020; 9:e016534
Kamran S, Singh R, Akhtar N, George P, ... Hamid T, Perkins JD
J Am Heart Assoc: 03 Aug 2020; 9:e016534 | PMID: 32750304
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Abstract

Active Case Finding for Rheumatic Fever in an Endemic Country.

Okello E, Ndagire E, Atala J, Bowen AC, ... Sable C, Beaton A

Background Despite the high burden of rheumatic heart disease in sub-Saharan Africa, diagnosis with acute rheumatic fever (ARF) is exceedingly rare. Here, we report the results of the first prospective epidemiologic survey to diagnose and characterize ARF at the community level in Africa. Methods and Results A cross-sectional study was conducted in Lira, Uganda, to inform the design of a broader epidemiologic survey. Key messages were distributed in the community, and children aged 3 to 17 years were included if they had either (1) fever and joint pain, (2) suspicion of carditis, or (3) suspicion of chorea, with ARF diagnoses made by the 2015 Jones Criteria. Over 6 months, 201 children met criteria for participation, with a median age of 11 years (interquartile range, 6.5) and 103 (51%) female. At final diagnosis, 51 children (25%) had definite ARF, 11 (6%) had possible ARF, 2 (1%) had rheumatic heart disease without evidence of ARF, 78 (39%) had a known alternative diagnosis (10 influenza, 62 malaria, 2 sickle cell crises, 2 typhoid fever, 2 congenital heart disease), and 59 (30%) had an unknown alternative diagnosis. Conclusions ARF persists within rheumatic heart disease-endemic communities in Africa, despite the low rates reported in the literature. Early data collection has enabled refinement of our study design to best capture the incidence of ARF and to answer important questions on community sensitization, healthcare worker and teacher education, and simplified diagnostics for low-resource areas. This study also generated data to support further exploration of the relationship between malaria and ARF diagnosis in rheumatic heart disease/malaria-endemic countries.



J Am Heart Assoc: 03 Aug 2020; 9:e016053
Okello E, Ndagire E, Atala J, Bowen AC, ... Sable C, Beaton A
J Am Heart Assoc: 03 Aug 2020; 9:e016053 | PMID: 32750303
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Abstract

Optimal Revascularization Strategy in Non-ST-Segment-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease: Culprit-Only Versus One-Stage Versus Multistage Revascularization.

Kim MC, Hyun JY, Ahn Y, Bae S, ... Cha KS, Oh SK

Background Few studies have investigated optimal revascularization strategies in non-ST-segment-elevation myocardial infarction with multivessel disease. We investigated 3-year clinical outcomes according to revascularization strategy in patients with non-ST-segment-elevation myocardial infarction and multivessel disease. Methods and Results This retrospective, observational, multicenter study included patients with non-ST-segment-elevation myocardial infarction and multivessel disease without cardiogenic shock. Data were analyzed at 3 years according to the percutaneous coronary intervention strategy: culprit-only revascularization (COR), 1-stage multivessel revascularization (MVR), and multistage MVR. The primary outcome was major adverse cardiac events (MACE: a composite of all-cause death, nonfatal spontaneous myocardial infarction, or any repeat revascularization). The COR group had a higher risk of MACE than those involving other strategies (COR versus 1-stage MVR; hazard ratio, 0.65; 95% CI, 0.54-0.77; <0.001; and COR versus multistage MVR; hazard ratio, 0.74; 95% CI, 0.57-0.97; =0.027). There was no significant difference in the incidence of MACE between 1-stage and multistage MVR (hazard ratio, 1.14; 95% CI, 0.86-1.51; =0.355). The results were consistent after multivariate regression, propensity score matching, inverse probability weighting, and Bayesian proportional hazards modeling. In subgroup analyses stratified by the Global Registry of Acute Coronary Events score, 1-stage MVR lowered the risk of MACE compared with multistage MVR in low-to-intermediate risk patients but not in patients at high risk. Conclusions MVR reduced 3-year MACE in patients with non-ST-segment-elevation myocardial infarction and multivessel disease compared with COR. However, 1-stage MVR was not superior to multistage MVR for reducing MACE except in low-to-intermediate risk patients.



J Am Heart Assoc: 03 Aug 2020; 9:e016575
Kim MC, Hyun JY, Ahn Y, Bae S, ... Cha KS, Oh SK
J Am Heart Assoc: 03 Aug 2020; 9:e016575 | PMID: 32750302
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Acute Coronary Syndrome and Ischemic Heart Disease in Pregnancy: Data From the EURObservational Research Programme-European Society of Cardiology Registry of Pregnancy and Cardiac Disease.

Baris L, Hakeem A, Moe T, Cornette J, ... Roos-Hesselink JW,

Background The prevalence of ischemic heart disease (IHD) in women of child-bearing age is rising. Data on pregnancies however are scarce. The objective is to describe the pregnancy outcomes in these women. Methods and Results The European Society of Cardiology-EURObservational Research Programme ROPAC (Registry of Pregnancy and Cardiac Disease) is a prospective registry in which data on pregnancies in women with heart disease were collected from 138 centers in 53 countries. Pregnant women with preexistent and pregnancy-onset IHD were included. Primary end point were maternal cardiac events. Secondary end points were obstetric and fetal complications. There were 117 women with IHD, of which 104 had preexisting IHD. Median age was 35.5 years and 17.1% of women were smoking. There was no maternal mortality, heart failure occurred in 5 pregnancies (4.8%). Of the 104 women with preexisting IHD, 11 women suffered from acute coronary syndrome during pregnancy. ST-segment‒elevation myocardial infarction were more common than non‒ST-segment‒elevation myocardial infarction, and atherosclerosis was the most common etiology. Women who had undergone revascularization before pregnancy did not have less events than women who had not. There were 13 women with pregnancy-onset IHD, in whom non‒ST-segment‒elevation myocardial infarction was the most common. Smoking during pregnancy was associated with acute coronary syndrome. Caesarean section was the primary mode of delivery (55.8% in preexisting IHD, 84.6% in pregnancy-onset IHD) and there were high rates of preterm births (20.2% and 38.5%, respectively). Conclusions Women with IHD tolerate pregnancy relatively well, however there is a high rate of ischemic events and these women should therefore be considered moderate- to high-risk. Ongoing cigarette smoking is associated with acute coronary syndrome during pregnancy.



J Am Heart Assoc: 03 Aug 2020; 9:e015490
Baris L, Hakeem A, Moe T, Cornette J, ... Roos-Hesselink JW,
J Am Heart Assoc: 03 Aug 2020; 9:e015490 | PMID: 32750301
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Abstract

Temporal Trends in Pregnancy-Associated Stroke and Its Outcomes Among Women With Hypertensive Disorders of Pregnancy.

Wu P, Jordan KP, Chew-Graham CA, Coutinho T, ... Maas AHEM, Mamas MA

Background Stroke is a serious complication of hypertensive disorders of pregnancy (HDP), with potentially severe and long-term sequelae. However, the temporal trends, predictors, and outcomes of stroke in women with HDP at delivery remain unknown. Methods and Results All HDP delivery hospitalizations with or without stroke event (ischemic, hemorrhagic, or unspecified) between 2004 and 2014 in the United States National Inpatient Sample were analyzed to examine incidence, predictors, and prognostic impact of stroke. Of 4 240 284 HDP delivery hospitalizations, 3391 (0.08%) women had stroke. While the prevalence of HDP increased over time, incident stroke rates decreased from 10 to 6 per 10 000 HDP delivery hospitalizations between 2004 and 2014. Women with stroke were increasingly multimorbid, with some risk factors being more strongly associated with ischemic strokes, including congenital heart disease, peripheral vascular disease, dyslipidemia, and sickle cell disease. Delivery complications were also associated with stroke, including cesarean section (odds ratio [OR], 1.58; 95% CI, 1.33-1.86), postpartum hemorrhage (OR, 1.91; 95% CI, 1.33-1.86), and maternal mortality (OR, 99.78; 95% CI, 59.15-168.31), independently of potential confounders. Women with stroke had longer hospital stays (median, 6 versus 3 days), higher hospital charges (median, $14 655 versus $4762), and a higher proportion of nonroutine discharge locations (38% versus 4%). Conclusions The incidence of stroke in women with HDP has declined over time. While a relatively rare event, identification of women at highest risk of ischemic or hemorrhagic stroke on admission for delivery is important to reduce long-term sequelae.



J Am Heart Assoc: 03 Aug 2020; 9:e016182
Wu P, Jordan KP, Chew-Graham CA, Coutinho T, ... Maas AHEM, Mamas MA
J Am Heart Assoc: 03 Aug 2020; 9:e016182 | PMID: 32750300
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Abstract

Highest Obesity Category Associated With Largest Decrease in N-Terminal Pro-B-Type Natriuretic Peptide in Patients Hospitalized With Heart Failure With Preserved Ejection Fraction.

Vaishnav J, Chasler JE, Lee YJ, Ndumele CE, ... Russell SD, Sharma K

Background Heart failure with preserved ejection fraction (HFpEF) constitutes half of hospitalized heart failure cases and is commonly associated with obesity. The role of natriuretic peptide levels in hospitalized obese patients with HFpEF, however, is not well defined. We sought to evaluate change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels by obesity category and related clinical outcomes in patients with HFpEF hospitalized for acute heart failure. Methods and Results A total of 89 patients with HFpEF hospitalized with acute decompensated heart failure were stratified into 3 obesity categories: nonobese (body mass index [BMI] <30.0 kg/m, 19%), obese (BMI 30.0-39.9 kg/m, 29%), and severely obese (BMI ≥40.0 kg/m, 52%), and compared for percent change in NT-proBNP during hospitalization and clinical outcomes. Clinical characteristics were compared between patients with normal NT-proBNP (≤125 pg/mL) and elevated NT-proBNP. Admission NT-proBNP was inversely related to BMI category (nonobese, 2607 pg/mL [interquartile range, IQR: 2112-5703]; obese, 1725 pg/mL [IQR: 889-3900]; and severely obese, 770.5 pg/mL [IQR: 128-1268]; <0.01). Severely obese patients had the largest percent change in NT-proBNP with diuresis (-64.8% [95% CI, -85.4 to -38.9] versus obese -40.4% [95% CI, -74.3 to -12.0] versus nonobese -46.9% [95% CI, -57.8 to -37.4]; =0.03). Nonobese and obese patients had significantly worse 1-year survival compared with severely obese patients (63% versus 76% versus 95%, respectively; <0.01). Patients with normal NT-proBNP (13%) were younger, with higher BMI, less atrial fibrillation, and less structural heart disease than those with elevated NT-proBNP. Conclusions In hospitalized patients with HFpEF, NT-proBNP was inversely related to BMI with the largest decrease in NT-proBNP seen in the highest obesity category. These findings have implications for the role of NT-proBNP in the diagnosis and assessment of treatment response in obese patients with HFpEF.



J Am Heart Assoc: 03 Aug 2020; 9:e015738
Vaishnav J, Chasler JE, Lee YJ, Ndumele CE, ... Russell SD, Sharma K
J Am Heart Assoc: 03 Aug 2020; 9:e015738 | PMID: 32750299
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Abstract

Increased Glucose Availability Attenuates Myocardial Ketone Body Utilization.

Brahma MK, Ha CM, Pepin ME, Mia S, ... Young ME, Wende AR

Background Perturbations in myocardial substrate utilization have been proposed to contribute to the pathogenesis of cardiac dysfunction in diabetic subjects. The failing heart in nondiabetics tends to decrease reliance on fatty acid and glucose oxidation, and increases reliance on ketone body oxidation. In contrast, little is known regarding the mechanisms mediating this shift among all 3 substrates in diabetes mellitus. Therefore, we tested the hypothesis that changes in myocardial glucose utilization directly influence ketone body catabolism. Methods and Results We examined ventricular-cardiac tissue from the following murine models: (1) streptozotocin-induced type 1 diabetes mellitus; (2) high-fat-diet-induced glucose intolerance; and transgenic inducible cardiac-restricted expression of (3) glucose transporter 4 (transgenic inducible cardiac restricted expression of glucose transporter 4); or (4) dominant negative -GlcNAcase. Elevated blood glucose (type 1 diabetes mellitus and high-fat diet mice) was associated with reduced cardiac expression of β-hydroxybutyrate-dehydrogenase and succinyl-CoA:3-oxoacid CoA transferase. Increased myocardial β-hydroxybutyrate levels were also observed in type 1 diabetes mellitus mice, suggesting a mismatch between ketone body availability and utilization. Increased cellular glucose delivery in transgenic inducible cardiac restricted expression of glucose transporter 4 mice attenuated cardiac expression of both Bdh1 and Oxct1 and reduced rates of myocardial BDH1 activity and β-hydroxybutyrate oxidation. Moreover, elevated cardiac protein -GlcNAcylation (a glucose-derived posttranslational modification) by dominant negative -GlcNAcase suppressed β-hydroxybutyrate dehydrogenase expression. Consistent with the mouse models, transcriptomic analysis confirmed suppression of BDH1 and OXCT1 in patients with type 2 diabetes mellitus and heart failure compared with nondiabetic patients. Conclusions Our results provide evidence that increased glucose leads to suppression of cardiac ketolytic capacity through multiple mechanisms and identifies a potential crosstalk between glucose and ketone body metabolism in the diabetic myocardium.



J Am Heart Assoc: 03 Aug 2020; 9:e013039
Brahma MK, Ha CM, Pepin ME, Mia S, ... Young ME, Wende AR
J Am Heart Assoc: 03 Aug 2020; 9:e013039 | PMID: 32750298
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Abstract

Up to 206 Million People Reached and Over 5.4 Million Trained in Cardiopulmonary Resuscitation Worldwide: The 2019 International Liaison Committee on Resuscitation World Restart a Heart Initiative.

Böttiger BW, Lockey A, Aickin R, Carmona M, ... Wong G, Perkins GD

Sudden out-of-hospital cardiac arrest is the third leading cause of death in industrialized nations. Many of these lives could be saved if bystander cardiopulmonary resuscitation rates were better. \"All citizens of the world can save a life-CHECK-CALL-COMPRESS.\" With these words, the International Liaison Committee on Resuscitation launched the 2019 global \"World Restart a Heart\" initiative to increase public awareness and improve the rates of bystander cardiopulmonary resuscitation and overall survival for millions of victims of cardiac arrest globally. All participating organizations were asked to train and to report the numbers of people trained and reached. Overall, social media impact and awareness reached up to 206 million people, and >5.4 million people were trained in cardiopulmonary resuscitation worldwide in 2019. Tool kits and information packs were circulated to 194 countries worldwide. Our simple and unified global message, \"CHECK-CALL-COMPRESS,\" will save hundreds of thousands of lives worldwide and will further enable many policy makers around the world to take immediate and sustainable action in this most important healthcare issue and initiative.



J Am Heart Assoc: 03 Aug 2020; 9:e017230
Böttiger BW, Lockey A, Aickin R, Carmona M, ... Wong G, Perkins GD
J Am Heart Assoc: 03 Aug 2020; 9:e017230 | PMID: 32750297
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Abstract

Disparities in Premature Cardiac Death Among US Counties From 1999-2017: Temporal Trends and Key Drivers.

Jin Y, Song S, Zhang L, Trisolini MG, ... Smith SC, Zheng ZJ

Background Disparities in premature cardiac death (PCD) might stagnate the progress toward the reduction of PCD in the United States and worldwide. We estimated disparities across US counties in PCD rates and investigated county-level factors related to the disparities. Methods and Results We used US mortality data for cause-of-death and demographic data from death certificates and county-level characteristics data from multiple databases. PCD was defined as any death that occurred at an age between 35 and 74 years with an underlying cause of death caused by cardiac disease based on(), codes. Of the 1 598 173 PCDs that occurred during 1999-2017, 60.9% were out of hospital. Although the PCD rates declined from 1999-2017, the proportion of out-of-hospital PCDs among all cardiac deaths increased from 58.3% to 61.5%. The geographic disparities in PCD rates across counties widened from 1999 (Theil index=0.10) to 2017 (Theil index=0.23), and within-state differences accounted for the majority of disparities (57.4% in 2017). The disparities in out-of-hospital PCD rates (and in-hospital PCD rates) associated with demographic composition were 36.51% (and 37.51%), socioeconomic features were 18.64% (and 18.36%), healthcare environment were 18.64% (and 13.90%), and population health status were 23.73% (and 30.23%). Conclusions Disparities in PCD rates exist across US counties, which may be related to the decelerated trend of decline in the rates among middle-aged adults. The slower declines in out-of-hospital rates warrants more precision targeting and sustained efforts to ensure progress at better levels of health (with lower PCD rates) against PCD.



J Am Heart Assoc: 03 Aug 2020; 9:e016340
Jin Y, Song S, Zhang L, Trisolini MG, ... Smith SC, Zheng ZJ
J Am Heart Assoc: 03 Aug 2020; 9:e016340 | PMID: 32750296
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Abstract

Extracellular Superoxide Dismutase Is Associated With Left Ventricular Geometry and Heart Failure in Patients With Cardiovascular Disease.

Li X, Lin Y, Wang S, Zhou S, ... Chen Y, Xia M

Background Extracellular superoxide dismutase (Ec-SOD) is a major scavenger of reactive oxygen species. However, its relationships with abnormal left ventricular (LV) geometry patterns and heart failure (HF) are still unknown in patients with cardiovascular disease. Methods and Results A cross-sectional study was carried out to evaluate the association of serum Ec-SOD activity with LV geometry, as well as HF in 1047 patients with cardiovascular disease. All participants underwent standard echocardiography examination and measurement of serum Ec-SOD activity. Overall, we found a significantly decreased trend of serum Ec-SOD activity from subjects with normal geometry (147.96±15.94 U/mL), subjects with abnormal LV geometry without HF (140.19±20.12 U/mL), and subjects with abnormal LV geometry and overt HF (129.32±17.92 U/mL) after adjustment for potential confounders ( for trend <0.001). The downward trends remained significant in the concentric hypertrophy and eccentric hypertrophy groups after stratification by different LV geometry patterns. Multinomial logistic regression analysis showed that each 10 U/mL increase in serum Ec-SOD activity was associated with a 16.5% decrease in the odds of concentric remodeling without HF (odds ratio [OR], 0.835; 95% CI, 0.736-0.948), a 40.4% decrease in the odds of concentric hypertrophy with HF (OR, 0.596; 95% CI, 0.486-0.730), a 16.1% decrease in the odds of eccentric hypertrophy without HF (OR, 0.839; 95% CI, 0.729-0.965) and a 34.0% decrease in the odds of eccentric hypertrophy with HF (OR, 0.660; 95% CI, 0.565-0.772). Conclusions Serum Ec-SOD activity was independently associated with abnormal LV geometry patterns with and without overt HF. Our results indicate that Ec-SOD might be a potential link between LV structure remodeling and the development of subsequent HF in patients with cardiovascular disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier NCT03351907.



J Am Heart Assoc: 03 Aug 2020; 9:e016862
Li X, Lin Y, Wang S, Zhou S, ... Chen Y, Xia M
J Am Heart Assoc: 03 Aug 2020; 9:e016862 | PMID: 32750295
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Abstract

Vital Roles of Gremlin-1 in Pulmonary Arterial Hypertension Induced by Systemic-to-Pulmonary Shunts.

Meng L, Teng X, Liu Y, Yang C, ... Duan L, Liu X

Background Heterozygous mutation in BMP (bone morphogenetic protein) receptor 2 is rare, but BMP cascade suppression is common in congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH); however, the underling mechanism of BMP cascade suppression independent of BMP receptor 2 mutation is unknown. Methods and Results Pulmonary hypertensive status observed in CHD-PAH was surgically reproduced in rats. Gremlin-1 expression was increased, but BMP cascade was suppressed, in lungs from CHD-PAH patients and shunted rats, whereas shunt correction retarded these trends in rats. Immunostaining demonstrated increased gremlin-1 was mainly in the endothelium and media of remodeled pulmonary arteries. However, mechanical stretch time- and amplitude-dependently stimulated gremlin-1 secretion and suppressed BMP cascade in distal pulmonary arterial smooth muscle cells from healthy rats. Under static condition, gremlin-1 significantly promoted the proliferation and inhibited the apoptosis of distal pulmonary arterial smooth muscle cells from healthy rats via BMP cascade. Furthermore, plasma gremlin-1 closely correlated with hemodynamic parameters in CHD-PAH patients and shunted rats. Conclusions Serving as an endogenous antagonist of BMP cascade, the increase of gremlin-1 in CHD-PAH may present a reasonable mechanism explanation for BMP cascade suppression independent of BMP receptor 2 mutation.



J Am Heart Assoc: 03 Aug 2020; 9:e016586
Meng L, Teng X, Liu Y, Yang C, ... Duan L, Liu X
J Am Heart Assoc: 03 Aug 2020; 9:e016586 | PMID: 32750294
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Abstract

Biomechanics of Aortic Dissection: A Comparison of Aortas Associated With Bicuspid and Tricuspid Aortic Valves.

Chung JC, Wong E, Tang M, Eliathamby D, ... Simmons CA, Ouzounian M

Background Current methods for aortic dissection risk assessment are inadequate for patients with ascending aortic aneurysms associated with either bicuspid aortic valves (BAVs) or tricuspid aortic valves (TAVs). Biomechanical testing of aortic tissue may provide novel insights and biomarkers. Methods and Results From March 2017 to August 2019, aneurysmal ascending aortas (BAV=23, TAV=23) were collected from elective aortic surgery, normal aortas from transplant donors (n=9), and dissected aortas from surgery for aortic dissection (n=7). These aortas underwent delamination testing in simulation of aortic dissection. Biaxial tensile testing was performed to determine modulus of elasticity (aortic stiffness), and energy loss (a measure of efficiency in performing the Windkessel function). Delamination strength () was lowest in dissected aortas (18±6 mN/mm) and highest in normal aortas (58±16 mN/mm), and aneurysms fell in between, with greaterin the BAV group (37±10 mN/mm) than the TAV group (27±10 mN/mm) (<0.001). Bicuspid aortopathy was associated with greater stiffness (<0.001), while aneurysms with TAV demonstrated greater energy loss (<0.001).decreased by 7.8±1.2 mmol/L per mm per decade of life (=0.45, <0.001), and it was significantly lower for patients with hypertension (=0.001).decreased by 6.1±2.1 mmol/L per mm with each centimeter increase in aortic diameter (=0.15, =0.007). Increased energy loss was associated with decreased(=0.41), whereas there was no relationship betweenand aortic stiffness. Conclusions Aneurysms with BAV had higherthan those with TAV, suggesting that BAV was protective. Energy loss was lower in aneurysms with BAV, and inversely associated with , representing a potential novel biomarker.



J Am Heart Assoc: 03 Aug 2020; 9:e016715
Chung JC, Wong E, Tang M, Eliathamby D, ... Simmons CA, Ouzounian M
J Am Heart Assoc: 03 Aug 2020; 9:e016715 | PMID: 32750292
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Abstract

Serum Activity Against G Protein-Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome.

Kharraziha I, Axelsson J, Ricci F, Di Martino G, ... Fedorowski A, Hamrefors V

Background Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein-coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell-based assay. Methods and Results Forty-eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10-item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein-coupled receptor: adrenergic α receptor, adrenergic β receptor, cholinergic muscarinic type 2 receptor, and opioid receptor-like 1 were treated with sera from all patients. Receptor response was analyzed using a β-arrestin-linked transcription factor driving transgenic β-lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein-coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls (<0.01 for all). The area under the curve was 0.88 (0.80-0.97, <0.001) combining all 4 receptors. Adrenergic α receptor activation associated with OHQ composite score (β=0.77 OHQ points per SD of activity, =0.009) and with reduced tolerability for prolonged standing (=0.037) and walking for short (=0.042) or long (=0.001) periods. All 4 receptors were associated with vision problems (<0.05 for all). Conclusions Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum-mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α receptor is associated with orthostatic symptoms severity in patients with POTS.



J Am Heart Assoc: 03 Aug 2020; 9:e015989
Kharraziha I, Axelsson J, Ricci F, Di Martino G, ... Fedorowski A, Hamrefors V
J Am Heart Assoc: 03 Aug 2020; 9:e015989 | PMID: 32750291
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Abstract

Heart Rate Variability Triangular Index as a Predictor of Cardiovascular Mortality in Patients With Atrial Fibrillation.

Hämmerle P, Eick C, Blum S, Schlageter V, ... Zuern CS,

Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5-minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal-to-normal intervals, square root of the mean squared differences of successive normal-to-normal intervals and mean heart rate) were calculated. During follow-up, an end point committee adjudicated each cause of death. During a mean follow-up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including β blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1-2.6; =0.01) and all-cause death (hazard ratio, 1.42; 95% CI, 1.02-1.98; =0.04). Conclusions The HRV index measured in a single 5-minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.



J Am Heart Assoc: 03 Aug 2020; 9:e016075
Hämmerle P, Eick C, Blum S, Schlageter V, ... Zuern CS,
J Am Heart Assoc: 03 Aug 2020; 9:e016075 | PMID: 32750290
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Abstract

Underuse of Cardiovascular Medications in Individuals With Known Lower Extremity Peripheral Artery Disease: HCHS/SOL.

Hua S, Isasi CR, Kizer JR, Matsushita K, ... Daviglus M, Kaplan RC

Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non-Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and comorbidities, using multivariable regression models. The overall prevalence for individuals with PAD taking antiplatelet therapy, lipid-lowering therapy and, among hypertensive individuals, antihypertensive therapy was 31%, 26% and 57%, respectively. Individuals of Mexican background had the lowest use for all classes of cardiovascular medications. Older age, number of doctor visits and existing hypertension and diabetes mellitus were significantly associated with taking cardiovascular therapies in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent coronary artery disease were 1.52 (95% CI, 1.20-1.93) and 1.74 (1.30-2.32) times more likely to use antiplatelet agents and statins according to multivariable analysis. No significant difference of antihypertensive medication use was found among PAD patients with or without coronary artery disease. Conclusions Hispanic/Latino individuals with known PAD underuse cardiovascular medications recommended in clinical guidelines. More efforts should be directed to improve treatment in this important group.



J Am Heart Assoc: 17 Aug 2020; 9:e015451
Hua S, Isasi CR, Kizer JR, Matsushita K, ... Daviglus M, Kaplan RC
J Am Heart Assoc: 17 Aug 2020; 9:e015451 | PMID: 32752978
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Abstract

Coronary Flow Reserve in Patients With Prior Spontaneous Coronary Artery Dissection and Recurrent Angina.

Sedlak T, Starovoytov A, Humphries K, Saw J

Background A significant proportion of patients with spontaneous coronary artery dissection (SCAD) have ongoing chronic chest pain despite healing of their dissection. We sought to determine whether coronary microvascular dysfunction contributes to post-SCAD chronic chest pain by performing coronary reactivity testing in the cardiac catheterization laboratory. Methods and Results Eighteen patients consented to coronary reactivity testing at least 3 months post-SCAD. Coronary flow reserve (CFR) and index of microcirculatory resistance were measured in the previously affected SCAD artery and 1 non-SCAD artery. CFR <2.5 was defined as diagnostic of coronary microvascular dysfunction. An abnormal index of microcirculatory resistance was defined as >25 units. Seventeen women underwent coronary reactivity testing (1 had chronic dissection and was excluded). All presented with myocardial infarction and 2 underwent coronary stenting during the initial SCAD event. Fibromuscular dysplasia was present in 70.6% upon screening renal, iliac, and cerebrovascular arteries. Twelve patients (70.6%) had CFR <2.5 and 13 (76.5%) had an index of microcirculatory resistance >25 in at least 1 artery. There was no difference in the frequency of a low CFR measurement between SCAD and non-SCAD arteries. Conclusions Among patients with chronic chest pain after an SCAD event, >70% had coronary microvascular dysfunction as indicated by abnormal CFR or index of microcirculatory resistance in at least 1 coronary artery on invasive coronary reactivity testing. Presence of coronary microvascular dysfunction in both SCAD and non-SCAD arteries suggests that underlying microvascular abnormalities from vasculopathies such as coronary fibromuscular dysplasia may be the underlying etiology.



J Am Heart Assoc: 17 Aug 2020; 9:e015834
Sedlak T, Starovoytov A, Humphries K, Saw J
J Am Heart Assoc: 17 Aug 2020; 9:e015834 | PMID: 32755255
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Abstract

Degree of Blood Pressure Control and Incident Diabetes Mellitus in Chinese Adults With Hypertension.

Zhang Y, Nie J, Zhang Y, Li J, ... Hou FF, Qin X

Background The association between blood pressure (BP) control and incident diabetes mellitus remains unknown. We aim to investigate the association between degree of time-averaged on-treatment systolic blood pressure (SBP) control and incident diabetes mellitus in hypertensive adults. Methods and Results A total of 14 978 adults with hypertension without diabetes mellitus at baseline were included from the CSPPT (China Stroke Primary Prevention Trial). Participants were randomized double-masked to daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. BP measurements were taken every 3 months after randomization. The primary outcome was incident diabetes mellitus, defined as physician-diagnosed diabetes mellitus, or use of glucose-lowering drugs during follow-up, or fasting glucose ≥126 mg/dL at the exit visit. Over a median of 4.5 years, a significantly higher risk of incident diabetes mellitus was found in participants with time-averaged on-treatment SBP 130 to <140 mm Hg (10.3% versus 7.4%; odds ratio [OR], 1.37; 95% CI, 1.15‒1.64), compared with those with SBP 120 to <130 mm Hg. Moreover, the risk of incident diabetes mellitus increased by 24% (OR, 1.24; 95% CI, 1.00‒1.53) and the incidence of regression to normal fasting glucose (<100 mg/dL) decreased by 29% (OR, 0.71; 95% CI, 0.57‒0.89) in participants with intermediate BP control (SBP/diastolic blood pressure, 130 to <140 and/or 80 to <90 mm Hg), compared with those with a tight BP control of <130/<80 mm Hg. Similar results were found when the time-averaged BP were calculated using the BP measurements during the first 6- or 24-month treatment period, or in the analysis using propensity scores. Conclusions In this non-diabetic, hypertensive population, SBP control in the range of 120 to <130 mm Hg, compared with the 130 to <140 mm Hg, was associated with a lower risk of incident diabetes mellitus.



J Am Heart Assoc: 17 Aug 2020; 9:e017015
Zhang Y, Nie J, Zhang Y, Li J, ... Hou FF, Qin X
J Am Heart Assoc: 17 Aug 2020; 9:e017015 | PMID: 32755254
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Abstract

Characteristics and Outcomes of Patients With Takotsubo Syndrome: Incremental Prognostic Value of Baseline Left Ventricular Systolic Function.

Alashi A, Isaza N, Faulx J, Popovic ZB, ... Griffin BP, Desai MY

Background We sought to determine (1) long-term outcomes in patients presenting with documented Takotsubo syndrome (TS), (2) whether left ventricular global longitudinal strain (LV-GLS) provides incremental prognostic value, and (3) prognostic cutoffs of LV ejection fraction (LVEF) and LV-GLS during an acute TS episode. Methods and Results We studied 650 patients with TS (aged 66±14 years, 88% women) who were diagnosed clinically and angiographically between 2006 and 2018. Baseline LVEF and LV-GLS (using velocity vector imaging) were recorded. The primary end point was all-cause mortality. TS triggers were unknown (34%), emotional (16%), physical (41%), and neurologic (10%). Mean LVEF and LV-GLS were 36±10% and -11.6±0.4%; in addition, 94% patients had LVEF <52%, and 80% had apical ballooning. No patient had obstructive coronary artery disease. At a median of 2.2 years (interquartile range, 0.7-4.4), 175 (27%) had died (9% in-hospital deaths). Multivariate Cox survival analysis revealed that higher age (hazard ratio [HR], 1.35), male sex (HR, 1.75), lower baseline LVEF (HR, 1.02), worse LV-GLS (HR, 1.04), neurologic trigger (HR, 2.66), and physical trigger (HR, 2.64) were associated with mortality, whereas aspirin (HR, 0.70) and β-blockers (HR, 0.73) improved survival (all <0.049). The addition of LVEF and LV-GLS to clinical markers (age, sex, cardiogenic shock at presentation, and peak troponin I) significantly increased log-likelihood ratios: clinical (-521.48), clinical plus LVEF (-511.32, <0.001), and clinical plus LVEF and LV-GLS (-500.68, <0.001). On penalized spline analysis, LVEF of 38% and LV-GLS of -10% were cutoffs below which survival was significantly worse. Conclusions Patients with TS with a neurologic or physical trigger had significantly worse survival than those without such a trigger, with baseline LVEF and LV-GLS providing incremental prognostic value.



J Am Heart Assoc: 17 Aug 2020; 9:e016537
Alashi A, Isaza N, Faulx J, Popovic ZB, ... Griffin BP, Desai MY
J Am Heart Assoc: 17 Aug 2020; 9:e016537 | PMID: 32755253
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Abstract

Derivation and External Validation of a High-Sensitivity Cardiac Troponin-Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease.

McCarthy CP, Neumann JT, Michelhaugh SA, Ibrahim NE, ... Westermann D, Januzzi JL

Background Current noninvasive modalities to diagnose coronary artery disease (CAD) have several limitations. We sought to derive and externally validate a hs-cTn (high-sensitivity cardiac troponin)-based proteomic model to diagnose obstructive coronary artery disease. Methods and Results In a derivation cohort of 636 patients referred for coronary angiography, predictors of ≥70% coronary stenosis were identified from 6 clinical variables and 109 biomarkers. The final model was first internally validated on a separate cohort (n=275) and then externally validated on a cohort of 241 patients presenting to the ED with suspected acute myocardial infarction where ≥50% coronary stenosis was considered significant. The resulting model consisted of 3 clinical variables (male sex, age, and previous percutaneous coronary intervention) and 3 biomarkers (hs-cTnI [high-sensitivity cardiac troponin I], adiponectin, and kidney injury molecule-1). In the internal validation cohort, the model yielded an area under the receiver operating characteristic curve of 0.85 for coronary stenosis ≥70% (<0.001). At the optimal cutoff, we observed 80% sensitivity, 71% specificity, a positive predictive value of 83%, and negative predictive value of 66% for ≥70% stenosis. Partitioning the score result into 5 levels resulted in a positive predictive value of 97% and a negative predictive value of 89% at the highest and lowest levels, respectively. In the external validation cohort, the score performed similarly well. Notably, in patients who had myocardial infarction neither ruled in nor ruled out via hs-cTnI testing (\"indeterminate zone,\" n=65), the score had an area under the receiver operating characteristic curve of 0.88 (<0.001). Conclusions A model including hs-cTnI can predict the presence of obstructive coronary artery disease with high accuracy including in those with indeterminate hs-cTnI concentrations.



J Am Heart Assoc: 17 Aug 2020; 9:e017221
McCarthy CP, Neumann JT, Michelhaugh SA, Ibrahim NE, ... Westermann D, Januzzi JL
J Am Heart Assoc: 17 Aug 2020; 9:e017221 | PMID: 32757795
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Abstract

Differences in Transforming Growth Factor-β1/BMP7 Signaling and Venous Fibrosis Contribute to Female Sex Differences in Arteriovenous Fistulas.

Cai C, Kilari S, Singh AK, Zhao C, ... Li Y, Misra S

Background Women have decreased hemodialysis arteriovenous fistula (AVF) maturation and patency rates. We determined the mechanisms responsible for the sex-specific differences in AVF maturation and stenosis formation by performing whole transcriptome RNA sequencing with differential gene expression and pathway analysis, histopathological changes, and in vitro cell culture experiments from male and female smooth muscle cells. Methods and Results Mice with chronic kidney disease and AVF were used. Outflow veins were evaluated for gene expression, histomorphometric analysis, Doppler ultrasound, immunohistologic analysis, and fibrosis. Primary vascular smooth muscle cells were collected from female and male aorta vessels. In female AVFs, RNA sequencing with real-time polymerase chain reaction analysis demonstrated a significant decrease in the average gene expression of(bone morphogenetic protein 7) and downstream , with increased transforming growth factor-β1 ( and transforming growth factor-β receptor 1 (. There was decreased peak velocity, negative vascular remodeling with higher venous fibrosis and an increase in synthetic vascular smooth muscle cell phenotype, decrease in proliferation, and increase in apoptosis in female outflow veins at day 28. In vitro primary vascular smooth muscle cell experiments performed under hypoxic conditions demonstrated, in female compared with male cells, that there was increased gene expression of , ,with increased migration. Conclusions In female AVFs, there is decreased gene expression ofandwith increasedand , and the cellular and vascular differences result in venous fibrosis with negative vascular remodeling.



J Am Heart Assoc: 17 Aug 2020; 9:e017420
Cai C, Kilari S, Singh AK, Zhao C, ... Li Y, Misra S
J Am Heart Assoc: 17 Aug 2020; 9:e017420 | PMID: 32757791
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Abstract

Platelet Reactivity in Hepatitis C Virus-Infected Patients on Dual Antiplatelet Therapy for Acute Coronary Syndrome.

Scudiero F, Valenti R, Marcucci R, Sanna GD, ... Canonico ME, Parodi G

Background Coronary artery disease (CAD) has been recognized as a serious and potentially life-threatening complication of Hepatitis C Virus (HCV) infection. High on-treatment platelet reactivity has been associated with high risk of ischemic events in patients with CAD, but data regarding the association with HCV infection are still lacking. This post hoc analysis aims to assess high on-treatment platelet reactivity, severity of CAD, and long-term outcomes of patients with acute coronary syndrome (ACS) who were infected with HCV. Methods and Results Patients with ACS who were infected with HCV (n=47) were matched to patients with ACS and without HCV (n=137) for age, sex, diabetes mellitus, hypertension, and renal function. HCV-infected patients with ACS had higher levels of platelet reactivity (ADP-light transmittance aggregometry, 56±18% versus 44±22% [=0.002]; arachidonic acid-light transmittance aggregometry, 25±21% versus 16±15% [=0.011]) and higher rates of high on-treatment platelet reactivity on clopidogrel and aspirin compared with patients without HCV. Moreover, HCV-infected patients with ACS had higher rates of multivessel disease (53% versus 30%; =0.004) and 3-vessel disease (32% versus 7%; <0.001) compared with patients without HCV. At long-term follow-up, estimated rates of major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, and ischemia-driven revascularization) were 57% versus 34% (=0.005) in HCV- and non-HCV-infected patients with ACS, respectively. In addition, thrombolysis In Myocardial Infarction (TIMI) major bleeding rates were higher in HCV-infected patients (11% versus 3%; =0.043) compared with noninfected patients. Multivariable analysis demonstrated that HCV infection was an independent predictor of high on-treatment platelet reactivity, severity of CAD, and long-term outcome. Conclusions In this hypothesis-generating study, patients with ACS and HCV infection showed increased on-treatment platelet reactivity, more severe CAD, and worse prognosis compared with patients without HCV.



J Am Heart Assoc: 14 Sep 2020; 9:e016441
Scudiero F, Valenti R, Marcucci R, Sanna GD, ... Canonico ME, Parodi G
J Am Heart Assoc: 14 Sep 2020; 9:e016441 | PMID: 32885738
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Abstract

Infective Endocarditis After Surgical and Transcatheter Aortic Valve Replacement: A State of the Art Review.

Alexis SL, Malik AH, George I, Hahn RT, ... Bhatt DL, Tang GHL

Prosthetic valve endocarditis (PVE) after surgical aortic valve replacement and transcatheter aortic valve replacement (TAVR) carries significant morbidity/mortality. Our review aims to compare incidence, predisposing factors, microbiology, diagnosis, management, and outcomes of PVE in surgical aortic valve replacement/TAVR patients. We searched PubMed and Embase to identify published studies from January 1, 2015 to March 13, 2020. Key words were indexed for original reports, clinical studies, and reviews. Reports were evaluated by 2 authors against a priori inclusion/exclusion criteria. Studies were included if they reported incidence and outcomes related to surgical aortic valve replacement/TAVR PVE and excluded if they were published pre-2015 or included a small population. We followed the Cochrane methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for all stages of the design and implementation. Study quality was based on the Newcastle-Ottawa Scale. Thirty-three studies with 311 to 41 025 patients contained relevant information. The majority found no significant difference in incidence of surgical aortic valve replacement/TAVR PVE (reported as 0.3%-1.2% per patient-year versus 0.6%-3.4%), but there were key differences in pathogenesis. TAVR has a specific set of infection risks related to entry site, procedure, and device, including nonstandardized protocols for infection control, valve crimping injury, paravalvular leak, neo-leaflet stress, intact/calcified native leaflets, and intracardiac hardware. With the expansion of TAVR to lower risk and younger patients, a better understanding of pathogenesis, patient presentation, and guideline-directed treatment is paramount. When operative intervention is necessary, mortality remains high at 20% to 30%. Unique TAVR infection risks present opportunities for PVE prevention, therefore, further investigation is imperative.



J Am Heart Assoc: 17 Aug 2020; 9:e017347
Alexis SL, Malik AH, George I, Hahn RT, ... Bhatt DL, Tang GHL
J Am Heart Assoc: 17 Aug 2020; 9:e017347 | PMID: 32772772
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