Journal: J Am Heart Assoc

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Abstract

Arterial Platelet Adhesion in Atherosclerosis-Prone Arteries of Obese, Insulin-Resistant Nonhuman Primates.

Brown E, Ozawa K, Moccetti F, Vinson A, ... Chen J, Lindner JR

Background:
Platelet-endothelial interactions are thought to contribute to early atherogenesis. These interactions are potentiated by oxidative stress. We used in vivo molecular imaging to test the hypothesis that platelet-endothelial interactions occur at early stages of plaque development in obese, insulin-resistant nonhuman primates, and are suppressed by NADPH-oxidase-2 inhibition. Methods and Results Six adult rhesus macaques fed a Western-style diet for a median of 4.0 years were studied at baseline and after 8 weeks of therapy with the NADPH-oxidase-2-inhibitor apocynin (50 mg/kg per day). Six lean control animals were also studied. Measurements included intravenous glucose tolerance test, body composition by dual-energy X-ray absorptiometry, carotid intimal medial thickness, carotid artery contrast ultrasound molecular imaging for platelet GPIbα (glycoprotein- Ibα) and vascular cell adhesion molecule-1, and blood oxidative markers on mass spectrometry. Compared with lean controls, animals on a Western-style diet were obese (median body mass: 16.0 versus 8.7 kg, P=0.003; median truncal fat: 49% versus 20%, P=0.002), were insulin resistant (4-fold higher insulin-glucose area under the curve on intravenous glucose tolerance test, P=0.002), had 40% larger carotid intimal medial thickness (P=0.004), and exhibited oxidative signatures on proteomics. In obese but not lean animals, signal enhancement on molecular imaging was significantly elevated for GPIbα and vascular cell adhesion molecule-1. The signal correlated modestly with intimal medial thickness but not with the degree of insulin resistance. Apocynin significantly (P<0.01) reduced median signal for GPIbα by >80% and vascular cell adhesion molecule-1 signal by 75%, but did not affect intimal medial thickness, body mass, or intravenous glucose tolerance test results.
Conclusion:
In nonhuman primates, diet-induced obesity and insulin resistance leads to platelet-endothelial adhesion at early atherosclerotic lesion sites, which is associated with the expression of pro-inflammatory adhesion molecules. These responses appear to be mediated, in part, through oxidative pathways.




J Am Heart Assoc: 20 Apr 2021:e019413; epub ahead of print
Brown E, Ozawa K, Moccetti F, Vinson A, ... Chen J, Lindner JR
J Am Heart Assoc: 20 Apr 2021:e019413; epub ahead of print | PMID: 33880941
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Abstract

Long-Term Outcomes of Acute Kidney Injury After Different Types of Cardiac Surgeries: A Population-Based Study.

Chen JJ, Chang CH, Wu VC, Chang SH, ... Chu PH, Chen SW

Background:
Dialysis-requiring acute kidney injury (D-AKI) is a major complication of cardiovascular surgery that results in worse prognosis. However, the incidence and impacts of D-AKI in different types of cardiac surgeries have not been fully investigated. Methods and Results Patients admitted for cardiovascular surgery between July 1, 2004, and December 31, 2013, were identified from the National Health Insurance Research Database of Taiwan. The patients were grouped into D-AKI (n=3089) and non-D-AKI (n=42 151) groups. The outcome was all-cause mortality and major adverse kidney event. The long-term outcomes were worse in the D-AKI group than the non-D-AKI group (hazard ratio [HR], 3.89; 95% CI, 3.79-3.99 for major adverse kidney event; HR, 2.89; 95% CI, 2.81-2.98 for all-cause mortality). Patients who underwent aortic surgery had higher risk for D-AKI than other types of surgeries, but they were also more likely to recover. The long-term dialysis rate for the patients who recovered from D-AKI was also lowest in those who underwent aortic surgery. Among all types of cardiac surgeries with D-AKI, patients who had heart valve surgery exhibited the greatest risks of all-cause mortality (HR, 6.04; 95% CI, 5.78-6.32).
Conclusions:
Compared with other heart surgeries, aortic surgery resulted in a higher incidence of D-AKI but better renal recovery, better short-term outcome, and lower incidences of long-term dialysis.




J Am Heart Assoc: 20 Apr 2021:e019718; epub ahead of print
Chen JJ, Chang CH, Wu VC, Chang SH, ... Chu PH, Chen SW
J Am Heart Assoc: 20 Apr 2021:e019718; epub ahead of print | PMID: 33880935
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Abstract

Electrocardiographic Imaging of Repolarization Abnormalities.

Bear LR, Cluitmans M, Abell E, Rogier J, ... Coronel R, Dubois R

Background:
Dispersion and gradients in repolarization have been associated with life-threatening arrhythmias, but are difficult to quantify precisely from surface electrocardiography. The objective of this study was to evaluate electrocardiographic imaging (ECGI) to noninvasively detect repolarization-based abnormalities. Methods and Results Ex vivo data were obtained from Langendorff-perfused pig hearts (n=8) and a human donor heart. Unipolar electrograms were recorded simultaneously during sinus rhythm from an epicardial sock and the torso-shaped tank within which the heart was suspended. Regional repolarization heterogeneities were introduced through perfusion of dofetilide and pinacidil into separate perfusion beds. In vivo data included torso and epicardial potentials recorded simultaneously in anesthetized, closed-chest pigs (n=5), during sinus rhythm, and ventricular pacing. For both data sets, ECGI accurately reconstructed T-wave electrogram morphologies when compared with those recorded by the sock (ex vivo: correlation coefficient, 0.85 [0.52-0.96], in vivo: correlation coefficient, 0.86 [0.52-0.96]) and repolarization time maps (ex-vivo: correlation coefficient, 0.73 [0.63-0.83], in vivo: correlation coefficient, 0.76 [0.67-0.82]). ECGI-reconstructed repolarization time distributions were strongly correlated to those measured by the sock (both data sets, R2 ≥0.92). Although the position of the gradient was slightly shifted by 8.3 (0-13.9) mm, the mean, max, and SD between ECGI and recorded gradient values were highly correlated (R2=0.87, 0.75, and 0.86 respectively). There was no significant difference in ECGI accuracy between ex vivo and in vivo data.
Conclusions:
ECGI reliably and accurately maps potentially critical repolarization abnormalities. This noninvasive approach allows imaging and quantifying individual parameters of abnormal repolarization-based substrates in patients with arrhythmogenesis, to improve diagnosis and risk stratification.




J Am Heart Assoc: 20 Apr 2021:e020153; epub ahead of print
Bear LR, Cluitmans M, Abell E, Rogier J, ... Coronel R, Dubois R
J Am Heart Assoc: 20 Apr 2021:e020153; epub ahead of print | PMID: 33880931
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Abstract

Epidemiology of Heart Failure Stages in Middle-Aged Black People in the Community: Prevalence and Prognosis in the Atherosclerosis Risk in Communities Study.

Vasan RS, Musani SK, Matsushita K, Beard W, ... Mosley TH, Fox E

Background:
Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993-1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) Stage 0: no risk factors; (2) Stage A: presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) Stage B: presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) Stage C/D: prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all-cause mortality on follow-up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow-up (median 19.0 years), 309 participants developed overt HF, 390 incurred new-onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person-years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5- to 2-fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A.
Conclusions:
In our large community-based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.




J Am Heart Assoc: 20 Apr 2021:e016524; epub ahead of print
Vasan RS, Musani SK, Matsushita K, Beard W, ... Mosley TH, Fox E
J Am Heart Assoc: 20 Apr 2021:e016524; epub ahead of print | PMID: 33880930
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Abstract

Hepatic Steatosis in Patients With Single Ventricle and a Fontan Circulation.

Katz DA, Peck D, Lubert AM, Possner M, ... Veldtman G, Alsaied T

Background:
Hepatic steatosis, caused by nonalcoholic fatty liver disease, is a leading cause of chronic liver disease. The interplay between hepatic steatosis and the development of liver disease following the Fontan procedure is not well understood. This study examined the prevalence and associations of hepatic steatosis in patients with a Fontan circulation. Methods and Results This was a single-center retrospective study of 95 patients with a Fontan circulation with liver magnetic resonance imaging performed between 2012 and 2019. The average age at magnetic resonance imaging was 21.5±8.5 years. The percent liver fat signal was determined using magnetic resonance chemical shift-encoded proton density fat fraction imaging. Hepatic steatosis was defined as liver fat ≥5% and was present in 10.5% of the cohort. The presence of hepatic steatosis was associated with higher body mass index (29±4 versus 24±6 kg/m2, P=0.006), a higher frequency of obesity (50% versus 12%, P=0.015), lower high-density lipoprotein cholesterol (35±9 versus 43±14 mg/dL, P=0.050), and greater subcutaneous fat thickness (2.6±0.7 versus 1.8±1.0 cm, P=0.043). There was no association between hepatic steatosis and cardiovascular imaging or hemodynamic variables from cardiac catheterization.
Conclusions:
Risk factors for hepatic steatosis in patients with Fontan circulation include obesity and dyslipidemia, similar to what is seen in the general population. Fontan hemodynamics were not associated with hepatic steatosis.




J Am Heart Assoc: 20 Apr 2021:e019942; epub ahead of print
Katz DA, Peck D, Lubert AM, Possner M, ... Veldtman G, Alsaied T
J Am Heart Assoc: 20 Apr 2021:e019942; epub ahead of print | PMID: 33880928
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Abstract

Effect of Active Cancer on the Cardiac Phenotype: A Cardiac Magnetic Resonance Imaging-Based Study of Myocardial Tissue Health and Deformation in Patients With Chemotherapy-Naïve Cancer.

Labib D, Satriano A, Dykstra S, Hansen R, ... Lee J, White JA

Background:
The overlap between cancer and cardiovascular care continues to expand, with intersections emerging before, during, and following cancer therapies. To date, emphasis has been placed on how cancer therapeutics influence downstream cardiac health. However, whether active malignancy itself influences chamber volumes, function, or overall myocardial tissue health remains uncertain. We sought to perform a comprehensive cardiovascular magnetic resonance-based evaluation of cardiac health in patients with chemotherapy-naïve cancer with comparison with a healthy volunteer population. Methods and Results Three-hundred and eighty-one patients with active breast cancer or lymphoma before cardiotoxic chemotherapy exposure were recruited in addition to 102 healthy volunteers. Both cohorts underwent standardized cardiovascular magnetic resonance imaging with quantification of chamber volumes, ejection fraction, and native myocardial T1. Left ventricular mechanics were incrementally assessed using three-dimensional myocardial deformation analysis, providing global longitudinal, circumferential, radial, and principal peak-systolic strain amplitude and systolic strain rate. The mean age of patients with cancer was 53.8±13.4 years; 79% being women. Despite similar left ventricular ejection fraction, patients with cancer showed smaller chambers, increased strain amplitude, and systolic strain rate in both conventional and principal directions, and elevated native T1 versus sex-matched healthy volunteers. Adjusting for age, sex, hypertension, and diabetes mellitus, the presence of cancer remained associated with these cardiovascular magnetic resonance parameters.
Conclusions:
The presence of cancer is independently associated with alterations in cardiac chamber size, function, and objective markers of tissue health. Dedicated research is warranted to elucidate pathophysiologic mechanisms underlying these findings and to explore their relevance to the management of patients with cancer referred for cardiotoxic therapies.




J Am Heart Assoc: 20 Apr 2021:e019811; epub ahead of print
Labib D, Satriano A, Dykstra S, Hansen R, ... Lee J, White JA
J Am Heart Assoc: 20 Apr 2021:e019811; epub ahead of print | PMID: 33878890
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Abstract

Screening for Atrial Fibrillation in American Indian Adults in a Tribal Primary Care Clinic.

Stavrakis S, Elkholey K, Lofgren MM, Asad ZUA, Stephens LD, Freedman B

Background:
American Indian adults have a higher risk of atrial fibrillation (AF) compared with other racial groups. We implemented opportunistic screening to detect silent AF in American Indian adults attending a tribal health system using a mobile, single-lead ECG device. Methods and Results American Indian patients aged ≥50 years followed in a tribal primary care clinic with no history of AF underwent a 30-second ECG. A cardiologist overread all tracings to confirm the diagnosis of AF. After AF was confirmed, patients were referred to their primary care physician for initiation of anticoagulation. Patients seen over the same time period, who were not undergoing screening, served as controls. A total of 1019 patients received AF screening (mean age, 61.5±8.9 years, 62% women). Age and sex distribution of those screened was similar to the overall clinic population. New AF was diagnosed in 15 of 1019 (1.5%) patients screened versus 4 of 1267 (0.3%) patients who were not screened (mean difference, 1.2%; 95% CI, 0.3%-2.2%, P=0.002). Eight of 15 with new screen-detected AF were aged <65 years. Those with screen-detected AF were slightly older and had a higher CHA2DS2-VASc score than those without AF. Fourteen of 15 patients diagnosed with new AF had a CHA2DS2-VASc score ≥1 and initiated anticoagulation.
Conclusions:
Opportunistic, mobile single-lead ECG screening for AF is feasible in tribal clinics, and detects more AF than usual care, leading to appropriate initiation of anticoagulation. AF develops at a younger age in American Indian adults who would likely benefit from earlier AF screening. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03740477.




J Am Heart Assoc: 20 Apr 2021:e020069; epub ahead of print
Stavrakis S, Elkholey K, Lofgren MM, Asad ZUA, Stephens LD, Freedman B
J Am Heart Assoc: 20 Apr 2021:e020069; epub ahead of print | PMID: 33878888
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Abstract

Anticoagulation Before Hospitalization Is a Potential Protective Factor for COVID-19: Insight From a French Multicenter Cohort Study.

Chocron R, Galand V, Cellier J, Gendron N, ... Smadja DM, Critical COVID‐19 France Investigators

Background:
Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes.
Conclusions:
Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.




J Am Heart Assoc: 19 Apr 2021; 10:e018624
Chocron R, Galand V, Cellier J, Gendron N, ... Smadja DM, Critical COVID‐19 France Investigators
J Am Heart Assoc: 19 Apr 2021; 10:e018624 | PMID: 33550816
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Abstract

Association of Pro-B-Type Natriuretic Peptide With Cardiac Magnetic Resonance-Measured Global and Regional Cardiac Function and Structure Over 10 Years: The MESA Study.

Rahsepar AA, Bluemke DA, Habibi M, Liu K, ... Lima JAC, Carr JC

Background:
NT-proBNP (N-terminal pro-B-type natriuretic peptide) is widely used to diagnose and manage patients with heart failure. We aimed to investigate associations between NT-proBNP levels and development of global and regional myocardial impairment, dyssynchrony, and risk of developing myocardial scar over time. Methods and Results We included 2416 adults (45-84 years) without baseline clinical cardiovascular disease from MESA (Multi-Ethnic Study of Atherosclerosis). NT-proBNP was assessed at baseline (2000-2002). Cardiac magnetic resonance-measured left ventricular parameters were assessed at baseline and year 10 (2010-2012). Tagged cardiac magnetic resonance and myocardial dyssynchrony were assessed. We used linear and logistic regression models to study the relationships between quartiles of NT-proBNP levels and outcome variables. Left ventricular parameters decreased over time. After 10-year follow-up and adjusting for cardiovascular disease risk factors, people in the highest quartile had significantly greater decline in left ventricular ejection fraction (-1.60%; 95% CI, -2.26 to -0.94; P<0.01) and smaller decline in left ventricular end systolic volume index (-0.47 mL/m2; 95% CI, -1.18 to 0.23; P<0.01) compared with those in the lowest quartile. Individuals in the highest quartile had more severe risk factor adjusted global, mid, and apical regional dyssynchrony compared with those in the lowest, second, and third quartiles (all P-trend<0.05). Compared with the lowest-quartile group, the adjusted odds ratios for having myocardial scar was 1.3 (95% CI, 0.7-2.2) for quartile 2; 1.2 (95% CI, 0.6-2.3) for quartile 3; and 2.7 (95% CI, 1.4-5.5) for quartile 4 (P-trend=0.012) for the total sample.
Conclusions:
Among participants without baseline clinical cardiovascular disease, higher baseline NT-proBNP concentration was significantly associated with subclinical changes in developing myocardial dysfunction, more severe cardiac dyssynchrony, and higher odds of having myocardial scar over a 10-year period independent of traditional cardiovascular disease risk factors.




J Am Heart Assoc: 19 Apr 2021; 10:e019243
Rahsepar AA, Bluemke DA, Habibi M, Liu K, ... Lima JAC, Carr JC
J Am Heart Assoc: 19 Apr 2021; 10:e019243 | PMID: 33821688
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Abstract

Factors Associated With PCSK9 Inhibitor Initiation Among US Veterans.

Derington CG, Colantonio LD, Herrick JS, Cook J, ... Muntner P, Bress AP

Background:
Few adults at high risk for atherosclerotic cardiovascular disease events use a PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitor). Methods and Results Using data from the US Veterans Health Administration, we identified veterans who initiated a PCSK9i between January 2018 and December 2019, matched 1:4 to veterans who did not initiate this medication over this time period (case-cohort study). Two cohorts of veterans were analyzed: (1) atherosclerotic cardiovascular disease, with a most recent low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL; and (2) severe hypercholesterolemia (ie, familial hypercholesterolemia or any prior LDL-C ≥190 mg/dL, with most recent LDL-C ≥100 mg/dL). Conditional logistic regression was used to analyze factors associated with PCSK9i initiation, adjusting for all factors, simultaneously. There were 2394 initiators and 9576 noninitiators in the atherosclerotic cardiovascular disease cohort (median LDL-C, 141 and 96 mg/dL, respectively; P<0.001). Factors associated with a higher likelihood of PCSK9i initiation included age 65 to <75 versus <65 years, highest versus lowest quartile of median area-level income, familial hypercholesterolemia, former statin use, and current ezetimibe use. PCSK9i initiation was lower among veterans of a race/ethnicity other than non-Hispanic White. There were 245 initiators and 980 noninitiators in the severe hypercholesterolemia cohort (median LDL-C, 183 and 151 mg/dL, respectively; P<0.001). Age ≥75 versus <65 years, history of chronic kidney disease, former statin use, and current ezetimibe use were associated with a higher likelihood of PCSK9i initiation.
Conclusions:
Several patient-level factors, including age, sex, and race/ethnicity, were significantly associated with PCSK9i initiation, suggesting an unmet treatment need in several patient groups.




J Am Heart Assoc: 19 Apr 2021; 10:e019254
Derington CG, Colantonio LD, Herrick JS, Cook J, ... Muntner P, Bress AP
J Am Heart Assoc: 19 Apr 2021; 10:e019254 | PMID: 33821686
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Abstract

Short-Term Effects of Inhaled Nitric Oxide on Right Ventricular Flow Hemodynamics by 4-Dimensional-Flow Magnetic Resonance Imaging in Children With Pulmonary Arterial Hypertension.

Schäfer M, Frank BS, Ivy DD, Abman SH, ... Morgan GJ, Truong U

Background:
Pulmonary arterial hypertension (PAH) manifests with progressive right ventricular (RV) dysfunction, which eventually impairs the left ventricular function. We hypothesized that 4-dimensional-flow magnetic resonance imaging can detect flow hemodynamic changes associated with efficient intracardiac flow during noninvasive inhaled nitric oxide (iNO) challenge in children with PAH. Methods and Results Children with PAH (n=10) underwent 2 same-day separate iNO challenge tests using: (1) 4-dimensional-flow magnetic resonance imaging and (2) standard catheterization hemodynamics. Intracardiac flow was evaluated using the particle tracking 4-flow component analysis technique evaluating the direct flow, retained inflow, delayed ejection flow, and residual volume. Respective flow hemodynamic changes were compared with the corresponding catheterization iNO challenge results. The RV analysis revealed decreased direct flow in patients with PAH when compared with controls (P<0.001) and increase in residual volume (P<0.001). Similarly, the left ventricular analysis revealed decreased direct flow in patients with PAH when compared with controls (P=0.004) and increased proportion of the residual volume (P=0.014). There was an increase in the RV direct flow during iNO delivery (P=0.009), with parallel decrease in the residual volume (P=0.008).
Conclusions:
Children with PAH have abnormal biventricular flow associated with impaired diastolic filling. The flow efficiency is significantly improved in the RV on iNO administration with no change in the left ventricle. The changes in the RV flow have occurred despite the minimal change in catheterization hemodynamics, suggesting that flow hemodynamic evaluation might provide more quantitative insights into vasoreactivity testing in PAH.




J Am Heart Assoc: 19 Apr 2021; 10:e020548
Schäfer M, Frank BS, Ivy DD, Abman SH, ... Morgan GJ, Truong U
J Am Heart Assoc: 19 Apr 2021; 10:e020548 | PMID: 33821682
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Abstract

Maternal and Neonatal Outcomes of Pregnancies in Women With Congenital Heart Disease: A Meta-Analysis.

Hardee I, Wright L, McCracken C, Lawson E, Oster ME

Background:
With advances in the treatment of congenital heart disease (CHD), more women with CHD survive childhood to reach reproductive age. The objective of this study was to evaluate the maternal and neonatal outcomes of pregnancies among women with CHD in the modern era. Methods and Results We conducted a meta-analysis of peer-reviewed literature published January 2007 through June 2019. Studies were included if they reported on maternal or fetal mortality and provided data by CHD lesion. Meta-analysis was performed using random effect regression modeling using Comprehensive Meta-Analysis (v3). CHD lesions were categorized as mild, moderate, and severe to allow for pooling of data across studies. Of 2200 articles returned by our search, 32 met inclusion criteria for this study. Overall, the rate of neonatal mortality was 1%, 3.1%, and 3.5% in mild, moderate, and severe lesions, respectively. There were too few maternal deaths in any group to pool data. The rates of maternal and neonatal morbidity among women with CHD increase with severity of lesion. Specifically, rates of maternal arrhythmia and heart failure, cesarean section, preterm birth, and small for gestational age neonate are all markedly increased as severity of maternal CHD increases.
Conclusions:
In the modern era, pregnancy in women with CHD typically has a successful outcome in both mother and child. However, as maternal CHD severity increases, so too does the risk of numerous morbidities and neonatal mortality. These findings may help in counseling women with CHD who plan to become pregnant, especially women with severe lesions.




J Am Heart Assoc: 19 Apr 2021; 10:e017834
Hardee I, Wright L, McCracken C, Lawson E, Oster ME
J Am Heart Assoc: 19 Apr 2021; 10:e017834 | PMID: 33821681
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Abstract

Reversible Cause of Cardiac Arrest and Secondary Prevention Implantable Cardioverter Defibrillators in Patients With Coronary Artery Disease: Value of Complete Revascularization and LGE-CMR.

van der Lingen ACJ, Becker MAJ, Kemme MJB, Rijnierse MT, ... Germans T, Allaart CP

Background:
In survivors of sudden cardiac arrest with obstructive coronary artery disease, it remains challenging to distinguish ischemia as a reversible cause from irreversible scar-related ventricular arrhythmias. We aimed to evaluate the value of implantable cardioverter-defibrillator (ICD) implantation in sudden cardiac arrest survivors with presumably reversible ischemia and complete revascularization. Methods and Results This multicenter retrospective cohort study included 276 patients (80% men, age 67±10 years) receiving ICD implantation for secondary prevention. Angiography was performed before ICD implantation. A subgroup of 166 (60%) patients underwent cardiac magnetic resonance imaging with late gadolinium enhancement before implantation. Patients were divided in 2 groups, (1) ICD-per-guideline, including 228 patients with incomplete revascularization or left ventricular ejection fraction ≤35%, and (2) ICD-off-label, including 48 patients with complete revascularization and left ventricular ejection fraction >35%. The primary outcome was time to appropriate device therapy (ADT). During 4.0 years (interquartile range, 3.5-4.6) of follow-up, ADT developed in 15% of the ICD-off-label group versus 43% of the ICD-per-guideline group. Time to ADT was comparable in the ICD-off-label and ICD-per-guideline groups (hazard ratio (HR), 0.46; P=0.08). No difference in mortality was observed (HR, 0.95; P=0.93). Independent predictors of ADT included age (HR, 1.03; P=0.01), left ventricular end-diastolic volume HR, (1.05 per 10 mL increase; P<0.01) and extent of transmural late gadolinium enhancement (HR, 1.12; P=0.04).
Conclusions:
This study demonstrates that sudden cardiac arrest survivors with coronary artery disease remain at high risk of recurrent ventricular arrhythmia, even after complete revascularization and with preserved left ventricular function. Late gadolinium enhancement-cardiac magnetic resonance imaging derived left ventricular volumes and extent of myocardial scar were independently associated with.




J Am Heart Assoc: 19 Apr 2021; 10:e019101
van der Lingen ACJ, Becker MAJ, Kemme MJB, Rijnierse MT, ... Germans T, Allaart CP
J Am Heart Assoc: 19 Apr 2021; 10:e019101 | PMID: 33821672
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Abstract

Troponin, A Predictor of Mortality in Methadone Exposure: An Observational Prospective Study.

Sheibani M, Mirfallah Nassiri AA, Abedtash A, McDonald R, Zamani N, Hassanian-Moghaddam H

Background:
Methadone poisoning/overdose is a global public health problem. We aimed to determine whether methadone poisoning increased cardiac troponin and whether high-sensitivity cardiac troponin I (hs-cTnI) levels predicted the need for intensive care unit admission, intubation, and mortality. Methods and Results This observational, prospective single-center study was done at Loghman-Hakim Hospital (Tehran, Iran) from June 2018 until February 2019. Patients aged >14 years admitted with a diagnosis of methadone exposure were included. Patients were excluded if they had coexisting conditions associated with elevated hs-cTnI levels. An ECG and hs-cTnI levels were obtained on emergency department presentation. Patients were followed up on their need for intubation, intensive care unit admission, and in-hospital mortality. Of 245 included patients (186 [75.9%] men; median age, 33 years), most referred to loss of consciousness (210 cases, 89%). Nineteen (7.7%) patients had hs-cTnI levels of >0.1 ng/mL (positive), and 41 (16.7%) had borderline levels of 0.019 to 0.1 ng/mL. Twenty-three (9.3%) cases were admitted to the intensive care unit, 21 (8.5%) needed intubation, and 5 (2%) died during hospitalization. An hs-cTnI cutoff value of 0.019 ng/mL independently predicted mortality. For optimal concomitant sensitivity and specificity, receiver operating characteristic curve analysis was conducted and showed that hs-cTnI had an independent significant association with mortality, with a cutoff value of 0.0365 ng/mL (odds ratio, 38.1; 95% CI, 2.3-641.9; P<0.001).
Conclusions:
Methadone exposure/toxicity is a newly identified cause of elevated hs-cTnI. Values >0.019 ng/mL, and particularly >0.0365 ng/mL, of hs-cTnI predicted mortality in our sample. Future studies should measure troponin levels in methadone maintenance treatment clients to assess the risk of myocardial injury from long-term exposure.




J Am Heart Assoc: 19 Apr 2021; 10:e018899
Sheibani M, Mirfallah Nassiri AA, Abedtash A, McDonald R, Zamani N, Hassanian-Moghaddam H
J Am Heart Assoc: 19 Apr 2021; 10:e018899 | PMID: 33821671
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Abstract

Left Ventricular Dysfunction in Arrhythmogenic Cardiomyopathy: Association With Exercise Exposure, Genetic Basis, and Prognosis.

Lie ØH, Chivulescu M, Rootwelt-Norberg C, Ribe M, ... Almaas V, Haugaa KH

Background:
Arrhythmogenic cardiomyopathy (AC) is characterized by biventricular dysfunction, exercise intolerance, and high risk of ventricular tachyarrhythmias and sudden death. Predisposing factors for left ventricular (LV) disease manifestation and its prognostic implication in AC are poorly described. We aimed to assess the associations of exercise exposure and genotype with LV dysfunction in AC, and to explore the impact of LV disease progression on adverse arrhythmic outcome. Methods and Results We included 168 patients with AC (50% probands, 45% women, 40±16 years old) with 715 echocardiographic exams (4.1±1.7 exams/patient, follow-up 7.6 [interquartile range (IQR), 5.4-10.9] years) and complete exercise and genetic data in a longitudinal study. LV function by global longitudinal strain was -18.8% [IQR, -19.2% to -18.3%] at presentation and was worse in patients with greater exercise exposure (global longitudinal strain worsening, 0.09% [IQR, 0.01%-0.17%] per 5 MET-hours/week, P=0.02). LV function by global longitudinal strain worsened, with 0.08% [IQR, 0.05%-0.12%] per year; (P<0.001), and progression was most evident in patients with desmoplakin genotype (P for interaction <0.001). Deterioration of LV function predicted incident ventricular tachyarrhythmia (aborted cardiac arrest, sustained ventricular tachycardia, or implantable cardioverter defibrillator shock) (adjusted odds ratio, 1.1 [IQR, 1.0-1.3] per 1% worsening by global longitudinal strain; P=0.02, adjusted for time and previous arrhythmic events).
Conclusions:
Greater exercise exposure was associated with worse LV function at first visit of patients with AC but did not significantly affect the rate of LV progression during follow-up. Progression of LV dysfunction was most pronounced in patients with desmoplakin genotypes. Deterioration of LV function during follow-up predicted subsequent ventricular tachyarrhythmia and should be considered in risk stratification.




J Am Heart Assoc: 19 Apr 2021; 10:e018680
Lie ØH, Chivulescu M, Rootwelt-Norberg C, Ribe M, ... Almaas V, Haugaa KH
J Am Heart Assoc: 19 Apr 2021; 10:e018680 | PMID: 33821670
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Impact:
Abstract

Survival Following Edge-to-Edge Transcatheter Mitral Valve Repair in Patients With Cardiogenic Shock: A Nationwide Analysis.

Tang GHL, Estevez-Loureiro R, Yu Y, Prillinger JB, Zaid S, Psotka MA

Background:
Edge-to-edge transcatheter mitral valve repair as salvage therapy in high surgical risk patients with severe mitral regurgitation presenting with cardiogenic shock (CS) has been described in small case series, but large clinical results have not been reported. This study aimed to evaluate outcomes of transcatheter mitral valve repair with MitraClip in patients with mitral regurgitation and CS using a large national database. Methods and Results From January 2014 to March 2019, we identified hospitalizations for CS in patients with mitral valve disease using data from Centers for Medicare and Medicaid Services. Those with a prior surgical or percutaneous mitral valve intervention were excluded. We compared survival between patients who underwent MitraClip during the index hospitalization and those who did not using propensity-matched analysis. The analysis included 38 166 patients (mean age, 71±11 years, 41.6% women) of whom 622 (1.6%) underwent MitraClip. MitraClip was increasingly used during CS hospitalizations over the study period (P<0.001). After matching, patients receiving MitraClip had significantly lower in-hospital mortality (odds ratio, 0.6; 95% CI, 0.47-0.77; P<0.001) and 1-year mortality (hazard ratio, 0.76; 95% CI, 0.65-0.88; P<0.001) compared with those without MitraClip. The survival benefit associated with MitraClip was consistent across subgroups of interest, with the exception of patients requiring acute mechanical circulatory support or hemodialysis at index.
Conclusions:
In patients with mitral regurgitation presenting with CS, use of MitraClip is increasing and associated with greater in-hospital and 1-year survival. Further studies are warranted to optimize patient selection and procedure timing for those receiving MitraClip as a treatment option in CS.




J Am Heart Assoc: 19 Apr 2021; 10:e019882
Tang GHL, Estevez-Loureiro R, Yu Y, Prillinger JB, Zaid S, Psotka MA
J Am Heart Assoc: 19 Apr 2021; 10:e019882 | PMID: 33821669
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Impact:
Abstract

All Roads Lead to Rome (the Heart): Cell Retention and Outcomes From Various Delivery Routes of Cell Therapy Products to the Heart.

Li J, Hu S, Zhu D, Huang K, ... López de Juan Abad B, Cheng K
In the past decades, numerous preclinical studies and several clinical trials have evidenced the feasibility of cell transplantation in treating heart diseases. Over the years, different delivery routes of cell therapy have emerged and broadened the width of the field. However, a common hurdle is shared by all current delivery routes: low cell retention. A myriad of studies confirm that cell retention plays a crucial role in the success of cell-mediated cardiac repair. It is important for any delivery route to maintain donor cells in the recipient heart for enough time to not only proliferate by themselves, but also to send paracrine signals to surrounding damaged heart cells and repair them. In this review, we first undertake an in-depth study of primary theories of cell loss, including low efficiency in cell injection, \"washout\" effects, and cell death, and then organize the literature from the past decade that focuses on cell transplantation to the heart using various cell delivery routes, including intracoronary injection, systemic intravenous injection, retrograde coronary venous injection, and intramyocardial injection. In addition to a recapitulation of these approaches, we also clearly evaluate their strengths and weaknesses. Furthermore, we conduct comparative research on the cell retention rate and functional outcomes of these delivery routes. Finally, we extend our discussion to state-of-the-art bioengineering techniques that enhance cell retention, as well as alternative delivery routes, such as intrapericardial delivery. A combination of these novel strategies and more accurate assessment methods will help to address the hurdle of low cell retention and boost the efficacy of cell transplantation to the heart.



J Am Heart Assoc: 19 Apr 2021; 10:e020402
Li J, Hu S, Zhu D, Huang K, ... López de Juan Abad B, Cheng K
J Am Heart Assoc: 19 Apr 2021; 10:e020402 | PMID: 33821664
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Impact:
Abstract

Cardiac Morphology, Function, and Hemodynamics in Patients With Morbid Obesity and Nonalcoholic Steatohepatitis.

Styczynski G, Kalinowski P, Michałowski Ł, Paluszkiewicz R, ... Szmigielski CA, Sinski M

Background:
The patients with nonalcoholic fatty liver disease demonstrate an increased cardiovascular risk. The adverse influence of liver abnormalities on cardiac function are among many postulated mechanisms behind this association. The aim of the study was to evaluate cardiac morphology and function in patients with morbid obesity referred for bariatric surgery with liver biopsy. Methods and Results We evaluated with echocardiography 171 consecutive patients without known cardiac disease (median age 42 [interquartile range, 37-48] years, median body mass index 43.7 [interquartile range, 41.0-47.5], 67% female patients. Based on the liver biopsy results, there were 44 patients with nonalcoholic steatohepatitis (NASH), 69 patients with isolated steatosis, and 58 patients without steatosis. Patients with NASH demonstrated signs of left ventricular concentric remodeling and hyperdynamic circulation, including indexed left ventricular end-diastolic diameter [cm/m2]: NASH 1.87 [0.22]; isolated steatosis 2.03 [0.33]; without steatosis 2.01 [0.19], P=0.001; relative wall thickness: NASH 0.49±0.05, isolated steatosis 0.47±0.06, without steatosis 0.46±0.06, P=0.011; cardiac index [L/m2]: NASH 3.05±0.54, isolated steatosis 2.80±0.44, without steatosis 2.79±0.50, P=0.013. After adjustment for sex, age, blood pressure, and heart rate, most of the measures of the left ventricular systolic and diastolic function, left atrial size, right ventricular function, and right ventricular size did not differ between groups.
Conclusions:
In a group of patients with extreme obesity, NASH was associated with left ventricular concentric remodeling and hyperdynamic circulation. Increased cardiac output in NASH may represent an additional risk factor for incident cardiovascular events in this population.




J Am Heart Assoc: 19 Apr 2021; 10:e017371
Styczynski G, Kalinowski P, Michałowski Ł, Paluszkiewicz R, ... Szmigielski CA, Sinski M
J Am Heart Assoc: 19 Apr 2021; 10:e017371 | PMID: 33847141
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Impact:
Abstract

Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study.

Dreier R, Andersen UB, Forman JL, Sheykhzade M, Egfjord M, Jeppesen JL

Background:
Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure-raising hormone aldosterone. Besides its well-described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors-independent actions are also thought to be involved. Methods and Results To gain further insight into the effect of increased potassium intake and potassium-stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo-controlled double-blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure-monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P=0.0002) and aldosterone (median [interquartile range], 440 [336-521] versus 237 [173-386] pmol/L; P<0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII-stimulated aldosterone secretion (P=0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo.
Conclusions:
Increased potassium intake potentiates AngII-stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. Registration EudraCT Number: 2013-004460-66; URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02380157.




J Am Heart Assoc: 18 Apr 2021:e018716; epub ahead of print
Dreier R, Andersen UB, Forman JL, Sheykhzade M, Egfjord M, Jeppesen JL
J Am Heart Assoc: 18 Apr 2021:e018716; epub ahead of print | PMID: 33870711
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Impact:
Abstract

Associations of Skeletal Muscle Mass and Fat Mass With Incident Cardiovascular Disease and All-Cause Mortality: A Prospective Cohort Study of UK Biobank Participants.

Knowles R, Carter J, Jebb SA, Bennett D, Lewington S, Piernas C

Background:
There is debate whether body mass index is a good predictor of health outcomes because different tissues, namely skeletal muscle mass (SMM) and fat mass (FM), may be differentially associated with risk. We investigated the association of appendicular SMM (aSMM) and FM with fatal and nonfatal cardiovascular disease (CVD) and all-cause mortality. We compared their prognostic value to that of body mass index. Methods and Results We studied 356 590 UK Biobank participants aged 40 to 69 years with bioimpedance analysis data for whole-body FM and predicted limb muscle mass (to calculate aSMM). Associations between aSMM and FM with CVD and all-cause mortality were examined using multivariable Cox proportional hazards models. Over 3 749 501 person-years of follow-up, there were 27 784 CVD events and 15 844 all-cause deaths. In men, aSMM was positively associated with CVD incidence (hazard ratio [HR] per 1 SD 1.07; 95% CI, 1.06-1.09) and there was a curvilinear association in women. There were stronger positive associations between FM and CVD with HRs per SD of 1.20 (95% CI, 1.19-1.22) and 1.25 (95% CI, 1.23-1.27) in men and women respectively. Within FM tertiles, the associations between aSMM and CVD risk largely persisted. There were J-shaped associations between aSMM and FM with all-cause mortality in both sexes. Body mass index was modestly better at discriminating CVD risk.
Conclusions:
FM showed a strong positive association with CVD risk. The relationship of aSMM with CVD risk differed between sexes, and potential mechanisms need further investigation. Body fat and SMM bioimpedance measurements were not superior to body mass index in predicting population-level CVD incidence or all-cause mortality.




J Am Heart Assoc: 18 Apr 2021:e019337; epub ahead of print
Knowles R, Carter J, Jebb SA, Bennett D, Lewington S, Piernas C
J Am Heart Assoc: 18 Apr 2021:e019337; epub ahead of print | PMID: 33870707
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Impact:
Abstract

Impact of Oral Anticoagulation Therapy Versus Left Atrial Appendage Occlusion on Cognitive Function and Quality of Life in Patients With Atrial Fibrillation.

Mohanty S, Mohanty P, Trivedi C, Assadourian J, ... Gurol ME, Natale A

Background:
We compared the cognitive status and quality of life in patients with atrial fibrillation undergoing left atrial appendage occlusion (LAAO) or remaining on oral anticoagulation (OAC) after atrial fibrillation ablation. Methods and Results Cognition was assessed by the Montreal Cognitive Assessment (MoCA) survey at baseline and follow-up. Consecutive patients receiving LAAO or OAC after atrial fibrillation ablation were screened, and patients with a score of ≤17 were excluded from the study. Quality of life was measured at baseline and 1 year using the Atrial Fibrillation Effect on Quality of Life survey. A total of 50 patients (CHA2DS2-VASc [congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category] score: 3.30±1.43) in the LAAO group and 48 (CHA2DS2-VASc score 2.73±1.25) in the OAC group were included in this prospective study. Mean baseline MoCA score was 26.18 and 26.08 in the LAAO and OAC groups, respectively (P=0.846). At 1 year, scores were 26.94 and 23.38 in the respective groups. MoCA score decreased by an estimated -2.74 (95% CI, -3.61 to -1.87; P<0.0001) points in the OAC group, whereas the change in the LAAO group was nonsignificant (0.79; (95% CI, -0.06 to 1.64; P=0.07). After adjusting for baseline clinical characteristics, remaining on OAC was an independent predictor of MoCA change at 1 year (regression coefficient, -3.38; 95% CI, -4.75 to -2.02; P<0.0001). Change in Atrial Fibrillation Effect on Quality of Life score did not differ significantly in achieving a clinically important difference between groups.
Conclusions:
In this series, a significant difference in the postprocedure MoCA score was observed in postablation patients with atrial fibrillation receiving LAAO versus remaining on OAC with a substantial decline in the score in the OAC group. However, quality of life improved similarly across groups. Registration https://www.ClinicalTrials.gov. Unique identifier: NCT01816308.




J Am Heart Assoc: 18 Apr 2021:e019664; epub ahead of print
Mohanty S, Mohanty P, Trivedi C, Assadourian J, ... Gurol ME, Natale A
J Am Heart Assoc: 18 Apr 2021:e019664; epub ahead of print | PMID: 33870705
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Impact:
Abstract

Predictors of Use and Outcomes of Mechanical Valve Replacement in the United States (2008-2017).

Alkhouli M, Alqahtani F, Simard T, Pislaru S, Schaff HV, Nishimura RA

Background:
Contemporary nationwide data on the use, predictors, and outcomes of mechanical valve replacement in patients less than 70 years of age are limited. Methods and Results We identified hospitalizations for aortic valve replacement (AVR) or mitral valve replacement (MVR) in the Nationwide Inpatient Sample between January 1, 2008, and December 31, 2017. The study\'s end points included predictors of mechanical valve replacement and risk-adjusted in-hospital mortality. Among 253 100 hospitalizations for AVR, the use rate of mechanical prosthesis decreased from 45.3% in 2008 to 17.0% in 2017. Among 284 962 hospitalizations for MVR, mechanical prosthesis use decreased from 59.5% in 2008 to 29.2% in 2017 (P for trend<0.001). In multilogistic regression analyses, female sex, prior sternotomy, prior defibrillator, and South/West geographic location were predictive of mechanical valve use. The presence of bicuspid valve was a negative predictor of mechanical AVR (odds ratio [OR], 0.68; 95% CI, 0.66-0.69; P<0.001), whereas mitral stenosis was associated with higher mechanical MVR (OR, 1.28; 95% CI, 1.22-1.33; P<0.001). Unadjusted in-hospital mortality decreased over time with AVR but not with MVR, regardless of prosthesis choice. Using years 2008 and 2009 as a reference, risk-adjusted mortality also decreased over time with AVR but did not decrease after MVR.
Conclusions:
There is a substantial decline in the use of mechanical valve replacement among patients aged ≤70 years in the United States. Long-term durability data on bioprosthetic valve replacement are needed to better define the future role of mechanical valves in this age group.




J Am Heart Assoc: 18 Apr 2021:e019929; epub ahead of print
Alkhouli M, Alqahtani F, Simard T, Pislaru S, Schaff HV, Nishimura RA
J Am Heart Assoc: 18 Apr 2021:e019929; epub ahead of print | PMID: 33870704
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Impact:
Abstract

Association of Carotid Intima-Media Thickness and Other Carotid Ultrasound Features With Incident Dementia in the ARIC-NCS.

Wang W, Norby FL, George KM, Alonso A, ... Meyer ML, Lutsey PL

Background:
Increased carotid intima-media thickness, interadventitial diameter, presence of carotid plaque, and lower distensibility are predictors for cardiovascular disease. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer disease-related dementia. Therefore, we assessed the relationship of carotid measurements and arterial stiffness with incident dementia in the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results A total of 12 459 ARIC participants with carotid arterial ultrasounds in 1990 to 1992 were followed through 2017 for dementia. Dementia cases were identified using in-person and phone cognitive status assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for incident dementia. Participants were aged 57±6 at baseline, 57% were women, and 23% were Black individuals. Over a median follow-up time of 24 years, 2224 dementia events were ascertained. After multivariable adjustments, the highest quintile of carotid intima-media thickness and interadventitial diameter in midlife was associated with increased risk of dementia (HR [95% CIs], 1.25 [1.08-1.45]; and 1.22 [1.04-1.43], respectively) compared with its respective lowest quintile. Presence of carotid plaque did not have a significant association with dementia (HR [95% CI], 1.06 [0.97-1.15]). Higher distensibility was associated with lower risk of dementia (HR [95% CI] highest versus lowest quintile, 0.76 [0.63-0.91]).
Conclusions:
Greater carotid intima-media thickness, interadventitial diameter, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.




J Am Heart Assoc: 16 Apr 2021:e020489; epub ahead of print
Wang W, Norby FL, George KM, Alonso A, ... Meyer ML, Lutsey PL
J Am Heart Assoc: 16 Apr 2021:e020489; epub ahead of print | PMID: 33870735
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Impact:
Abstract

Preoperative Right Ventricular Free-Wall Longitudinal Strain as a Prognosticator in Isolated Surgery for Severe Functional Tricuspid Regurgitation.

Kim M, Lee HJ, Park JB, Kim J, ... Chang SA, Kim HK

Background:
Severe tricuspid regurgitation (TR) should be intervened before the development of irreversible right ventricular (RV) dysfunction. However, current guidelines do not provide criterion related to RV systolic function to guide optimal surgical timing. We investigated the prognostic value of RV longitudinal strain in patients undergoing isolated surgery for severe functional TR. Methods and Results We enrolled 115 consecutive patients (aged 62±10 years; 23.5% men; 62.6% [n=72] with previous left-sided valve surgery) who underwent isolated surgery for severe functional TR at 2 tertiary centers. Preoperative clinical and echocardiographic parameters, including RV free-wall longitudinal strain (RVFWSL), were collected. The primary end point was a composite of cardiac death and unplanned readmission attributable to cardiovascular causes 5 years after surgery. Forty patients (34.8%) reached the primary end point during 333 person-years of follow-up. There were 11 cardiac deaths and 34 unplanned readmissions attributable to cardiovascular causes, with 5 patients experiencing both. An absolute preoperative RVFWSL <24% was associated with the primary end point (hazard ratio, 2.30; 95% CI, 1.22-4.36; P=0.011), independent of clinical risk factors, including European System for Cardiac Operative Risk Evaluation II and hemoglobin levels. Meanwhile, other conventional echocardiographic measures of RV systolic function were not significant. The addition of an absolute RVFWSL <24% provided incremental prognostic value to the clinical model for predicting the primary end point.
Conclusions:
Preoperative RVFWSL as an indicator of RV dysfunction was an independent prognosticator in patients undergoing isolated surgery for severe functional TR. Thus, preoperative RVFWSL could help determine the optimal surgical timing for severe functional TR.




J Am Heart Assoc: 16 Apr 2021:e019856; epub ahead of print
Kim M, Lee HJ, Park JB, Kim J, ... Chang SA, Kim HK
J Am Heart Assoc: 16 Apr 2021:e019856; epub ahead of print | PMID: 33870734
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Impact:
Abstract

Impaired High-Density Lipoprotein Function in Patients With Heart Failure.

Emmens JE, Jia C, Ng LL, van Veldhuisen DJ, ... de Boer RA, Tietge UJF

Background:
We recently showed that, in patients with heart failure, lower high-density lipoprotein (HDL) cholesterol concentration was a strong predictor of death or hospitalization for heart failure. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to the prognosis of patients with heart failure has not been addressed. Methods and Results We measured 3 key protective HDL function metrics, namely, cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected patients with heart failure from BIOSTAT-CHF (A Systems Biology Study to Tailored Treatment in Chronic Heart Failure). Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients with heart failure. From baseline to 9 months, HDL cholesterol concentrations were unchanged, but HDL cholesterol efflux and anti-inflammatory capacity declined (both P<0.001). In contrast, antioxidative capacity increased (P<0.001). Higher HDL cholesterol efflux was associated with lower mortality after adjusting for BIOSTAT-CHF risk models and log HDL cholesterol (hazard ratio, 0.81; 95% CI, 0.71-0.92; P=0.001). Other functionality measures were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux. Apolipoprotein A1 emerged as the main protein associated with all 3 HDL functionality measures.
Conclusions:
Better HDL cholesterol efflux at baseline was associated with lower mortality during follow-up, independent of HDL cholesterol. HDL cholesterol efflux and anti-inflammatory capacity declined during follow-up in patients with heart failure. Measures of HDL function may provide clinical information in addition to HDL cholesterol concentration in patients with heart failure.




J Am Heart Assoc: 16 Apr 2021:e019123; epub ahead of print
Emmens JE, Jia C, Ng LL, van Veldhuisen DJ, ... de Boer RA, Tietge UJF
J Am Heart Assoc: 16 Apr 2021:e019123; epub ahead of print | PMID: 33870728
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Impact:
Abstract

Rotigaptide Infusion for the First 7 Days After Myocardial Infarction-Reperfusion Reduced Late Complexity of Myocardial Architecture of the Healing Border-Zone and Arrhythmia Inducibility.

Chowdhury RA, Debney MT, Protti A, Handa BS, ... Ng FS, Peters NS

Background:
Survivors of myocardial infarction are at increased risk of late ventricular arrhythmias, with infarct size and scar heterogeneity being key determinants of arrhythmic risk. Gap junctions facilitate the passage of small ions and morphogenic cell signaling between myocytes. We hypothesized that gap junctions enhancement during infarction-reperfusion modulates structural and electrophysiological remodeling and reduces late arrhythmogenesis. Methods and Results Infarction-reperfusion surgery was carried out in male Sprague-Dawley rats followed by 7 days of rotigaptide or saline administration. The in vivo and ex vivo arrhythmogenicity was characterized by programmed electrical stimulation 3 weeks later, followed by diffusion-weighted magnetic resonance imaging and Masson\'s trichrome histology. Three weeks after 7-day postinfarction administration of rotigaptide, ventricular tachycardia/ventricular fibrillation was induced on programmed electrical stimulation in 20% and 53% of rats, respectively (rotigaptide versus control), resulting in reduction of arrhythmia score (3.2 versus 1.4, P=0.018), associated with the reduced magnetic resonance imaging parameters fractional anisotropy (fractional anisotropy: -5% versus -15%; P=0.062) and mean diffusivity (mean diffusivity: 2% versus 6%, P=0.042), and remodeling of the 3-dimensional laminar structure of the infarct border zone with reduction of the mean (16° versus 19°, P=0.013) and the dispersion (9° versus 12°, P=0.015) of the myofiber transverse angle. There was no change in ECG features, spontaneous arrhythmias, or mortality.
Conclusions:
Enhancement of gap junctions function by rotigaptide administered during the early healing phase in reperfused infarction reduces later complexity of infarct scar morphology and programmed electrical stimulation-induced arrhythmias, and merits further exploration as a feasible and practicable intervention in the acute myocardial infarction management to reduce late arrhythmic risk.




J Am Heart Assoc: 16 Apr 2021:e020006; epub ahead of print
Chowdhury RA, Debney MT, Protti A, Handa BS, ... Ng FS, Peters NS
J Am Heart Assoc: 16 Apr 2021:e020006; epub ahead of print | PMID: 33870715
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Impact:
Abstract

Risk Factors and Outcomes of Recurrent Drug-Eluting Stent Thrombosis: Insights From the REAL-ST Registry.

Enomoto S, Kuramitsu S, Shinozaki T, Ohya M, ... Kimura T, REAL‐ST investigators †

Background:
Stent thrombosis (ST) after drug-eluting stent (DES) implantation remains a life-threatening complication. Recurrent ST (RST) is not a rare phenomenon, potentially contributing to high mortality after the index ST events. However, little evidence is available about the incidence, risk factors, and clinical outcomes of definite RST after DES thrombosis. Methods and Results From REAL-ST (Retrospective Multicenter Registry of ST After First- and Second- Generation DES Implantation), this study evaluated 595 patients with definite ST (first-generation DES thrombosis, n=314; second-generation DES thrombosis, n=281). During a median follow-up of 31 months, we identified 32 patients with definite RST after first-generation DES thrombosis (n=18) and second-generation DES thrombosis (n=15). Cumulative incidence of RST was 4.5% and 6.0% at 1 and 5 years, respectively, which did not significantly differ between first-generation DES thrombosis and second-generation DES thrombosis. Independent predictors of definite RST were early ST (hazard ratio [HR], 2.38; 95% CI, 1.06-5.35 [P=0.035]) and multivessel ST (HR, 3.47; 95% CI, 1.03-11.7 [P=0.044]). Definite RST was associated with a 2.8-fold increased risk of mortality (adjusted HR, 2.78; 95% CI, 1.35-5.73 [P=0.006]).
Conclusions:
Cumulative incidence of definite RST did not significantly differ between first-generation DES thrombosis and second-generation DES thrombosis. Early ST and multivessel ST were risk factors of definite RST. Definite RST significantly increased mortality after DES thrombosis, highlighting the clinical importance of preventing RST to improve outcomes of patients with ST. Registration URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000025181.




J Am Heart Assoc: 16 Apr 2021:e018972; epub ahead of print
Enomoto S, Kuramitsu S, Shinozaki T, Ohya M, ... Kimura T, REAL‐ST investigators †
J Am Heart Assoc: 16 Apr 2021:e018972; epub ahead of print | PMID: 33870710
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Impact:
Abstract

Associations of Visceral Adipose Tissue and Skeletal Muscle Density With Incident Stroke, Myocardial Infarction, and All-Cause Mortality in Community-Dwelling 70-Year-Old Individuals: A Prospective Cohort Study.

Ballin M, Nordström P, Niklasson J, Nordström A

Background:
Aging leads to increased visceral adipose tissue (VAT) and reduced skeletal muscle density. To which extent these are associated with the risk of stroke, myocardial infarction (MI), and all-cause mortality in older adults is unknown. Methods and Results A total of 3294 70-year-old individuals (49.6% women) underwent a health examination in Umeå, Sweden, during 2012 to 2018. VAT and muscle density were measured using dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. Cases of stroke, MI, and all-cause mortality were collected through national registers. Cox regressions were used to calculate hazard ratios (HRs) and 95% CIs per SD greater VAT and per SD lower muscle density. During a mean follow-up of 3.6 years, there were 108 cases of stroke or MI, and 97 deaths. Greater VAT (adjusted HR [aHR], 1.56; 95% CI, 1.09-2.22), but not lower muscle density (aHR, 1.14; 95% CI, 0.97-1.34), was associated with increased risk of stroke or MI. Neither VAT (aHR, 0.95; 95% CI, 0.65-1.41) nor muscle density (aHR, 1.11; 95% CI, 0.92-1.34) was associated with all-cause mortality. The association of VAT with stroke or MI was only significant in men (aHR, 1.86; 95% CI, 1.19-2.91) but not women (aHR, 0.60; 95% CI, 0.25-1.42) (Pinteraction=0.038).
Conclusions:
With the limitation of being an observational study, these findings suggest that VAT is an important obesity-related predictor of cardiovascular risk in 70-year-old men, and by implication, that decreasing VAT may potentially reduce their risk of cardiovascular disease.




J Am Heart Assoc: 16 Apr 2021:e020065; epub ahead of print
Ballin M, Nordström P, Niklasson J, Nordström A
J Am Heart Assoc: 16 Apr 2021:e020065; epub ahead of print | PMID: 33870709
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Impact:
Abstract

Impact of Chronic Hypertension and Antihypertensive Treatment on Adverse Perinatal Outcomes: Systematic Review and Meta-Analysis.

Al Khalaf SY, O\'Reilly ÉJ, Barrett PM, B Leite DF, ... McCarthy FP, Khashan AS

Background:
Maternal chronic hypertension is associated with adverse pregnancy outcomes. Previous studies examined the association between either chronic hypertension or antihypertensive treatment and adverse pregnancy outcomes. We aimed to synthesize the evidence on the effect of chronic hypertension/antihypertensive treatment on adverse pregnancy outcomes. Methods and Results Medline/PubMed, EMBASE, and Web of Science were searched; we included observational studies and assessed the effect of race/ethnicity, where possible, following a registered protocol (CRD42019120088). Random-effects meta-analyses were used. A total of 81 studies were identified on chronic hypertension, and a total of 16 studies were identified on antihypertensive treatment. Chronic hypertension was associated with higher odds of preeclampsia (adjusted odd ratio [aOR], 5.43; 95% CI, 3.85-7.65); cesarean section (aOR, 1.87; 95% CI, 1.6-2.16); maternal mortality (aOR, 4.80; 95% CI, 3.04-7.58); preterm birth (aOR, 2.23; 95% CI, 1.96-2.53); stillbirth (aOR, 2.32; 95% CI, 2.22-2.42); and small for gestational age (SGA) (aOR, 1.96; 95% CI, 1.6-2.40). Subgroup analyses indicated that maternal race/ethnicity does not influence the observed associations. Women with chronic hypertension on antihypertensive treatment (versus untreated) had higher odds of SGA (aOR, 1.86; 95% CI, 1.38-2.50).
Conclusions:
Chronic hypertension is associated with adverse pregnancy outcomes, and these associations appear to be independent of maternal race/ethnicity. In women with chronic hypertension, those on treatment had a higher risk of SGA, although the number of studies was limited. This could result from a direct effect of the treatment or because severe hypertension during pregnancy is a risk factor for SGA and women with severe hypertension are more likely to be treated. The effect of antihypertensive treatment on SGA needs to be further tested with large randomized controlled trials.




J Am Heart Assoc: 16 Apr 2021:e018494; epub ahead of print
Al Khalaf SY, O'Reilly ÉJ, Barrett PM, B Leite DF, ... McCarthy FP, Khashan AS
J Am Heart Assoc: 16 Apr 2021:e018494; epub ahead of print | PMID: 33870708
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Impact:
Abstract

Duration of Antiplatelet Therapy Following Transcatheter Aortic Valve Replacement: Systematic Review and Network Meta-Analysis.

Kuno T, Yokoyama Y, Briasoulis A, Mori M, ... Takagi H, Bangalore S

Background:
Although current guidelines recommend dual antiplatelet therapy (DAPT) for 3 to 6 months following transcatheter aortic valve replacement (TAVR), there are no studies directly comparing outcomes of different durations of DAPT following TAVR. Methods and Results PubMed, EMBASE, and Cochrane Database were searched through November 2020 to identify clinical studies that investigated single antiplatelet therapy versus DAPT use following TAVR. Studies using oral anticoagulants and antiplatelet therapy concomitantly were excluded. The DAPT group was subdivided by the duration of DAPT. We extracted the risk ratios (RRs) of major or life-threatening bleeding, stroke, and all-cause mortality. Four randomized controlled trials, 2 propensity-score matched studies, and 1 observational study were identified, yielding a total of 2498 patients who underwent TAVR assigned to the single antiplatelet therapy group (n=1249), 3-month DAPT group (n=485), or 6-month DAPT group (n=764). Pooled analyses demonstrated that when compared with the single antiplatelet therapy group, the rates of major or life-threatening bleeding were significantly higher in the 3- and 6-month DAPT groups (RR [95% CI]=2.13 [1.33-3.40], P=0.016; RR [95% CI]=2.54 [1.49-4.33], P=0.007, respectively) with no difference between the 3-month DAPT versus 6-month DAPT groups. The rates of stroke and all-cause mortality were similar among the 3 groups.
Conclusions:
In this network meta-analysis of antiplatelet therapy following TAVR, single antiplatelet therapy with aspirin had lower bleeding without increasing stroke or death when compared with either 3- or 6-month DAPT.




J Am Heart Assoc: 16 Apr 2021:e019490; epub ahead of print
Kuno T, Yokoyama Y, Briasoulis A, Mori M, ... Takagi H, Bangalore S
J Am Heart Assoc: 16 Apr 2021:e019490; epub ahead of print | PMID: 33870703
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Impact:
Abstract

Aspirin Alone Versus Dual Antiplatelet Therapy After Transcatheter Aortic Valve Implantation: A Systematic Review and Patient-Level Meta-Analysis.

Brouwer J, Nijenhuis VJ, Rodés-Cabau J, Stabile E, ... Mahmoodi BK, Ten Berg JM

Background:
In patients undergoing transcatheter aortic valve implantation without an indication for oral anticoagulation, it is unclear whether single or dual antiplatelet therapy (DAPT) is necessary to minimize both the bleeding and thromboembolic risk. In this patient-level meta-analysis, we further investigate the effect of aspirin alone compared with DAPT for preventing both thromboembolic and bleeding events after transcatheter aortic valve implantation. Methods and Results We conducted a systematic review of all available randomized controlled trials comparing aspirin with DAPT. In total, 1086 patients were included across 4 eligible trials. The primary outcomes were the composite of all-cause mortality, major or life-threatening bleeding, stroke or myocardial infarction (first composite outcome), and the same composite excluding bleeding (second composite outcome), both tested at 30 days and 3 months. The first composite outcome occurred significantly less in the aspirin-alone group at 30 days (10.3% versus 14.7%, odds ratio [OR], 0.67; 95% CI, 0.46-0.97, P=0.034) and 3 months (11.0% versus 16.5%, hazard ratio [HR], 0.66; 95% CI, 0.47-0.94, P=0.02), compared with the DAPT group. The second composite outcome occurred in 5.5% and 6.6% at 30 days (OR, 0.83; 95% CI, 0.50-1.38, P=0.47) and in 6.9% and 8.5% at 3 months in the aspirin-alone group compared with the DAPT group (HR, 0.82; 95% CI, 0.52-1.29, P=0.39), respectively.
Conclusions:
In patients without an indication for oral anticoagulation undergoing transcatheter aortic valve implantation, aspirin alone significantly reduced the composite of thromboembolic and bleeding events, and does not increase the composite of thromboembolic events after transcatheter aortic valve implantation, compared with DAPT.




J Am Heart Assoc: 15 Apr 2021:e019604; epub ahead of print
Brouwer J, Nijenhuis VJ, Rodés-Cabau J, Stabile E, ... Mahmoodi BK, Ten Berg JM
J Am Heart Assoc: 15 Apr 2021:e019604; epub ahead of print | PMID: 33860685
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Impact:
Abstract

Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs at a Higher Risk of Acute Coronary Syndrome.

Hsu CY, Su YJ, Chen JF, Sun CC, ... Chang CC, Chen TH

Background:
Cardiovascular disease is the most common cause of death in patients with rheumatoid arthritis. It is believed that using disease-modifying antirheumatic drugs (DMARDs) to control inflammation can reduce the risk of cardiovascular disease. In this study, we investigated whether patients who responded differently to DMARDs might sustain different cardiovascular events. Methods and Results We designed a cohort study using the Chang Gung Research Database. We identified 7114 patients diagnosed with rheumatoid arthritis. After strict exclusion criteria, we collected 663 individuals as an inadequate response to DMARDs group. Then, 2034 individuals were included as the control group. The end point was composite vascular outcomes, including acute coronary syndrome or ischemic stroke. We used the inverse probability of treatment weighting to keep the covariates between these 2 groups well balanced. We compared the risk of these outcomes using the Cox proportional hazards model. The mean follow-up time was 4.7 years. During follow-up, there were 7.5% and 6.4% of patients with composite vascular outcomes in the DMARD-inadequate response and control groups, respectively. There was no significant difference in the risk of composite vascular outcomes (95% CI, 0.94-1.41) and ischemic stroke (95% CI, 0.84-1.36). The risk of acute coronary syndrome was significantly higher in the DMARD-inadequate response group (hazard ratio, 1.45; 95% CI, 1.02-2.05).
Conclusions:
Patients with DMARD-inadequate response rheumatoid arthritis have a higher risk of developing acute coronary syndrome than those whose disease can be controlled by DMARDs.




J Am Heart Assoc: 15 Apr 2021:e018290; epub ahead of print
Hsu CY, Su YJ, Chen JF, Sun CC, ... Chang CC, Chen TH
J Am Heart Assoc: 15 Apr 2021:e018290; epub ahead of print | PMID: 33860677
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Impact:
Abstract

Systematic Review and Meta-Analysis of Peak Wall Stress and Peak Wall Rupture Index in Ruptured and Asymptomatic Intact Abdominal Aortic Aneurysms.

Singh TP, Moxon JV, Gasser TC, Golledge J

Background:
Prior studies have suggested aortic peak wall stress (PWS) and peak wall rupture index (PWRI) can estimate the rupture risk of an abdominal aortic aneurysm (AAA), but whether these measurements have independent predictive ability over assessing AAA diameter alone is unclear. The aim of this systematic review was to compare PWS and PWRI in participants with ruptured and asymptomatic intact AAAs of similar diameter. Methods and Results Web of Science, Scopus, Medline, and The Cochrane Library were systematically searched to identify studies assessing PWS and PWRI in ruptured and asymptomatic intact AAAs of similar diameter. Random-effects meta-analyses were performed using inverse variance-weighted methods. Leave-one-out sensitivity analyses were conducted to assess the robustness of findings. Risk of bias was assessed using a modification of the Newcastle-Ottawa scale and standard quality assessment criteria for evaluating primary research papers. Seven case-control studies involving 309 participants were included. Meta-analyses suggested that PWRI (standardized mean difference, 0.42; 95% CI, 0.14-0.70; P=0.004) but not PWS (standardized mean difference, 0.13; 95% CI, -0.18 to 0.44; P=0.418) was greater in ruptured than intact AAAs. Sensitivity analyses suggested that the findings were not dependent on the inclusion of any single study. The included studies were assessed to have a medium to high risk of bias.
Conclusions:
Based on limited evidence, this study suggested that PWRI, but not PWS, is greater in ruptured than asymptomatic intact AAAs of similar maximum aortic diameter.




J Am Heart Assoc: 14 Apr 2021:e019772; epub ahead of print
Singh TP, Moxon JV, Gasser TC, Golledge J
J Am Heart Assoc: 14 Apr 2021:e019772; epub ahead of print | PMID: 33855866
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Impact:
Abstract

Joint Associations Between Body Mass Index and Waist Circumference With Atrial Fibrillation in Men and Women.

Poorthuis MHF, Sherliker P, de Borst GJ, Carter JL, ... Lewington S, Bulbulia R

Background:
Associations between adiposity and atrial fibrillation (AF) might differ between sexes. We aimed to determine precise estimates of the risk of AF by body mass index (BMI) and waist circumference (WC) in men and women. Methods and Results Between 2008 and 2013, over 3.2 million adults attended commercial screening clinics. Participants completed health questionnaires and underwent physical examination along with cardiovascular investigations, including an ECG. We excluded those with cardiovascular and cardiac disease. We used multivariable logistic regression and determined joint associations of BMI and WC and the risk of AF in men and women by comparing likelihood ratio χ2 statistics. Among 2.1 million included participants 12 067 (0.6%) had AF. A positive association between BMI per 5 kg/m2 increment and AF was observed, with an odds ratio of 1.65 (95% CI, 1.57-1.73) for men and 1.36 (95% CI, 1.30-1.42) for women among those with a BMI above 20 kg/m2. We found a positive association between AF and WC per 10 cm increment, with an odds ratio of 1.47 (95% CI, 1.36-1.60) for men and 1.37 (95% CI, 1.26-1.49) for women. Improvement of likelihood ratio χ2 was equal after adding BMI and WC to models with all participants. In men, WC showed stronger improvement of likelihood ratio χ2 than BMI (30% versus 23%). In women, BMI showed stronger improvement of likelihood ratio χ2 than WC (23% versus 12%).
Conclusions:
We found a positive association between BMI (above 20 kg/m2) and AF and between WC and AF in both men and women. BMI seems a more informative measure about risk of AF in women and WC seems more informative in men.




J Am Heart Assoc: 14 Apr 2021:e019025; epub ahead of print
Poorthuis MHF, Sherliker P, de Borst GJ, Carter JL, ... Lewington S, Bulbulia R
J Am Heart Assoc: 14 Apr 2021:e019025; epub ahead of print | PMID: 33853362
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Impact:
Abstract

Cardiac-Specific Deletion of Orai3 Leads to Severe Dilated Cardiomyopathy and Heart Failure in Mice.

Gammons J, Trebak M, Mancarella S

Background:
Orai3 is a mammalian-specific member of the Orai family (Orai1‒3) and a component of the store-operated Ca2+ entry channels. There is little understanding of the role of Orai channels in cardiomyocytes, and its role in cardiac function remains unexplored. Thus, we developed mice lacking Orai1 and Orai3 to address their role in cardiac homeostasis. Methods and Results We generated constitutive and inducible cardiomyocyte-specific Orai3 knockout (Orai3cKO) mice. Constitutive Orai3-loss led to ventricular dysfunction progressing to dilated cardiomyopathy and heart failure. Orai3cKO mice subjected to pressure overload developed a fulminant dilated cardiomyopathy with rapid heart failure onset, characterized by interstitial fibrosis and apoptosis. Ultrastructural analysis of Orai3-deficient cardiomyocytes showed abnormal M- and Z-line morphology. The greater density of condensed mitochondria in Orai3-deficient cardiomyocytes was associated with the upregulation of DRP1 (dynamin-related protein 1). Cardiomyocytes isolated from Orai3cKO mice exhibited profoundly altered myocardial Ca2+ cycling and changes in the expression of critical proteins involved in the Ca2+ clearance mechanisms. Upregulation of TRPC6 (transient receptor potential canonical type 6) channels was associated with upregulation of the RCAN1 (regulator of calcineurin 1), indicating the activation of the calcineurin signaling pathway in Orai3cKO mice. A more dramatic cardiac phenotype emerged when Orai3 was removed in adult mice using a tamoxifen-inducible Orai3cKO mouse. The removal of Orai1 from adult cardiomyocytes did not change the phenotype of tamoxifen-inducible Orai3cKO mice.
Conclusions:
Our results identify a critical role for Orai3 in the heart. We provide evidence that Orai3-mediated Ca2+ signaling is required for maintaining sarcomere integrity and proper mitochondrial function in adult mammalian cardiomyocytes.




J Am Heart Assoc: 13 Apr 2021:e019486; epub ahead of print
Gammons J, Trebak M, Mancarella S
J Am Heart Assoc: 13 Apr 2021:e019486; epub ahead of print | PMID: 33849280
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Impact:
Abstract

Plasma Omega-3 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome in MERLIN-TIMI 36.

Zelniker TA, Morrow DA, Scirica BM, Furtado JD, ... Sabatine MS, O\'Donoghue ML

Background:
Plasma omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3-PUFA composition (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case-cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event-free subjects as controls from MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation-Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non-ST-segment-elevation -acute coronary syndrome. After inverse-probability-weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long-chain ω3-PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68-0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55-0.97). Long-chain ω3-PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27-0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16-0.56). An attenuated relationship was seen for α-linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74-1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67-1.25). No significant relationship was observed between any ω3-PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post-acute coronary syndrome ventricular tachycardia.
Conclusions:
In patients after non-ST-segment-elevation-acute coronary syndrome, plasma long-chain ω3-PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.




J Am Heart Assoc: 11 Apr 2021:e017401; epub ahead of print
Zelniker TA, Morrow DA, Scirica BM, Furtado JD, ... Sabatine MS, O'Donoghue ML
J Am Heart Assoc: 11 Apr 2021:e017401; epub ahead of print | PMID: 33840228
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Impact:
Abstract

Consensus Decision-Making for the Management of Antiplatelet Therapy before Non-Cardiac Surgery in Patients Who Underwent Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents: A Cohort Study.

Kim C, Kim JS, Kim H, Ahn SG, ... Hong MK, Jang Y

Background:
Although antiplatelet therapy (APT) has been recommended to balance ischemic-bleeding risks, it has been left to an individualized decision-making based on physicians\' perspectives before non-cardiac surgery. The study aimed to assess the advantages of a consensus among physicians, surgeons, and anesthesiologists on continuation and regimen of preoperative APT in patients with coronary drug-eluting stents. Methods and Results A total of 3582 adult patients undergoing non-cardiac surgery after percutaneous coronary intervention with second-generation stents was retrospectively included from a multicenter cohort. Physicians determined whether APT should be continued or discontinued for a recommended period before non-cardiac surgery. There were 3103 patients who complied with a consensus decision. Arbitrary APT, not based on a consensus decision, was associated with urgent surgery, high bleeding risk of surgery, female sex, and dual APT at the time of preoperative evaluation. Arbitrary APT independently increased the net clinical adverse event (adjusted odds ratio [ORadj], 1.98; 95% CI, 1.98-3.11), major adverse cardiac event (ORadj, 3.11; 95% CI, 1.31-7.34), and major bleeding (ORadj, 2.34; 95% CI, 1.45-3.76) risks. The association was consistently noted, irrespective of the surgical risks, recommendations, and practice on discontinuation of APT.
Conclusions:
Most patients were treated in agreement with a consensus decision about preoperative APT based on a referral system among physicians, surgeons, and anesthesiologists. The risk of perioperative adverse events increased if complying with a consensus decision was failed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03908463.




J Am Heart Assoc: 09 Apr 2021:e020079; epub ahead of print
Kim C, Kim JS, Kim H, Ahn SG, ... Hong MK, Jang Y
J Am Heart Assoc: 09 Apr 2021:e020079; epub ahead of print | PMID: 33843258
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Impact:
Abstract

Antenatal Hypoxia Affects Pulmonary Artery Contractile Functions via Downregulating L-type Ca Channels Subunit Alpha1 C in Adult Male Offspring.

Li H, Ji B, Xu T, Zhao M, ... Xu Z, Gao Q

Background:
Antenatal intrauterine fetal hypoxia is a common pregnancy complication that has profound adverse effects on an individual\'s vascular health later in life. Pulmonary arteries are sensitive to hypoxia, but adverse effects of antenatal hypoxia on pulmonary vasoreactivities in the offspring remain unknown. This study aimed to determine the effects and related mechanisms of antenatal hypoxia on pulmonary artery functions in adult male offspring. Methods and Results Pregnant Sprague-Dawley rats were housed in a normoxic or hypoxic (10.5% O2) chamber from gestation days 10 to 20. Male offspring were euthanized at 16 weeks old (adult offspring). Pulmonary arteries were collected for vascular function, electrophysiology, target gene expression, and promoter methylation studies. In pulmonary artery rings, contractions to serotonin hydrochloride, angiotensin II, or phenylephrine were reduced in the antenatal hypoxic offspring, which resulted from inactivated L-type Ca2+ channels. In pulmonary artery smooth muscle cells, the basal whole-cell Ca2+ currents, as well as vasoconstrictor-induced Ca2+ transients were significantly reduced in antenatal hypoxic offspring. In addition, increased promoter methylations within L-type Ca2+ channel subunit alpha1 C were compatible with its reduced expressions.
Conclusions:
This study indicated that antenatal hypoxia programmed long-lasting vascular hypocontractility in the male offspring that is linked to decreases of L-type Ca2+ channel subunit alpha1 C in the pulmonary arteries. Antenatal hypoxia resulted in pulmonary artery adverse outcomes in postnatal offspring, was strongly associated with reprogrammed L-type Ca2+ channel subunit alpha1 C expression via a DNA methylation-mediated epigenetic mechanism, advancing understanding toward the effect of antenatal hypoxia in early life on long-term vascular health.




J Am Heart Assoc: 09 Apr 2021:e019922; epub ahead of print
Li H, Ji B, Xu T, Zhao M, ... Xu Z, Gao Q
J Am Heart Assoc: 09 Apr 2021:e019922; epub ahead of print | PMID: 33843249
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Impact:
Abstract

Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation.

Benz AP, Aeschbacher S, Krisai P, Moschovitis G, ... BEAT‐AF, Swiss‐AF Investigators

Background:
Hospitalization for heart failure (HF) is very common in patients with atrial fibrillation (AF). We hypothesized that biomarkers of inflammation can identify patients with AF at increased risk of this important complication. Methods and Results Patients with established AF were prospectively enrolled. Levels of hs-CRP (high-sensitivity C-reactive protein) and interleukin-6 were measured from plasma samples obtained at baseline. We calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile). Individual associations of biomarkers and the inflammation score with HF hospitalization were obtained from multivariable Cox proportional hazards models. A total of 3784 patients with AF (median age 72 years, 24% prior HF) were followed for a median of 4.0 years. The median (interquartile range) plasma levels of hs-CRP and interleukin-6 were 1.64 (0.81-3.69) mg/L and 3.42 (2.14-5.60) pg/mL, respectively. The overall incidence of HF hospitalization was 3.04 per 100 person-years and increased from 1.34 to 7.31 per 100 person-years across inflammation score categories. After multivariable adjustment, both biomarkers were significantly associated with the risk of HF hospitalization (per increase in 1 SD, adjusted hazard ratio [HR], 1.22; 95% CI, 1.11-1.34 for log-transformed hs-CRP; adjusted HR, 1.48; 95% CI, 1.35-1.62 for log-transformed interleukin-6). Similar results were obtained for the inflammation score (highest versus lowest score, adjusted HR, 2.43; 95% CI, 1.80-3.30; P value for trend <0.001).
Conclusions:
Biomarkers of inflammation strongly predicted HF hospitalization in a large, contemporary sample of patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.




J Am Heart Assoc: 09 Apr 2021:e019168; epub ahead of print
Benz AP, Aeschbacher S, Krisai P, Moschovitis G, ... BEAT‐AF, Swiss‐AF Investigators
J Am Heart Assoc: 09 Apr 2021:e019168; epub ahead of print | PMID: 33843247
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Impact:
Abstract

Genetically Proxied Inhibition of Coagulation Factors and Risk of Cardiovascular Disease: A Mendelian Randomization Study.

Yuan S, Burgess S, Laffan M, Mason AM, ... Gill D, Larsson SC

Background:
We conducted Mendelian randomization analyses investigating the linear associations of genetically proxied inhibition of different coagulation factors with risk of common cardiovascular diseases. Methods and Results Genetic instruments proxying coagulation factor inhibition were identified from genome-wide association studies for activated partial thromboplastin time and prothrombin time in BioBank Japan (up to 58 110 participants). Instruments were identified for 9 coagulation factors (fibrinogen alpha, beta, and gamma chain; and factors II, V, VII, X, XI, and XII). Age- and sex-adjusted estimates for associations of the instruments with the outcomes were derived from UK Biobank and the FinnGen, CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis), and MEGASTROKE consortia with numbers of incident and prevalent cases of 820 to 60 810. Genetically proxied inhibition of fibrinogen alpha, beta, and gamma chain, factor II, and factor XI were associated with reduced risk of venous thromboembolism (P<0.001). With the exception of fibrinogen beta and factor II, inhibition of these factors was also associated with reduced risk of any ischemic stroke and cardioembolic stroke (P≤0.002). Genetically proxied inhibition of fibrinogen beta and gamma were associated with reduced large-artery stroke risk (P=0.001). There were suggestive protective associations of genetically proxied inhibition of factors V, VII, and X with ischemic stroke (P<0.05), and suggestive adverse associations of genetically proxied inhibition of factors II and XII with subarachnoid hemorrhage.
Conclusions:
This study supports targeting fibrinogen and factor XI for reducing venous thromboembolism and ischemic stroke risk, and showed suggestive evidence that inhibition of factors V, VII, and X might reduce ischemic stroke risk.




J Am Heart Assoc: 08 Apr 2021:e019644; epub ahead of print
Yuan S, Burgess S, Laffan M, Mason AM, ... Gill D, Larsson SC
J Am Heart Assoc: 08 Apr 2021:e019644; epub ahead of print | PMID: 33834859
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Impact:
Abstract

Association Between Depression and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy.

Hu HL, Chen H, Zhu CY, Yue X, ... Zhai CL, He CJ

Background:
Hypertrophic cardiomyopathy (HCM) is considered to be the most common cause of sudden death in young people and is associated with an elevated risk of mood disorders. Depression has emerged as a critical risk factor for development and progression of coronary artery disease; however, the association between depression and HCM outcomes is less clear. We sought to examine the impact of depression on clinical outcomes in patients with HCM. Methods and Results Between January 2014 and December 2017, 820 patients with HCM were recruited and followed for an average of 4.2 years. End points were defined as sudden cardiac death (SCD) events and HCM-related heart failure events. A Chinese version of the Structured Clinical Interview followed the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition and was used to diagnose depression. During the follow-up period, SCD events occurred in 75 individuals (21.8 per 1000 person-years), and HCM-related heart failure events developed in 149 individuals (43.3 per 1000 person-years). Kaplan-Meier cumulative incidence curves showed a significant association of depression disorders with SCD events (log-rank P=0.001) and HCM-related heart failure events (log-rank P=0.005). A multivariate Cox regression analysis indicated that depression was an independent predictor of SCD events and HCM-related heart failure events (41.9 versus 21.7 per 1000 person-years; adjusted hazard ratio [HR], 1.9; 95% CI, 1.6-2.3; P<0.001; and 69.9 versus 38.6 per 1000 person-years; HR, 1.8; 95% CI, 1.6-2.1; P<0.001, respectively).
Conclusions:
Depression is common among patients with HCM. The diagnosis of depression is significantly and independently associated with an increased risk of SCD events and heart failure events in patients with HCM.




J Am Heart Assoc: 08 Apr 2021:e019071; epub ahead of print
Hu HL, Chen H, Zhu CY, Yue X, ... Zhai CL, He CJ
J Am Heart Assoc: 08 Apr 2021:e019071; epub ahead of print | PMID: 33834850
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Impact:
Abstract

Novel Approach to Risk Stratification in Left Ventricular Non-Compaction Using A Combined Cardiac Imaging and Plasma Biomarker Approach.

Ramchand J, Podugu P, Obuchowski N, Harb SC, ... Kwon DH, Flamm SD

Background:
Left ventricular non-compaction remains a poorly described entity, which has led to challenges of overdiagnosis. We aimed to evaluate if the presence of a thin compacted myocardial layer portends poorer outcomes in individuals meeting cardiac magnetic resonance criteria for left ventricular non-compaction . Methods and Results This was an observational, retrospective cohort study involving individuals selected from the Cleveland Clinic Foundation cardiac magnetic resonance database (N=26 531). Between 2000 and 2018, 328 individuals ≥12 years, with left ventricular non-compaction or excessive trabeculations based on the cardiac magnetic resonance Petersen criteria were included. The cohort comprised 42% women, mean age 43 years. We assessed the predictive ability of myocardial thinning for the primary composite end point of major adverse cardiac events (composite of all-cause mortality, heart failure hospitalization, left ventricular assist device implantation/heart transplant, ventricular tachycardia, or ischemic stroke). At mean follow-up of 3.1 years, major adverse cardiac events occurred in 102 (31%) patients. After adjusting for comorbidities, the risk of major adverse cardiac events was nearly doubled in the presence of significant compacted myocardial thinning (hazard ratio [HR], 1.88 [95% CI, 1.18‒3.00]; P=0.016), tripled in the presence of elevated plasma B-type natriuretic peptide (HR, 3.29 [95% CI, 1.52‒7.11]; P=0.006), and increased by 5% for every 10-unit increase in left ventricular end-systolic volume (HR, 1.01 [95% CI, 1.00‒1.01]; P=0.041).
Conclusions:
The risk of adverse clinical events is increased in the presence of significant compacted myocardial thinning, an elevated B-type natriuretic peptide or increased left ventricular dimensions. The combination of these markers may enhance risk assessment to minimize left ventricular non-compaction overdiagnosis whilst facilitating appropriate diagnoses in those with true disease.




J Am Heart Assoc: 08 Apr 2021:e019209; epub ahead of print
Ramchand J, Podugu P, Obuchowski N, Harb SC, ... Kwon DH, Flamm SD
J Am Heart Assoc: 08 Apr 2021:e019209; epub ahead of print | PMID: 33834849
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Impact:
Abstract

Greater Acculturation is Associated With Poorer Cardiovascular Health in the Multi-Ethnic Study of Atherosclerosis.

Osibogun O, Ogunmoroti O, Mathews L, Okunrintemi V, Tibuakuu M, Michos ED

Background:
Greater acculturation is associated with increased risk of cardiovascular disease. However, little is known about the association between acculturation and ideal cardiovascular health (CVH) as measured by the American Heart Association\'s 7 CVH metrics. We investigated the association between acculturation and ideal CVH among a multi-ethnic cohort of US adults free of clinical cardiovascular disease at baseline. Methods and Results This was a cross-sectional analysis of 6506 men and women aged 45 to 84 years of 4 races/ethnicities. We examined measures of acculturation(birthplace, language spoken at home, and years lived in the United States [foreign-born participants]) by CVH score. Scores of 0 to 8 indicate inadequate, 9 to 10 average and 11 to 14 optimal CVH. We used multivariable regression to examine associations between acculturation and CVH, adjusting for age, sex, race/ethnicity, education, income and health insurance. The mean (SD) age was 62 (10) years, 53% were women, 39% non-Hispanic White-, 26% non-Hispanic Black-, 12% Chinese- and 22% Hispanic-Americans. US-born participants had lower odds of optimal CVH (odds ratio [OR]: 0.63 [0.50-0.79], P<0.001) compared with foreign-born participants. Participants who spoke Chinese and other foreign languages at home had greater odds of optimal CVH compared with those who spoke English (1.91 [1.08-3.36], P=0.03; and 1.65 [1.04-2.63], P=0.03, respectively). Foreign-born participants who lived the longest in the United States had lower odds of optimal CVH (0.62 [0.43-0.91], P=0.02).
Conclusions:
Greater US acculturation was associated with poorer CVH. This finding suggests that the promotion of ideal CVH should be encouraged among immigrant populations since more years lived in the United States was associated with poorer CVH.




J Am Heart Assoc: 08 Apr 2021:e019828; epub ahead of print
Osibogun O, Ogunmoroti O, Mathews L, Okunrintemi V, Tibuakuu M, Michos ED
J Am Heart Assoc: 08 Apr 2021:e019828; epub ahead of print | PMID: 33834848
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Impact:
Abstract

Risk of Major Bleeding With Potent Antiplatelet Agents After an Acute Coronary Event: A Comparison of Ticagrelor and Clopidogrel in 5116 Consecutive Patients in Clinical Practice.

Mullen L, Meah MN, Elamin A, Aggarwal S, ... Thatchil J, Khand A

Background:
Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all-cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3-5, hazard ratio [HR], 1.23; 95% CI, 0.90-1.68; P=0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98-1.74; P=0.07) except in the non-coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3-5, adjusted HR, 1.58; 95% CI, 1.09-2.31; P=0.017; and PLATO major HR, 1.67; 95% CI, 1.18-2.37; P=0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87-1.64; P=0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76-1.10; P=0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52-1.32; P=0.42).
Conclusions:
This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02484924.




J Am Heart Assoc: 08 Apr 2021:e019467; epub ahead of print
Mullen L, Meah MN, Elamin A, Aggarwal S, ... Thatchil J, Khand A
J Am Heart Assoc: 08 Apr 2021:e019467; epub ahead of print | PMID: 33834845
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Abstract

Relationship Between Influenza, Temperature, and Type 1 Myocardial Infarction: An Ecological Time-Series Study.

García-Lledó A, Rodríguez-Martín S, Tobías A, García-de-Santiago E, ... Alonso-Martín J, de Abajo FJ

Background:
Previous studies investigating the relationship of influenza with acute myocardial infarction (AMI) have not distinguished between AMI types 1 and 2. Influenza and cold temperature can explain the increased incidence of AMI during winter but, because they are closely related in temperate regions, their relative contribution is unknown. Methods and Results The temporal relationship between incidence rates of AMI with demonstrated culprit plaque (type 1 AMI) from the regional primary angioplasty network and influenza, adjusted for ambient temperature, was studied in Madrid region (Spain) during 5 influenza seasons (from June 2013 to June 2018). A time-series analysis with quasi-Poisson regression models and distributed lag-nonlinear models was used. The incidence rate of type 1 AMI according to influenza vaccination status was also explored. A total of 8240 cases of confirmed type 1 AMI were recorded. The overall risk ratio (RR) of type 1 AMI during epidemic periods, adjusted for year, month, and temperature, was 1.23 (95% CI, 1.03-1.47). An increase of weekly influenza rate of 50 cases per 100 000 inhabitants resulted in an RR for type 1 AMI of 1.16 (95% CI, 1.09-1.23) during the same week, disappearing 1 week after. When adjusted for influenza, a decrease of 1ºC in the minimum temperature resulted in an increase of 2.5% type 1 AMI. Influenza vaccination was associated with a decreased risk of type 1 AMI in subjects aged 60 to 64 years (RR, 0.58; 95% CI, 0.47-0.71) and ≥65 years (RR, 0.53; 95% CI, 0.49-0.57).
Conclusions:
Influenza and cold temperature were both independently associated with an increased risk of type 1 AMI, whereas vaccination was associated with a reduced risk among older patients.




J Am Heart Assoc: 07 Apr 2021:e019608; epub ahead of print
García-Lledó A, Rodríguez-Martín S, Tobías A, García-de-Santiago E, ... Alonso-Martín J, de Abajo FJ
J Am Heart Assoc: 07 Apr 2021:e019608; epub ahead of print | PMID: 33829851
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Impact:
Abstract

Decade-Long Nationwide Trends and Disparities in Use of Comfort Care Interventions for Patients With Ischemic Stroke.

Chu KM, Jones EM, Meeks JR, Pan AP, ... Taffet GE, Vahidy FS

Background:
Stroke remains one of the leading causes of disability and death in the United States. We characterized 10-year nationwide trends in use of comfort care interventions (CCIs) among patients with ischemic stroke, particularly pertaining to acute thrombolytic therapy with intravenous tissue-type plasminogen activator and endovascular thrombectomy, and describe in-hospital outcomes and costs. Methods and Results We analyzed the National Inpatient Sample from 2006 to 2015 and identified adult patients with ischemic stroke with or without thrombolytic therapy and CCIs using validated International Classification of Diseases, Ninth Revision (ICD-9) codes. We report adjusted odds ratios (ORs) and 95% CI of CCI usage across five 2-year periods. Of 4 249 201 ischemic stroke encounters, 3.8% had CCI use. CCI use increased over time (adjusted OR, 4.80; 95% CI, 4.15-5.55) regardless of acute treatment type. Advanced age, female sex, White race, non-Medicare insurance, higher income, disease severity, comorbidity burden, and discharge from non-northeastern teaching hospitals were independently associated with receiving CCIs. In the fully adjusted model, thrombolytic therapy and endovascular thrombectomy, respectively, conferred a 6% and 10% greater likelihood of receiving CCIs. Among CCI users, there was a significant decline in in-hospital mortality compared with all other dispositions over time (adjusted OR, 0.46; 95% CI, 0.38-0.56). Despite longer length of stay, CCI hospitalizations incurred 16% lower adjusted costs.
Conclusions:
CCI use among patients with ischemic stroke has increased regardless of acute treatment type. Nonetheless, considerable disparities persist. Closing the disparities gap and optimizing access, outcomes, and costs for CCIs among patients with stroke are important avenues for further research.




J Am Heart Assoc: 06 Apr 2021:e019785; epub ahead of print
Chu KM, Jones EM, Meeks JR, Pan AP, ... Taffet GE, Vahidy FS
J Am Heart Assoc: 06 Apr 2021:e019785; epub ahead of print | PMID: 33823605
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Impact:
Abstract

Genomic Context Differs Between Human Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy.

Puckelwartz MJ, Pesce LL, Dellefave-Castillo LM, Wheeler MT, ... Dorn GW, McNally EM

Background:
Inherited cardiomyopathies display variable penetrance and expression, and a component of phenotypic variation is genetically determined. To evaluate the genetic contribution to this variable expression, we compared protein coding variation in the genomes of those with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Methods and Results Nonsynonymous single-nucleotide variants (nsSNVs) were ascertained using whole genome sequencing from familial cases of HCM (n=56) or DCM (n=70) and correlated with echocardiographic information. Focusing on nsSNVs in 102 genes linked to inherited cardiomyopathies, we correlated the number of nsSNVs per person with left ventricular measurements. Principal component analysis and generalized linear models were applied to identify the probability of cardiomyopathy type as it related to the number of nsSNVs in cardiomyopathy genes. The probability of having DCM significantly increased as the number of cardiomyopathy gene nsSNVs per person increased. The increase in nsSNVs in cardiomyopathy genes significantly associated with reduced left ventricular ejection fraction and increased left ventricular diameter for individuals carrying a DCM diagnosis, but not for those with HCM. Resampling was used to identify genes with aberrant cumulative allele frequencies, identifying potential modifier genes for cardiomyopathy.
Conclusions:
Participants with DCM had more nsSNVs per person in cardiomyopathy genes than participants with HCM. The nsSNV burden in cardiomyopathy genes did not correlate with the probability or manifestation of left ventricular measures in HCM. These findings support the concept that increased variation in cardiomyopathy genes creates a genetic background that predisposes to DCM and increased disease severity.




J Am Heart Assoc: 05 Apr 2021; 10:e019944
Puckelwartz MJ, Pesce LL, Dellefave-Castillo LM, Wheeler MT, ... Dorn GW, McNally EM
J Am Heart Assoc: 05 Apr 2021; 10:e019944 | PMID: 33764162
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Impact:
Abstract

Association of Transcatheter Mitral Valve Repair Availability With Outcomes of Mitral Valve Surgery.

Alkhouli M, Alqahtani F, Kawsara A, Guerrero M, ... Rihal CS, Crestanello JA

Background:
Transcatheter mitral valve repair (TMVr) is currently offered at selected centers that meet certain operator and institutional requirements. We sought to explore the hypothesis that the availability of TMVr is associated with improved outcomes of MV surgery. Methods and Results We used the Nationwide Readmissions Database to identify patients who underwent MV surgery at centers with or without TMVr capabilities between January 1 and December 31, 2017. The primary end point was in-hospital mortality. Secondary end points were postoperative complications, resource use, and 30-day readmissions. A total of 24 477 patients from 595 centers (446 TMVr, 149 non-TMVr) were included. There were modest but statistically significant differences in the prevalence of comorbidities between the groups. Patients at non-TMVr centers had higher unadjusted in-hospital mortality than those at TMVr centers (5.6% versus 3.6%, P<0.001). They also had higher rates of postoperative complications, longer hospitalizations, higher cost, and fewer home discharges but similar 30-day readmission rates. After propensity matching, mortality remained higher at non-TMVr centers (5.5% versus 4.0%, P<0.001). Rates of postoperative complications, prolonged hospitalizations, and nonhome discharges also remained higher. Postoperative mortality was consistently higher at non-TMVr centers in multiple risk-adjustment analyses incrementally accounting for differences in risk factors, surgical volume, availability of surgical repair, and excluding concomitant procedures. In the most comprehensive model, surgery at non-TMVr centers was associated with higher odds of death (odds ratio, 1.41; 95% CI, 1.14-1.73; P=0.002).
Conclusions:
Mitral valve surgery at TMVr centers is associated with improved in-hospital outcomes compared with non-TMVr centers.




J Am Heart Assoc: 05 Apr 2021; 10:e019314
Alkhouli M, Alqahtani F, Kawsara A, Guerrero M, ... Rihal CS, Crestanello JA
J Am Heart Assoc: 05 Apr 2021; 10:e019314 | PMID: 33754835
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Impact:
Abstract

Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E-Deficient Mice.

Huang K, Liu C, Peng M, Su Q, ... Li Z, Chang G

Background:
Although glycoursodeoxycholic acid (GUDCA) has been associated with the improvement of metabolic disorders, its effect on atherosclerosis remains elusive. This study aimed to investigate the role of GUDCA in the development of atherosclerosis and its potential mechanisms. Methods and Results Human THP-1 macrophages were used to investigate the effect of GUDCA on oxidized low-density lipoprotein-induced foam cell formation in vitro. We found that GUDCA downregulated scavenger receptor A1 mRNA expression, reduced oxidized low-density lipoprotein uptake, and inhibited macrophage foam cell formation. In an in vivo study, apolipoprotein E-deficient mice were fed a Western diet for 10 weeks to induce atherosclerosis, and then were gavaged once daily with or without GUDCA for 18 weeks. Parameters of systemic metabolism and atherosclerosis were detected. We found that GUDCA improved cholesterol homeostasis and protected against atherosclerosis progression as evidenced by reduced plaque area along with lipid deposition, ameliorated local chronic inflammation, and elevated plaque stability. In addition, 16S rDNA sequencing showed that GUDCA administration partially normalized the Western diet-associated gut microbiota dysbiosis. Interestingly, the changes of bacterial genera (Alloprevotella, Parabacteroides, Turicibacter, and Alistipes) modulated by GUDCA were correlated with the plaque area in mice aortas.
Conclusions:
Our study for the first time indicates that GUDCA attenuates the development of atherosclerosis, probably attributable to the inhibition of foam cell formation, maintenance of cholesterol homeostasis, and modulation of gut microbiota.




J Am Heart Assoc: 05 Apr 2021; 10:e019820
Huang K, Liu C, Peng M, Su Q, ... Li Z, Chang G
J Am Heart Assoc: 05 Apr 2021; 10:e019820 | PMID: 33787322
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Impact:
Abstract

Cost-Effectiveness of Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention in Patients With Chronic Kidney Disease and Acute Coronary Syndromes in the US Medicare Program.

Reynolds MR, Gong T, Li S, Herzog CA, Charytan DM

Background:
Coronary revascularization provides important long-term clinical benefits to patients with high-risk presentations of coronary artery disease, including those with chronic kidney disease. The cost-effectiveness of coronary interventions in this setting is not known. Methods and Results We developed a Markov cohort simulation model to assess the cost-effectiveness of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with chronic kidney disease who were hospitalized with acute myocardial infarction or unstable angina. Model inputs were primarily drawn from a sample of 14 300 patients identified using the Medicare 20% sample. Survival, quality-adjusted life-years, costs, and cost-effectiveness were projected over a 20-year time horizon. Multivariable models indicated higher 30-day mortality and end-stage renal disease with both PCI and CABG, and higher stroke with CABG, relative to medical therapy. However, the model projected long-term gains of 0.72 quality-adjusted life-years (0.97 life-years) for PCI compared with medical therapy, and 0.93 quality-adjusted life-years (1.32 life-years) for CABG compared with PCI. Incorporation of long-term costs resulted in incremental cost-effectiveness ratios of $65 326 per quality-adjusted life-year gained for PCI versus medical therapy, and $101 565 for CABG versus PCI. Results were robust to changes in input parameters but strongly influenced by the background costs of the population, and the time horizon.
Conclusions:
For patients with chronic kidney disease and high-risk coronary artery disease presentations, PCI and CABG were both associated with markedly increased costs as well as gains in quality-adjusted life expectancy, with incremental cost-effectiveness ratios indicating intermediate value in health economic terms.




J Am Heart Assoc: 05 Apr 2021; 10:e019391
Reynolds MR, Gong T, Li S, Herzog CA, Charytan DM
J Am Heart Assoc: 05 Apr 2021; 10:e019391 | PMID: 33787323
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Impact:
Abstract

Dutch Outcome in Implantable Cardioverter-Defibrillator Therapy: Implantable Cardioverter-Defibrillator-Related Complications in a Contemporary Primary Prevention Cohort.

van Barreveld M, Verstraelen TE, van Dessel PFHM, Boersma LVA, ... Dijkgraaf MGW, DO‐IT Registry Investigators

Background:
One third of primary prevention implantable cardioverter-defibrillator patients receive appropriate therapy, but all remain at risk of defibrillator complications. Information on these complications in contemporary cohorts is limited. This study assessed complications and their risk factors after defibrillator implantation in a Dutch nationwide prospective registry cohort and forecasts the potential reduction in complications under distinct scenarios of updated indication criteria. Methods and Results Complications in a prospective multicenter registry cohort of 1442 primary implantable cardioverter-defibrillator implant patients were classified as major or minor. The potential for reducing complications was derived from a newly developed prediction model of appropriate therapy to identify patients with a low probability of benefitting from the implantable cardioverter-defibrillator. During a follow-up of 2.2 years (interquartile range, 2.0-2.6 years), 228 complications occurred in 195 patients (13.6%), with 113 patients (7.8%) experiencing at least one major complication. Most common ones were lead related (n=93) and infection (n=18). Minor complications occurred in 6.8% of patients, with lead-related (n=47) and pocket-related (n=40) complications as the most prevailing ones. A surgical reintervention or additional hospitalization was required in 53% or 61% of complications, respectively. Complications were strongly associated with device type. Application of stricter implant indication results in a comparable proportional reduction of (major) complications.
Conclusions:
One in 13 patients experiences at least one major implantable cardioverter-defibrillator-related complication, and many patients undergo a surgical reintervention. Complications are related to defibrillator implantations, and these should be discussed with the patient. Stricter implant indication criteria and careful selection of device type implanted may have significant clinical and financial benefits.




J Am Heart Assoc: 05 Apr 2021; 10:e018063
van Barreveld M, Verstraelen TE, van Dessel PFHM, Boersma LVA, ... Dijkgraaf MGW, DO‐IT Registry Investigators
J Am Heart Assoc: 05 Apr 2021; 10:e018063 | PMID: 33787324
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Impact:
Abstract

Physiological Evaluation of Anomalous Aortic Origin of a Coronary Artery Using Computed Tomography-Derived Fractional Flow Reserve.

Adjedj J, Hyafil F, Halna du Fretay X, Dupouy P, ... Aubry P, Abnormal Coronary Origin investigators *

Background:
With the emergence of coronary computed tomography (CT) angiography, anomalous aortic origin of a coronary artery (ANOCOR) is more frequently diagnosed. Fractional flow reserve derived from CT (FFRCT) is a noninvasive functional test providing anatomical and functional evaluation of the overall coronary tree. These unique features of anatomical and functional evaluation derived from CT could help for the management of patients with ANOCOR. We aimed to retrospectively evaluate the physiological and clinical impact of FFRCT analysis in the ANOCOR registry population. Methods and Results The ANOCOR registry included patients with ANOCOR detected during invasive coronary angiography or coronary CT angiography between January 2010 and January 2013, with a planned 5-year follow-up. We retrospectively performed FFRCT analysis in patients with coronary CT angiography of adequate quality. Follow-up was performed with a clinical composite end point (cardiac death, myocardial infarction, and unplanned revascularization). We obtained successful FFRCT analyses and 5-year clinical follow-up in 54 patients (average age, 60±13 years). Thirty-eight (70%) patients had conservative treatment, and 16 (30%) patients had coronary revascularization after coronary CT angiography. The presence of an ANOCOR course was associated with a moderate reduction of FFRCT value from 1.0 at the ostium to 0.90±0.10 downstream the ectopic course and 0.82±0.11 distally. No significant difference in FFRCT values was identified between at-risk and not at-risk ANOCOR. After a 5-year follow-up, only one unplanned percutaneous revascularization was reported.
Conclusions:
The presence of ANOCOR was associated with a moderate hemodynamic decrease of FFRCT values and associated with a low risk of cardiovascular events after a 5-year follow-up in this middle-aged population.




J Am Heart Assoc: 05 Apr 2021; 10:e018593
Adjedj J, Hyafil F, Halna du Fretay X, Dupouy P, ... Aubry P, Abnormal Coronary Origin investigators *
J Am Heart Assoc: 05 Apr 2021; 10:e018593 | PMID: 33728970
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Impact:
Abstract

Use of a Clinical Electrocardiographic Database to Enhance Atrial Fibrillation/Atrial Flutter Identification Algorithms Based on Administrative Data.

Liu H, Collins R, Miller RJH, Southern DA, ... James MT, Wilton SB

Background:
Administrative data have limited sensitivity for case finding of atrial fibrillation/atrial flutter (AF/AFL). Linkage with clinical repositories of interpreted ECGs may enhance diagnostic yield of AF/AFL. Methods and Results We retrieved 369 ECGs from the institutional Marquette Universal System for Electrocardiography (MUSE) repository as validation samples, with rhythm coded as AF (n=49), AFL (n=50), or other competing rhythm diagnoses (n=270). With blinded, duplicate review of ECGs as the reference comparison, we compared multiple MUSE coding definitions for identifying AF/AFL. We tested the agreement between MUSE diagnosis and reference comparison, and calculated the sensitivity and specificity. Using a data set linking clinical registries, administrative data, and the MUSE repository (n=11 662), we assessed the incremental diagnostic yield of AF/AFL by incorporating ECG data to administrative data-based algorithms. The agreement between MUSE diagnosis and reference comparison depended on the coding definitions applied, with the Cohen κ ranging from 0.57 to 0.75. Sensitivity ranged from 60.6% to 79.1%, and specificity ranged from 93.2% to 98.0%. A coding definition with AF/AFL appearing in the first 3 ECG statements had the highest sensitivity (79.1%), with little loss of specificity (94.5%). Compared with the algorithms with only administrative data, incorporating ECG data increased the diagnostic yield of preexisting AF/AFL by 14.5% and incident AF/AFL by 7.5% to 16.1%.
Conclusions:
Routine ECG interpretation using MUSE coding is highly specific and moderately sensitive for AF/AFL detection. Inclusion of MUSE ECG data in AF/AFL case identification algorithms can identify cases missed using administrative data-based algorithms alone.




J Am Heart Assoc: 05 Apr 2021; 10:e018511
Liu H, Collins R, Miller RJH, Southern DA, ... James MT, Wilton SB
J Am Heart Assoc: 05 Apr 2021; 10:e018511 | PMID: 33719522
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Impact:
Abstract

Disparities in Mortality and Cardiovascular Events by Income and Blood Pressure Levels Among Patients With Hypertension in South Korea.

Shin JH, Jung MH, Kwon CH, Lee CJ, ... Cho MC, Sung KC

Background:
Socioeconomic status is associated with differences in risk factors of cardiovascular disease and increased risks of cardiovascular disease and mortality. However, it is unclear whether an association exists between cardiovascular disease and income, a common measure of socioeconomic status, among patients with hypertension. Methods and Results This population-based longitudinal study comprised 479 359 patients aged ≥19 years diagnosed with essential hypertension. Participants were categorized by income and blood pressure levels. Primary end point was all-cause and cardiovascular mortality and secondary end points were cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Low income was significantly associated with high all-cause (hazard ratio [HR], 1.26; 95% CI, 1.23-1.29, lowest versus highest income) and cardiovascular mortality (HR, 1.31; 95% CI, 1.25-1.38) as well as cardiovascular events (HR, 1.07; 95% CI, 1.05-1.10) in patients with hypertension after adjusting for age, sex, systolic blood pressure, body mass index, smoking status, alcohol consumption, physical activity, fasting glucose, total cholesterol, and the use of aspirin or statins. In each blood pressure category, low-income levels were associated with high all-cause and cardiovascular mortality and cardiovascular events. The excess risks of all-cause and cardiovascular mortality and cardiovascular events associated with uncontrolled blood pressure were more prominent in the lowest income group.
Conclusions:
Low income and uncontrolled blood pressure are associated with increased all-cause and cardiovascular mortality and cardiovascular events in patients with hypertension. These findings suggest that income is an important aspect of social determinants of health that has an impact on cardiovascular outcomes in the care of hypertension.




J Am Heart Assoc: 05 Apr 2021; 10:e018446
Shin JH, Jung MH, Kwon CH, Lee CJ, ... Cho MC, Sung KC
J Am Heart Assoc: 05 Apr 2021; 10:e018446 | PMID: 33719521
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Impact:
Abstract

Objective Sleep Efficiency Predicts Cardiovascular Disease in a Community Population: The Sleep Heart Health Study.

Yan B, Yang J, Zhao B, Fan Y, Wang W, Ma X

Background:
There was little evidence about the role of objective sleep efficiency (SE) in the incidence of major cardiovascular disease (CVD) events. The purpose of this study was to investigate the correlation between objective SE and CVD based on polysomnography. Methods and Results A total of 3810 participants from the SHHS (Sleep Heart Health Study) were selected in the current study. CVD was assessed during an almost 11-year follow-up period. The primary composite cardiovascular outcome was major adverse cardiovascular events, defined as CVD mortality, congestive heart failure, myocardial infarction, and stroke. The secondary composite cardiovascular outcome was major adverse cardiovascular event plus revascularization. Objective measured SE, including SE and wake after sleep onset, was based on in-home polysomnography records. Cox regression analysis was used to explore the association between SE and CVD. After multivariate Cox regression analysis, poor SE (<80%) was significantly associated with primary (hazard ratio [HR], 1.338; 95% CI, 1.025-1.745; P=0.032) and secondary composite cardiovascular outcomes (HR, 1.250; 95% CI, 1.027-1.521; P=0.026); it was also found to be a predictor of CVD mortality (HR, 1.887; 95% CI, 1.224-2.909; P=0.004). Moreover, wake after sleep onset of fourth quartile (>78.0 minutes) was closely correlated with primary (HR, 1.436; 95% CI, 1.066-1.934; P=0.017), secondary composite cardiovascular outcomes (HR, 1.374; 95% CI, 1.103-1.712; P=0.005), and CVD mortality (HR, 2.240; 95% CI, 1.377-3.642; P=0.001).
Conclusions:
Poor SE and long wake after sleep onset, objectively measured by polysomnography, were associated with the increased risk of incident CVD.




J Am Heart Assoc: 05 Apr 2021; 10:e016201
Yan B, Yang J, Zhao B, Fan Y, Wang W, Ma X
J Am Heart Assoc: 05 Apr 2021; 10:e016201 | PMID: 33719504
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Impact:
Abstract

Estrogen Plays a Crucial Role in Rab9-Dependent Mitochondrial Autophagy, Delaying Arterial Senescence.

Sasaki Y, Ikeda Y, Uchikado Y, Akasaki Y, Sadoshima J, Ohishi M

Background:
The risk of cardiovascular disease is known to increase after menopause. Mitochondria, which undergo quality control via mitochondrial autophagy, play a crucial role in the regulation of cellular senescence. The aim of this study was to investigate whether the effect of estrogen-mediated protection from senescence on arteries is attributed to the induction of mitochondrial autophagy. Methods and Results We used human umbilical vein cells, vascular smooth muscle cells, and 12-week-old female C57BL/6 mice. The administration of 17β-estradiol (E2) to cells inhibited cellular senescence and mitochondrial dysfunction. Furthermore, E2 increased mitochondrial autophagy, maintaining mitochondrial function, and retarding cellular senescence. Of note, E2 did not modulate LC3 (light chain 3), and ATG7 (autophagy related 7) deficiency did not suppress mitochondrial autophagy in E2-treated cells. Conversely, E2 increased the colocalization of Rab9 with LAMP2 (lysosomal-associated membrane protein 2) signals. The E2-mediated effects on mitochondrial autophagy were abolished by the knockdown of either Ulk1 or Rab9. These results suggest that E2-mediated mitochondrial autophagy is associated with Rab9-dependent alternative autophagy. E2 upregulated SIRT1 (sirtuin 1) and activated LKB1 (liver kinase B1), AMPK (adenosine monophosphate-activated protein kinase), and Ulk1, indicating that the effect of E2 on the induction of Rab9-dependent alternative autophagy is mediated by the SIRT1/LKB1/AMPK/Ulk1 pathway. Compared with the sham-operated mice, ovariectomized mice showed reduced mitochondrial autophagy and accelerated mitochondrial dysfunction and arterial senescence; these detrimental alterations were successfully rescued by the administration of E2.
Conclusions:
We showed that E2-induced mitochondrial autophagy plays a crucial role in the delay of vascular senescence. The Rab9-dependent alternative autophagy is behind E2-induced mitochondrial autophagy.




J Am Heart Assoc: 05 Apr 2021; 10:e019310
Sasaki Y, Ikeda Y, Uchikado Y, Akasaki Y, Sadoshima J, Ohishi M
J Am Heart Assoc: 05 Apr 2021; 10:e019310 | PMID: 33719502
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Impact:
Abstract

Testosterone Metabolite 6β-Hydroxytestosterone Contributes to Angiotensin II-Induced Abdominal Aortic Aneurysms in Male Mice.

Mukherjee K, Pingili AK, Singh P, Dhodi AN, ... Gonzalez FJ, Malik KU

Background:
Sex is a prominent risk factor for abdominal aortic aneurysms (AAAs), and angiotensin II (Ang II) induces AAA formation to a greater degree in male than in female mice. We previously reported that cytochrome P450 1B1 contributes to the development of hypertension, as well as AAAs, in male mice. We also found that a cytochrome P450 1B1-generated metabolite of testosterone, 6β-hydroxytestosterone (6β-OHT), contributes to Ang II-induced hypertension and associated cardiovascular and renal pathogenesis in male mice. The current study was conducted to determine the contribution of 6β-OHT to Ang II-induced AAA development in Apoe-/- male mice. Methods and Results Intact or castrated Apoe-/-/Cyp1b1+/+ and Apoe-/-/Cyp1b1-/- male mice were infused with Ang II or its vehicle for 28 days, and administered 6β-OHT every third day for the duration of the experiment. Abdominal aortas were then evaluated for development of AAAs. We observed a significant increase in the incidence and severity of AAAs in intact Ang II-infused Apoe-/-/Cyp1b1+/+ mice, compared with vehicle-treated mice, which were minimized in castrated Apoe-/-/Cyp1b1+/+ and intact Apoe-/-/Cyp1b1-/- mice infused with Ang II. Treatment with 6β-OHT significantly restored the incidence and severity of AAAs in Ang II-infused castrated Apoe-/-/Cyp1b1+/+ and intact Apoe-/-/Cyp1b1-/- mice. However, administration of testosterone failed to increase AAA incidence and severity in Ang II-infused intact Apoe-/-/Cyp1b1-/- mice.
Conclusions:
Our results indicate that the testosterone-cytochrome P450 1B1-generated metabolite 6β-OHT contributes to Ang II-induced AAA development in Apoe-/- male mice.




J Am Heart Assoc: 05 Apr 2021; 10:e018536
Mukherjee K, Pingili AK, Singh P, Dhodi AN, ... Gonzalez FJ, Malik KU
J Am Heart Assoc: 05 Apr 2021; 10:e018536 | PMID: 33719500
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Abstract

Elevated Pulmonary Pressure Noted on Echocardiogram: A Simplified Approach to Next Steps.

Kanwar MK, Tedford RJ, Thenappan T, De Marco T, Park M, McLaughlin V
An elevated right ventricular/pulmonary artery systolic pressure suggestive of pulmonary hypertension (PH) is a common finding noted on echocardiography and is considered a marker for poor clinical outcomes, regardless of the cause. Even mild elevation of pulmonary pressure can be considered a modifiable risk factor, informing the trajectory of patients\' clinical outcome. Although guidelines have been published detailing diagnostic and management algorithms, this echocardiographic finding is often underappreciated or not acted upon. Hence, patients with PH are often diagnosed in clinical practice when hemodynamic abnormalities are already moderate or severe. This results in delayed initiation of potentially effective therapies, referral to PH centers, and greater patient morbidity and mortality. This mini-review presents a succinct, simplified case-based approach to the \"next steps\" in the work-up of PH, once elevated pulmonary pressures have been noted on an echocardiogram. Our goal is for clinicians to develop a good overview of diagnostic approach to PH and recognition of high-risk features that may require early referral.



J Am Heart Assoc: 05 Apr 2021; 10:e017684
Kanwar MK, Tedford RJ, Thenappan T, De Marco T, Park M, McLaughlin V
J Am Heart Assoc: 05 Apr 2021; 10:e017684 | PMID: 33719491
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Abstract

Associations Between Preoperative Glucose and Hemoglobin A1c Level and Myocardial Injury After Noncardiac Surgery.

Park J, Oh AR, Lee SH, Lee JH, ... Ahn J, Lee SM

Background:
Perioperative blood glucose level has shown an association with postoperative outcomes. We compared the incidences of myocardial injury after noncardiac surgery (MINS) and 30-day mortality, according to preoperative blood glucose and hemoglobin A1c (HbA1c) levels. Methods and Results The patients were divided according to blood glucose level within 1 day before surgery. The hyperglycemia group was defined with fasting glucose >140 mg/dL or random glucose >180 mg/dL. In addition, we compared the outcomes according to HbA1c >6.5% among patients with available HbA1c within 3 months before surgery. The primary outcome was MINS, and 30-day mortality was also compared. A total of 12 304 patients were enrolled and divided into 2 groups: 8324 (67.7%) in the normal group and 3980 (32.3%) in the hyperglycemia group. After adjustment with inverse probability of weighting, the hyperglycemia group exhibited significantly higher incidences of MINS and 30-day mortality (18.7% versus 27.6%; odds ratio, 1.29; 95% CI, 1.18-1.42; P<0.001; and 2.0% versus 5.1%; hazard ratio, 2.00; 95% CI, 1.61-2.49; P<0.001, respectively). In contrast to blood glucose, HbA1c was not associated with MINS or 30-day mortality.
Conclusions:
Preoperative hyperglycemia was associated with MINS and 30-day mortality, whereas HbA1c was not. Immediate glucose control may be more crucial than long-term glucose control in patients undergoing noncardiac surgery. Registration URL: https://www.cris.nih.go.kr; Unique identifier: KCT0004244.




J Am Heart Assoc: 05 Apr 2021; 10:e019216
Park J, Oh AR, Lee SH, Lee JH, ... Ahn J, Lee SM
J Am Heart Assoc: 05 Apr 2021; 10:e019216 | PMID: 33728934
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Impact:
Abstract

Association of Small Intestinal Bacterial Overgrowth With Heart Failure and Its Prediction for Short-Term Outcomes.

Song Y, Liu Y, Qi B, Cui X, ... Zhou J, Ge J

Background:
Small intestinal bacterial overgrowth (SIBO) is a common pathological condition of intestinal microbiota. The prevalence of SIBO and its prognostic value in patients with heart failure (HF) are unknown. Methods and Results A total of 287 patients tested for SIBO using lactulose hydrogen-methane breath test were evaluated. At least 1 of the following criteria fulfilled was SIBO positive: patients with fasting hydrogen level ≥20 parts per million (ppm) or a ≥20 ppm rise in hydrogen by 90 minutes were diagnosed with SIBO (H2) positive; and patients with methane levels ≥10 ppm at any test point were diagnosed with SIBO (CH4) positive. The association between SIBO and the composite of cardiovascular death and HF rehospitalization was investigated. In 287 consecutive patients with HF, 128 (45%) were positive for SIBO. Our result showed SIBO increased the risk of HF rehospitalization in patients with HF with reduced ejection fraction (P<0.001), and the risk of cardiovascular death in patients with HF with preserved EF (P=0.011). SIBO was an independent risk factor of primary end point in patients with HF (hazard ratio [HR], 2.13; 95% CI; 1.26-3.58; P=0.005). In addition, SIBO (CH4) showed a prognostic value on adverse outcomes (HR, 2.35; 95% CI, 1.38-4.02; P<0.001), whereas the association between SIBO (H2) and outcomes was not statistically significant.
Conclusions:
There was high prevalence of SIBO in patients with HF, and SIBO was independently associated with poor outcomes. Proactive treatment for SIBO may provide extra benefit for patients with HF.




J Am Heart Assoc: 05 Apr 2021; 10:e015292
Song Y, Liu Y, Qi B, Cui X, ... Zhou J, Ge J
J Am Heart Assoc: 05 Apr 2021; 10:e015292 | PMID: 33728933
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Abstract

Metabolic Dyslipidemia and Cardiovascular Outcomes in Type 2 Diabetes Mellitus: Findings From the Look AHEAD Study.

Kaze AD, Santhanam P, Musani SK, Ahima R, Echouffo-Tcheugui JB

Background:
Metabolic dyslipidemia (high triglyceride) and low high-density lipoprotein cholesterol (HDL-C) is highly prevalent in type 2 diabetes mellitus (T2DM). The extent to which diabetes mellitus-related abnormalities in the triglyceride-HDL-C profile associates with cardiovascular disease (CVD) risk is incompletely understood. We evaluated the associations of triglyceride and HDL-C status with CVD outcomes in individuals with T2DM. Methods and Results We analyzed data from 4199 overweight/obese adults with T2DM free of CVD with available data on triglyceride and HDL-C at baseline (2001-2004) in the Look AHEAD (Action for Health in Diabetes) study. We used Cox proportional models to estimate hazard ratios (HRs) and 95% CIs of: (1) composite CVD outcome (myocardial infarction, stroke, hospitalization for angina, and/or death from cardiovascular causes); (2) coronary artery disease events; and (3) cerebrovascular accidents (stroke). Of the 4199 participants, 62% (n=2600) were women, with a mean age of 58 years (SD, 7), and 40% (n=1659) had metabolic dyslipidemia at baseline. Over a median follow-up of 9.5 years (interquartile range, 8.7-10.3), 500 participants experienced the composite CVD outcome, 396 experienced coronary artery disease events, and 100 experienced stroke. Low HDL-C was associated with higher hazards of the composite CVD outcome (HR, 1.36; 95% CI, 1.12-1.64 [P=0.002]) and coronary artery disease events (HR, 1.46; 95% CI, 1.18-1.81 [P=0.001]) but not stroke (HR, 1.38; 95% CI, 0.90-2.11 [P=0.140]). Compared with patients with normal triglyceride and normal HDL, participants with metabolic dyslipidemia had higher risks of the composite CVD outcome (HR, 1.30; 95% CI, 1.03-1.63 [P=0.025]) and coronary artery disease events (HR, 1.48; 95% CI, 1.14-1.93 [P=0.003]) but not stroke (HR, 1.23; 95% CI, 0.74-2.05 [P=0.420]).
Conclusions:
In a large sample of overweight/obese individuals with T2DM, metabolic dyslipidemia was associated with higher risks of CVD outcomes. Our findings highlight the necessity to account for metabolic dyslipidemia in CVD risk stratification among patients with T2DM. Registration URL: https://www.lookaheadtrial.org; Unique identifier: NCT00017953.




J Am Heart Assoc: 05 Apr 2021; 10:e016947
Kaze AD, Santhanam P, Musani SK, Ahima R, Echouffo-Tcheugui JB
J Am Heart Assoc: 05 Apr 2021; 10:e016947 | PMID: 33728932
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Abstract

Surgical and Transcatheter Mitral Valve Replacement in Mitral Annular Calcification: A Systematic Review.

Alexis SL, Malik AH, El-Eshmawi A, George I, ... Adams DH, Tang GHL
Mitral annular calcification with mitral valve disease is a challenging problem that could necessitate surgical mitral valve replacement (SMVR). Transcatheter mitral valve replacement (TMVR) is emerging as a feasible alternative in high-risk patients with appropriate anatomy. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to December 25, 2019 for studies discussing SMVR or TMVR in patients with mitral annular calcification; 27 of 1539 articles were selected for final review. TMVR was used in 15 studies. Relevant data were available on 82 patients who underwent hybrid transatrial TMVR, and 354 patients who underwent transapical or transseptal TMVR. Outcomes on SMVR were generally reported as small case series (447 patients from 11 studies); however, 1 large study recently reported outcomes in 9551 patients. Patients who underwent TMVR had a shorter median follow-up of 9 to 12 months (range, in-hospital‒19 months) compared with patients with SMVR (54 months; range, in-hospital‒120 months). Overall, those undergoing TMVR were older and had higher Society of Thoracic Surgeons risk scores. SMVR showed a wide range of early (0%-27%; median 6.3%) and long-term mortality (0%-65%; median at 1 year, 15.8%; 5 years, 38.8%, 10 years, 62.4%). The median in-hospital, 30-day, and 1-year mortality rates were 16.7%, 22.7%, and 43%, respectively, for transseptal/transapical TMVR, and 9.5%, 20.0%, and 40%, respectively, for transatrial TMVR. Mitral annular calcification is a complex disease and TMVR, with a versatile option of transatrial approach in patients with challenging anatomy, offers a promising alternative to SMVR in high-risk patients. However, further studies are needed to improve technology, patient selection, operative expertise, and long-term outcomes.



J Am Heart Assoc: 05 Apr 2021; 10:e018514
Alexis SL, Malik AH, El-Eshmawi A, George I, ... Adams DH, Tang GHL
J Am Heart Assoc: 05 Apr 2021; 10:e018514 | PMID: 33728929
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Impact:
Abstract

Levels of Prebeta-1 High-Density Lipoprotein Are a Strong Independent Positive Risk Factor for Coronary Heart Disease and Myocardial Infarction: A Meta-Analysis.

Pullinger CR, O\'Connor PM, Naya-Vigne JM, Kunitake ST, ... Malloy MJ, Kane JP

Background:
We previously showed that levels of prebeta-1 high-density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from cells, including artery wall macrophages, are positively associated with coronary heart disease (CHD) and myocardial infarction (MI) risk. Methods and Results In a multiethnic follow-up cohort of 1249 individuals from University of California-San Francisco clinics, we determined the degree to which prebeta-1 HDL levels, both absolute and percentage of apolipoprotein AI, are associated with CHD and history of MI. Independent, strong, positive associations were found. Meta-analysis revealed for the absolute prebeta-1 HDL for the top tertile versus the lowest, unadjusted odds ratios of 1.90 (95% CI, 1.40-2.58) for CHD and 1.79 (95% CI, 1.35-2.36) for MI. For CHD, adjusting for established risk factors, the top versus bottom tertiles, quintiles, and deciles yielded sizable odds ratios of 2.37 (95% CI, 1.74-3.25, P<0.001), 3.20 (95% CI, 2.07-4.94, P<0.001), and 4.00 (95% CI, 2.11-7.58, P<0.001), respectively. Men and women were analyzed separately in a combined data set of 2507 individuals. The odds ratios for CHD and MI risk were similar. Higher levels of prebeta-1 HDL were associated with all 5 metabolic syndrome features. Addition of prebeta-1 HDL to these 5 features resulted in significant improvements in risk-prediction models.
Conclusions:
Analysis of 2507 subjects showed conclusively that levels of prebeta-1 HDL are strongly associated with a history of CHD or MI, independently of traditional risk factors. Addition of prebeta-1 HDL can significantly improve clinical assessment of risk of CHD and MI.




J Am Heart Assoc: 05 Apr 2021; 10:e018381
Pullinger CR, O'Connor PM, Naya-Vigne JM, Kunitake ST, ... Malloy MJ, Kane JP
J Am Heart Assoc: 05 Apr 2021; 10:e018381 | PMID: 33728928
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Impact:
Abstract

Non-Vitamin K Antagonist Oral Anticoagulants Provide Less Adverse Renal Outcomes Than Warfarin In Non-Valvular Atrial Fibrillation: A Systematic Review and MetaAnalysis.

Sitticharoenchai P, Takkavatakarn K, Boonyaratavej S, Praditpornsilpa K, Eiam-Ong S, Susantitaphong P

Background:
Non-vitamin K antagonist oral anticoagulants (NOACs) have better pharmacologic properties than warfarin and are recommended in preference to warfarin in most patients with non-valvular atrial fibrillation. Besides lower bleeding complications, other advantages of NOACs over warfarin particularly renal outcomes remain inconclusive. Methods and Results Electronic searches were conducted through Medline, Scopus, Cochrane Library databases, and ClinicalTrial.gov. Randomized controlled trials and observational cohort studies reporting incidence rates and hazard ratio (HR) of renal outcomes (including acute kidney injury, worsening renal function, doubling serum creatinine, and end-stage renal disease) were selected. The random-effects model was used to calculate pooled incidence and HR with 95% CI. Eighteen studies were included. A total of 285 201 patients were enrolled, 118 863 patients with warfarin and 166 338 patients with NOACs. The NOACs group yielded lower incidence rates of all renal outcomes when compared with the warfarin group. Patients treated with NOACs showed significantly lower HR of risk of acute kidney injury (HR, 0.70, 95% CI, 0.64-0.76; P<0.001), worsening renal function (HR, 0.83; 95% CI, 0.73-0.95; P=0.006), doubling serum creatinine (HR, 0.58; 95% CI, 0.41-0.82; P=0.002), and end-stage renal disease (HR, 0.82; 95% CI, 0.78-0.86; P<0.001).
Conclusions:
In non-valvular atrial fibrillation, patients treated with NOACs have a lower risk of both acute kidney injury and end-stage renal disease when compared with warfarin.




J Am Heart Assoc: 05 Apr 2021; 10:e019609
Sitticharoenchai P, Takkavatakarn K, Boonyaratavej S, Praditpornsilpa K, Eiam-Ong S, Susantitaphong P
J Am Heart Assoc: 05 Apr 2021; 10:e019609 | PMID: 33728927
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Impact:
Abstract

Mucosal-Associated Invariant T Cells Are Involved in Acute Ischemic Stroke by Regulating Neuroinflammation.

Nakajima S, Tanaka R, Yamashiro K, Chiba A, ... Miyake S, Hattori N

Background:
Mucosal-associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ischemic stroke in mice. Methods and Results We used MR1 knockout C57BL/6 (MR1-/-) mice and wild-type littermates (MR1+/+). After performing a transient middle cerebral artery occlusion (tMCAO), we evaluated the association with inflammation and prognosis in the acute cerebral ischemia. Furthermore, we analyzed the tMCAO C57BL/6 mice administered with the suppressive MR1 ligand and the vehicle control. We also evaluated the infiltration of MAIT cells into the ischemic brain by flow cytometry. Results showed a reduction of infarct volume and an improvement of neurological impairment in MR1-/- mice (n=8). There was a reduction in the number of infiltrating microglia/macrophages (n=3-5) and in their activation (n=5) in the peri-infarct area of MR1-/- mice. The cytokine levels of interleukin-6 and interleukin-17 at 24 hours after tMCAO (n=3-5), and for interleukin-17 at 72 hours after tMCAO (n=5), were lower in the MR1-/- mice. The administration of the suppressive MR1 ligand reduced the infarct volume and improved functional impairment (n=5). Flow cytometric analysis demonstrated there was a reduction of MAIT cells infiltrating into the ischemic brain at 24 hours after tMCAO (n=17).
Conclusions:
Our results showed that MAIT cells play an important role in neuroinflammation after focal cerebral ischemia and the use of MAIT cell regulation has a potential role as a novel neuroprotectant for the treatment of acute ischemic stroke.




J Am Heart Assoc: 05 Apr 2021; 10:e018803
Nakajima S, Tanaka R, Yamashiro K, Chiba A, ... Miyake S, Hattori N
J Am Heart Assoc: 05 Apr 2021; 10:e018803 | PMID: 33733818
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Abstract

Impact of Reactive Oxidative Metabolites Among New Categories of Nonischemic Heart Failure.

Nishihara T, Yamamoto E, Sueta D, Fujisue K, ... Kaikita K, Tsujita K

Background:
We investigated the clinical significance of derivatives of reactive oxygen metabolites (DROMs), a new marker of reactive oxygen species, in patients with nonischemic heart failure (HF) and compared them among new categories of HF. Methods and Results We recruited 201 consecutively hospitalized patients with HF and measured DROM under stable conditions. Then, we divided them according to new categories of HF (HF with reduced ejection fraction [EF], HF with midrangeEF, and HF with preserved EF) without coronary artery disease. In subgroup analysis, we followed EF changes in patients with HF with reduced EF and classified them into HF with recovered EF or nonrecovered EF according to whether EF had improved to >40%. DROMs are significantly and independently associated with HF-related events in patients with NIHF. There were no significant differences in DROM and the probability of HF-related events among HF categories in Kaplan-Meier analysis. However, patients with HF with reduced EF and HF with preserved EF but not HF with midrange EF with HF-related events had higher DROM than those without HF-related events. In subgroup analysis, Kaplan-Meier analysis demonstrated that the probabilities of HF-related events in HF with recovered EF were dramatically decreased. DROM were significantly higher in patients with HF with nonrecovered EF than in HF with recovered EF. In receiver operating characteristic analysis, the cutoff level of DROM for predicting improvements in HF with recovered EF was 347 Carratelli units. Furthermore, the C-statistic value for predicting EF improvement for the DROM levels was 0.703. In multivariable logistic regression analysis, DROM was independently and significantly associated with the prediction of HF with recovered EF.
Conclusions:
DROM measurements can provide important prognostic information for risk stratification in any category of NIHF. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000035827.




J Am Heart Assoc: 05 Apr 2021; 10:e016765
Nishihara T, Yamamoto E, Sueta D, Fujisue K, ... Kaikita K, Tsujita K
J Am Heart Assoc: 05 Apr 2021; 10:e016765 | PMID: 33733816
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Impact:
Abstract

Tuberculosis and the Heart.

López-López JP, Posada-Martínez EL, Saldarriaga C, Wyss F, ... Neglected Tropical Diseases, Other Infectious Diseases Affecting the Heart (the NET‐Heart Project)
Acquired tuberculosis continues to be a challenge worldwide. Although tuberculosis has been considered a global public health emergency, it remains poorly controlled in many countries. Despite being primarily a pulmonary disease, tuberculosis could involve the heart. This systematic review is part of the \"Neglected Tropical Diseases and Other Infectious Diseases Involving the Heart\" (the NET-Heart Project) initiative from the Interamerican Society of Cardiology. This project aims to review the cardiovascular involvement of these heterogeneous diseases, advancing original algorithms to help healthcare providers diagnose and manage cardiovascular complications. In tuberculosis, pericardium involvement is relatively common, especially in AIDS, and tuberculosis is the most common cause of constrictive pericarditis in endemic countries. Myocarditis and aortitis by tuberculosis are rare. Clinical manifestations of cardiovascular involvement by tuberculosis differ from those typically found for bacteria or viruses. Prevailing systemic symptoms and the pericarditis diagnostic index should be taken into account. An echocardiogram is the first step for diagnosing cardiovascular involvement; however, several image modalities can be used, depending on the suspected site of infection. Adenosine deaminase levels, gamma interferon, or polymerase chain reaction testing could be used to confirm tuberculosis infection; each has a high diagnostic performance. Antituberculosis chemotherapy and corticosteroids are treatment mainstays that significantly reduce mortality, constriction, and hospitalizations, especially in patients with HIV. In conclusion, tuberculosis cardiac involvement is frequent and could lead to heart failure, constrictive pericarditis, or death. Early detection of complications should be a cornerstone of overall management.



J Am Heart Assoc: 05 Apr 2021; 10:e019435
López-López JP, Posada-Martínez EL, Saldarriaga C, Wyss F, ... Neglected Tropical Diseases, Other Infectious Diseases Affecting the Heart (the NET‐Heart Project)
J Am Heart Assoc: 05 Apr 2021; 10:e019435 | PMID: 33733808
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Impact:
Abstract

Effect of First-Pass Reperfusion on Outcome After Endovascular Treatment for Ischemic Stroke.

den Hartog SJ, Zaidat O, Roozenbeek B, van Es ACGM, ... Dippel DWJ, MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry Investigators

Background:
First-pass reperfusion (FPR) is associated with favorable outcome after endovascular treatment. It is unknown whether this effect is independent of patient characteristics and whether FPR has better outcomes compared with excellent reperfusion (Expanded Thrombolysis in Cerebral Infarction [eTICI] 2C-3) after multiple-passes reperfusion. We aimed to evaluate the association between FPR and outcome with adjustment for patient, imaging, and treatment characteristics to single out the contribution of FPR. Methods and Results FPR was defined as eTICI 2C-3 after 1 pass. Multivariable regression models were used to investigate characteristics associated with FPR and to investigate the effect of FPR on outcomes. We included 2686 patients of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. Factors associated with FPR were as follows: history of hyperlipidemia (adjusted odds ratio [OR], 1.05; 95% CI, 1.01-1.10), middle cerebral artery versus intracranial carotid artery occlusion (adjusted OR, 1.11; 95% CI, 1.06-1.16), and aspiration versus stent thrombectomy (adjusted OR, 1.07; 95% CI, 1.03-1.11). Interventionist experience increased the likelihood of FPR (adjusted OR, 1.03 per 50 patients previously treated; 95% CI, 1.01-1.06). Adjusted for patient, imaging, and treatment characteristics, FPR remained associated with a better 24-hour National Institutes of Health Stroke Scale (NIHSS) score (-37%; 95% CI, -43% to -31%) and a better modified Rankin Scale (mRS) score at 3 months (adjusted common OR, 2.16; 95% CI, 1.83-2.54) compared with no FPR (multiple-passes reperfusion+no excellent reperfusion), and compared with multiple-passes reperfusion alone (24-hour NIHSS score, (-23%; 95% CI, -31% to -14%), and mRS score (adjusted common OR, 1.45; 95% CI, 1.19-1.78)).
Conclusions:
FPR compared with multiple-passes reperfusion is associated with favorable outcome, independently of patient, imaging, and treatment characteristics. Factors associated with FPR were the experience of the interventionist, history of hyperlipidemia, location of occluded artery, and use of an aspiration device compared with stent thrombectomy.




J Am Heart Assoc: 05 Apr 2021; 10:e019988
den Hartog SJ, Zaidat O, Roozenbeek B, van Es ACGM, ... Dippel DWJ, MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry Investigators
J Am Heart Assoc: 05 Apr 2021; 10:e019988 | PMID: 33739141
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Impact:
Abstract

Natural Course of New-Onset Postoperative Atrial Fibrillation after Noncardiac Surgery.

Hyun J, Cho MS, Nam GB, Kim M, ... Choi KJ, Kim YH

Background:
Postoperative atrial fibrillation (POAF) is common after cardiac surgery, but little is known about its incidence and natural course after noncardiac surgery. We evaluated the natural course and clinical impact of POAF and the long-term impact of anticoagulation therapy in patients without a history of atrial fibrillation (AF) undergoing noncardiac surgery. Methods and Results We retrospectively analyzed the database of Asan Medical Center (Seoul, Korea) to identify patients who developed new-onset POAF after undergoing noncardiac surgery between January 2006 and January 2016. The main outcomes were AF recurrence, thromboembolic event, and major bleeding during follow-up. Of 322 688 patients who underwent noncardiac surgery, 315 patients (mean age, 66.4 years; 64.4% male) had new-onset POAF with regular rhythm monitoring after discharge. AF recurred in 53 (16.8%) during 2 years of follow-up. Hypertension (hazard ratio, 2.12; P=0.02), moderate-to-severe left atrial enlargement (hazard ratio, 2.33; P=0.007) were independently associated with recurrence. Patients with recurrent AF had higher risks of thromboembolic events (11.2% versus 0.8%; P<0.001) and major bleeding (26.9% versus 4.1%; P<0.001) than those without recurrence. Patients with recurrent AF and without anticoagulation were especially predisposed to thromboembolic events (P<0.001). Overall, anticoagulation therapy was not significantly associated with thromboembolic events (1.4% versus 2.5%, P=0.95).
Conclusions:
AF recurred in 16.8% of patients with POAF after noncardiac surgery. AF recurrence was associated with higher risks of adverse clinical outcomes. Considering the high risk of anticoagulation-related bleeding, the benefits of routine anticoagulation should be carefully weighed in this population. Active surveillance for AF recurrence is warranted.




J Am Heart Assoc: 05 Apr 2021; 10:e018548
Hyun J, Cho MS, Nam GB, Kim M, ... Choi KJ, Kim YH
J Am Heart Assoc: 05 Apr 2021; 10:e018548 | PMID: 33739130
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Impact:
Abstract

Association of Serum Testosterone and Luteinizing Hormone With Blood Pressure and Risk of Cardiovascular Disease in Middle-Aged and Elderly Men.

Qu M, Feng C, Wang X, Gu Y, ... Xiong C, Li H

Background:
The age-related decline in testosterone levels is thought to be of great importance for male aging and cardiovascular diseases. However, data are controversial on whether abnormal sex hormones are linked to the presence of cardiovascular diseases and it is also uncertain how blood pressure modifies the association between testosterone levels and major cardiovascular diseases. Methods and Results This is a multicenter, population-based, cross-sectional study of 6296 men conducted between 2013 and 2016. Basic information and clinical symptoms were obtained by questionnaires. Blood pressure and plasma levels of total testosterone, sex hormone-binding globulin, luteinizing hormone, and free testosterone were determined in men in a multistage random, cluster sampling in 6 provinces of China. There were 5786 Chinese men (mean [SD] age 55.0 [10.1] years) included after exclusion criteria were applied; 37.2% (2150) of them were diagnosed with hypertension. Total testosterone, free testosterone, and sex hormone-binding globulin were inversely associated with the prevalence of hypertension. Age >65 years or body mass index ≥24 negatively impacted the inverse correlation between testosterone levels and hypertension, whereas smoking and family history of hypertension strengthened the correlation. In participants with grade 2 hypertension, total testosterone was positively associated with the presence of stroke, and luteinizing hormone was also positively correlated with cardiovascular and cerebrovascular diseases.
Conclusions:
Lower total testosterone could be a promising risk marker for prevalent hypertension. Both low and high levels of testosterone are associated with greater cardiovascular risk. Primary hypogonadism may be a risk marker for major cardiovascular diseases in men with severe hypertension.




J Am Heart Assoc: 05 Apr 2021; 10:e019559
Qu M, Feng C, Wang X, Gu Y, ... Xiong C, Li H
J Am Heart Assoc: 05 Apr 2021; 10:e019559 | PMID: 33739129
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Impact:
Abstract

Factors Related to Major Bleeding After Ticagrelor Therapy: Results from the TICO Trial.

Cho JY, Lee SY, Yun KH, Kim BK, ... Hong MK, Jang Y

Background:
There is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation. Methods and Results From the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate <60 mL/min per 1.73 m2 were associated with an increased risk of major bleeding. In contrast, 3-month aspirin therapy with continued ticagrelor (versus 12-month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3-month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39-0.90; Pinteraction=0.74).
Conclusions:
Low body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk. Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02494895.




J Am Heart Assoc: 05 Apr 2021; 10:e019630
Cho JY, Lee SY, Yun KH, Kim BK, ... Hong MK, Jang Y
J Am Heart Assoc: 05 Apr 2021; 10:e019630 | PMID: 33739127
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Impact:
Abstract

Office Blood Pressure Range and Cardiovascular Events in Patients With Hypertension: A Nationwide Cohort Study in South Korea.

Kwon CH, Kim W, Shin JH, Lee CJ, ... Pyun WB, Sung KC

Background:
It is unclear what office blood pressure (BP) is the optimal treatment target range in patients with hypertension. Methods and Results Using the Korean National Health Insurance Service database, we extracted the data on 479 359 patients with hypertension with available BP measurements and no history of cardiovascular events from 2002 to 2011. The study end point was major cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, or stroke. This cohort study evaluated the association of BP levels (<120/<70, 120-129/70-79, 130-139/80-89, 140-149/90-99, and ≥150/≥100 mm Hg) with MACE. During a median follow-up of 9 years, 55 401 MACE were documented in our cohort. The risk of MACE was the lowest (adjusted hazard ratio [HR], 0.79; 95% CI, 0.76-0.84) at BP level of <120/<70 mm Hg, and was the highest (HR, 1.32; 95% CI, 1.29-1.36) at ≥150/≥100 mm Hg in comparison with 130 to 139/80 to 89 mm Hg. These results were consistent in all age groups and both sexes. Among patients treated with antihypertensive medication (n=237 592, 49.5%), in comparison with a BP level of 130 to 139/80 to 89 mm Hg, the risk of MACE was significantly higher in patients with elevated BP (≥140/≥90 mm Hg), but not significantly lower in patients with BP of <130/<80 mm Hg. Low BP <120/70 mm Hg was associated with increased risk of all-cause or cardiovascular death in all age groups.
Conclusions:
BP level is significantly correlated with the risk of MACE in all Korean patients with hypertension. However, there were no additional benefits for MACE amongst those treated for hypertension with BP <120/70 mm Hg.




J Am Heart Assoc: 05 Apr 2021; 10:e017890
Kwon CH, Kim W, Shin JH, Lee CJ, ... Pyun WB, Sung KC
J Am Heart Assoc: 05 Apr 2021; 10:e017890 | PMID: 33739126
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Impact:
Abstract

Local Passive Heat for the Treatment of Hypertension in Autonomic Failure.

Okamoto LE, Celedonio JE, Smith EC, Gamboa A, ... Crandall CG, Biaggioni I

Background:
Supine hypertension affects a majority of patients with autonomic failure; it is associated with end-organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP-lowering effect in patients with autonomic failure and could be used to treat their supine hypertension. Methods and Results In Protocol 1 (n=22), the acute effects of local heat (40-42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion. Heat acutely decreased systolic BP by -19±4 mm Hg (versus 3±4 with sham, P<0.001) owing to decreases in stroke volume (-18±5% versus -4±4%, P=0.013 ) and cardiac output (-15±5% versus -2±4%, P=0.013). In Protocol 2 (proof-of-concept overnight study; n=12), we compared the effects of local heat (38°C applied with a water-perfused heating pad placed under the torso from 10 pm to 6 am) versus placebo pill. Heat decreased nighttime systolic BP (maximal change -28±6 versus -2±6 mm Hg, P<0.001). BP returned to baseline by 8 am. The nocturnal systolic BP decrease correlated with a decrease in urinary volume (r=0.57, P=0.072) and an improvement in the morning upright systolic BP (r=-0.76, P=0.007).
Conclusions:
Local heat therapy effectively lowered overnight BP in patients with autonomic failure and supine hypertension and offers a novel approach to treat this condition. Future studies are needed to assess the long-term safety and efficacy in improving nighttime fluid loss and daytime orthostatic hypotension. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02417415 and NCT03042988.




J Am Heart Assoc: 05 Apr 2021; 10:e018979
Okamoto LE, Celedonio JE, Smith EC, Gamboa A, ... Crandall CG, Biaggioni I
J Am Heart Assoc: 05 Apr 2021; 10:e018979 | PMID: 33739123
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Impact:
Abstract

Associations Between HIV Serostatus and Cardiac Structure and Function Evaluated by 2-Dimensional Echocardiography in the Multicenter AIDS Cohort Study.

Doria de Vasconcellos H, Post WS, Ervin AM, Haberlen SA, ... Lima JAC, Wu KC

Background:
We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2-dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross-sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction <50%) was low and HIV serostatus was not associated with left ventricular ejection fraction. Multivariable adjustment models showed that men who were HIV+ versus those who were HIV- had greater LV mass index and larger left atrial diameter and right ventricular (RV) end-diastolic area; lower RV function; and higher prevalence of diastolic dysfunction. Higher current CD4+ T cell count ≥400 cell/mm3 versus <400 was associated with smaller LV diastolic volume and RV area. Virally suppressed men who were HIV+ versus those who were HIV- had higher indexed LV mass and left atrial areas and greater diastolic dysfunction.
Conclusions:
HIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.




J Am Heart Assoc: 05 Apr 2021; 10:e019709
Doria de Vasconcellos H, Post WS, Ervin AM, Haberlen SA, ... Lima JAC, Wu KC
J Am Heart Assoc: 05 Apr 2021; 10:e019709 | PMID: 33749311
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Impact:
Abstract

Dapagliflozin Improves Cardiac Hemodynamics and Mitigates Arrhythmogenesis in Mitral Regurgitation-Induced Myocardial Dysfunction.

Lin YW, Chen CY, Shih JY, Cheng BC, ... Fisch S, Chang WT

Background:
Mitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR-induced HF. Methods and Results Using a novel, mini-invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10 mg/kg per day for 6 weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR-induced impairment including partial restoration of left ventricular ejection fraction and end-systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing-induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress-associated proteins.
Conclusions:
DAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR-induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio-protective function, provides a plausible point of DAPA as a potential strategy for MR-induced HF.




J Am Heart Assoc: 05 Apr 2021; 10:e019274
Lin YW, Chen CY, Shih JY, Cheng BC, ... Fisch S, Chang WT
J Am Heart Assoc: 05 Apr 2021; 10:e019274 | PMID: 33749310
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Impact:
Abstract

Small Left Ventricle and Clinical Outcomes After Transcatheter Aortic Valve Replacement.

Saito T, Inohara T, Yoshijima N, Yashima F, ... Yamamoto M, Hayashida K

Background:
In patients undergoing transcatheter aortic valve replacement (TAVR), those with small left ventricle (LV) may have an increased risk of poor outcomes, because small LV is associated with low-flow (LF), left ventricular hypertrophy. However, the impact of small LV on patients undergoing TAVR remains unknown. Methods and Results We examined 2584 patients who underwent TAVR between October 2013 and May 2017 using data from the Japanese multicenter registry. On the basis of the American Society of Echocardiography guidelines, small LV was defined as left ventricular end-diastolic dimension <42.0 mm for men or <37.8 mm for women. The 2-year clinical outcomes were compared between patients with and without small LV using multivariable Cox regression analyses and propensity score matching. Subgroup analyses by LF, left ventricular hypertrophy were performed. Of 2584 patients who underwent TAVR, 466 (18.0%) had small LV. Patients with small LV had smaller body size and less comorbidity, and were more likely to have LF status compared with those without. Small LV was associated with a higher 2-year all-cause (20.8% versus 14.3%; adjusted hazard ratio [HR],1.58 [95% CI, 1.20-2.09]; P=0.0013) and cardiovascular mortality (8.8% versus 5.5%; adjusted HR, 1.93 [95% CI, 1.25-2.98]; P=0.0028). Propensity score matching analysis showed consistent findings. In subgroup analyses, LF, left ventricular hypertrophy did not interact with small LV.
Conclusions:
Small LV, determined by a simple echocardiographic parameter, was associated with poorer clinical outcomes after TAVR regardless of LF, left ventricular hypertrophy. LV size may be useful for assessing clinical outcomes after TAVR. Registration URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000020423.




J Am Heart Assoc: 05 Apr 2021; 10:e019543
Saito T, Inohara T, Yoshijima N, Yashima F, ... Yamamoto M, Hayashida K
J Am Heart Assoc: 05 Apr 2021; 10:e019543 | PMID: 33749309
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Impact:
Abstract

Segmental Cardiac Radiation Dose Determines Magnitude of Regional Cardiac Dysfunction.

Trivedi SJ, Tang S, Byth K, Stefani L, ... Koh ES, Thomas L

Background:
Subclinical left ventricular dysfunction detected by 2-dimensional global longitudinal strain post breast radiotherapy has been described in patients with breast cancer. We hypothesized that left ventricular dysfunction postradiotherapy may be site specific, based on differential segmental radiotherapy dose received. Methods and Results Transthoracic echocardiograms were performed at baseline, 6 weeks, and 12 months postradiotherapy on 61 chemotherapy-naïve women with left-sided breast cancer undergoing tangential breast radiotherapy. Radiation received within basal, mid, and apical regions for the 6 left ventricular walls was quantified from the radiotherapy treatment planning system. Anterior, anteroseptal, and anterolateral walls received the highest radiation doses, while inferolateral and inferior walls received the lowest. There was a progressive increase in the radiation dose received from basal to apical regions. At 6 weeks, the most significant percentage deterioration in strain was seen in the apical region, with greatest reductions in the anterior wall followed by the anteroseptal and anterolateral walls, with a similar pattern persisting at 12 months. There was a within-patient dose-response association between the segment-specific percentage deterioration in strain at 6 weeks and 12 months and the radiation dose received.
Conclusions:
Radiotherapy for left-sided breast cancer causes differential segmental dysfunction, with myocardial segments that receive the highest radiation dose demonstrating greatest strain impairment. Percentage deterioration in strain observed 6 weeks postradiotherapy persisted at 12 months and demonstrated a dose-response relationship with radiotherapy dose received. Radiotherapy-induced subclinical cardiac dysfunction is of importance because it could be additive to chemotherapy-related cardiotoxicity in patients with breast cancer. Long-term outcomes in patients with asymptomatic strain reduction require further investigation.




J Am Heart Assoc: 05 Apr 2021; 10:e019476
Trivedi SJ, Tang S, Byth K, Stefani L, ... Koh ES, Thomas L
J Am Heart Assoc: 05 Apr 2021; 10:e019476 | PMID: 33749308
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Impact:
Abstract

Deficiency of ITGAM Attenuates Experimental Abdominal Aortic Aneurysm in Mice.

Zhou M, Wang X, Shi Y, Ding Y, ... Shi Z, Fu W

Background:
Integrin αM (CD11b), which is encoded by the Integrin Subunit Alpha M (ITGAM) gene, is not only a surface marker of monocytes but also an essential adhesion molecule. In this study, we investigated the effect of CD11b on experimental abdominal aortic aneurysm and the potential underlying mechanisms. Methods and Results The incidence of abdominal aortic aneurysm was not significantly lower in ITGAM(-/-) mice than in control mice. Nevertheless, knockout of CD11b reduced the maximum abdominal aortic diameter, macrophage infiltration, matrix metalloproteinase-9 expression, and elastin and collagen degradation. Additionally, lower expression of IL-6 was found in both the peripheral blood and abdominal aortas of ITGAM(-/-) mice, indicating a biological correlation between CD11b and the inflammatory response in abdominal aortic aneurysm. In vitro, the number of ITGAM(-/-) bone marrow-derived macrophages (BMDMs) that adhered to endothelial cells was significantly lower than the number of wild-type BMDMs. Moreover, the CD11b monoclonal antibody and CD11b agonist leukadherin-1 decreased and increased the number of adherent wild-type BMDMs, respectively. Through RNA sequencing, genes associated with leukocyte transendothelial migration were found to be downregulated in ITGAM(-/-) BMDMs. Furthermore, immunoprecipitation-mass spectrometry analysis predicted that the Akt pathway might be responsible for the impaired transmigratory ability of ITGAM(-/-) BMDMs. The reduced activation of Akt was then confirmed, and the Akt agonist SC79 partially rescued the transendothelial migratory function of ITGAM(-/-) BMDMs.
Conclusions:
CD11b might promote the development and progression of abdominal aortic aneurysm by mediating the endothelial cells adhesion and transendothelial migration of circulating monocytes/macrophages.




J Am Heart Assoc: 05 Apr 2021; 10:e019900
Zhou M, Wang X, Shi Y, Ding Y, ... Shi Z, Fu W
J Am Heart Assoc: 05 Apr 2021; 10:e019900 | PMID: 33749307
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Impact:
Abstract

Low Birth Weight Increases the Risk of Sudden Cardiac Death in the Young: A Nationwide Study of 2.2 Million People.

Waaler Loland V, Ågesen FN, Lynge TH, Pinborg A, ... Winkel BG, Tfelt-Hansen J

Background:
Sudden cardiac death (SCD) constitutes a major health problem worldwide. We investigated whether birth weight (BW), small for gestational age (SGA), and large for gestational age are associated with altered risk of SCD among the young (aged 1-36 years). Methods and Results We included all people born in Denmark from 1973 to 2008 utilizing the Danish Medical Birth Register. All SCDs in Denmark in 2000 to 2009 have previously been identified. We defined 5 BW groups, SGA, and large for gestational age as exposure and SCD as the outcome. We estimated the age-specific relative risk of SCD with 95% CI. Additionally, we investigated if SGA and large for gestational age are associated with pathological findings at autopsy. The study population for the BW analyses comprised 2 234 501 people with 389 SCD cases, and the SGA and large for gestational age analyses comprised 1 786 281 people with 193 SCD cases. The relative risk for SCD was 6.69 for people with BW between 1500 and 2499 g (95% CI, 2.38-18.80, P<0.001) and 5.89 for people with BW ≥4500 g (95% CI, 1.81-19.12, P=0.003) at age 5 years. BW 2500 to 3400 g was the reference group. Compared with an appropriate gestational age, the relative risk for SGA was 2.85 (95% CI, 1.35-6.00, P=0.006) at age 10 years. For the autopsied cases, the relative risk of sudden arrhythmic death syndrome at age 5 years was 4.19 for SGA (95% CI, 1.08-16.22, P=0.038).
Conclusions:
We found an association between BW and SCD in the young, with an increased risk among SGA infants. In addition, we found an association between SGA and sudden arrhythmic death syndrome.




J Am Heart Assoc: 05 Apr 2021; 10:e018314
Waaler Loland V, Ågesen FN, Lynge TH, Pinborg A, ... Winkel BG, Tfelt-Hansen J
J Am Heart Assoc: 05 Apr 2021; 10:e018314 | PMID: 33749305
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Impact:
Abstract

Abnormal Left-Hemispheric Sulcal Patterns in Adults With Simple Congenital Heart Defects Repaired in Childhood.

Asschenfeldt B, Evald L, Yun HJ, Heiberg J, ... Im K, Eskildsen SF

Background:
Children operated on for a simple congenital heart defect (CHD) are at risk of neurodevelopmental abnormalities. Abnormal cortical development and folding have been observed in fetuses with CHD. We examined whether sulcal folding patterns in adults operated on for simple CHD in childhood differ from those of healthy controls, and whether such differences are associated with neuropsychological outcomes. Methods and Results Patients (mean age, 24.5 years) who underwent childhood surgery for isolated atrial septal defect (ASD; n=33) or ventricular septal defect (VSD; n=30) and healthy controls (n=37) were enrolled. Sulcal pattern similarity to healthy controls was determined using magnetic resonance imaging and looking at features of sulcal folds, their intersulcal relationships, and sulcal graph topology. The sulcal pattern similarity values were tested for associations with comprehensive neuropsychological scores. Patients with both ASD and VSD had decreased sulcal pattern similarity in the left hemisphere compared with controls. The differences were found in the left temporal lobe in the ASD group and in the whole left hemisphere in the VSD group (P=0.033 and P=0.039, respectively). The extent of abnormal left hemispheric sulcal pattern similarity was associated with worse neuropsychological scores (intelligence, executive function, and visuospatial abilities) in the VSD group, and special educational support in the ASD group.
Conclusions:
Adults who underwent surgery for simple CHD in childhood display altered left hemisphere sulcal folding patterns, commensurate with neuropsychological scores for patients with VSD and special educational support for ASD. This may indicate that simple CHD affects early brain development. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871881.




J Am Heart Assoc: 05 Apr 2021; 10:e018580
Asschenfeldt B, Evald L, Yun HJ, Heiberg J, ... Im K, Eskildsen SF
J Am Heart Assoc: 05 Apr 2021; 10:e018580 | PMID: 33745293
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Impact:
Abstract

Cigarette Smoking, Incident Coronary Heart Disease, and Coronary Artery Calcification in Black Adults: The Jackson Heart Study.

Oshunbade AA, Kassahun-Yimer W, Valle KA, Hamid A, ... Correa A, Hall ME

Background:
Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study). Methods and Results We classified JHS participants without a history of CHD (n=4432) by self-reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000-2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1-19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow-up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39-3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0-1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose-response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score >0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88-3.68).
Conclusions:
In a large prospective cohort of Black adults, current smoking was associated with a >2-fold increased risk of CHD over a median follow-up of greater than a decade.




J Am Heart Assoc: 05 Apr 2021; 10:e017320
Oshunbade AA, Kassahun-Yimer W, Valle KA, Hamid A, ... Correa A, Hall ME
J Am Heart Assoc: 05 Apr 2021; 10:e017320 | PMID: 33754833
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Impact:
Abstract

Cardio/Kidney Composite End Points: A Post Hoc Analysis of the EMPA-REG OUTCOME Trial.

Ferreira JP, Kraus BJ, Zwiener I, Lauer S, ... Wanner C, Zannad F

Background:
Cardio/kidney composite end points are clinically relevant but rarely analyzed in cardiovascular trials. This post hoc analysis of the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial evaluated cardio/kidney composite end points by 2 statistical approaches. Methods and Results A total of 7020 patients with type 2 diabetes mellitus and established cardiovascular disease were treated with empagliflozin 10 or 25 mg (n=4687) or placebo (n=2333) on top of standard care. Cardio/kidney composite end points studied were: (1) cardiac or kidney death, kidney failure, hospitalization for heart failure, sustained decline in estimated glomerular filtration rate ≥40% from baseline, or sustained progression to macroalbuminuria; (2) cardiac or kidney death, kidney failure, hospitalization for heart failure, or sustained estimated glomerular filtration rate decline ≥40% from baseline; and (3) cardiac or kidney death, kidney failure, hospitalization for heart failure, or sustained doubling in serum creatinine from baseline. Cox regression using time-to-first-event analysis and win ratio (WR) using hierarchical order of events were applied. Empagliflozin reduced the risk of all cardio/kidney composites. The results varied only slightly between Cox and WR (eg, composite 1: hazard ratio, 0.56 [95% CI, 0.49-0.64]; WR, 1.76 [95% CI, 1.53-2.02]. WR prioritizes events by clinical importance; in particular, all fatal events are evaluated, whereas Cox regression ignores deaths when preceded by nonfatal events. Of the 285 cardio/kidney deaths in the analysis, 44 to 56 (15%-20%), depending on the composite, occurred after a nonfatal event and were not evaluated in Cox regression but evaluated by the WR.
Conclusions:
By considering the clinical relevance of different event types, the WR represents an appropriate method to complement the traditional time-to-first-event analysis in cardio/kidney outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01131676.




J Am Heart Assoc: 05 Apr 2021; 10:e020053
Ferreira JP, Kraus BJ, Zwiener I, Lauer S, ... Wanner C, Zannad F
J Am Heart Assoc: 05 Apr 2021; 10:e020053 | PMID: 33754809
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Impact:
Abstract

Atrial Fibrillation Is Associated With Mortality in Intermediate Surgical Risk Patients With Severe Aortic Stenosis: Analyses From the PARTNER 2A and PARTNER S3i Trials.

Brener MI, George I, Kosmidou I, Nazif T, ... Kodali S, Biviano AB

Background:
The impact of atrial fibrillation (AF) in intermediate surgical risk patients with severe aortic stenosis who undergo either transcatheter or surgical aortic valve replacement (AVR) is not well established. Methods and Results Data were assessed in 2663 patients from the PARTNER (Placement of Aortic Transcatheter Valve) 2A or S3i trials. Analyses grouped patients into 3 categories according to their baseline and discharge rhythms (ie, sinus rhythm [SR]/SR, SR/AF, or AF/AF). Among patients with transcatheter AVR (n=1867), 79.2% had SR/SR, 17.6% had AF/AF, and 3.2% had SR/AF. Among patients with surgical AVR (n=796), 71.7% had SR/SR, 14.1% had AF/AF, and 14.2% had SR/AF. Patients with transcatheter AVR in AF at discharge had increased 2-year mortality (SR/AF versus SR/SR; hazard ratio [HR], 2.73; 95% CI, 1.68-4.44; P<0.0001; AF/AF versus SR/SR; HR, 1.56; 95% CI, 1.16-2.09; P=0.003); patients with SR/AF also experienced increased 2-year mortality relative to patients with AF/AF (HR, 1.77; 95% CI, 1.04-3.00; P=0.03). For patients with surgicalAVR, the presence of AF at discharge was also associated with increased 2-year mortality (SR/AF versus SR/SR; HR, 1.93; 95% CI, 1.25-2.96; P=0.002; and AF/AF versus SR/SR; HR, 1.67; 95% CI, 1.06-2.63; P=0.027). Rehospitalization and persistent advanced heart failure symptoms were also more common among patients with transcatheter AVR and surgical AVR discharged in AF, and major bleeding was more common in the transcatheter AVR cohort.
Conclusions:
The presence of AF at discharge in patients with intermediate surgical risk aortic stenosis was associated with worse outcomes-especially in patients with baseline SR-including increased all-cause mortality at 2-year follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01314313 and NCT03222128.




J Am Heart Assoc: 05 Apr 2021; 10:e019584
Brener MI, George I, Kosmidou I, Nazif T, ... Kodali S, Biviano AB
J Am Heart Assoc: 05 Apr 2021; 10:e019584 | PMID: 33754803
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Impact:
Abstract

Mildly Elevated Pulmonary Arterial Pressure Is Associated With a High Risk of Progression to Pulmonary Hypertension and Increased Mortality: A Systematic Review and Meta-Analysis.

Xue L, Yang Y, Sun B, Liu B, Zeng Q, Xiong C

Background:
Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (PAP) ≥25 mm Hg measured by right heart catheterization. However, the upper limit of a normal mean PAP is 20 mm Hg. There is a gap between the upper limit of normal and the threshold for diagnosing PH. Therefore, we aimed to investigate whether individuals with a mildly elevated PAP, defined as 20 mm Hg < mean PAP <25 mm Hg, are at an increased risk of progression to PH or mortality than those with a normal PAP. Methods and Results We reviewed studies evaluating the risk of progression to PH and/or mortality in individuals with a mildly elevated PAP versus those with a normal PAP. The mean PAP value of each participant was confirmed by right heart catheterization. We reviewed 1213 studies and 8 fulfilled our inclusion criteria. Our results indicated that individuals with a mildly elevated PAP were 1.81 to 2.45 times more likely to progress to PH than individuals with a normal PAP. There was a statistically significant difference in mortality between the mildly elevated PAP and normal PAP groups (hazard ratio, 2.48; 95% CI, 1.69-3.64). We also pooled survival probabilities in each arm to obtain a summary survival curve for each group, and the pooled survival rates in the mildly elevated PAP group were numerically lower than those in the normal PAP group.
Conclusions:
Our study revealed that individuals with a mildly elevated PAP were at an increased risk of progression to PH and mortality than those with a normal PAP.




J Am Heart Assoc: 05 Apr 2021; 10:e018374
Xue L, Yang Y, Sun B, Liu B, Zeng Q, Xiong C
J Am Heart Assoc: 05 Apr 2021; 10:e018374 | PMID: 33754797
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Impact:
Abstract

Characteristics of Populations Excluded From Clinical Trials Supporting Intensive Blood Pressure Control Guidelines.

Anderson TS, Odden MC, Penko J, Kazi DS, Bellows BK, Bibbins-Domingo K

Background:
Only one third of patients recommended intensified treatment by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline for high blood pressure would have been eligible for the clinical trials on which recommendations were largely based. We sought to identify characteristics of adults who would have been trial-ineligible in order to inform clinical practice and research priorities. Methods and Results We examined the proportion of adults diagnosed with hypertension who met trial inclusion and exclusion criteria, stratified by age, diabetes mellitus status, and guideline recommendations in a cross-sectional study of the National Health and Nutrition Examination Survey, 2013-2016. Of the 107.7 million adults (95% CI, 99.3-116.0 million) classified as having hypertension by the ACC/AHA guideline, 23.1% (95% CI, 20.8%-25.5%) were below the target blood pressure of 130/80 mm Hg, 22.2% (95% CI, 20.1%-24.4%) would be recommended nonpharmacologic treatment, and 54.6% (95% CI, 52.5%-56.7%) would be recommended additional pharmacotherapy. Only 20.6% (95% CI, 18.8%-22.4%) of adults with hypertension would be trial-eligible. The majority of adults <50 years were excluded because of low cardiovascular risk and lack of access to primary care. The majority of adults aged ≥70 years were excluded because of multimorbidity and limited life expectancy. Reasons for trial exclusion were similar for patients with and without diabetes mellitus.
Conclusions:
Intensive blood pressure treatment trials were not representative of many younger adults with low cardiovascular risk and older adults with multimorbidity who are now recommended more intensive blood pressure goals.




J Am Heart Assoc: 05 Apr 2021; 10:e019707
Anderson TS, Odden MC, Penko J, Kazi DS, Bellows BK, Bibbins-Domingo K
J Am Heart Assoc: 05 Apr 2021; 10:e019707 | PMID: 33754796
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Abstract

Potential Effects of Bariatric Surgery on the Incidence of Heart Failure and Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus and Obesity and on Mortality in Patients With Preexisting Heart Failure: A Nationwide, Matched, Observational Cohort Study.

Höskuldsdóttir G, Sattar N, Miftaraj M, Näslund I, ... Svensson AM, Eliasson B

Background:
Obesity and diabetes mellitus are strongly associated with heart failure (HF) and atrial fibrillation (AF). The benefits of bariatric surgery on cardiovascular outcomes are known in people with or without diabetes mellitus. Surgical treatment of obesity might also reduce the incidence of HF and AF in individuals with obesity and type 2 diabetes mellitus (T2DM). Methods and Results In this register-based nationwide cohort study we compared individuals with T2DM and obesity who underwent Roux-en-Y gastric bypass surgery with matched individuals not treated with surgery. The main outcome measures were hospitalization for HF and/or AF and mortality in patients with preexisting HF. We identified 5321 individuals with T2DM and obesity who had undergone Roux-en-Y gastric bypass surgery between January 2007 and December 2013 and 5321 matched controls. The individuals included were 18 to 65 years old and had a body mass index >27.5 kg/m2. The follow-up time for hospitalization was until the end of 2015 (mean 4.5 years) and the end of 2016 for death. Our results show a 73% lower risk for HF (hazard ratio [HR], 0.27; CI, 0.19-0.38), 41% for AF (HR, 0.59; CI, 0.44-0.78), and 77% for concomitant AF and HF (HR, 0.23; CI, 0.12-0.46) in the surgically treated group. In patients with preexisting HF we observed significantly lower mortality in the group who underwent surgery (HR, 0.23; 95% CI, 0.12-0.43).
Conclusions:
Bariatric surgery may reduce risk for HF and AF in patients with T2DM and obesity, speculatively via positive cardiovascular and renal effects. Obesity treatment with surgery may also be a valuable alternative in selected patients with T2DM and HF.




J Am Heart Assoc: 05 Apr 2021; 10:e019323
Höskuldsdóttir G, Sattar N, Miftaraj M, Näslund I, ... Svensson AM, Eliasson B
J Am Heart Assoc: 05 Apr 2021; 10:e019323 | PMID: 33754795
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Abstract

Obesity and Serial NT-proBNP Levels in Guided Medical Therapy for Heart Failure With Reduced Ejection Fraction: Insights From the GUIDE-IT Trial.

Parcha V, Patel N, Kalra R, Suri SS, ... Wang TJ, Arora P

Background:
Obese patients have lower NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The prognostic implications of achieving NT-proBNP levels ≤1000 pg/mL in obese patients with heart failure (HF) receiving biomarker-guided therapy are not completely known. We evaluated the prognostic implications of obesity and having NT-proBNP levels (≤1000 pg/mL) in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial participants. Methods and Results The risk of adverse cardiovascular events (HF hospitalization or cardiovascular mortality) was assessed using multivariable-adjusted Cox proportional hazard models based on having NT-proBNP ≤1000 pg/mL (taken as a time-varying covariate), stratified by obesity status. The study outcome was also assessed on the basis of the body mass index at baseline. The predictive ability of NT-proBNP for adverse cardiovascular events was assessed using the likelihood ratio test. Compared with nonobese patients, obese patients were mostly younger, Black race, and more likely to be women. NT-proBNP levels were 59.0% (95% CI, 39.5%-83.5%) lower among obese individuals. The risk of adverse cardiovascular events was lower in obese (hazard ratio [HR], 0.48; 95% CI, 0.29-0.59) and nonobese (HR, 0.32; 95% CI, 0.19-0.57) patients with HF who had NT-proBNP levels ≤1000 pg/mL, compared with those who did not. There was no interaction between obesity and having NT-proBNP ≤1000 pg/mL on the study outcome (P>0.10). Obese patients had a greater risk of developing adverse cardiovascular events (HR, 1.39; 95% CI, 1.01-1.90) compared with nonobese patients. NT-proBNP was the strongest predictor of adverse cardiovascular event risk in both obese and nonobese patients.
Conclusions:
On-treatment NT-proBNP level ≤1000 pg/mL has favorable prognostic implications, irrespective of obesity status. NT-proBNP levels were the strongest predictor of cardiovascular events in both obese and nonobese individuals in this trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.




J Am Heart Assoc: 05 Apr 2021; 10:e018689
Parcha V, Patel N, Kalra R, Suri SS, ... Wang TJ, Arora P
J Am Heart Assoc: 05 Apr 2021; 10:e018689 | PMID: 33754794
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Abstract

Recombinant Soluble Corin Improves Cardiac Function in Mouse Models of Heart Failure.

Niu Y, Zhang S, Gu X, Zhou T, ... Wu Q, Dong N

Background:
Corin is a transmembrane protease that activates ANP and BNP (atrial and B-type natriuretic peptides). Impaired corin expression and function are associated with heart failure. In this study, we characterized a soluble form of corin (sCorin) and examined its effects on cardiac morphology and function in mouse heart failure models. Methods and Results sCorin, consisting of the full-length extracellular fragment of human corin with an engineered activation site, was expressed in Chinese hamster ovary cells, purified from the conditioned medium with affinity chromatography, and characterized in pro-ANP processing assays in vitro and pharmacokinetic studies in mice. Effects of sCorin on mouse models of heart failure induced by left coronary artery ligation and transverse aortic constriction were assessed by ELISA analysis of plasma markers, histologic examination, and echocardiography. We showed that purified and activated sCorin converted pro-ANP to ANP that stimulated cGMP production in cultured cells. In mice, intravenously and intraperitoneally administered sCorin had plasma half-lives of 3.5±0.1 and 8.3±0.3 hour, respectively. In the mouse heart failure models, intraperitoneal injection of sCorin increased plasma ANP, BNP, and cGMP levels; lowered plasma levels of NT-proANP (N-terminal-pro-ANP), angiotensin II, and aldosterone; reduced cardiac hypertrophy and fibrosis; and improved cardiac function.
Conclusions:
We show that sCorin treatment enhanced natriuretic peptide processing and activity, suppressed the renin-angiotensin-aldosterone system, and improved cardiac morphology and function in mice with failing hearts.




J Am Heart Assoc: 05 Apr 2021; 10:e019961
Niu Y, Zhang S, Gu X, Zhou T, ... Wu Q, Dong N
J Am Heart Assoc: 05 Apr 2021; 10:e019961 | PMID: 33759549
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Abstract

Transplantation of Apoptosis-Resistant Endothelial Progenitor Cells Improves Renal Function in Diabetic Kidney Disease.

Kundu N, Nandula SR, Asico LD, Fakhri M, ... Jose PA, Sen S

Background:
Diabetic kidney disease is associated with glomerulosclerosis and poor renal perfusion. Increased capillary formation and improved perfusion may help to halt or reverse the injury. Transplanting apoptosis-resistant p53-silenced endothelial progenitor cells (p53sh-EPCs) may help improve vascularization and renal perfusion and could be more beneficial than another stem cell such as the mouse mesenchymal stromal cell (mMSC). Methods and Results Hyperglycemia and proteinuria were confirmed at 8 to 10 weeks in streptozotocin-induced type1 diabetic C57Bl/6 mice, followed by transplantation of 0.3 million p53sh-EPCs, Null-EPCs (control), or mMSC under each kidney capsule. Urine was collected weekly for creatinine and protein levels. Blood pressure was measured by direct arterial cannulation and renal perfusion was measured by renal ultrasound. The kidneys were harvested for histology and mRNA expression. Reduction of protein/creatinine (AUC) was observed in p53sh-EPC-transplanted mice more than null-EPC (1.8-fold, P=0.03) or null-mMSC (1.6-fold, P=0.04, n=4) transplanted mice. Markers for angiogenesis, such as endothelial nitric oxide synthase (1.7-fold, P=0.06), were upregulated post p53sh-EPC transplantation compared with null EPC. However, vascular endothelial growth factor-A expression was reduced (7-fold, P=0.0004) in mMSC-transplanted mice, compared with p53sh-EPC-transplanted mice. Isolectin-B4 staining of kidney section showed improvement of glomerular sclerosis when p53sh-EPC was transplanted, compared with null-EPC or mMSC. In addition, mean and peak renal blood velocity (1.3-fold, P=0.01, 1.4-fold, P=0.001, respectively) were increased in p53sh-EPC-transplanted mice, relative to null-EPC transplanted mice.
Conclusions:
Apoptosis-resistant p53sh EPC transplantation could be beneficial in the treatment of diabetic kidney disease by decreasing proteinuria, and improving renal perfusion and glomerular architecture.




J Am Heart Assoc: 05 Apr 2021; 10:e019365
Kundu N, Nandula SR, Asico LD, Fakhri M, ... Jose PA, Sen S
J Am Heart Assoc: 05 Apr 2021; 10:e019365 | PMID: 33759548
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Abstract

Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model.

Takami M, Hara T, Okimoto T, Suga M, ... Takahara H, Hirata KI

Background:
Medium-dose (25 gray) x-ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x-ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium-dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3-month or 6-month follow-up, the animals underwent an open-chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed.
Conclusions:
Medium-dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.




J Am Heart Assoc: 05 Apr 2021; 10:e019687
Takami M, Hara T, Okimoto T, Suga M, ... Takahara H, Hirata KI
J Am Heart Assoc: 05 Apr 2021; 10:e019687 | PMID: 33759547
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