Journal: J Am Heart Assoc

Sorted by: date / impact
Abstract

Resting Heartbeat Complexity Predicts All-Cause and Cardiorespiratory Mortality in Middle- to Older-Aged Adults From the UK Biobank.

Gao L, Gaba A, Cui L, Yang HW, ... Hu K, Li P


Background:
Spontaneous heart rate fluctuations contain rich information related to health and illness in terms of physiological complexity, an accepted indicator of plasticity and adaptability. However, it is challenging to make inferences on complexity from shorter, more practical epochs of data. Distribution entropy (DistEn) is a recently introduced complexity measure that is designed specifically for shorter duration heartbeat recordings. We hypothesized that reduced DistEn predicted increased mortality in a large population cohort. Method and Results The prognostic value of DistEn was examined in 7631 middle-older-aged UK Biobank participants who had 2-minute resting ECGs conducted (mean age, 59.5 years; 60.4% women). During a median follow-up period of 7.8 years, 451 (5.9%) participants died. In Cox proportional hazards models with adjustment for demographics, lifestyle factors, physical activity, cardiovascular risks, and comorbidities, for each 1-SD decrease in DistEn, the risk increased by 36%, 56%, and 73% for all-cause, cardiovascular, and respiratory disease-related mortality, respectively. These effect sizes were equivalent to the risk of death from being >5 years older, having been a former smoker, or having diabetes mellitus. Lower DistEn was most predictive of death in those <55 years with a prior myocardial infarction, representing an additional 56% risk for mortality compared with older participants without prior myocardial infarction. These observations remained after controlling for traditional mortality predictors, resting heart rate, and heart rate variability.
Conclusions:
Resting heartbeat complexity from short, resting ECGs was independently associated with mortality in middle- to older-aged adults. These risks appear most pronounced in middle-aged participants with prior MI, and may uniquely contribute to mortality risk screening.



J Am Heart Assoc: 18 Jan 2021:e018483; epub ahead of print
Gao L, Gaba A, Cui L, Yang HW, ... Hu K, Li P
J Am Heart Assoc: 18 Jan 2021:e018483; epub ahead of print | PMID: 33461311
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Identification of Phenotypic Lipidomic Signatures in Response to Long Chain n-3 Polyunsaturated Fatty Acid Supplementation in Humans.

Picklo M, Vallée Marcotte B, Bukowski M, de Toro-Martín J, ... Guénard F, Vohl MC


Background:
Supplementation with long chain n-3 polyunsaturated fatty acids is used to reduce total circulating triacylglycerol (TAG) concentrations. However, in about 30% of people, supplementation with long chain n-3 polyunsaturated fatty acids does not result in decreased plasma TAG. Lipidomic analysis may provide insight into this inter-individual variability. Methods Lipidomic analyses using targeted, mass spectrometry were performed on plasma samples obtained from a clinical study in which participants were supplemented with 3 g/day of long chain n-3 in the form of fish oil capsules over a 6-week period. TAG species and cholesteryl esters (CE) were quantified for 130 participants pre- and post-supplementation. Participants were segregated into 3 potential responder phenotypes: (1) positive responder (R; TAG decrease), (2) non-responder (R; lacking TAG change), and (3) negative responder (R; TAG increase) representing 67%, 18%, and 15% of the study participants, respectively. Separation of the 3 phenotypes was attributed to differential responses in TAG with 50 to 54 carbons with 1 to 4 desaturations. Elevated TAG with higher carbon number and desaturation were common to all phenotypes following supplementation. Using the TAG responder phenotype for grouping, decreases in total CE and specific CE occurred in the R phenotype versus the R phenotype with intermediate responses in the R phenotype. CE 20:5, containing eicosapentaenoic acid (20:5n-3), was elevated in all phenotypes. A classifier combining lipidomic and genomic features was built to discriminate triacylglycerol response phenotypes and reached a high predictive performance with a balanced accuracy of 75%.
Conclusions:
These data identify lipidomic signatures, TAG and CE, associated with long chain n-3 response p henotypes and identify a novel phenotype based upon CE changes. Registration URL: https://www.ClinicalTrials.gov; Unique Identifier: NCT01343342.



J Am Heart Assoc: 18 Jan 2021:e018126; epub ahead of print
Picklo M, Vallée Marcotte B, Bukowski M, de Toro-Martín J, ... Guénard F, Vohl MC
J Am Heart Assoc: 18 Jan 2021:e018126; epub ahead of print | PMID: 33461307
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of Race, Cardiac Mass, and Cardiac Load on Myocardial Function Trajectories from Childhood to Young Adulthood: The Augusta Heart Study.

Kapuku G, Howie M, Ghosh S, Doshi V, ... Harshfield G, George V


Background:
The overall goal of this longitudinal study was to determine if the Black population has decreased myocardial function, which has the potential to lead to the early development of congestive heart failure, compared with the White population. Methods and Results A total of 673 subjects were evaluated over a period of 30 years including similar percentages of Black and White participants. Left ventricular systolic function was probed using the midwall fractional shortening (MFS). A longitudinal analysis of the MFS using a mixed effect growth curve model was performed. Black participants had greater body mass index, higher blood pressure readings, and greater left ventricular mass compared with White participants (all <0.01). Black participants had a 0.54% decrease of MFS compared with White participants. As age increased by 1 year, MFS increased by 0.05%. As left ventricular mass increased by 1 g, MFS decreased by 0.01%. As circumferential end systolic stress increased by 1 unit, MFS decreased by 0.04%. The MFS trajectories for race differed from early age to young adulthood.
Conclusions:
Changes in myocardial function mirror the race-dependent variations in blood pressure, afterload, and cardiac mass, suggesting that myocardial function depression occurs early in childhood in populations at high cardiovascular risk such as Black participants.



J Am Heart Assoc: 17 Jan 2021:e015612; epub ahead of print
Kapuku G, Howie M, Ghosh S, Doshi V, ... Harshfield G, George V
J Am Heart Assoc: 17 Jan 2021:e015612; epub ahead of print | PMID: 33459030
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Electrocardiographic Strain Pattern Is a Major Determinant of Rehospitalization for Heart Failure After Transcatheter Aortic Valve Replacement.

Heger J, Trimaille A, Kibler M, Marchandot B, ... Ohlmann P, Morel O


Background:
Electrocardiographic strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis and after surgical aortic valve replacement. Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after transcatheter aortic valve replacement. Methods and Results A total of 585 patients with severe aortic stenosis (mean age, 83±7 years; men, 39.8%) were enrolled for transcatheter aortic valve replacement from November 2012 to May 2018. ESP was defined as ≥1-mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. The primary end points of the study were all-cause mortality, rehospitalization for heart failure, myocardial infarction, and stroke. A total of 178 (30.4%) patients were excluded because of left bundle-branch block (n=103) or right bundle-branch block (n=75). Among the 407 remaining patients, 106 had ESP (26.04%). At a median follow-up of 20.00 months (11.70-29.42 months), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for heart failure was significantly higher (33/106 [31.1%] versus 33/301 [11%]; <0.001) in patients with ESP. By multivariate analyses, ESP remained a strong predictor of rehospitalization for heart failure (hazard ratio, 2.75 [95% CI, 1.61-4.67]; <0.001).
Conclusions:
In patients with aortic stenosis who were eligible for transcatheter aortic valve replacement, ESP is frequent and associated with an increased risk of postinterventional heart failure regardless of preoperative left ventricular hypertrophy. ESP represents an easy, objective, reliable, and low-cost tool to identify patients who may benefit from intensified postinterventional follow-up.



J Am Heart Assoc: 16 Jan 2021:e014481; epub ahead of print
Heger J, Trimaille A, Kibler M, Marchandot B, ... Ohlmann P, Morel O
J Am Heart Assoc: 16 Jan 2021:e014481; epub ahead of print | PMID: 33459031
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

In Search of an Optimal Subset of ECG Features to Augment the Diagnosis of Acute Coronary Syndrome at the Emergency Department.

Bouzid Z, Faramand Z, Gregg RE, Frisch SO, ... Sejdić E, Al-Zaiti S


Background:
Classical ST-T waveform changes on standard 12-lead ECG have limited sensitivity in detecting acute coronary syndrome (ACS) in the emergency department. Numerous novel ECG features have been previously proposed to augment clinicians\' decision during patient evaluation, yet their clinical utility remains unclear. Methods and Results This was an observational study of consecutive patients evaluated for suspected ACS (Cohort 1 n=745, age 59±17, 42% female, 15% ACS; Cohort 2 n=499, age 59±16, 49% female, 18% ACS). Out of 554 temporal-spatial ECG waveform features, we used domain knowledge to select a subset of 65 physiology-driven features that are mechanistically linked to myocardial ischemia and compared their performance to a subset of 229 data-driven features selected by multiple machine learning algorithms. We then used random forest to select a final subset of 73 most important ECG features that had both data- and physiology-driven basis to ACS prediction and compared their performance to clinical experts. On testing set, a regularized logistic regression classifier based on the 73 hybrid features yielded a stable model that outperformed clinical experts in predicting ACS, with 10% to 29% of cases reclassified correctly. Metrics of nondipolar electrical dispersion (ie, circumferential ischemia), ventricular activation time (ie, transmural conduction delays), QRS and T axes and angles (ie, global remodeling), and principal component analysis ratio of ECG waveforms (ie, regional heterogeneity) played an important role in the improved reclassification performance.
Conclusions:
We identified a subset of novel ECG features predictive of ACS with a fully interpretable model highly adaptable to clinical decision support applications. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04237688.



J Am Heart Assoc: 16 Jan 2021:e017871; epub ahead of print
Bouzid Z, Faramand Z, Gregg RE, Frisch SO, ... Sejdić E, Al-Zaiti S
J Am Heart Assoc: 16 Jan 2021:e017871; epub ahead of print | PMID: 33459029
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Habitation Altitude and Left Ventricular Diastolic Function: A Population-Based Study.

Zheng C, Wang X, Tang H, Chen Z, ... Huang G, Wang Z


Background:
Although numerous studies have been published evaluating the positive or negative effects of altitude on cardiovascular disease, many of them are conflicting. Methods and Results Data come from 2 cross-sectional surveys using a similar method in China; and a total of 34 215 residents, aged ≥35 years, were eligible and recruited in the study. Left ventricular diastolic dysfunction (LVDD), according to the 2009 American Society of Echocardiography guidelines, was defined and evaluated. Altitude was divided into low (<1500 m), middle (1500-3500 m), and high (≥3500 m) level groups. Among the 34 215 participants (aged 55.87 years; men, 45.92%; altitude ranging from 3.1 ~ 4507 m), 15 099 (crude prevalence, 44.13%), 517 (crude prevalence, 1.51%), and 272 (crude prevalence, 0.79%) were diagnosed as having grades I, II, and LVDD, respectively. Compared with low-level group, the odds ratios (ORs) (95% CIs) of LVDD for middle- and high-level groups were 1.65 (1.49-1.82) and 1.89 (1.63-2.19), respectively (<0.001). The ORs (95% CI) were 1.43 (1.31-1.56) and 2.03 (1.67-2.47) per 500-m increment for middle- and high-level groups. There was a nonlinear relationship (upward-sloping \"W\" shape) between altitude and the risk of LVDD, assessed by the restricted cubic spline. For each LVDD grade, ORs (95% CIs) of grade I LVDD for middle- and high-level groups were 1.75 (1.59-1.92) and 1.95 (1.69-2.25), respectively; for grade II, ORs (95% CIs) for middle- and high-level groups were 6.19 (3.67-10.42) and 5.27 (2.18-12.74), respectively. The stratified analyses indicated that LVDD was much more remarkably influenced by elevated altitude in men (=0.0019).
Conclusions:
Higher altitude is associated with increased risk of LVDD among people living over 1500 m, especially for men.



J Am Heart Assoc: 16 Jan 2021:e018079; epub ahead of print
Zheng C, Wang X, Tang H, Chen Z, ... Huang G, Wang Z
J Am Heart Assoc: 16 Jan 2021:e018079; epub ahead of print | PMID: 33459026
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: Treatment Strategy, Characteristics of Consecutive Atrial Tachycardia and Long-Term Outcome.

Dinshaw L, Münkler P, Schäffer B, Klatt N, ... Willems S, Meyer C


Background:
Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and is associated with a deterioration of clinical status. Ablation of symptomatic AF is an established therapy, but in HCM, the characteristics of recurrent atrial arrhythmias and the long-term outcome are uncertain. Methods and Results Sixty-five patients with HCM (aged 64.5±9.9 years, 42 [64.6%] men) underwent AF ablation. The ablation strategy included pulmonary vein isolation in all patients and ablation of complex fractionated atrial electrograms or subsequent atrial tachycardias (AT) if appropriate. Paroxysmal, persistent AF, and a primary AT was present in 13 (20.0%), 51 (78.5%), and 1 (1.5%) patients, respectively. Twenty-five (38.4%) patients developed AT with a total number of 54 ATs. Stable AT was observed in 15 (23.1%) and unstable AT in 10 (15.3%) patients. The mechanism was characterized as a macroreentry in 37 (68.5%), as a localized reentry in 12 (22.2%), a focal mechanism in 1 (1.9%), and not classified in 4 (7.4%) ATs. After 1.9±1.2 ablation procedures and a follow-up of 48.1±32.5 months, freedom of AF/AT recurrences was demonstrated in 60.0% of patients. No recurrences occurred in 84.6% and 52.9% of patients with paroxysmal and persistent AF, respectively (<0.01). Antiarrhythmic drug therapy was maintained in 24 (36.9%) patients.
Conclusions:
AF ablation in patients with HCM is effective for long-term rhythm control, and especially patients with paroxysmal AF undergoing pulmonary vein isolation have a good clinical outcome. ATs after AF ablation are frequently observed in HCM. Freedom of atrial arrhythmia is achieved by persistent AF ablation in a reasonable number of patients even though the use of antiarrhythmic drug therapy remains high.



J Am Heart Assoc: 16 Jan 2021:e017451; epub ahead of print
Dinshaw L, Münkler P, Schäffer B, Klatt N, ... Willems S, Meyer C
J Am Heart Assoc: 16 Jan 2021:e017451; epub ahead of print | PMID: 33455428
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Vascular Aging Detected by Peripheral Endothelial Dysfunction Is Associated With ECG-Derived Physiological Aging.

Toya T, Ahmad A, Attia Z, Cohen-Shelly M, ... Friedman PA, Lerman A


Background:
An artificial intelligence algorithm that detects age using the 12-lead ECG has been suggested to signal \"physiologic age.\" This study aimed to investigate the association of peripheral microvascular endothelial function (PMEF) as an index of vascular aging, with accelerated physiologic aging gauged by ECG-derived artificial intelligence-estimated age. Methods and Results This study included 531 patients who underwent ECG and a noninvasive PMEF assessment using reactive hyperemia peripheral arterial tonometry. Abnormal PMEF was defined as reactive hyperemia peripheral arterial tonometry index ≤2.0. Accelerated or delayed physiologic aging was calculated by the Δ age (ECG-derived artificial intelligence-estimated age minus chronological age), and the association between Δ age and PMEF as well as its impact on composite major adverse cardiovascular events were investigated. Δ age was higher in patients with abnormal PMEF than in patients with normal PMEF (2.3±7.8 versus 0.5±7.7 years; =0.01). Reactive hyperemia peripheral arterial tonometry index was negatively associated with Δ age after adjustment for cardiovascular risk factors (standardized β coefficient, -0.08; =0.048). The highest quartile of Δ age was associated with an increased risk of major adverse cardiovascular events compared with the first quartile of Δ age in patients with abnormal PMEF, even after adjustment for cardiovascular risk factors (hazard ratio, 4.72; 95% CI, 1.24-17.91; =0.02).
Conclusions:
Vascular aging detected by endothelial function is associated with accelerated physiologic aging, as assessed by the artificial intelligence-ECG Δ age. Patients with endothelial dysfunction and the highest quartile of accelerated physiologic aging have a marked increase in risk for cardiovascular events.



J Am Heart Assoc: 16 Jan 2021:e018656; epub ahead of print
Toya T, Ahmad A, Attia Z, Cohen-Shelly M, ... Friedman PA, Lerman A
J Am Heart Assoc: 16 Jan 2021:e018656; epub ahead of print | PMID: 33455414
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic Impacts of Comorbid Significant Coronary Stenosis and Coronary Artery Spasm in Patients With Stable Coronary Artery Disease.

Hao K, Takahashi J, Kikuchi Y, Suda A, ... Yasuda S, Shimokawa H


Background:
Stable coronary artery disease is caused by a variable combination of organic coronary stenosis and functional coronary abnormalities, such as coronary artery spasm. Thus, we examined the clinical importance of comorbid significant coronary stenosis and coronary spasm.
Methods and results:
We enrolled 236 consecutive patients with suspected angina who underwent acetylcholine provocation testing for coronary spasm and fractional flow reserve (FFR) measurement. Among them, 175 patients were diagnosed as having vasospastic angina (VSA), whereas the remaining 61 had no VSA (non-VSA group). The patients with VSA were further divided into the following 3 groups based on angiography and FFR: no organic stenosis (≤50% luminal stenosis; VSA-alone group, n=110), insignificant stenosis of FFR>0.80 (high-FFR group, n=36), and significant stenosis of FFR≤0.80 (low-FFR group, n=29). The incidence of major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, urgent percutaneous coronary intervention, and hospitalization attributed to unstable angina was evaluated. All patients with VSA received calcium channel blockers, and 28 patients (95%) in the low-FFR group underwent a planned percutaneous coronary intervention. During a median follow-up period of 656 days, although the incidence of major adverse cardiovascular events was low and comparable among non-VSA, VSA-alone, and high-FFR groups, the low-FFR group had an extremely poor prognosis (non-VSA group, 1.6%; VSA-alone group, 3.6%; high-FFR group, 5.6%; low-FFR group, 27.6%) (<0.001). Importantly, all 8 patients with major adverse cardiovascular events in the low-FFR group were appropriately treated with percutaneous coronary intervention and calcium channel blockers. CONCLUSIONS These results indicate that patients with VSA with significant coronary stenosis represent a high-risk population despite current guideline-recommended therapies, suggesting the importance of routine coronary functional testing in this population.



J Am Heart Assoc: 15 Jan 2021:e017831; epub ahead of print
Hao K, Takahashi J, Kikuchi Y, Suda A, ... Yasuda S, Shimokawa H
J Am Heart Assoc: 15 Jan 2021:e017831; epub ahead of print | PMID: 33455423
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Structural Thickening of Medial Layer in Coronary Artery With Spasm in Patients With Myocardial Infarction.

Nakamura T, Horikoshi T, Kugiyama K


Background:
The underlying pathophysiology of coronary artery spasm (CAS) remains unclear. We aim to determine whether coronary artery medial layer thickness is associated with CAS using optical coherence tomography. Methods and Results A total of 50 patients with previous myocardial infarction underwent optical coherence tomography of the left anterior descending artery: 20 with CAS and 30 without CAS. Intimal and medial layer areas were measured by planimetric analysis of optical coherence tomography images. The medial area/external elastic membrane (EEM) area was significantly greater in patients with than without CAS (0.13±0.01 versus 0.09±0.01, respectively, <0.01), whereas the intimal area/EEM area was similar in the 2 groups. In patients without CAS, the relationship of intimal area/EEM area with medial area/EEM area and coronary diameter response to intracoronary injection of acetylcholine was characterized by an inverted U-shaped curve (=-1.85+0.81+0.01, =0.43, <0.001) and a U-shaped curve (=2993.2-1359.6+117.1, =0.53, <0.001), respectively. Thus, the medial layer became thin and the contractile response became weak in coronary arteries with greater intimal area in the non-CAS patients. In contrast, in patients with CAS, the intimal area/EEM area had no significant relationship with the medial area/EEM area in either linear correlation analysis or quadratic regression analysis. Thus, even when the intimal layer thickened, the medial layer did not thin in patients with CAS.
Conclusions:
The structural thickness of the coronary medial layer was increased in patients with CAS, which may provide mechanistic insight into the pathogenesis of CAS. Registration URL: https://www.upload.umin.ac.jp; Unique identifier: UMIN000018432.



J Am Heart Assoc: 13 Jan 2021:e018028; epub ahead of print
Nakamura T, Horikoshi T, Kugiyama K
J Am Heart Assoc: 13 Jan 2021:e018028; epub ahead of print | PMID: 33442998
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Investigation of Left Atrial Structure and Stroke Etiology: The I-LASER Study.

Johansen MC, Doria de Vasconcellos H, Nazarian S, Lima JAC, Gottesman RF


Background:
Left atrial (LA) function is important in stroke, but often poorly characterized. We evaluated the association of 2-dimensional speckle tracking echocardiography LA variables with stroke subtype (cardioembolic stroke [CS]cryptogenic stroke versus other). The hypothesis is worse LA active function is associated with CS, but not cryptogenic strokes. Methods and Results In this prospective cohort (2017-2019), left ventricular/LA structure and function were quantified by 2-dimensional and speckle tracking echocardiography in 151 patients with stroke. Strain/strain rate curves for the 3 components of the LA cycle, ie, (1) Reservoir (global longitudinal strain [Srmax]), (2) Conductive (early LA Sr [Sre]), and (3) Active (late LA strain [Sra]) were evaluated, masked to stroke subtype. Associations of cardiac features with stroke subtype were tested using multivariable logistic regressions. Odds of CS were increased in patients with a larger LA systolic diameter (odds ratio [OR], 2.96, 95% CI, 1.14-7.69) but reduced in patients with a higher Srmax (better reservoir) (OR, 0.80, 95% CI, 0.67-0.97). Lower Sra (worse function) was associated with an increased odds of CS (OR, 1.72, 95% CI, 1.07-2.76) but not independent of atrial fibrillation. Higher active LA emptying fraction (better active phase) was associated with reduced odds of CS (OR, 0.74, 95% CI, 0.57-0.95) or cryptogenic stroke (OR, 0.82, 95% CI, 0.68-0.98) versus other subtypes; other associations between cryptogenic stroke and speckle tracking echocardiography were not found.
Conclusions:
Markers of LA structure and function were associated with CS. Similar associations were not found for cryptogenic stroke, which might suggest different underlying mechanisms, given study limitations. Further understanding could aid stroke diagnosis and secondary stroke prevention research.



J Am Heart Assoc: 13 Jan 2021:e018766; epub ahead of print
Johansen MC, Doria de Vasconcellos H, Nazarian S, Lima JAC, Gottesman RF
J Am Heart Assoc: 13 Jan 2021:e018766; epub ahead of print | PMID: 33442991
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Death and Myocardial Infarction Following Initial Revascularization Versus Optimal Medical Therapy in Chronic Coronary Syndromes With Myocardial Ischemia: A Systematic Review and Meta-Analysis of Contemporary Randomized Controlled Trials.

Soares A, Boden WE, Hueb W, Brooks MM, ... Hardi A, Brown DL


Background:
In chronic coronary syndromes, myocardial ischemia is associated with a greater risk of death and nonfatal myocardial infarction (MI). We sought to compare the effect of initial revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) plus optimal medical therapy (OMT) with OMT alone in patients with chronic coronary syndrome and myocardial ischemia on long-term death and nonfatal MI. Methods and Results Ovid Medline, Embase, Scopus, and Cochrane Library databases were searched for randomized controlled trials of PCI or CABG plus OMT versus OMT alone for patients with chronic coronary syndromes. Studies were screened and data were extracted independently by 2 authors. Random-effects models were used to generate pooled treatment effects. The search yielded 7 randomized controlled trials that randomized 10 797 patients. Median follow-up was 5 years. Death occurred in 640 of the 5413 patients (11.8%) randomized to revascularization and in 647 of the 5384 patients (12%) randomized to OMT (odds ratio [OR], 0.97; 95% CI, 0.86-1.09; =0.60). Nonfatal MI was reported in 554 of 5413 patients (10.2%) in the revascularization arms compared with 627 of 5384 patients (11.6%) in the OMT arms (OR, 0.75; 95% CI, 0.57-0.99; =0.04). In subgroup analysis, nonfatal MI was significantly reduced by CABG (OR, 0.35; 95% CI, 0.21-0.59; <0.001) but was not reduced by PCI (OR, 0.92; 95% CI, 0.75-1.13; =0.43) (-interaction <0.001).
Conclusions:
In patients with chronic coronary syndromes and myocardial ischemia, initial revascularization with PCI or CABG plus OMT did not reduce long-term mortality compared with OMT alone. CABG plus OMT reduced nonfatal MI compared with OMT alone, whereas PCI did not.



J Am Heart Assoc: 13 Jan 2021:e019114; epub ahead of print
Soares A, Boden WE, Hueb W, Brooks MM, ... Hardi A, Brown DL
J Am Heart Assoc: 13 Jan 2021:e019114; epub ahead of print | PMID: 33442990
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Parent and Physician Understanding of Prognosis in Hospitalized Children With Advanced Heart Disease.

Morell E, Miller MK, Lu M, Friedman KG, ... Sleeper LA, Blume ED


Background:
The unpredictable trajectory of pediatric advanced heart disease makes prognostication difficult for physicians and informed decision-making challenging for families. This study evaluated parent and physician understanding of disease burden and prognosis in hospitalized children with advanced heart disease. Methods and Results A longitudinal survey study of parents and physicians caring for patients with advanced heart disease age 30 days to 19 years admitted for ≥7 days was performed over a 1-year period (n=160 pairs). Percentage agreement and weighted kappa statistics were used to assess agreement. Median patient age was 1 year (interquartile range, 1-5), 39% had single-ventricle lesions, and 37% were in the cardiac intensive care unit. Although 92% of parents reported understanding their child\'s prognosis \"extremely well\" or \"well,\" 28% of physicians thought parents understood the prognosis only \"a little,\" \"somewhat,\" or \"not at all.\" Better parent-reported prognostic understanding was associated with greater preparedness for their child\'s medical problems (odds ratio, 4.7; 95% CI, 1.4-21.7, =0.02). There was poor parent-physician agreement in assessing functional class, symptom burden, and likelihood of limitations in physical activity and learning/behavior; on average, parents were more optimistic. Many parents (47%) but few physicians (6%) expected the child to have normal life expectancy.
Conclusions:
Parents and physicians caring for children with advanced heart disease differed in their perspectives regarding prognosis and disease burden. Physicians tended to underestimate the degree of parent-reported symptom burden. Parents were less likely to expect limitations in physical activity, learning/behavior, and life expectancy. Combined interventions involving patient-reported outcomes, parent education, and physician communication tools may be beneficial.



J Am Heart Assoc: 13 Jan 2021:e018488; epub ahead of print
Morell E, Miller MK, Lu M, Friedman KG, ... Sleeper LA, Blume ED
J Am Heart Assoc: 13 Jan 2021:e018488; epub ahead of print | PMID: 33442989
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Optimal Combination of Chest Compression Depth and Rate in Virtual Reality Resuscitation Training: A Post Hoc Analysis of the Randomized Lowlands Saves Lives Trial.

Nas J, Thannhauser J, van Geuns RM, van Royen N, Bonnes JL, Brouwer MA


Background:
Dissemination of cardiopulmonary resuscitation (CPR) skills is essential for cardiac arrest survival. Virtual reality (VR)-training methods are low cost and easily available, but to meet depth requirements adaptations are required, as confirmed in a recent randomized study on currently prevailing CPR quality criteria. Recently, the promising clinical performance of new CPR quality criteria was demonstrated, based on the optimal combination of compression depth and rate. We now study compliance with these newly proposed CPR quality criteria. Methods and Results Post hoc analysis of a randomized trial compared standardized 20-minute face-to-face CPR training with VR training using the Lifesaver VR smartphone application. During a posttraining test, compression depth and rate were measured using CPR mannequins. We assessed compliance with the newly proposed CPR criteria, that is, compression rate within ±20% of 107/minute and depth within ±20% of 47 mm. We studied 352 participants, age 26 (22-31) years, 56% female, and 15% with CPR training ≤2 years. Among VR-trained participants, there was a statistically significant difference between the proportions complying with newly proposed versus the currently prevailing quality criteria (52% versus 23%, <0.001). The difference in proportions complying with rate requirements was statistically significant (96% for the new versus 50% for current criteria, <0.001), whereas there was no significant difference with regard to the depth requirements (55% versus 51%, =0.45).
Conclusions:
Lifesaver VR training, although previously found to be inferior to face-to-face training, may lead to CPR quality compliant with recently proposed, new quality criteria. If the prognostic importance of these new criteria is confirmed in additional studies, Lifesaver VR in its current form would be an easily available vector to disseminate CPR skills.



J Am Heart Assoc: 13 Jan 2021:e017367; epub ahead of print
Nas J, Thannhauser J, van Geuns RM, van Royen N, Bonnes JL, Brouwer MA
J Am Heart Assoc: 13 Jan 2021:e017367; epub ahead of print | PMID: 33442988
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-Term Survival of Patients With Left Ventricular Noncompaction.

Vaidya VR, Lyle M, Miranda WR, Farwati M, ... Connolly HM, Melduni RM


Background:
The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end-systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end-diastolic trough of trabeculation-to-epicardium (X):peak of trabeculation-to-epicardium (Y) ratio <0.5 (Chin criteria) by echocardiography; and end-diastolic noncompacted:compacted ratio >2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction <50% was present in 57% of patients and isolated apical noncompaction in 48%. During a median follow-up of 6.3 years, 59 patients died. On multivariable Cox regression analysis, age (hazard ratio [HR] 1.04; 95% CI, 1.02-1.06), left ventricular ejection fraction <50% (HR, 2.37; 95% CI, 1.17-4.80), and noncompaction extending from the apex to the mid or basal segments (HR, 2.11; 95% CI, 1.21-3.68) were associated with all-cause mortality. Compared with the expected survival for age- and sex-matched US population, patients with LVNC had reduced overall survival (<0.001). However, patients with LVNC with preserved left ventricular ejection fraction and patients with isolated apical noncompaction had similar survival to the general population.
Conclusions:
Overall survival is reduced in patients with LVNC compared with the expected survival of age- and sex-matched US population. However, survival rate in those with preserved left ventricular ejection fraction and isolated apical noncompaction was comparable with that of the general population.



J Am Heart Assoc: 13 Jan 2021:e015563; epub ahead of print
Vaidya VR, Lyle M, Miranda WR, Farwati M, ... Connolly HM, Melduni RM
J Am Heart Assoc: 13 Jan 2021:e015563; epub ahead of print | PMID: 33441029
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Arrhythmic Risk Profile and Outcomes of Patients Undergoing Cardiac Sympathetic Denervation for Recurrent Monomorphic Ventricular Tachycardia After Ablation.

Dusi V, Gornbein J, Do DH, Sorg JM, ... Shivkumar K, Vaseghi M


Background:
Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar-related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population. Methods and Results Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter-defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter-defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar-mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person-months, =0.01) and the sustained VT/implantable cardioverter-defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person-months, =0.03). The median number of sustained VT/implantable cardioverter-defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1, <0.0001).
Conclusions:
Patients referred for CSD for refractory scar-mediated monomorphic VT are at a higher risk of VT recurrence after ablation as compared with those not requiring CSD, mostly because of their cardiac comorbidities. CSD significantly reduced both the expected risk of recurrences and VT burden.



J Am Heart Assoc: 13 Jan 2021:e018371; epub ahead of print
Dusi V, Gornbein J, Do DH, Sorg JM, ... Shivkumar K, Vaseghi M
J Am Heart Assoc: 13 Jan 2021:e018371; epub ahead of print | PMID: 33441022
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Low miR-19b-1-5p Expression Is Related to Aspirin Resistance and Major Adverse Cardio- Cerebrovascular Events in Patients With Acute Coronary Syndrome.

Singh S, de Ronde MWJ, Creemers EE, Van der Made I, ... Yan BP, Pinto-Sietsma SJ


Background:
Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR-19b-1-5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio-cerebrovascular (MACCE) events in patients with ACS. Methods and Results In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR-19b-1-5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow-up time of 1.01±0.43 years. Low miR-19b-1-5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (-Log-miR-19b-1-5p, [unstandardized beta, 44.50; 95% CI, 2.20-86.80; <0.05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR-19b-1-5p expression was independently associated with a higher risk of MACCE (-Log-miR-19b-1-5p, [hazard ratio, 1.85; 95% CI, 1.23-2.80; <0.05]). Furthermore, a significant interaction was noted between the inverse miR-19b-1-5p expression and family history of premature coronary artery disease (=0.01) on the risk of MACCE.
Conclusions:
Lower miR-19b-1-5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR-19b-1-5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.



J Am Heart Assoc: 13 Jan 2021:e017120; epub ahead of print
Singh S, de Ronde MWJ, Creemers EE, Van der Made I, ... Yan BP, Pinto-Sietsma SJ
J Am Heart Assoc: 13 Jan 2021:e017120; epub ahead of print | PMID: 33441016
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Coxsackievirus B3 Infection Early in Pregnancy Induces Congenital Heart Defects Through Suppression of Fetal Cardiomyocyte Proliferation.

Sharma V, Goessling LS, Brar AK, Joshi CS, Mysorekar IU, Eghtesady P


Background:
Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation. Methods and Results We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose-response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of ventricular septal defect (33.6%), abnormal myocardial architecture resembling noncompaction (23.5%), and double-outlet right ventricle (4.4%) among 209 viable fetuses examined. We observed a direct relationship between viral titers and severity of congenital heart defects, with apparent predominance among female fetuses. Infected dams remained healthy; we did not observe any maternal heart or placental injury suggestive of direct viral effects on developing heart as likely cause of congenital heart defects. We examined signaling pathways in CVB3-exposed hearts using RNA sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and immunohistochemistry. Signaling proteins of the Hippo, tight junction, transforming growth factor-β1, and extracellular matrix proteins were the most highly enriched in CVB3-infected fetuses with ventricular septal defects. Moreover, cardiomyocyte proliferation was 50% lower in fetuses with ventricular septal defects compared with uninfected controls.
Conclusions:
We conclude prenatal CVB3 infection induces congenital heart defects. Alterations in myocardial proliferate capacity and consequent changes in cardiac architecture and trabeculation appear to account for most of observed phenotypes.



J Am Heart Assoc: 13 Jan 2021:e017995; epub ahead of print
Sharma V, Goessling LS, Brar AK, Joshi CS, Mysorekar IU, Eghtesady P
J Am Heart Assoc: 13 Jan 2021:e017995; epub ahead of print | PMID: 33440998
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic Value of Abdominal Aortic Calcification: A Systematic Review and Meta-Analysis of Observational Studies.

Leow K, Szulc P, Schousboe JT, Kiel DP, ... Wong G, Lewis JR


Background:
The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain. Methods and Results We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all-cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random-effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older-elderly (median, 68 years; range, 60-80 years) populations (26%) had sufficient data to meta-analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40-2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44-2.39), and all-cause mortality (RR, 1.98; 95% CI, 1.55-2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21-5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32-5.84), and all-cause mortality (RR, 2.40; 95% CI, 1.95-2.97).
Conclusions:
Higher-risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients\' cardiovascular risk better.



J Am Heart Assoc: 12 Jan 2021:e017205; epub ahead of print
Leow K, Szulc P, Schousboe JT, Kiel DP, ... Wong G, Lewis JR
J Am Heart Assoc: 12 Jan 2021:e017205; epub ahead of print | PMID: 33439672
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association Between ECG Abnormalities and Fatal Cardiovascular Disease Among Patients With and Without Severe Mental Illness.

Polcwiartek C, Atwater BD, Kragholm K, Friedman DJ, ... Torp-Pedersen C, Jensen SE


Background:
ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. Methods and Results We cross-linked data from Danish nationwide registries and included primary care patients with digital ECGs from 2001 to 2015. Patients had SMI if they were diagnosed with schizophrenia, bipolar disorder, or severe depression before ECG recording. Controls were required to be without any prior mental illness or psychotropic medication use. Fatal CVD was assessed using hazard ratios (HRs) with 95% CIs and standardized 10-year absolute risks. Of 346 552 patients, 10 028 had SMI (3%; median age, 54 years; male, 45%), and 336 524 were controls (97%; median age, 56 years; male, 48%). We observed an interaction between SMI and ECG abnormalities on fatal CVD (<0.001). Severe mental illness was associated with fatal CVD across no (HR, 2.17; 95% CI, 1.95-2.43), minor (HR, 1.90; 95% CI, 1.49-2.42), and major (HR, 1.40; 95% CI, 1.26-1.55) ECG abnormalities compared with controls. Across age- and sex-specific subgroups, SMI patients with ECG abnormalities but no CVD at baseline had highest standardized 10-year absolute risks of fatal CVD.
Conclusions:
ECG abnormalities conferred a poorer prognosis among patients with SMI compared with controls without mental illness. SMI patients with ECG abnormalities but no CVD represent a high-risk population that may benefit from greater surveillance and risk management.



J Am Heart Assoc: 11 Jan 2021:e019416; epub ahead of print
Polcwiartek C, Atwater BD, Kragholm K, Friedman DJ, ... Torp-Pedersen C, Jensen SE
J Am Heart Assoc: 11 Jan 2021:e019416; epub ahead of print | PMID: 33432845
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Gaps in Evidence-Based Therapy Use in Insured Patients in the United States With Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease.

Nelson AJ, Ardissino M, Haynes K, Shambhu S, ... Pagidipati NJ, Granger CB


Background:
Evidence-based therapies are generally underused for cardiovascular risk reduction; however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Methods and Results Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence-based therapies on, or covering, the index date ±30 days: high-intensity statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence-based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the sample, 24.7% were using a high-intensity statin, 53.1% were using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence-based therapies, and 37.4% were on none of them. Over a 12-month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence-based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients.
Conclusions:
Alarming gaps exist in the contemporary use of evidence-based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.



J Am Heart Assoc: 11 Jan 2021:e016835; epub ahead of print
Nelson AJ, Ardissino M, Haynes K, Shambhu S, ... Pagidipati NJ, Granger CB
J Am Heart Assoc: 11 Jan 2021:e016835; epub ahead of print | PMID: 33432843
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Health Service Utilization Patterns Among Adults With Congenital Heart Disease: A Population-Based Study.

Benderly M, Buber J, Kalter-Leibovici O, Blieden L, ... Hirsch R, Israeli Adult Congenital Heart Disease Research Group


Background:
Several studies have examined hospitalizations among patients with adult congenital heart disease (ACHD). Few investigated other services or utilization patterns. Our aim was to study service utilization patterns and predictors among patients with ACHD. Methods and Results We identified 11 653 patients with ACHD aged ≥18 years (median, 47 years), through electronic records of 2 large Israeli healthcare providers (2007-2011). The association between patient, disease, and sociogeographic characteristics and healthcare resource utilization were modeled as recurrent events accounting for the competing death risk. Patients with ACHD had high healthcare utilization rates compared with the general population. The highest standardized service utilization ratios (SSRs) were found among patients with complex congenital heart disease including primary care visits (SSR, 1.53; 95% CI, 1.47-1.58), cardiology outpatient visits (SSR, 5.17; 95% CI, 4.69-5.64), hospitalizations (SSR, 6.68; 95% CI, 5.82-7.54), and days in hospital (SSR, 15.37; 95% CI, 14.61-16.12). Adjusted resource utilization hazard increased with increasing lesion complexity. Hazard ratios (HRs) for complex versus simple disease were: primary care (HR, 1.14; 95% CI, 1.06-1.23); cardiology outpatient visits (HR, 1.40; 95% CI, 1.24-1.59); emergency department visits (HR, 1.19; 95% CI, 1.02-1.39); and hospitalizations (HR, 1.75; 95% CI, 1.49-2.05). Effects attenuated with age for cardiology outpatient visits and hospitalizations and increased for emergency department visits. Female sex, geographic periphery, and ethnic minority were associated with more primary care visits, and female sex (HR versus men, 0.89 [95% CI, 0.84-0.94]) and periphery (HR, 0.72 [95% CI, 0.58-0.90] for very peripheral versus very central) were associated with fewer cardiology visits. Arab minority patients also had high hospitalization rates compared with the majority group of Jewish or other patients.
Conclusions:
Healthcare utilization rates were high among patients with ACHD. Female sex, geographic periphery, and ethnicity were associated with less optimal service utilization patterns. Further research should examine strategies to optimize service utilization in these groups.



J Am Heart Assoc: 11 Jan 2021:e018037; epub ahead of print
Benderly M, Buber J, Kalter-Leibovici O, Blieden L, ... Hirsch R, Israeli Adult Congenital Heart Disease Research Group
J Am Heart Assoc: 11 Jan 2021:e018037; epub ahead of print | PMID: 33432841
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pharmacotherapy in the Management of Anxiety and Pain During Acute Coronary Syndromes and the Risk of Developing Symptoms of Posttraumatic Stress Disorder.

von Känel R, Schmid JP, Meister-Langraf RE, Barth J, ... Princip M, Pazhenkottil AP


Background:
Benzodiazepines and morphine are given during acute coronary syndromes (ACSs) to alleviate anxiety and pain, and β-blockers may also reduce pain. ACS may induce posttraumatic stress disorder (PTSD) symptoms (PTSS). When taken during trauma other than ACS, benzodiazepines increase the risk of PTSS, but it is unknown if benzodiazepines increase the risk of PTSS in ACS. We examined the effects of drug exposure during ACS on the development of PTSS. Methods and Results Study participants were 154 patients with a verified ACS. Baseline demographics, clinical variables, and psychological measures were obtained through a medical history, through a psychometric assessment, and from patient records, and used as covariates in linear regression analysis. Three months after ACS, the severity of PTSS was assessed with the Clinician-Administered PTSD Scale. During ACS, 37.7% of patients were exposed to benzodiazepines, whereas 72.1% were exposed to morphine and 88.3% were exposed to β-blockers, but only 7.1% were exposed to antidepressants. Eighteen (11.7%) patients developed clinical PTSD. Adjusting for all covariates, benzodiazepine use was significantly associated with the Clinician-Administered PTSD Scale total severity score (unstandardized coefficient B [SE], 0.589 [0.274]; partial =0.18; =0.032) and the reexperiencing subscore (B [SE], 0.433 [0.217]; partial =0.17; =0.047). Patients exposed to benzodiazepines had an almost 4-fold increased relative risk of developing clinical PTSD, adjusting for acute stress disorder symptoms (odds ratio, 3.75; 95% CI, 1.31-10.77). Morphine, β-blockers, and antidepressants showed no predictive value.
Conclusions:
Notwithstanding short-term antianxiety effects during ACS, benzodiazepine use might increase the risk of ACS-induced PTSS with clinical significance, thereby compromising patients\' quality of life and prognosis. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01781247.



J Am Heart Assoc: 11 Jan 2021:e018762; epub ahead of print
von Känel R, Schmid JP, Meister-Langraf RE, Barth J, ... Princip M, Pazhenkottil AP
J Am Heart Assoc: 11 Jan 2021:e018762; epub ahead of print | PMID: 33432839
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development.

Parker LE, Landstrom AP

Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left-sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. These defects can arise in isolation or as a component of a defined syndrome; however, nonsyndromic defects are often observed in multiple family members and associated with high sibling recurrence risk. This clear evidence for a heritable basis has driven a lengthy search for disease-causing variants that has uncovered both rare and common variants in genes that, when perturbed in cardiac development, can result in LSOLs. Despite advancements in genetic sequencing platforms and broadening use of exome sequencing, the currently accepted LSOL-associated genes explain only 10% to 20% of patients. Further, the combinatorial effects of common and rare variants as a cause of LSOLs are emerging. In this review, we highlight the genes and variants associated with the different LSOLs and discuss the strengths and weaknesses of the present genetic associations. Furthermore, we discuss the research avenues needed to bridge the gaps in our current understanding of the genetic basis of nonsyndromic congenital heart disease.



J Am Heart Assoc: 11 Jan 2021:e019006; epub ahead of print
Parker LE, Landstrom AP
J Am Heart Assoc: 11 Jan 2021:e019006; epub ahead of print | PMID: 33432820
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Level and Increase in D-Dimer With All-Cause Death and Poor Functional Outcome After Ischemic Stroke or Transient Ischemic Attack.

Hou H, Xiang X, Pan Y, Li H, Meng X, Wang Y


Background:
D-dimer is involved in poor outcomes of stroke as a coagulation biomarker. We aimed to investigate the associations of the level and increase in D-dimer between baseline and 90 days with all-cause death or poor functional outcome in patients after ischemic stroke or transient ischemic attack. Methods and Results We collected data from the CNSRIII (Third China National Stroke Registry) study. The present substudy included 10 518 patients within 7 days (baseline) of ischemic stroke or transient ischemic attack and 6268 patients at 90 days. Poor functional outcome at 1 year was assessed on the basis of the modified Rankin Scale (≥3). Multivariable Cox regression or logistic regression was used to assess the association of D-dimer levels with all-cause death or poor functional outcome. D-dimer levels at 90 days were lower than those at baseline (1.4 µg/mL versus 1.7 µg/mL; <0.001). Higher baseline D-dimer level was associated with all-cause death (adjusted hazard ratio [HR], 1.77; 95% CI, 1.25-2.52; =0.001) and poor functional outcome (adjusted odds ratio [OR], 1.49; 95% CI, 1.23-1.80; <0.001) during 1-year follow-up. Higher D-dimer level at 90 days was also associated with poor outcomes independently. Furthermore, an increase in D-dimer levels between baseline and 90 days was associated with all-cause death (since 90 days to 1 year after index event) (adjusted HR, 1.99; 95% CI, 1.12-3.53; =0.019) but not with poor functional outcome (adjusted OR, 1.08; 95% CI, 0.82-1.41).
Conclusions:
Our study shows that high level and an increase in D-dimer between baseline and 90 days are associated with poor outcomes in patients after ischemic stroke or transient ischemic attack.



J Am Heart Assoc: 07 Jan 2021:e018600; epub ahead of print
Hou H, Xiang X, Pan Y, Li H, Meng X, Wang Y
J Am Heart Assoc: 07 Jan 2021:e018600; epub ahead of print | PMID: 33412918
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Influence of Atrial Fibrillation on Functional Tricuspid Regurgitation in Patients With HeartMate 3.

Hayashi H, Naka Y, Sanchez J, Takayama H, ... Uriel N, Takeda K


Background:
Functional tricuspid regurgitation (TR) can occur secondary to atrial fibrillation (AF). The impact of AF on functional TR and cardiovascular events is uncertain in patients with left ventricular assist devices. This study aimed to investigate the effect of AF on functional TR and cardiovascular events in patients with a HeartMate 3 left ventricular assist device. Methods and Results We retrospectively reviewed 133 patients who underwent HeartMate 3 implantation at our center between November 2014 and November 2018. We excluded patients who had undergone previous or concomitant tricuspid valve procedures and those whose echocardiographic images were of insufficient quality. The primary end point was death and the presence of a cardiovascular event at 1 year. We defined cardiovascular event as a composite of death, stroke, and hospital readmission due to recurrent heart failure and significant residual TR as vena contracta width ≥3 mm. In total, 110 patients were included in this analysis. Patients were divided into 3 groups: no AF (n=51), paroxysmal AF (n=40), and persistent AF (PeAF) (n=19). Kaplan-Meier analysis showed that patients with PeAF had the worst survival (no AF 98%, paroxysmal AF 98%, PeAF 84%, log-rank =0.038) and event-free rate (no AF 93%, paroxysmal AF 89%, PeAF 72%, log-rank =0.048) at 1 year. Thirty-one (28%) patients had residual TR 1 month after left ventricular assist device implantation. Patients with residual TR had a significantly poor prognosis compared with those without residual TR (log-rank =0.014).
Conclusions:
PeAF was associated with increased mortality, cardiovascular events, and residual TR compared with no AF and paroxysmal AF.



J Am Heart Assoc: 07 Jan 2021:e018334; epub ahead of print
Hayashi H, Naka Y, Sanchez J, Takayama H, ... Uriel N, Takeda K
J Am Heart Assoc: 07 Jan 2021:e018334; epub ahead of print | PMID: 33412902
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Transition From an Open to Closed Staffing Model in the Cardiac Intensive Care Unit Improves Clinical Outcomes.

Miller PE, Chouairi F, Thomas A, Kunitomo Y, ... Velazquez EJ, Brennan J


Background:
Several studies have shown improved outcomes in closed compared with open medical and surgical intensive care units. However, very little is known about the ideal organizational structure in the modern cardiac intensive care unit (CICU). Methods and Results We retrospectively reviewed consecutive unique admissions (n=3996) to our tertiary care CICU from September 2013 to October 2017. The aim of our study was to assess for differences in clinical outcomes between an open compared with a closed CICU. We used multivariable logistic regression adjusting for demographics, comorbidities, and severity of illness. The primary outcome was in-hospital mortality. We identified 2226 patients in the open unit and 1770 in the closed CICU. The unadjusted in-hospital mortality in the open compared with closed unit was 9.6% and 8.9%, respectively (=0.42). After multivariable adjustment, admission to the closed unit was associated with a lower in-hospital mortality (odds ratio [OR], 0.69; 95% CI: 0.53-0.90, =0.007) and CICU mortality (OR, 0.70; 95% CI, 0.52-0.94, =0.02). In subgroup analysis, admissions for cardiac arrest (OR, 0.42; 95% CI, 0.20-0.88, =0.02) and respiratory insufficiency (OR, 0.43; 95% CI, 0.22-0.82, =0.01) were also associated with a lower in-hospital mortality in the closed unit. We did not find a difference in CICU length of stay or total hospital charges (>0.05).
Conclusions:
We found an association between lower in-hospital and CICU mortality after the transition to a closed CICU. These results may help guide the ongoing redesign in other tertiary care CICUs.



J Am Heart Assoc: 07 Jan 2021:e018182; epub ahead of print
Miller PE, Chouairi F, Thomas A, Kunitomo Y, ... Velazquez EJ, Brennan J
J Am Heart Assoc: 07 Jan 2021:e018182; epub ahead of print | PMID: 33412899
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Short P-Wave Duration is a Marker of Higher Rate of Atrial Fibrillation Recurrences after Pulmonary Vein Isolation: New Insights into the Pathophysiological Mechanisms Through Computer Simulations.

Auricchio A, Özkartal T, Salghetti F, Neumann L, ... Schotten U, Conte G


Background:
Short ECG P-wave duration has recently been demonstrated to be associated with higher risk of atrial fibrillation (AF). The aim of this study was to assess the rate of AF recurrence after pulmonary vein isolation in patients with a short P wave, and to mechanistically elucidate the observation by computer modeling. Methods and Results A total of 282 consecutive patients undergoing a first single-pulmonary vein isolation procedure for paroxysmal or persistent AF were included. Computational models studied the effect of adenosine and sodium conductance on action potential duration and P-wave duration (PWD). About 16% of the patients had a PWD of 110 ms or shorter (median PWD 126 ms, interquartile range, 115 ms-138 ms; range, 71 ms-180 ms). At Cox regression, PWD was significantly associated with AF recurrence (=0.012). Patients with a PWD <110 ms (hazard ratio [HR], 2.20; 95% CI, 1.24-3.88; =0.007) and patients with a PWD ≥140 (HR, 1.87, 95% CI, 1.06-3.30; =0.031) had a nearly 2-fold increase in risk with respect to the other group. In the computational model, adenosine yielded a significant reduction of action potential duration 90 (52%) and PWD (7%). An increased sodium conductance (up to 200%) was robustly accompanied by an increase in conduction velocity (26%), a reduction in action potential duration 90 (28%), and PWD (22%).
Conclusions:
One out of 5 patients referred for pulmonary vein isolation has a short PWD which was associated with a higher rate of AF after the index procedure. Computer simulations suggest that shortening of atrial action potential duration leading to a faster atrial conduction may be the cause of this clinical observation.



J Am Heart Assoc: 06 Jan 2021:e018572; epub ahead of print
Auricchio A, Özkartal T, Salghetti F, Neumann L, ... Schotten U, Conte G
J Am Heart Assoc: 06 Jan 2021:e018572; epub ahead of print | PMID: 33410337
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

CD4 T Cell-Specific Proteomic Pathways Identified in Progression of Hypertension Across Postmenopausal Transition.

Uhlorn JA, Husband NA, Romero-Aleshire MJ, Moffett C, ... Langlais PR, Brooks HL


Background:
Menopause is associated with an increase in the prevalence and severity of hypertension in women. Although premenopausal females are protected against T cell-dependent immune activation and development of angiotensin II (Ang II) hypertension, this protection is lost in postmenopausal females. Therefore, the current study hypothesized that specific CD4 T cell pathways are regulated by sex hormones and Ang II to mediate progression from premenopausal protection to postmenopausal hypertension. Methods and Results Menopause was induced in C57BL/6 mice via repeated 4-vinylcyclohexene diepoxide injections, while premenopausal females received sesame oil vehicle. A subset of premenopausal mice and all menopausal mice were infused with Ang II for 14 days (Control, Ang II, Meno/Ang II). Proteomic and phosphoproteomic profiles of CD4 T cells isolated from spleens were examined. Ang II markedly increased CD4 T cell protein abundance and phosphorylation associated with DNA and histone methylation in both premenopausal and postmenopausal females. Compared with premenopausal T cells, Ang II infusion in menopausal mice increased T cell phosphorylation of MP2K2, an upstream regulator of ERK, and was associated with upregulated phosphorylation at ERK targeted sites. Additionally, Ang II infusion in menopausal mice decreased T cell phosphorylation of TLN1, a key regulator of IL-2Rα and FOXP3 expression.
Conclusions:
These findings identify novel, distinct T cell pathways that influence T cell-mediated inflammation during postmenopausal hypertension.



J Am Heart Assoc: 06 Jan 2021:e018038; epub ahead of print
Uhlorn JA, Husband NA, Romero-Aleshire MJ, Moffett C, ... Langlais PR, Brooks HL
J Am Heart Assoc: 06 Jan 2021:e018038; epub ahead of print | PMID: 33410333
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Early Aspirin Discontinuation After Coronary Stenting: A Systematic Review and Meta-Analysis.

Wiebe J, Ndrepepa G, Kufner S, Lahmann AL, ... Kastrati A, Cassese S


Background:
The clinical impact of early aspirin discontinuation compared with dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention with stenting remains poorly studied. We investigated the clinical outcomes of patients assigned to either early aspirin discontinuation or DAPT after percutaneous coronary intervention with stenting. Methods and Results We performed a meta-analysis of aggregate data from randomized clinical trials enrolling participants receiving a percutaneous coronary intervention with stenting and assigned to either early aspirin discontinuation or DAPT. Scientific databases were searched from inception through March 30, 2020. Trial-level hazard ratios (HRs) and 95% CIs were pooled using a random effects model with inverse variance weighting. The primary outcome was all-cause death. Secondary outcomes were myocardial infarction, stent thrombosis, stroke, and major bleeding. Overall, 36 206 participants were allocated to either early aspirin discontinuation (experimental therapy, n=18 088) or DAPT (control therapy, n=18 118) in 7 trials. Median follow-up was 12 months. All-cause death occurred in 2.5% of patients assigned to experimental and 2.9% of patients assigned control therapy (hazard ratio [HR], 0.91, 95% CI, 0.75-1.11; =0.37). Overall, patients treated with experimental versus control therapy showed no significant difference in terms of myocardial infarction (HR, 1.02 [0.85-1.22], =0.81), stent thrombosis (HR, 1.02 [0.87-1.20], =0.83), or stroke (HR, 1.01 [0.68-1.49], =0.96). However, the risk for major bleeding (HR, 0.58 [0.43-0.77], <0.01) was significantly reduced by experimental as compared with control therapy.
Conclusions:
In patients treated with percutaneous coronary intervention and stenting, assigned to a strategy of early aspirin discontinuation versus DAPT, the risk of death and ischemic events is not significantly different but the risk of bleeding is lower.



J Am Heart Assoc: 06 Jan 2021:e018304; epub ahead of print
Wiebe J, Ndrepepa G, Kufner S, Lahmann AL, ... Kastrati A, Cassese S
J Am Heart Assoc: 06 Jan 2021:e018304; epub ahead of print | PMID: 33410332
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Aneurysm Wall Enhancement in Unruptured Intracranial Aneurysms: A Histopathological Evaluation.

Zhong W, Su W, Li T, Tan X, ... Su W, Wang Y


Background:
Unruptured intracerebral aneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging scans may be a promising predictor for rupture-prone intracerebral aneurysms. However, the pathophysiology of AWE remains unclear. To this end, the association between AWE and histopathological changes was assessed in this study. Methods and Results A total of 35 patients with 41 unruptured intracerebral aneurysms who underwent surgical clipping were prospectively enrolled. A total of 27 aneurysms were available for histological evaluation. The macroscopic and microscopic features of unruptured intracerebral aneurysms with and without enhancement were assessed. The microscopic features studied included inflammatory cell invasion and vasa vasorum, which were assessed using immunohistochemical staining with CD68, CD3, CD20, and myeloperoxidase for the former and CD34 for the latter. A total of 21 (51.2%) aneurysms showed AWE (partial AWE, n=7; circumferential AWE, n=14). Atherosclerotic and translucent aneurysms were identified in 17 and 14 aneurysms, respectively. Aneurysm size, irregularity, and atherosclerotic and translucent aneurysms were associated with AWE on univariate analysis (<0.05). Multivariate logistic regression analysis showed that atherosclerosis was the only factor significantly and independently associated with AWE (=0.027). Histological assessment revealed that inflammatory cell infiltration, intraluminal thrombus, and vasa vasorum were significantly associated with AWE (<0.05).
Conclusions:
Though AWE on vessel wall magnetic resonance imaging scans may be associated with the presence of atherosclerotic lesions in unruptured intracerebral aneurysms, inflammatory cell infiltration within atherosclerosis, intraluminal thrombus, and vasa vasorum may be the main pathological features associated with AWE. However, the underlying pathological mechanism for AWE still needs to be further studied.



J Am Heart Assoc: 06 Jan 2021:e018633; epub ahead of print
Zhong W, Su W, Li T, Tan X, ... Su W, Wang Y
J Am Heart Assoc: 06 Jan 2021:e018633; epub ahead of print | PMID: 33410330
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Statin Exposure and Risk of Heart Failure After Anthracycline- or Trastuzumab-Based Chemotherapy for Early Breast Cancer: A Propensity Score‒Matched Cohort Study.

Abdel-Qadir H, Bobrowski D, Zhou L, Austin PC, ... Lee DS, Thavendiranathan P


Background:
Statins are hypothesized to reduce the risk of cardiotoxicity associated with anthracyclines and trastuzumab. Our aim was to study the association of statin exposure with hospitalization or emergency department visits (hospital presentations) for heart failure (HF) after anthracycline- and/or trastuzumab-containing chemotherapy for early breast cancer. Methods and Results Using linked administrative databases, we conducted a retrospective cohort study of women aged ≥66 years without prior HF who received anthracyclines or trastuzumab for newly diagnosed early breast cancer in Ontario between 2007 to 2017. Statin-exposed and unexposed women were matched 1:1 using propensity scores. Trastuzumab-treated women were also matched on anthracycline exposure. We matched 666 statin-discordant pairs of anthracycline-treated women and 390 pairs of trastuzumab-treated women (median age, 69 and 71 years, respectively). The 5-year cumulative incidence of HF hospital presentations after anthracyclines was 1.2% (95% CI, 0.5%-2.6%) in statin-exposed women and 2.9% (95% CI, 1.7%-4.6%) in unexposed women ( value, 0.01). The cause-specific hazard ratio associated with statins in the anthracycline cohort was 0.45 (95% CI, 0.24-0.85;value, 0.01). After trastuzumab, the 5-year cumulative incidence of HF hospital presentations was 2.7% (95% CI, 1.2%-5.2%) in statin-exposed women and 3.7% (95% CI, 2.0%-6.2%) in unexposed women ( value 0.09). The cause-specific hazard ratio associated with statins in the trastuzumab cohort was 0.46 (95% CI, 0.20-1.07;value, 0.07).
Conclusions:
Statin-exposed women had a lower risk of HF hospital presentations after early breast cancer chemotherapy involving anthracyclines, with non-significant trends towards lower risk following trastuzumab. These findings support the development of randomized controlled trials of statins for prevention of cardiotoxicity.



J Am Heart Assoc: 05 Jan 2021:e018393; epub ahead of print
Abdel-Qadir H, Bobrowski D, Zhou L, Austin PC, ... Lee DS, Thavendiranathan P
J Am Heart Assoc: 05 Jan 2021:e018393; epub ahead of print | PMID: 33401953
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Light-Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes.

Figueiro MG, Goo YH, Hogan R, Plitnick B, ... Yechoor VK, Paul A


Background:
Despite compelling epidemiological evidence that circadian disruption inherent to long-term shift work enhances atherosclerosis progression and vascular events, the underlying mechanisms remain poorly understood. A challenge to the use of mouse models for mechanistic and interventional studies involving light-dark patterns is that the spectral and absolute sensitivities of the murine and human circadian systems are very different, and light stimuli in nocturnal mice should be scaled to represent the sensitivities of the human circadian system. Methods and Results We used calibrated devices to deliver to low-density lipoprotein receptor knockout mice light-dark patterns representative of that experienced by humans working day shifts or rotating shift schedules. Mice under day shifts were maintained under regular 12 hours of light and 12 hours of dark cycles. Mice under rotating shift schedules were subjected for 11 weeks to reversed light-dark patterns 4 days in a row per week, followed by 3 days of regular light-dark patterns. In both protocols the light phases consisted of monochromatic green light at an irradiance of 4 µW/cm. We found that the shift work paradigm disrupts the foam cell\'s molecular clock and increases endoplasmic reticulum stress and apoptosis. Lesions of mice under rotating shift schedules were larger and contained less prostabilizing fibrillar collagen and significantly increased areas of necrosis.
Conclusions:
Low-density lipoprotein receptor knockout mice under light-dark patterns analogous to that experienced by rotating shift workers develop larger and more vulnerable plaques and may represent a valuable model for further mechanistic and/or interventional studies against the deleterious vascular effects of rotating shift work.



J Am Heart Assoc: 05 Jan 2021:e018151; epub ahead of print
Figueiro MG, Goo YH, Hogan R, Plitnick B, ... Yechoor VK, Paul A
J Am Heart Assoc: 05 Jan 2021:e018151; epub ahead of print | PMID: 33401929
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Admission Cardiac Diagnostic Testing with Electrocardiography and Troponin Measurement Prognosticates Increased 30-Day Mortality in COVID-19.

Poterucha TJ, Elias P, Jain SS, Sayer G, ... Uriel N, Wan EY


Background:
Cardiovascular involvement in coronavirus disease 2019 (COVID-19) is common and leads to worsened mortality. Diagnostic cardiovascular studies may be helpful for resource appropriation and identifying patients at increased risk for death. Methods and Results We analyzed 887 patients (aged 64±17 years) admitted with COVID-19 from March 1 to April 3, 2020 in New York City with 12 lead electrocardiography within 2 days of diagnosis. Demographics, comorbidities, and laboratory testing, including high sensitivity cardiac troponin T (hs-cTnT), were abstracted. At 30 days follow-up, 556 patients (63%) were living without requiring mechanical ventilation, 123 (14%) were living and required mechanical ventilation, and 203 (23%) had expired. Electrocardiography findings included atrial fibrillation or atrial flutter (AF/AFL) in 46 (5%) and ST-T wave changes in 306 (38%). 27 (59%) patients with AF/AFL expired as compared to 181 (21%) of 841 with other non-life-threatening rhythms (<0.001). Multivariable analysis incorporating age, comorbidities, AF/AFL, QRS abnormalities, and ST-T wave changes, and initial hs-cTnT ≥20 ng/L showed that increased age (HR 1.04/year), elevated hs-cTnT (HR 4.57), AF/AFL (HR 2.07), and a history of coronary artery disease (HR 1.56) and active cancer (HR 1.87) were associated with increased mortality.
Conclusions:
Myocardial injury with hs-cTnT ≥20 ng/L, in addition to cardiac conduction perturbations, especially AF/AFL, upon hospital admission for COVID-19 infection is associated with markedly increased risk for mortality than either diagnostic abnormality alone.



J Am Heart Assoc: 04 Jan 2021; 10:e018476
Poterucha TJ, Elias P, Jain SS, Sayer G, ... Uriel N, Wan EY
J Am Heart Assoc: 04 Jan 2021; 10:e018476 | PMID: 33169643
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel-Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events.

Kalantzi K, Tentolouris N, Melidonis AJ, Papadaki S, ... Tsolakis I, Tselepis AD


Background:
Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti-inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2-arm, multicenter, open-label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow-up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex-adjusted hazard ratio [HR], 0.468; 95% CI, 0.252-0.870; =0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; =0.046) and improved the ankle-brachial index and pain-free walking distance values (=0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex-adjusted HR, 1.080; 95% CI, 0.579-2.015; =0.809).
Conclusions:
Adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.



J Am Heart Assoc: 04 Jan 2021; 10:e018184
Kalantzi K, Tentolouris N, Melidonis AJ, Papadaki S, ... Tsolakis I, Tselepis AD
J Am Heart Assoc: 04 Jan 2021; 10:e018184 | PMID: 33327737
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry.

Taha A, Nielsen SJ, Bergfeldt L, Ahlsson A, ... Franzén S, Jeppsson A


Background:
The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow-up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82).
Conclusions:
POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.



J Am Heart Assoc: 04 Jan 2021; 10:e017966
Taha A, Nielsen SJ, Bergfeldt L, Ahlsson A, ... Franzén S, Jeppsson A
J Am Heart Assoc: 04 Jan 2021; 10:e017966 | PMID: 33251914
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme.

Tutarel O, Ramlakhan KP, Baris L, Subirana MT, ... Roos-Hesselink JW,


Background:
In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed.
Conclusions:
Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate.



J Am Heart Assoc: 04 Jan 2021; 10:e018176
Tutarel O, Ramlakhan KP, Baris L, Subirana MT, ... Roos-Hesselink JW,
J Am Heart Assoc: 04 Jan 2021; 10:e018176 | PMID: 33350866
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Soluble Urokinase-Type Plasminogen Activator Receptor, Changes of 24-Hour Blood Pressure, and Progression of Chronic Kidney Disease.

Jhee JH, Nam BY, Lee CJ, Park JT, ... Park S, Yoo TH


Background:
Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24-hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC-HI (Cardiovascular and Metabolic Disease Etiology Research Center-High Risk) cohort study (2013-2018). The relationship of serum suPAR levels to 24-hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2-2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24-hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27-6.76; =0.01). During a follow-up of 43.2 (interquartile range, 27.0-55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37-3.21; =0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02-2.01; =0.03) with every 1-unit increase in serum suPAR levels.
Conclusions:
Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.



J Am Heart Assoc: 04 Jan 2021; 10:e017225
Jhee JH, Nam BY, Lee CJ, Park JT, ... Park S, Yoo TH
J Am Heart Assoc: 04 Jan 2021; 10:e017225 | PMID: 33325248
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies.

Daviglus ML, Ferdinand KC, López JAG, Wu Y, Monsalvo ML, Rodriguez CJ


Background:
Prevalence of cardiovascular disease risk factors and rates of atherosclerotic cardiovascular disease outcomes vary across racial/ethnic groups. This analysis examined the effects of evolocumab on LDL-C (low-density lipoprotein cholesterol) levels and LDL-C goals achievement by race/ethnicity. Methods and Results Data from 15 phase 2 and 3 studies of treatment with evolocumab versus placebo or ezetimibe were pooled (n=7669). Results were analyzed by participant clinical characteristics and by self-identified race/ethnicity. Key outcomes included percent change from baseline in LDL-C, achievement of LDL-C <70 mg/dL, and LDL-C reduction of ≥50% at 12 weeks and at 1 to 5 years. Across 12-week studies, mean percent change in LDL-C from baseline in evolocumab-treated participants was -52% to -59% for White and -46% to -67% for non-White participants, across clinical characteristics groups. LDL-C <70 mg/dL was achieved in 43% to 84% and 62% to 94% and LDL-C reduction of ≥50% in 63% to 78% and 58% to 86%, respectively. In 1- to 5-year studies, mean percent change in LDL-C was -46% to -52% for White and -49% to -55% for non-White participants. LDL-C <70 mg/dL was achieved in 53% to 84% and 66% to 77%, and LDL-C reduction of ≥50% in 53% to 67% and 58% to 68%, respectively. The treatment effect on mean percent change in LDL-C differed only in participants with type 2 diabetes mellitus, with a larger reduction in Asian participants. The qualitative interactionvalues were nonsignificant, indicating consistent directionality of effect.
Conclusions:
Similar reduction in LDL-C levels with evolocumab was observed across racial/ethnic groups in 12-week and 1- to 5-year studies. Among those with diabetes mellitus, Asian participants had greater LDL-C reduction.



J Am Heart Assoc: 04 Jan 2021; 10:e016839
Daviglus ML, Ferdinand KC, López JAG, Wu Y, Monsalvo ML, Rodriguez CJ
J Am Heart Assoc: 04 Jan 2021; 10:e016839 | PMID: 33325247
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Refining Safe Contrast Limits for Preventing Acute Kidney Injury After Percutaneous Coronary Intervention.

Yuan N, Latif K, Botting PG, Elad Y, ... Cheng S, Ebinger JE


Background:
Contrast-associated acute kidney injury (CA-AKI) is associated with substantial morbidity and may be prevented by using less contrast during percutaneous coronary intervention (PCI). However, tools for determining safe contrast volumes are limited. We developed risk models to tailor safe contrast volume limits during PCI. Methods and Results Using data from all PCIs performed at 18 hospitals from January 2015 to March 2018, we developed logistic regression models for predicting CA-AKI, including simpler models (\"pragmatic full,\" \"pragmatic minimum\") using only predictors easily derivable from electronic health records. We prospectively validated these models using PCI data from April 2018 to December 2018 and compared them to preexisting safe contrast models using the area under the receiver operating characteristic curve (AUC). The model derivation data set included 20 579 PCIs with 2102 CA-AKI cases. When applying models to the separate validation data set (5423 PCIs, 488 CA-AKI cases), prior safe contrast limits (5*Weight/Creatinine, 2*CreatinineClearance) were poor measures of safety with accuracies of 53.7% and 56.6% in predicting CA-AKI, respectively. The full, pragmatic full, and pragmatic minimum models performed significantly better (accuracy, 73.1%, 69.3%, 66.6%; AUC, 0.80, 0.76, 0.72 versus 0.59 for 5 * Weight/Creatinine, 0.61 for 2*CreatinineClearance). We found that applying safe contrast limits could meaningfully reduce CA-AKI risk in one-quarter of patients.
Conclusions:
Compared with preexisting equations, new multivariate models for safe contrast limits were substantially more accurate in predicting CA-AKI and could help determine which patients benefit most from limiting contrast during PCI. Using readily available electronic health record data, these models could be implemented into electronic health records to provide actionable information for improving PCI safety.



J Am Heart Assoc: 04 Jan 2021; 10:e018890
Yuan N, Latif K, Botting PG, Elad Y, ... Cheng S, Ebinger JE
J Am Heart Assoc: 04 Jan 2021; 10:e018890 | PMID: 33325246
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Sirolimus as a Primary Immunosuppressant on Myocardial Fibrosis and Diastolic Function Following Heart Transplantation.

Alnsasra H, Asleh R, Oh JK, Maleszewski JJ, ... Bois MC, Kushwaha SS


Background:
Myocardial fibrosis is an important contributor for development of diastolic dysfunction. We investigated the impact of sirolimus as primary immunosuppression on diastolic dysfunction and fibrosis progression among heart transplantation recipients. Methods and Results In 100 heart transplantation recipients who were either treated with a calcineurin inhibitor (CNI) (n=51) or converted from CNI to sirolimus (n=49), diastolic function parameters were assessed using serial echocardiograms and right heart catheterizations. Myocardial fibrosis was quantified on serial myocardial biopsies. After 3 years, lateral e\' increased within the sirolimus group but decreased in the CNI group (0.02±0.04 versus -0.02±0.04 m/s delta change; =0.003, respectively). Both pulmonary capillary wedge pressure and diastolic pulmonary artery pressure significantly decreased in the sirolimus group but remained unchanged in the CNI group (-1.50±2.59 versus 0.20±2.20 mm Hg/year; =0.02; and -1.72±3.39 versus 0.82±2.59 mm Hg/year; =0.005, respectively). A trend for increased percentage of fibrosis was seen in the sirolimus group (8.48±3.17 to 10.10±3.0%; =0.07) as compared with marginally significant progression in the CNI group (8.76±3.87 to 10.56±4.34%; =0.04). The percent change in fibrosis did not differ significantly between the groups (1.62±4.67 versus 1.80±5.31%, respectively; =0.88).
Conclusions:
Early conversion to sirolimus is associated with improvement in diastolic dysfunction and filling pressures as compared with CNI therapy. Whether this could be attributed to attenuation of myocardial fibrosis progression with sirolimus treatment warrants further investigation.



J Am Heart Assoc: 04 Jan 2021; 10:e018186
Alnsasra H, Asleh R, Oh JK, Maleszewski JJ, ... Bois MC, Kushwaha SS
J Am Heart Assoc: 04 Jan 2021; 10:e018186 | PMID: 33325244
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

van den Berg VJ, Oemrawsingh RM, Umans VAWM, Kardys I, ... Boersma E,


Background:
Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up. Post-ACS kinetics were studied by linear mixed-effect models. Using the samples collected in the 6- to 12-month post-ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs-cTnI and average hs-cTnT concentration, and the intra- and interindividual variation for both biomarkers. Compared with hs-cTnT, hs-cTnI peaked higher (median 3506 ng/L versus 494 ng/L; <0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; <0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation (=0.60), whereas the average hs-cTnT concentration was 5 times more likely to be above the upper reference limit than hs-cTnI. The intraindividual variations of hs-cTnI and hs-cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%.
Conclusions:
Hs-cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post-6-month samples, hs-cTnI and hs-cTnT were clearly not interchangeable, and average hs-cTnT concentrations were much more often above the upper reference limit than hs-cTnI. For both markers, the within-patient variation fell largely below beween-patient variation. Registration URL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.



J Am Heart Assoc: 04 Jan 2021; 10:e017393
van den Berg VJ, Oemrawsingh RM, Umans VAWM, Kardys I, ... Boersma E,
J Am Heart Assoc: 04 Jan 2021; 10:e017393 | PMID: 33325242
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Disparities in Cardiovascular Disease Outcomes Among Pregnant and Post-Partum Women.

Gad MM, Elgendy IY, Mahmoud AN, Saad AM, ... Jneid H, Kapadia SR


Background:
The incidence of cardiovascular disease among pregnant women is rising in the United States. Data on racial disparities for the major cardiovascular events during pregnancy are limited. Methods and Results Pregnant and post-partum women hospitalized from January 2007 to December 2017 were identified from the Nationwide Inpatient Sample. The outcomes of interest included: in-hospital mortality, myocardial infarction, stroke, pulmonary embolism, and peripartum cardiomyopathy. Multivariate regression analysis was used to assess the independent association between race and in-hospital outcomes. Among 46 700 637 pregnancy-related hospitalizations, 21 663 575 (46.4%) were White, 6 302 089 (13.5%) were Black, and 8 914 065 (19.1%) were Hispanic. The trends of mortality and stroke declined significantly in Black women, but however, were mostly unchanged among White women. The incidence of mortality and cardiovascular morbidity was highest among Black women followed by White women, then Hispanic women. The majority of Blacks (62.3%) were insured by Medicaid while the majority of White patients had private insurance (61.9%). Most of Black women were below-median income (71.2%) while over half of the White patients were above the median income (52.7%). Compared with White women, Black women had the highest mortality with adjusted odds ratio (aOR) of 1.45, 95% CI (1.21-1.73); myocardial infarction with aOR of 1.23, 95% CI (1.06-1.42); stroke with aOR of 1.57, 95% CI (1.41-1.74); pulmonary embolism with aOR of 1.42, 95% CI (1.30-1.56); and peripartum cardiomyopathy with aOR of 1.71, 95 % CI (1.66-1.76).
Conclusions:
Significant racial disparities exist in major cardiovascular events among pregnant and post-partum women. Further efforts are needed to minimize these differences.



J Am Heart Assoc: 04 Jan 2021; 10:e017832
Gad MM, Elgendy IY, Mahmoud AN, Saad AM, ... Jneid H, Kapadia SR
J Am Heart Assoc: 04 Jan 2021; 10:e017832 | PMID: 33322915
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Novel Receptor for Advanced Glycation End Products-Blocking Antibody to Treat Diabetic Peripheral Artery Disease.

Johnson LL, Johnson J, Ober R, Holland A, ... Ali Z, Tekabe Y


Background:
Expression of receptor for advanced glycation end products (RAGE) plays an important role in diabetic peripheral artery disease. We proposed to show that treatment with an antibody blocking RAGE would improve hind limb perfusion and muscle viability in diabetic pig with femoral artery (FA) ligation. Methods and Results Purpose-bred diabetic Yucatan minipigs with average fasting blood sugar of 357 mg/dL on insulin to maintain a glucose range of 300 to 500 mg/dL were treated with either a humanized monoclonal anti-RAGE antibody (CR-3) or nonimmune IgG. All pigs underwent intravascular occlusion of the anterior FA. Animals underwent (Tl) single-photon emission computed tomography/x-ray computed tomography imaging on days 1 and 28 after FA occlusion, angiogenesis imaging with [Tc]dodecane tetra-acetic acid-polyethylene glycol-single chain vascular endothelial growth factor (scVEGF), muscle biopsies on day 7, and contrast angiogram day 28. Results showed greater increases in perfusion to the gastrocnemius from day 1 to day 28 in CR-3 compared with IgG treated pigs (=0.0024), greater uptake of [99mTc]dodecane tetra-acetic acid-polyethylene glycol-scVEGF (scV/Tc) in the proximal gastrocnemius at day 7, confirmed by tissue staining for capillaries and vascular endothelial growth factor A, and less muscle loss and fibrosis at day 28. Contrast angiograms showed better reconstitution of the distal FA from collaterals in the CR-3 versus IgG treated diabetic pigs (=0.01). The gastrocnemius on nonoccluded limb at necropsy had higher Tl uptake (percentage injected dose per gram) and reduced RAGE staining in arterioles in CR-3 treated compared with IgG treated animals (=0.04).
Conclusions:
A novel RAGE-blocking antibody improved hind limb perfusion and angiogenesis in diabetic pigs with FA occlusion. Contributing factors are increased collaterals and reduced vascular RAGE expression. CR-3 shows promise for clinical treatment in diabetic peripheral artery disease.



J Am Heart Assoc: 04 Jan 2021; 10:e016696
Johnson LL, Johnson J, Ober R, Holland A, ... Ali Z, Tekabe Y
J Am Heart Assoc: 04 Jan 2021; 10:e016696 | PMID: 33327730
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention.

Vaidya K, Tucker B, Kurup R, Khandkar C, ... Cochran BJ, Patel S


Background:
Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with periprocedural myocardial infarction, as a result of microvascular obstruction via pro-inflammatory and prothrombotic pathways. Colchicine is a well-established anti-inflammatory agent with growing evidence to support use in patients with coronary disease. However, its effects on post-PCI NET formation in ACS have not been explored. Methods and Results Sixty patients (40 ACS; 20 stable angina pectoris) were prospectively recruited and allocated to colchicine or no treatment. Within 24 hours of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 patients with ACS post-PCI and 4 healthy controls were treated in vitro with colchicine (25 nmol/L) and stimulated with either ionomycin (5 μmol/L) or phorbol 12-myristate 13-acetate (50 nmol/L). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst 3342 and anti-alpha tubulin. Baseline characteristics were similar across both treatment and control arms. Patients with ACS had higher NET release versus patients with stable angina pectoris (<0.001), which was reduced with colchicine treatment (area under the curve: 0.58 versus 4.29; <0.001). In vitro, colchicine suppressed unstimulated (<0.001), phorbol 12-myristate 13-acetate-induced (=0.009) and ionomycin-induced (=0.002) NET formation in neutrophils isolated from patients with ACS post-PCI, but not healthy controls. Tubulin organization was impaired in neutrophils from patients with ACS but was restored by colchicine treatment.
Conclusions:
Colchicine suppresses NET formation in patients with ACS post-PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomized trials powered for clinical end points. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12619001231134.



J Am Heart Assoc: 04 Jan 2021; 10:e018993
Vaidya K, Tucker B, Kurup R, Khandkar C, ... Cochran BJ, Patel S
J Am Heart Assoc: 04 Jan 2021; 10:e018993 | PMID: 33346683
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Safety of 3-Month Dual Antiplatelet Therapy After Implantation of Ultrathin Sirolimus-Eluting Stents With Biodegradable Polymer (Orsiro): Results From the SMART-CHOICE Trial.

Yun KH, Lee SY, Cho BR, Jang WJ, ... Hahn JY,


Background:
This study sought to investigate the safety of 3-month dual antiplatelet therapy (DAPT) in patients receiving ultrathin sirolimus-eluting stents with biodegradable polymer (Orsiro). Methods and Results The SMART-CHOICE (Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Anti- platelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents) randomized trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT in 2993 patients undergoing percutaneous coronary intervention. The present analysis was a prespecified subgroup analysis for patients receiving Orsiro stents. As a post hoc analysis, comparisons between Orsiro and everolimus-eluting stents were also done among patients receiving 3-month DAPT. Of 972 patients receiving Orsiro stents, 481 patients were randomly assigned to 3-month DAPT and 491 to 12-month DAPT. At 12 months, the target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization, occurred in 8 patients (1.7%) in the 3-month DAPT group and in 14 patients (2.9%) in the 12-month DAPT group (hazard ratio [HR], 0.58; 95% CI, 0.24-1.39; =0.22). In whole population who were randomly assigned to receive 3-month DAPT (n=1495), there was no significant difference in the target vessel failure between the Orsiro group and the everolimus-eluting stent group (n=1014) (1.7% versus 1.8%; HR, 0.96; 95% CI, 0.41-2.22; =0.92).
Conclusions:
In patients receiving Orsiro stents, clinical outcomes at 1 year were similar between the 3-month DAPT followed by P2Y12 inhibitor monotherapy and 12-month DAPT strategies. With 3-month DAPT, there was no significant difference in target vessel failure between Orsiro and everolimus-eluting stents. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02079194.



J Am Heart Assoc: 04 Jan 2021; 10:e018366
Yun KH, Lee SY, Cho BR, Jang WJ, ... Hahn JY,
J Am Heart Assoc: 04 Jan 2021; 10:e018366 | PMID: 33345567
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Direct Admission of Patients With ST-Segment-Elevation Myocardial Infarction to the Catheterization Laboratory Shortens Pain-to-Balloon and Door-to-Balloon Time Intervals but Only the Pain-to-Balloon Interval Impacts Short- and Long-Term Mortality.

Meisel SR, Kleiner-Shochat M, Abu-Fanne R, Frimerman A, ... Shotan A, Roguin A


Background:
Shortening the pain-to-balloon (P2B) and door-to-balloon (D2B) intervals in patients with ST-segment-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) is essential in order to limit myocardial damage. We investigated whether direct admission of PPCI-treated patients with STEMI to the catheterization laboratory, bypassing the emergency department, expedites reperfusion and improves prognosis. Methods and Results Consecutive PPCI-treated patients with STEMI included in the ACSIS (Acute Coronary Syndrome in Israel Survey), a prospective nationwide multicenter registry, were divided into patients admitted directly or via the emergency department. The impact of the P2B and D2B intervals on mortality was compared between groups by logistic regression and propensity score matching. Of the 4839 PPCI-treated patients with STEMI, 1174 were admitted directly and 3665 via the emergency department. Respective median P2B and D2B were shorter among the directly admitted patients with STEMI (160 and 35 minutes) compared with those admitted via the emergency department (210 and 75 minutes, <0.001). Decreased mortality was observed with direct admission at 1 and 2 years and at the end of follow-up (median 6.4 years, <0.001). Survival advantage persisted after adjustment by logistic regression and propensity matching. P2B, but not D2B, impacted survival (<0.001).
Conclusions:
Direct admission of PPCI-treated patients with STEMI decreased mortality by shortening P2B and D2B intervals considerably. However, P2B, but not D2B, impacted mortality. It seems that the D2B interval has reached its limit of effect. Thus, all efforts should be extended to shorten P2B by educating the public to activate early the emergency medical services to bypass the emergency department and allow timely PPCI for the best outcome.



J Am Heart Assoc: 04 Jan 2021; 10:e018343
Meisel SR, Kleiner-Shochat M, Abu-Fanne R, Frimerman A, ... Shotan A, Roguin A
J Am Heart Assoc: 04 Jan 2021; 10:e018343 | PMID: 33345559
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Fetal Cerebral Oxygenation Is Impaired in Congenital Heart Disease and Shows Variable Response to Maternal Hyperoxia.

Peyvandi S, Xu D, Wang Y, Hogan W, ... McQuillen P, Liu J


Background:
Impairments in fetal oxygen delivery have been implicated in brain dysmaturation seen in congenital heart disease (CHD), suggesting a role for in utero transplacental oxygen therapy. We applied a novel imaging tool to quantify fetal cerebral oxygenation by measuring T2* decay. We compared T2* in fetuses with CHD with controls with a focus on cardiovascular physiologies (transposition or left-sided obstruction) and described the effect of brief administration of maternal hyperoxia on T2* decay. Methods and Results This is a prospective study performed on pregnant mothers with a prenatal diagnosis of CHD compared with controls in the third trimester. Participants underwent a fetal brain magnetic resonance imaging scan including a T2* sequence before and after maternal hyperoxia. Comparisons were made between control and CHD fetuses including subgroup analyses by cardiac physiology. Forty-four mothers (CHD=24, control=20) participated. Fetuses with CHD had lower total brain volume (238.2 mm, 95% CI, 224.6-251.9) compared with controls (262.4 mm, 95% CI, 245.0-279.8, =0.04). T2* decay time was faster in CHD compared with controls (beta=-14.4, 95% CI, -23.3 to -5.6, =0.002). The magnitude of change in T2* with maternal hyperoxia was higher in fetuses with transposition compared with controls (increase of 8.4 ms, 95% CI, 0.5-14.3, =0.01), though between-subject variability was noted.
Conclusions:
Cerebral tissue oxygenation is lower in fetuses with complex CHD. There was variability in the response to maternal hyperoxia by CHD subgroup that can be tested in future larger studies. Cardiovascular physiology is critical when designing neuroprotective clinical trials in the fetus with CHD.



J Am Heart Assoc: 04 Jan 2021; 10:e018777
Peyvandi S, Xu D, Wang Y, Hogan W, ... McQuillen P, Liu J
J Am Heart Assoc: 04 Jan 2021; 10:e018777 | PMID: 33345557
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Racial/Ethnic Disparities in Screening for and Awareness of High Cholesterol Among Pregnant Women Receiving Prenatal Care.

Mszar R, Gopal DJ, Chowdary R, Smith CL, ... Nemiroff R, Lewey J


Background:
Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality among women, with younger women being disproportionately affected by traditional cardiovascular risk factors such as dyslipidemia. Despite recommendations for lipid screening in early adulthood and the risks associated with maternal dyslipidemia during pregnancy, many younger women lack access to and utilization of early screening. Accordingly, our objective was to assess the prevalence of and disparities in lipid screening and awareness of high cholesterol as an atherosclerotic cardiovascular disease risk factor among pregnant women receiving prenatal care. Methods and Results We invited 234 pregnant women receiving prenatal care at 1 of 3 clinics affiliated with the University of Pennsylvania Health System to complete our survey. A total of 200 pregnant women (86% response rate) completed the survey. Overall, 59% of pregnant women (mean age 32.2 [±5.7] years) self-reported a previous lipid screening and 79% of women were aware of high cholesterol as an atherosclerotic cardiovascular disease risk factor. Stratified by racial/ethnic subgroups, non-Hispanic Black women were less likely to report a prior screening (43% versus 67%, =0.022) and had lower levels of awareness (66% versus 92%, <0.001) compared with non-Hispanic White women. Non-Hispanic Black women were more likely to see an obstetrician/gynecologist for their usual source of non-pregnancy care compared with non-Hispanic White women (18% versus 5%, =0.043). Those seeing an obstetrician/gynecologist for usual care were less likely to report a prior lipid screening compared with those seeing a primary care physician (29% versus 63%, =0.007).
Conclusions:
Significant racial/ethnic disparities persist in lipid screening and risk factor awareness among pregnant women. Prenatal care may represent an opportunity to enhance access to and uptake of screening among younger women and reduce variations in accessing preventive care services.



J Am Heart Assoc: 04 Jan 2021; 10:e017415
Mszar R, Gopal DJ, Chowdary R, Smith CL, ... Nemiroff R, Lewey J
J Am Heart Assoc: 04 Jan 2021; 10:e017415 | PMID: 33345544
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Outcomes in Guideline-Based Class I Indication Versus Earlier Referral for Surgical Myectomy in Hypertrophic Obstructive Cardiomyopathy.

Alashi A, Smedira NG, Hodges K, Popovic ZB, ... Lever HM, Desai MY


Background:
In patients with obstructive hypertrophic cardiomyopathy, surgical myectomy (SM) is indicated for severe symptoms. We sought to compare long-term outcomes of patients with obstructive hypertrophic cardiomyopathy where SM was based on guideline-recommended Class I indication (Functional Class or FC ≥3 or angina/exertional syncope despite maximal medical therapy) versus earlier (FC 2 and/or impaired exercise capacity on exercise echocardiography with severe obstruction). Methods and Results We studied 2268 consecutive patients (excluding <18 years, ≥ moderate aortic stenosis and subaortic membrane, 56±14 years, 55% men), who underwent SM at our center between June 2002 and March 2018. Clinical data, including left ventricular outflow tract gradient, were recorded. Death and/or appropriate internal defibrillator discharge were primary composite end points. One thousand three hundred eighteen (58%) patients met Class I indication and 950 (42%) underwent earlier surgery; 222 (10%) had a history of obstructive coronary artery disease. Basal septal thickness, and resting and maximal left ventricular outflow tract gradient were 2.0±0.3 cm, 61±44 mm Hg, and 100±31 mm Hg, respectively. At 6.2±4 years after SM, 248 (11%) had composite events (13 [0.6%] in-hospital deaths). Age (hazard ratio [HR], 1.61; 95% CI, 1.26-1.91), obstructive coronary artery disease (HR, 1.46; 95% CI, 1.06-1.91), and Class I versus earlier SM (HR, 1.61; 95% CI, 1.14-2.12) were associated with higher primary composite events (all <0.001). Earlier surgery had better longer-term survival (similar to age-sex-matched normal population) versus surgery for Class I indication (76 [8%] versus 193 [15%], <0.001).
Conclusions:
In patients with obstructive hypertrophic cardiomyopathy, earlier versus surgery for Class I indication had a better long-term survival, similar to the age-sex-matched US population.



J Am Heart Assoc: 04 Jan 2021; 10:e016210
Alashi A, Smedira NG, Hodges K, Popovic ZB, ... Lever HM, Desai MY
J Am Heart Assoc: 04 Jan 2021; 10:e016210 | PMID: 33342243
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-Term Clinical Outcomes Following Revascularization in High-Risk Coronary Anatomy Patients With Stable Ischemic Heart Disease.

Bainey KR, Alemayehu W, Welsh RC, Kumar A, King SB, Kirtane AJ


Background:
The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial failed to show a reduction in hard clinical end points with an early invasive strategy in stable ischemic heart disease (SIHD). However, the influence of left main disease and high-risk coronary anatomy was left unaddressed. In a large angiographic disease-based registry, we examined the modulating effect of revascularization on long-term outcomes in anatomically high-risk SIHD. Methods and Results 9016 patients with SIHD with high-risk coronary anatomy (3 vessel disease with ≥70% stenosis in all 3 epicardial vessels or left main disease ≥50% stenosis [isolated or in combination with other disease]) were selected for study from April 1, 2002 to March 31, 2016. The primary composite of all-cause death or myocardial infarction (MI) was compared between revascularization versus conservative management. A total of 5487 (61.0%) patients received revascularization with either coronary artery bypass graft surgery (n=3312) or percutaneous coronary intervention (n=2175), while 3529 (39.0%) patients were managed conservatively. Selection for coronary revascularization was associated with improved all-cause death/MI as well as longer survival compared with selection for conservative management (Inverse Probability Weighted hazard ratio [IPW-HR] 0.62; 95% CI 0.58 to 0.66; <0.001; IPW-HR 0.57; 95% CI 0.53-0.61; <0.001, respectively). Similar risk reduction was noted with percutaneous coronary intervention (IPW-HR 0.64, 95% CI 0.59-0.70, <0.001) and coronary artery bypass graft surgery (IPW-HR 0.61; 95% CI 0.57-0.66; <0.001).
Conclusions:
Revascularization in patients with SIHD with high-risk coronary anatomy was associated with improved long-term outcome compared with conservative therapy. As such, coronary anatomical profile should be considered when contemplating treatment for SIHD.



J Am Heart Assoc: 04 Jan 2021; 10:e018104
Bainey KR, Alemayehu W, Welsh RC, Kumar A, King SB, Kirtane AJ
J Am Heart Assoc: 04 Jan 2021; 10:e018104 | PMID: 33342230
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Optical Coherence Tomography Predictors for a Favorable Vascular Response to Statin Therapy.

Nakajima A, Minami Y, Araki M, Kurihara O, ... Nakamura S, Jang IK


Background:
Specific plaque phenotypes that predict a favorable response to statin therapy have not been systematically studied. This study aimed to identify optical coherence tomography predictors for a favorable vascular response to statin therapy. Methods and Results Patients who had serial optical coherence tomography imaging at baseline and at 6 months were included. Thin-cap area (defined as an area with fibrous cap thickness <200 μm) was measured using a 3-dimensional computer-aided algorithm, and changes in the thin-cap area at 6 months were calculated. A favorable vascular response was defined as the highest tertile in the degree of reduction of the thin-cap area. Macrophage index was defined as the product of the average macrophage arc and length of the lesion with macrophage infiltration. Layered plaque was defined as a plaque with 1 or more layers of different optical density. In 84 patients, 140 nonculprit lipid plaques were identified. Inanalysis, baseline thin-cap area (odds ratio [OR] 1.442; 95% CI, 1.024-2.031, =0.036), macrophage index (OR, 1.031; 95% CI, 1.002-1.061, =0.036), and layered plaque (OR, 2.767; 95% CI, 1.024-7.479, =0.045) were identified as the significant predictors for a favorable vascular response. Favorable vascular response was associated with a decrease in the macrophage index.
Conclusions:
Three optical coherence tomography predictors for a favorable vascular response to statin therapy have been identified: large thin-cap area, high macrophage index, and layered plaque. Favorable vascular response to statin was correlated with signs of decreased inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01110538.



J Am Heart Assoc: 04 Jan 2021; 10:e018205
Nakajima A, Minami Y, Araki M, Kurihara O, ... Nakamura S, Jang IK
J Am Heart Assoc: 04 Jan 2021; 10:e018205 | PMID: 33342228
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Difference in Medication Adherence Between Patients Prescribed a 30-Day Versus 90-Day Supply After Acute Myocardial Infarction.

Rymer JA, Fonseca E, Bhandary DD, Kumar D, Khan ND, Wang TY


Background:
Evidence-based medication adherence rates after a myocardial infarction are low. We hypothesized that 90-day prescriptions are underused and may lead to higher evidence-based medication adherence compared with 30-day fills. Methods and Results We examined patients with myocardial infarction treated with percutaneous coronary intervention between 2011 and 2015 in the National Cardiovascular Data Registry. Linking to Symphony Health pharmacy data, we described the prevalence of patients filling 30-day versus 90-day prescriptions of statins, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and P2Y inhibitors after discharge. We compared 12-month medication adherence rates by evidence-based medication class and prescription days\' supply and rates of medication switches and dosing changes. Among 353 259 patients with myocardial infarction treated with percutaneous coronary intervention, 90-day evidence-based medication fill rates were low: 13.0% (statins), 12.3% (β-blockers), 14.6% (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers), and 9.7% (P2Y inhibitors). Patients filling 90-day prescriptions were more likely older (median 69 versus 62 years) with a history of prior myocardial infarction (25.0% versus 17.9%) or percutaneous coronary intervention (30.3% versus 19.5%; <0.01 for all) than patients filling 30-day prescriptions. The 12-month adherence rates were higher for patients who filled 90-day versus 30-day supplies: statins, 83.1% versus 75.3%; β-blockers, 72.7% versus 62.9%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 71.1% versus 60.9%; and P2Y inhibitors, 78.5% versus 66.6% (<0.01 for all). Medication switches and dosing changes within 12 months were infrequent for patients filling 30-day prescriptions-14.7% and 0.3% for 30-day P2Y inhibitor fills versus 6.3% and 0.2% for 90-day fills, respectively.
Conclusions:
Patients who filled 90-day prescriptions had higher adherence and infrequent medication changes within 1 year after discharge. Ninety-day prescription strategies should be encouraged to improve post-myocardial infarction medication adherence.



J Am Heart Assoc: 04 Jan 2021; 10:e016215
Rymer JA, Fonseca E, Bhandary DD, Kumar D, Khan ND, Wang TY
J Am Heart Assoc: 04 Jan 2021; 10:e016215 | PMID: 33342227
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-Term Outcomes Among a Nationwide Cohort of Patients Using an Implantable Cardioverter-Defibrillator: UMBRELLA Study Final Results.

Briongos-Figuero S, García-Alberola A, Rubio J, Segura JM, ... Pérez L,


Background:
Large-scale studies describing modern populations using an implantable cardioverter-defibrillator (ICD) are lacking. We aimed to analyze the incidence of arrhythmia, device interventions, and mortality in a broad spectrum of real-world ICD patients with different heart disorders. Methods and Results The UMBRELLA study is a prospective, multicenter, nationwide study of contemporary patients using an ICD followed up by remote monitoring, with a blinded review of arrhythmic episodes. From November 2005 to November 2017, 4296 patients were followed up. After 46.6±27.3 months, 16 067 episodes of sustained ventricular arrhythmia occurred in 1344 patients (31.3%). Appropriate ICD therapy occurred in 27.3% of study population. Patients with ischemic cardiomyopathy (hazard ratio [HR], 1.51; 95% CI, 1.29-1.78), dilated cardiomyopathy (HR, 1.28; 95% CI, 1.07-1.53), and valvular heart disease (HR, 1.94; 95% CI, 1.43-2.62) exhibited a higher risk of appropriate ICD therapies, whereas patients with hypertrophic cardiomyopathy (HR, 0.72; 95% CI, 0.54-0.96) and Brugada syndrome (HR, 0.25; 95% CI, 0.14-0.45) showed a lower risk. All-cause death was 13.4% at follow-up. Ischemic cardiomyopathy (HR, 3.09; 95% CI, 2.58-5.90), dilated cardiomyopathy (HR, 3.33; 95% CI, 2.18-5.10), and valvular heart disease (HR, 3.97; 95% CI, 2.25-6.99) had the worst prognoses. Delayed high-rate detection was enabled in 39.7% of patients, and single-zone programming occurred in 52.6% of primary prevention patients. Both parameters correlated with lower risk of first appropriate ICD therapy, with no excess risk of mortality. The rate of inappropriate shocks at follow-up was low (6%) and did not differ among type of ICD but was lower in SmartShock-capable devices.
Conclusions:
Irrespective of the cause, contemporary ICD patients with heart failure-related disorders had a similar risk of ICD life-saving interventions and death. Current ICD programming recommendations still need to be implemented. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NTC01561144.



J Am Heart Assoc: 04 Jan 2021; 10:e018108
Briongos-Figuero S, García-Alberola A, Rubio J, Segura JM, ... Pérez L,
J Am Heart Assoc: 04 Jan 2021; 10:e018108 | PMID: 33356406
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Associations of DASH Diet in Pregnancy With Blood Pressure Patterns, Placental Hemodynamics, and Gestational Hypertensive Disorders.

Wiertsema CJ, Mensink-Bout SM, Duijts L, Mulders AGMGJ, Jaddoe VWV, Gaillard R


Background:
The Dietary Approaches to Stop Hypertension (DASH) diet improves blood pressure in nonpregnant populations. We hypothesized that adherence to the DASH diet during pregnancy improves hemodynamic adaptations, leading to a lower risk of gestational hypertensive disorders. Methods and Results We examined whether the DASH diet score was associated with blood pressure, placental hemodynamics, and gestational hypertensive disorders in a population-based cohort study among 3414 Dutch women. We assessed DASH score using food-frequency questionnaires. We measured blood pressure in early-, mid-, and late pregnancy (medians, 95% range: 12.9 [9.8-17.9], 20.4 [16.6-23.2], 30.2 [28.6-32.6] weeks gestation, respectively), and placental hemodynamics in mid- and late pregnancy (medians, 95% range: 20.5 [18.7-23.1], 30.4 [28.5-32.8] weeks gestation, respectively). Information on gestational hypertensive disorders was obtained from medical records. Lower DASH score quartiles were associated with a higher mid pregnancy diastolic blood pressure, compared with the highest quartile (<0.05). No associations were present for early- and late pregnancy diastolic blood pressure and systolic blood pressure throughout pregnancy. Compared with the highest DASH score quartile, the lower DASH score quartiles were associated with a higher mid- and late pregnancy umbilical artery pulsatility index (≤0.05) but not with uterine artery resistance index. No associations with gestational hypertensive disorders were present.
Conclusions:
A higher DASH diet score is associated with lower mid pregnancy diastolic blood pressure and mid- and late pregnancy fetoplacental vascular function but not with uteroplacental vascular function or gestational hypertensive disorders within a low-risk population. Further studies need to assess whether the effects of the DASH diet on gestational hemodynamic adaptations are more pronounced among higher-risk populations.



J Am Heart Assoc: 04 Jan 2021; 10:e017503
Wiertsema CJ, Mensink-Bout SM, Duijts L, Mulders AGMGJ, Jaddoe VWV, Gaillard R
J Am Heart Assoc: 04 Jan 2021; 10:e017503 | PMID: 33356384
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Role of the Variant in Vascular Outcomes in Patients With Intracranial Atherosclerosis.

Kim HJ, Choi EH, Chung JW, Kim JH, ... Kim GM, Bang OY


Background:
The( gene) variant R4810K is a susceptibility allele not only for Moyamoya disease (MMD) but also for intracranial atherosclerosis (ICAS) in East Asian populations. We hypothesized that this variant would affect the distribution of ICAS and recurrence of cerebrovascular events. Methods and Results We conducted a prospective study of patients with ICAS and MMD using high-resolution magnetic resonance imaging andR4810K genotyping. Patients were included in the ICAS group when relevant plaques existed on high-resolution magnetic resonance imagingand in the MMD group when they carried the variant and high-resolution magnetic resonance imaging showed no plaques but characteristic features of MMD. We compared clinical and neuroimaging features of patients with ICAS-+ with patients with ICAS-- and of patients with MMD. Of 477 patients, 238 patients were in the ICAS group and 239 were in the MMD group. Among patients with ICAS, 79 patients (33.2%) were in the ICAS-+ group and 159 (66.8%) in the ICAS-- group. Tandem lesions were significantly more common in the ICAS- group than in the ICAS-- group (40.3% versus 72.2%, <0.001), and their distributions were similar between the ICAS- and MMD groups. The presence of the R4810K variant (hazard ratio [HR], 3.203; 95% CI, 1.149-9.459; =0.026) and tandem lesions (≥3) (HR, 8.315; 95% CI, 1.930-39.607; =0.005) were independently associated with recurrent cerebrovascular events.
Conclusions:
Patients with ICAS carrying theR4810K variant showed clinical and imaging features distinct from patients with ICAS without the variant, suggesting that the R4810K variant plays a role in intracranial atherosclerosis in East Asian patients.



J Am Heart Assoc: 04 Jan 2021; 10:e017660
Kim HJ, Choi EH, Chung JW, Kim JH, ... Kim GM, Bang OY
J Am Heart Assoc: 04 Jan 2021; 10:e017660 | PMID: 33356381
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Collagen Cross-Linking Is Associated With Cardiac Remodeling in Hypertrophic Obstructive Cardiomyopathy.

Bi X, Song Y, Song Y, Yuan J, ... Zhao S, Qiao S


Background:
Collagen cross-linking is covalent bonds among collagen fibers from catalysis of lysyl oxidase (LOX) and advanced glycation end products (AGEs). We aimed to evaluate the formation of enzymatic and nonenzymatic collagen cross-linking and its clinical significance in patients with hypertrophic obstructive cardiomyopathy. Methods and Results Forty-four patients with hypertrophic obstructive cardiomyopathy who underwent surgical myectomy were consecutively enrolled. Cardiovascular magnetic resonance parameters of left atrial/left ventricular function were measured, including peak filling rate (PFR) and early peak emptying rate (PER-E). Total collagen was the sum of soluble and insoluble collagen, which were assessed by collagen assay. The myocardial LOX and AGEs expression were measured by molecular and biochemical methods. Compared with patients without atrial fibrillation, insoluble collagen (=0.018), insoluble collagen fraction (=0.017), and AGEs (=0.039) were higher in patients with atrial fibrillation, whereas LOX expression was similar (=0.494). The insoluble collagen fraction was correlated with PFR index (PFR normalized by left ventricular filling volume) (r=-0.44, =0.005), left atrial diameters (r=0.36, =0.021) and PER-E index (PER-E normalized by left ventricular filling volume) (r=-0.49, =0.001).Myocardial LOX was positively correlated with total collagen (r=0.37, =0.025) and insoluble collagen fraction (r=0.53,  < 0.001), but inversely correlated with PFR index (r=-0.43, =0.006) and PER-E index (r=-0.35, =0.027). In multiple regression analysis, myocardial LOX was independently associated with PFR, while insoluble collagen fraction showed independent correlation with PER-E after adjustment for clinical confounders.
Conclusions:
Collagen cross-linking plays an important role on heart remodeling in hypertrophic obstructive cardiomyopathy. Myocardial LOX expression is independently correlated with left ventricular stiffness, while accumulation of AGEs cross-links might be associated with the occurrence of atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy.



J Am Heart Assoc: 04 Jan 2021; 10:e017752
Bi X, Song Y, Song Y, Yuan J, ... Zhao S, Qiao S
J Am Heart Assoc: 04 Jan 2021; 10:e017752 | PMID: 33356379
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Blood Pressure Visit-to-Visit Variability on Adverse Events in Patients With Nonvalvular Atrial Fibrillation: Subanalysis of the J-RHYTHM Registry.

Kodani E, Inoue H, Atarashi H, Okumura K, ... Origasa H,


Background:
Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit-to-visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J-RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2-year follow-up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all-cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP-SD (<8.20, 8.20-10.49, 10.50-13.19, and ≥13.20 mm Hg), hazard ratios (HRs) for all adverse events were significantly high in the highest quartile compared with the lowest quartile (HR, 2.00, 95% CI, 1.15-3.49, =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36-4.97, =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11-3.07, =0.018 for all-cause death) after adjusting for components of the CHADS-VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP-coefficient of variation was used instead of BP-SD.
Conclusions:
Systolic BP visit-to-visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/; Unique Identifier: UMIN000001569.



J Am Heart Assoc: 04 Jan 2021; 10:e018585
Kodani E, Inoue H, Atarashi H, Okumura K, ... Origasa H,
J Am Heart Assoc: 04 Jan 2021; 10:e018585 | PMID: 33372541
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association Between Frailty and Atrial Fibrillation in Older Adults: The Framingham Heart Study Offspring Cohort.

Orkaby AR, Kornej J, Lubitz SA, McManus DD, ... Benjamin EJ, Preis SR


Background:
Frailty is associated bidirectionally with cardiovascular disease. However, the relations between frailty and atrial fibrillation (AF) have not been fully elucidated. Methods and Results Using the FHS (Framingham Heart Study) Offspring cohort, we sought to examine both the association between frailty (2005-2008) and incident AF through 2016 and the association between prevalent AF and frailty status (2011-2014). Frailty was defined using the Fried phenotype. Models adjusted for age, sex, and smoking. Cox proportional hazards models, adjusted for competing risk of death, assessed the association between prevalent frailty and incident AF. Logistic regression models assessed the association between prevalent AF and new-onset frailty. For the incident AF analysis, we included 2053 participants (56% women; mean age, 69.7±6.9 years). By Fried criteria, 1018 (50%) were robust, 903 (44%) were prefrail, and 132 (6%) were frail. In total, 306 incident cases of AF occurred during an average 9.2 (SD, 3.1) follow-up years. After adjustment, there was no statistically significant association between prevalent frailty status and incident AF (prefrail versus robust: hazard ratio [HR], 1.22 [95% CI, 0.95-1.55]; frail versus robust: HR, 0.92 [95% CI, 0.57-1.47]). At follow-up, there were 111 new cases of frailty. After adjustment, there was no statistically significant association between prevalent AF and new-onset frailty (odds ratio, 0.48 [95% CI, 0.17-1.36]).
Conclusions:
Although a bidirectional association between frailty and cardiovascular disease has been suggested, we did not find evidence of an association between frailty and AF. Our findings may be limited by sample size and should be further explored in other populations.



J Am Heart Assoc: 04 Jan 2021; 10:e018557
Orkaby AR, Kornej J, Lubitz SA, McManus DD, ... Benjamin EJ, Preis SR
J Am Heart Assoc: 04 Jan 2021; 10:e018557 | PMID: 33372538
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association Between Silent Myocardial Infarction and Long-Term Risk of Sudden Cardiac Death.

Cheng YJ, Jia YH, Yao FJ, Mei WY, ... Zhang M, Wu SH


Background:
Although silent myocardial infarction (SMI) is prognostically important, the risk of sudden cardiac death (SCD) among patients with incident SMI is not well established. Methods and Results We examined 2 community-based cohorts: the ARIC (Atherosclerosis Risk in Communities) study (n=13 725) and the CHS (Cardiovascular Health Study) (n=5207). Incident SMI was defined as electrocardiographic evidence of new myocardial infarction during follow-up visits that was not present at the baseline. The primary study end point was physician-adjudicated SCD. In the ARIC study, 513 SMIs, 441 clinically recognized myocardial infarctions (CMIs), and 527 SCD events occurred during a median follow-up of 25.4 years. The multivariable hazard ratios of SMI and CMI for SCD were 5.20 (95% CI, 3.81-7.10) and 3.80 (95% CI, 2.76-5.23), respectively. In the CHS, 1070 SMIs, 632 CMIs, and 526 SCD events occurred during a median follow-up of 12.1 years. The multivariable hazard ratios of SMI and CMI for SCD were 1.70 (95% CI, 1.32-2.19) and 4.08 (95% CI, 3.29-5.06), respectively. The pooled hazard ratios of SMI and CMI for SCD were 2.65 (2.18-3.23) and 3.99 (3.34-4.77), respectively. The risk of SCD associated with SMI is stronger with White individuals, men, and younger age. The population-attributable fraction of SCD was 11.1% for SMI, and SMI was associated with an absolute risk increase of 8.9 SCDs per 1000 person-years. Addition of SMI significantly improved the predictive power for both SCD and non-SCD.
Conclusions:
Incident SMI is independently associated with an increased risk of SCD in the general population. Additional research should address screening for SMI and the role of standard post-myocardial infarction therapy.



J Am Heart Assoc: 04 Jan 2021; 10:e017044
Cheng YJ, Jia YH, Yao FJ, Mei WY, ... Zhang M, Wu SH
J Am Heart Assoc: 04 Jan 2021; 10:e017044 | PMID: 33372536
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Occult Blood in Feces Is Associated With an Increased Risk of Ischemic Stroke and Myocardial Infarction: A Nationwide Population Study.

Moon JM, Lee HJ, Han K, Kim DH, ... Im JP, Kim JS


Background:
Although occult hemoglobin in feces is universally valued as a screening tool for colorectal cancer (CRC), only few studies investigated the clinical meaning of fecal immunochemical test (FIT) in other diseases. We evaluated the clinical utility of FIT in patients with cardiovascular diseases (namely, ischemic stroke and myocardial infarction [MI]). Methods and Results Using the National Health Insurance database, participants (aged >50 years) with CRC screening records from 2009 to 2012 were screened and followed up. Subjects with a history of cardiovascular diseases and CRC were excluded. Ischemic stroke, MI, and other comorbidities were defined by(), codes. Age, sex, smoking, alcohol consumption, regular exercise, diabetes mellitus, hypertension, dyslipidemia, and body mass index were adjusted in a multivariate analysis. A total of 6 277 446 subjects were eligible for analysis. During the mean 6.79 years of follow-up, 168 570 participants developed ischemic stroke, 105 983 developed MI, and 11 253 deaths were observed. A multivariate-adjusted model revealed that the risk of ischemic stroke was higher in the FIT-positive population (adjusted hazard ratio [HR], 1.09; 95% CI, 1.07-1.11). Similarly, FIT-positive subjects were at an increased risk of MI (adjusted HR, 1.09; 95% CI, 1.06-1.12). Moreover, increased all-cause mortality was observed in the FIT-positive population (adjusted HR, 1.15; 95% CI, 1.07-1.23). The increased risk remained consistent in the stratified analysis on anemia and CRC status.
Conclusions:
Positive FIT findings were associated with ischemic stroke, MI, and mortality. Occult blood in feces may offer more clinical information than its well-known conventional role in CRC screening.



J Am Heart Assoc: 04 Jan 2021; 10:e017783
Moon JM, Lee HJ, Han K, Kim DH, ... Im JP, Kim JS
J Am Heart Assoc: 04 Jan 2021; 10:e017783 | PMID: 33372535
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension.

Sun X, Zhou M, Wen G, Huang Y, ... Lu Y, Cai J


Background:
ADRB1 (adrenergic receptor beta 1) responds to neuroendocrine stimulations, which have great implications in hypertension. GRK2 (G protein-coupled receptor kinase 2) is an essential regulator for many G protein-coupled receptors and subsequent cell signaling cascades, but its role as a regulator of ADRB1 and associated cardiac hypertrophy in hypertension remains to be elucidated. Methods and Results In this study, we found the expressions of GRK2 and ADRB1 in peripheral blood mononuclear cells were positively associated with blood pressure levels in hypertensive patients and with their expression in heart. In vitro evidence showed a direct interaction in ADRB1 and GRK2 and genetic depletion of GRK2 blocks epinephrine-induced upregulation of hypertrophic and fibrotic genes in cardiomyocytes. Meanwhile, we discovered a selective serotonin reuptake inhibitor paroxetine specifically blockades GRK2 and ADRB1 interaction. In vivo, paroxetine treatment ameliorates hypertension-induced cardiac hypertrophy, dysfunction, and fibrosis in animal models. We found that paroxetine suppressed sympathetic overdrive and increased the adrenergic receptor sensitivity to catecholamines. Paroxetine treatment also blocks epinephrine-induced upregulation of hypertrophic and fibrotic genes as well as ADRB1 internalization in cardiomyocytes. Coadministration of paroxetine further potentiates metoprolol-induced reductions in blood pressure and heart rate, further attenuating cardiac hypertrophy in spontaneously hypertensive rats. Furthermore, in patients with hypertension accompanied with depression, we observed that cardiac remodeling was less severe in those with paroxetine treatment compared with those with other types of anti-depressive agents.
Conclusions:
Paroxetine promotes ADRB1 sensitivity and attenuates cardiac hypertrophy partially via blocking GRK2-mediated ADRB1 activation and internalization in the context of hypertension.



J Am Heart Assoc: 04 Jan 2021; 10:e016364
Sun X, Zhou M, Wen G, Huang Y, ... Lu Y, Cai J
J Am Heart Assoc: 04 Jan 2021; 10:e016364 | PMID: 33372534
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Proteomic Signatures of Lifestyle Risk Factors for Cardiovascular Disease: A Cross-Sectional Analysis of the Plasma Proteome in the Framingham Heart Study.

Corlin L, Liu C, Lin H, Leone D, ... Larson MG, Vasan RS


Background:
Proteomic biomarkers related to cardiovascular disease risk factors may offer insights into the pathogenesis of cardiovascular disease. We investigated whether modifiable lifestyle risk factors for cardiovascular disease are associated with distinctive proteomic signatures. Methods and Results We analyzed 1305 circulating plasma proteomic biomarkers (assayed using the SomaLogic platform) in 897 FHS (Framingham Heart Study) Generation 3 participants (mean age 46±8 years; 56% women; discovery sample) and 1121 FOS (Framingham Offspring Study) participants (mean age 52 years; 54% women; validation sample). Participants were free of hypertension, diabetes mellitus, and clinical cardiovascular disease. We used linear mixed effects models (adjusting for age, sex, body mass index, and family structure) to relate levels of each inverse-log transformed protein to 3 lifestyle factors (ie, smoking, alcohol consumption, and physical activity). A Bonferroni-adjustedvalue indicated statistical significance (based on number of proteins and traits tested, <4.2×10 in the discovery sample; <6.85×10 in the validation sample). We observed statistically significant associations of 60 proteins with smoking (37/40 top proteins validated in FOS), 30 proteins with alcohol consumption (23/30 proteins validated), and 5 proteins with physical activity (2/3 proteins associated with the physical activity index validated). We assessed the associations of protein concentrations with previously identified genetic variants (protein quantitative trait loci) linked to lifestyle-related disease traits in the genome-wide-association study catalogue. The protein quantitative trait loci were associated with coronary artery disease, inflammation, and age-related mortality.
Conclusions:
Our cross-sectional study from a community-based sample elucidated distinctive sets of proteins associated with 3 key lifestyle factors.



J Am Heart Assoc: 04 Jan 2021; 10:e018020
Corlin L, Liu C, Lin H, Leone D, ... Larson MG, Vasan RS
J Am Heart Assoc: 04 Jan 2021; 10:e018020 | PMID: 33372532
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Five-Year Risk of Acute Myocardial Infarction After Acute Ischemic Stroke in Korea.

Lee KJ, Kim SE, Kim JY, Kang J, ... Bae HJ,


Background:
The long-term incidence of acute myocardial infarction (AMI) in patients with acute ischemic stroke (AIS) has not been well defined in large cohort studies of various race-ethnic groups. Methods and Results A prospective cohort of patients with AIS who were registered in a multicenter nationwide stroke registry (CRCS-K [Clinical Research Collaboration for Stroke in Korea] registry) was followed up for the occurrence of AMI through a linkage with the National Health Insurance Service claims database. The 5-year cumulative incidence and annual risk were estimated according to predefined demographic subgroups, stroke subtypes, a history of coronary heart disease (CHD), and known risk factors of CHD. A total of 11 720 patients with AIS were studied. The 5-year cumulative incidence of AMI was 2.0%. The annual risk was highest in the first year after the index event (1.1%), followed by a much lower annual risk in the second to fifth years (between 0.16% and 0.27%). Among subgroups, annual risk in the first year was highest in those with a history of CHD (4.1%) compared with those without a history of CHD (0.8%). The small-vessel occlusion subtype had a much lower incidence (0.8%) compared with large-vessel occlusion (2.2%) or cardioembolism (2.4%) subtypes. In the multivariable analysis, history of CHD (hazard ratio, 2.84; 95% CI, 2.01-3.93) was the strongest independent predictor of AMI after AIS.
Conclusions:
The incidence of AMI after AIS in South Korea was relatively low and unexpectedly highest during the first year after stroke. CHD was the most substantial risk factor for AMI after stroke and conferred an approximate 5-fold greater risk.



J Am Heart Assoc: 04 Jan 2021; 10:e018807
Lee KJ, Kim SE, Kim JY, Kang J, ... Bae HJ,
J Am Heart Assoc: 04 Jan 2021; 10:e018807 | PMID: 33372531
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ambient Particle Components and Newborn Blood Pressure in Project Viva.

Zanobetti A, Coull BA, Luttmann-Gibson H, van Rossem L, ... Koutrakis P, Gold DR


Background:
Both elemental metals and particulate air pollution have been reported to influence adult blood pressure (BP). The aim of this study is to examine which elemental components of particle mass with diameter ≤2.5 μm (PM) are responsible for previously reported associations between PM and neonatal BP. Methods and Results We studied 1131 mother-infant pairs in Project Viva, a Boston-area prebirth cohort. We measured systolic BP (SBP) and diastolic BP (DBP) at a mean age of 30 hours. We calculated average exposures during the 2 to 7 days before birth for the PM components-aluminum, arsenic, bromine, sulfur, copper, iron, zinc, nickel, vanadium, titanium, magnesium, potassium, silicon, sodium, chlorine, calcium, and lead-measured at the Harvard supersite. Adjusting for covariates and PM, we applied regression models to examine associations between PM components and median SBP and DBP, and used variable selection methods to select which components were more strongly associated with each BP outcome. We found consistent results with higher nickel associated with significantly higher SBP and DBP, and higher zinc associated with lower SBP and DBP. For an interquartile range increase in the log Z score (1.4) of nickel, we found a 1.78 mm Hg (95% CI, 0.72-2.84) increase in SBP and a 1.30 (95% CI, 0.54-2.06) increase in DBP. Increased zinc (interquartile range log Z score 1.2) was associated with decreased SBP (-1.29 mm Hg; 95% CI, -2.09 to -0.50) and DBP (-0.85 mm Hg; 95% CI: -1.42 to -0.29).
Conclusions:
Our findings suggest that prenatal exposures to particulate matter components, and particularly nickel, may increase newborn BP.



J Am Heart Assoc: 04 Jan 2021; 10:e016935
Zanobetti A, Coull BA, Luttmann-Gibson H, van Rossem L, ... Koutrakis P, Gold DR
J Am Heart Assoc: 04 Jan 2021; 10:e016935 | PMID: 33372530
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Excess Mortality and Undertreatment of Women With Severe Aortic Stenosis.

Tribouilloy C, Bohbot Y, Rusinaru D, Belkhir K, ... Maréchaux S, Enriquez Sarano M


Background:
Although women represent half of the population burden of aortic stenosis (AS), little is known whether sex affects the presentation, management, and outcome of patients with AS. Methods and Results In a cohort of 2429 patients with severe AS (49.5% women) we aimed to evaluate 5-year excess mortality and performance of aortic valve replacement (AVR) stratified by sex. At presentation, women were older (<0.001), with less comorbidities (=0.030) and more often symptomatic (=0.007) than men. Women had smaller aortic valve area (<0.001) than men but similar mean transaortic pressure gradient (=0.18). The 5-year survival was lower compared with expected survival, especially for women (62±2% versus 71% for women and 69±1% versus 71% for men). Despite longer life expectancy in women than men, women had lower 5-year survival than men (66±2% [expected-75%] versus 68±2% [expected-70%], <0.001) after matching for age. Overall, 5-year AVR incidence was 79±2% for men versus 70±2% for women (<0.001) with male sex being independently associated with more frequent early AVR performance (odds ratio, 1.49; 1.18-1.97). After age matching, women remained more often symptomatic (=0.004) but also displayed lower AVR use (64.4% versus 69.1%; =0.018).
Conclusions:
Women with severe AS are diagnosed at later ages and have more symptoms than men. Despite prevalent symptoms, AVR is less often performed in women and 5-year excess mortality is noted in women versus men, even after age matching. These imbalances should be addressed to ensure that both sexes receive equivalent care for severe AS.



J Am Heart Assoc: 04 Jan 2021; 10:e018816
Tribouilloy C, Bohbot Y, Rusinaru D, Belkhir K, ... Maréchaux S, Enriquez Sarano M
J Am Heart Assoc: 04 Jan 2021; 10:e018816 | PMID: 33372529
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Genetic Liability to Depression and Risk of Coronary Artery Disease, Myocardial Infarction, and Other Cardiovascular Outcomes.

Lu Y, Wang Z, Georgakis MK, Lin H, Zheng L


Background:
Observational studies have indicated that depression is associated with coronary artery disease (CAD) and myocardial infarction. Nevertheless, causal associations between depression and cardiovascular diseases remain controversial. Hence, we conducted a Mendelian randomization and mediation analysis to evaluate the associations of depression-related genetic variants with CAD and myocardial infarction. Methods and Results Summary statistics from genome-wide association studies of depression (807 553 individuals), and CAD (60 801 cases, including 43 676 with myocardial infarction, and 123 504 controls) were used. We pooled Mendelian randomization estimates using a fixed-effects inverse-variance weighted meta-analysis and multivariable Mendelian randomization. The mediation effects of potential cardiovascular risk factors on depression-CAD and myocardial infarction risk were investigated by using mediation analysis. We also explored the relationship of genetic liability to depression with heart failure, atrial fibrillation, and ischemic stroke. Genetic liability to depression was associated with higher CAD (odds ratio [OR], 1.14; 95% CI, 1.06-1.24; =1.0×10) and myocardial infarction (OR, 1.21; 95% CI, 1.11-1.33; =4.8×10) risks. Results were consistent in all sensitivity analyses. Type 2 diabetes mellitus and smoking demonstrated significant mediation effects. Furthermore, our Mendelian randomization analyses revealed that the genetic liability to depression was associated with higher risks of heart failure and small vessel stroke.
Conclusions:
Genetic liability to depression is associated with higher CAD and myocardial infarction risks, partly mediated by type 2 diabetes mellitus and smoking. The potential preventive value of depression treatment on cardiovascular diseases should be investigated in the future.



J Am Heart Assoc: 04 Jan 2021; 10:e017986
Lu Y, Wang Z, Georgakis MK, Lin H, Zheng L
J Am Heart Assoc: 04 Jan 2021; 10:e017986 | PMID: 33372528
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Treatment With Cardiovascular Medications: Prognosis in Patients With Myocardial Injury.

Kadesjö E, Roos A, Siddiqui AJ, Sartipy U, Holzmann MJ


Background:
There is no clinical guidance on treatment in patients with non-ischemic myocardial injury and type 2 myocardial infarction (T2MI). Methods and Results In a cohort of 22 589 patients in the emergency department at Karolinska University Hospital in Sweden during 2011 to 2014 we identified 3853 patients who were categorized into either type 1 myocardial infarction, T2MI, non-ischemic acute and chronic myocardial injury. Data from all dispensed prescriptions within 180 days of the visit to the emergency department were obtained concerning β-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, statins, and platelet inhibitors. We estimated adjusted hazard ratios (HR) with 95% CI for all-cause mortality in relationship to the number of medications (categorized into 0-1 [referent], 2-3 and 4 medications) in the groups of myocardial injury. In patients with T2MI, treatment with 2 to 3 and 4 medications was associated with a 50% and 56% lower mortality, respectively (adjusted HR [95% CI], 0.50 [0.25-1.01], and 0.43 [0.19-0.96]), while corresponding associations in patients with acute myocardial injury were 24% and 29%, respectively (adjusted HR [95% CI], 0.76 [0.59-0.99] and 0.71 [0.5-1.02]), and in patients with chronic myocardial injury 27% and 37%, respectively (adjusted HR [95% CI], 0.73 [0.58-0.92] and 0.63 [0.46-0.87]).
Conclusions:
Patients with T2MI and non-ischemic acute or chronic myocardial injury are infrequently prescribed common cardiovascular medications compared with patients with type 1 myocardial infarction. However, treatment with guideline recommended drugs in patients with T2MI and acute or chronic myocardial injury is associated with a lower risk of death after adjustment for confounders.



J Am Heart Assoc: 04 Jan 2021; 10:e017239
Kadesjö E, Roos A, Siddiqui AJ, Sartipy U, Holzmann MJ
J Am Heart Assoc: 04 Jan 2021; 10:e017239 | PMID: 33372527
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association Between Low Muscle Mass and Prognosis of Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

Kim CH, Rhee TM, Woo Park K, Soon Park C, ... Koo BK, Kim HS


Background:
Low muscle mass has been associated with poor prognosis in certain chronic diseases, but its clinical significance in patients with coronary artery disease is unclear. We assessed the clinical significance of 2 easily measured surrogate markers of low muscle mass: the ratio of serum creatinine to serum cystatin C (Scr/Scys), and the ratio of estimated glomerular filtration rate by Scys to Scr (eGFRcys/eGFRcr). Methods and Results Patients with coronary artery disease undergoing percutaneous coronary intervention were prospectively enrolled from a single tertiary center, and Scr and Scys levels were simultaneously measured at admission. Best cut-off values for Scr/Scys and eGFRcys/eGFRcr to discriminate 3-year mortality were determined; 1.0 for men and 0.8 for women in Scr/Scys, and 1.1 for men and 1.0 for women in eGFRcys/eGFRcr. The prognostic values on 3-year mortality and the additive values of 2 markers on the predictive model were compared. In 1928 patients enrolled (mean age 65.2±9.9 years, 70.8% men), the risk of 3-year mortality increased proportionally according to the decrease of the surrogate markers. Both Scr/Scys- and eGFRcys/eGFRcr-based low muscle mass groups showed significantly higher risk of death, after adjusting for possible confounders. They also increased predictive power of the mortality prediction model. Low Scr/Scys values were associated with high mortality rate in patients who were ≥65 years, nonobese, male, had renal dysfunction at baseline, and presented with acute myocardial infarction.
Conclusions:
Serum surrogate markers of muscle mass, Scr/Scys, and eGFRcys/eGFRcr may have clinical significance for detecting patients with coronary artery disease at high risk for long-term mortality.



J Am Heart Assoc: 04 Jan 2021; 10:e018554
Kim CH, Rhee TM, Woo Park K, Soon Park C, ... Koo BK, Kim HS
J Am Heart Assoc: 04 Jan 2021; 10:e018554 | PMID: 33372526
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

New Cardiomyokine Reduces Myocardial Ischemia/Reperfusion Injury by PI3K-AKT Pathway Via a Putative KDEL-Receptor Binding.

Maciel L, de Oliveira DF, Mesquita F, Souza HADS, ... Nascimento JHM, Foguel D


Background:
CDNF (cerebral dopamine neurotrophic factor) belongs to a new family of neurotrophic factors that exert systemic beneficial effects beyond the brain. Little is known about the role of CDNF in the cardiac context. Herein we investigated the effects of CDNF under endoplasmic reticulum-stress conditions using cardiomyocytes (humans and mice) and isolated rat hearts, as well as in rats subjected to ischemia/reperfusion (I/R). Methods and Results We showed that CDNF is secreted by cardiomyocytes stressed by thapsigargin and by isolated hearts subjected to I/R. Recombinant CDNF (exoCDNF) protected human and mouse cardiomyocytes against endoplasmic reticulum stress and restored the calcium transient. In isolated hearts subjected to I/R, exoCDNF avoided mitochondrial impairment and reduced the infarct area to 19% when administered before ischemia and to 25% when administered at the beginning of reperfusion, compared with an infarct area of 42% in the untreated I/R group. This protection was completely abrogated by AKT (protein kinase B) inhibitor. Heptapeptides containing the KDEL sequence, which binds to the KDEL-R (KDEL receptor), abolished exoCDNF beneficial effects, suggesting the participation of KDEL-R in this cardioprotection. CDNF administered intraperitoneally to rats decreased the infarct area in an in vivo model of I/R (from an infarct area of ≈44% in the I/R group to an infarct area of ≈27%). Moreover, a shorter version of CDNF, which lacks the last 4 residues (CDNF-ΔKTEL) and thus allows CDNF binding to KDEL-R, presented no cardioprotective activity in isolated hearts.
Conclusions:
This is the first study to propose CDNF as a new cardiomyokine that induces cardioprotection via KDEL receptor binding and PI3K/AKT activation.



J Am Heart Assoc: 04 Jan 2021; 10:e019685
Maciel L, de Oliveira DF, Mesquita F, Souza HADS, ... Nascimento JHM, Foguel D
J Am Heart Assoc: 04 Jan 2021; 10:e019685 | PMID: 33372525
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Relationship of Circulating Endothelial Cells With Obesity and Cardiometabolic Risk Factors in Children and Adolescents.

Soltero EG, Solovey AN, Hebbel RP, Palzer EF, ... Evanoff NG, Kelly AS


Background:
Circulating endothelial cells (CECs) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well described. Methods and Results Youth in this study (N=271; aged 8-20 years) were classified into normal weight (body mass index [BMI] percentage <85th; n=114), obesity (BMI percentage ≥95th to <120% of the 95th; n=63), and severe obesity (BMI percentage ≥120% of the 95th; n=94) catagories. CEC enumeration was determined using immunohistochemical examination of buffy coat smears and activated CEC (percentage of vascular cell adhesion molecule-1 expression) was assessed using immunofluorescent staining. Cardiovascular risk factors included measures of body composition, blood pressure, glucose, insulin, lipid profile, C-reactive protein, leptin, adiponectin, oxidized low-density lipoprotein cholesterol, carotid artery intima-media thickness, and pulse wave velocity. Linear regression models examined associations between CEC number and activation with BMI and cardiovascular risk factors. CEC number did not differ among BMI classes (>0.05). Youth with severe obesity had a higher degree of CEC activation compared with normal weight youth (8.3%; 95% CI, 1.1-15.6 [=0.024]). Higher CEC number was associated with greater body fat percentage (0.02 per percentage; 95% CI, 0.00-0.03 [=0.020]) and systolic blood pressure percentile (0.01 per percentage; 95% CI, 0.00-0.01 [=0.035]). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg; 95% CI, 0.4-10.9 [=0.034]) and non-high-density lipoprotein cholesterol (0.11% per mg/dL; 95% CI, 0.01-0.21 [=0.039]).
Conclusions:
Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.



J Am Heart Assoc: 04 Jan 2021; 10:e018092
Soltero EG, Solovey AN, Hebbel RP, Palzer EF, ... Evanoff NG, Kelly AS
J Am Heart Assoc: 04 Jan 2021; 10:e018092 | PMID: 33372524
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-Term PM Exposure and Risks of Ischemic Heart Disease and Stroke Events: Review and Meta-Analysis.

Alexeeff SE, Liao NS, Liu X, Van Den Eeden SK, Sidney S


Background:
Fine particulate matter <2.5 µm in diameter (PM) has known effects on cardiovascular morbidity and mortality. However, no study has quantified and compared the risks of incident myocardial infarction, incident stroke, ischemic heart disease (IHD) mortality, and cerebrovascular mortality in relation to long-term PM exposure. Methods and Results We sought to quantitatively summarize studies of long-term PM exposure and risk of IHD and stroke events by conducting a review and meta-analysis of studies published by December 31, 2019. The main outcomes were myocardial infarction, stroke, IHD mortality, and cerebrovascular mortality. Random effects meta-analyses were used to estimate the combined risk of each outcome among studies. We reviewed 69 studies and included 42 studies in the meta-analyses. In meta-analyses, we found that a 10-µg/m increase in long-term PM exposure was associated with an increased risk of 23% for IHD mortality (95% CI, 15%-31%), 24% for cerebrovascular mortality (95% CI, 13%-36%), 13% for incident stroke (95% CI, 11%-15%), and 8% for incident myocardial infarction (95% CI, -1% to 18%). There were an insufficient number of studies of recurrent stroke and recurrent myocardial infarction to conduct meta-analyses.
Conclusions:
Long-term PM exposure is associated with increased risks of IHD mortality, cerebrovascular mortality, and incident stroke. The relationship with incident myocardial infarction is suggestive of increased risk but not conclusive. More research is needed to understand the relationship with recurrent events.



J Am Heart Assoc: 04 Jan 2021; 10:e016890
Alexeeff SE, Liao NS, Liu X, Van Den Eeden SK, Sidney S
J Am Heart Assoc: 04 Jan 2021; 10:e016890 | PMID: 33381983
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Temporal Trends, Predictors, and Outcomes of Acute Ischemic Stroke in Acute Myocardial Infarction in the United States.

Aggarwal G, Patlolla SH, Aggarwal S, Cheungpasitporn W, ... Cohen M, Vallabhajosyula S


Background:
There are limited contemporary data prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI). Methods and Results Adult (>18 years) AMI admissions using the National Inpatient Sample database (2000-2017) were evaluated for in-hospital AIS. Outcomes of interest included in-hospital mortality, hospitalization costs, length of stay, discharge disposition, and use of tracheostomy and percutaneous endoscopic gastrostomy. The discharge destination was used to classify survivors into good and poor outcomes. Of a total 11 622 528 AMI admissions, 183 896 (1.6%) had concomitant AIS. As compared with 2000, in 2017, AIS rates increased slightly among ST-segment-elevation AMI (adjusted odds ratio, 1.10 [95% CI, 1.04-1.15]) and decreased in non-ST-segment-elevation AMI (adjusted odds ratio, 0.47 [95% CI, 0.46-0.49]) admissions (<0.001). Compared with those without, the AIS cohort was on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias. The AMI-AIS admissions received less frequent coronary angiography (46.9% versus 63.8%) and percutaneous coronary intervention (22.7% versus 41.8%) (<0.001). The AIS cohort had higher in-hospital mortality (16.4% versus 6.0%; adjusted odds ratio, 1.75 [95% CI, 1.72-1.78]; <0.001), longer hospital length of stay, higher hospitalization costs, greater use of tracheostomy and percutaneous endoscopic gastrostomy, and less frequent discharges to home (all <0.001). Among AMI-AIS survivors (N=153 318), 57.3% had a poor functional outcome at discharge with relatively stable temporal trends.
Conclusions:
AIS is associated with significantly higher in-hospital mortality and poor functional outcomes in AMI admissions.



J Am Heart Assoc: 04 Jan 2021:e017693; epub ahead of print
Aggarwal G, Patlolla SH, Aggarwal S, Cheungpasitporn W, ... Cohen M, Vallabhajosyula S
J Am Heart Assoc: 04 Jan 2021:e017693; epub ahead of print | PMID: 33399018
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Determinants of Morbidity and Mortality Associated With Isolated Tricuspid Valve Surgery.

Kawsara A, Alqahtani F, Nkomo VT, Eleid MF, ... Crestanello JA, Alkhouli M


Background:
Whether the poor outcomes of isolated tricuspid valve surgery are related to the operation itself or to certain patient characteristics including late referral is unknown. Methods and Results Adult patients who underwent isolated tricuspid valve surgery were identified in the Nationwide Readmissions Database (2016-2017). Patients who had redo tricuspid valve surgery, endocarditis, or congenital heart disease were excluded. Multivariable logistic regression was performed to identify contributors to postoperative mortality. A total of 1513 patients were included (mean age 55.7±16.6 years, 49.6% women). Surrogates of late referral were frequent: 41% of patients were admitted with decompensated heart failure, 44.3% had a nonelective surgery status, 16.8% had advanced liver disease, and 31% had an unplanned hospitalization in the prior 90 days. The operation was performed on day 0 to 1 of the hospitalization in only 50% of patients, and beyond day 10 in 22% of patients. In-hospital mortality occurred in 8.7% of patients. Median length of stay was 14 days (7-35 days), and median cost was $87 223 ($43 122-$200 872). In multivariable logistic regression analysis, surrogates for late referrals (acute heart failure decompensation, nonelective surgery status, or advanced liver disease) were the strongest predictors of in-hospital mortality (odds ratio [OR], 4.75; 95% CI, 2.74-8.25 [<0.001]). This was also consistent in a second model incorporating unplanned hospitalizations in the 90 days before surgery as a surrogate for late referral (OR, 5.50; 95% CI, 2.28-10.71 [<0.001]).
Conclusions:
The poor outcomes of isolated tricuspid valve surgery may be largely explained by the late referral for intervention. Studies are needed to determine the role of early intervention for severe isolated tricuspid regurgitation.



J Am Heart Assoc: 04 Jan 2021:e018417; epub ahead of print
Kawsara A, Alqahtani F, Nkomo VT, Eleid MF, ... Crestanello JA, Alkhouli M
J Am Heart Assoc: 04 Jan 2021:e018417; epub ahead of print | PMID: 33399012
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Trends, Management, and Outcomes of Acute Myocardial Infarction Hospitalizations With In-Hospital-Onset Versus Out-of-Hospital Onset: The ARIC Study.

Caughey MC, Arora S, Qamar A, Chunawala Z, ... Smith SC, Matsushita K


Background:
Acute myocardial infarction (AMI) with in-hospital onset (AMI-IHO) has poor prognosis but is clinically underappreciated. Whether its occurrence has changed over time is uncertain. Methods and Results Since 1987, the ARIC (Atherosclerosis Risk in Communities) study has conducted adjudicated surveillance of AMI hospitalizations in 4 US communities. Our analysis was limited to patients aged 35 to 74 years with symptomatic AMI. Patients with symptoms initiating after hospital arrival were considered AMI-IHO. A total of 26 678 weighted hospitalizations (14 276 unweighted hospitalizations) for symptomatic AMI were identified from 1995 to 2014, with 1137 (4%) classified as in-hospital onset. The population incidence rate of AMI-IHO increased in the 4 ARIC communities from 1995 through 2004 to 2005 through 2014 (12.7-16.9 events per 100 000 people;for 20-year trend <0.0001), as did the proportion of AMI hospitalizations with in-hospital onset (3.7%-6.1%;for 20-year trend =0.03). The 10-year proportions were stable for patients aged 35 to 64 years (3.0%-3.4%;for 20-year trend =0.3) but increased for patients aged ≥65 years (4.6%-7.8%;for 20-year trend =0.008;for interaction by age group =0.04). AMI-IHO had a more severe clinical course with lower use of AMI therapies or invasive strategies and higher in-hospital (7% versus 3%), 28-day (19% versus 5%), and 1-year (29% versus 12%) mortality (0.0001 for all).
Conclusions:
In this population-based community surveillance, AMI-IHO increased from 2005 to 2014, particularly among older patients. Quality initiatives to improve recognition and management of AMI-IHO should be especially focused on hospitalized patients aged >65.



J Am Heart Assoc: 04 Jan 2021:e018414; epub ahead of print
Caughey MC, Arora S, Qamar A, Chunawala Z, ... Smith SC, Matsushita K
J Am Heart Assoc: 04 Jan 2021:e018414; epub ahead of print | PMID: 33399008
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival.

Bermejo J, González-Mansilla A, Mombiela T, Fernández AI, ... Fernández-Avilés F,


Background:
The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long-term follow-up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32-44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18-26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow-up of 4.5 years, 91 deaths accounted for 4.21 higher-than-expected mortality in the age-matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance-either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six-month changes in the composite clinical score and in the 6-minute walk test distance were related to survival.
Conclusions:
Persistent valvular heart disease-pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.



J Am Heart Assoc: 04 Jan 2021:e019949; epub ahead of print
Bermejo J, González-Mansilla A, Mombiela T, Fernández AI, ... Fernández-Avilés F,
J Am Heart Assoc: 04 Jan 2021:e019949; epub ahead of print | PMID: 33399006
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Changes in Cardiomyocyte Cell Cycle and Hypertrophic Growth During Fetal to Adult in Mammals.

Bishop SP, Zhou Y, Nakada Y, Zhang J

The failure of adult cardiomyocytes to reproduce themselves to repair an injury results in the development of severe cardiac disability leading to death in many cases. The quest for an understanding of the inability of cardiac myocytes to repair an injury has been ongoing for decades with the identification of various factors which have a temporary effect on cell-cycle activity. Fetal cardiac myocytes are continuously replicating until the time that the developing fetus reaches a stage of maturity sufficient for postnatal life around the time of birth. Recent reports of the ability for early neonatal mice and pigs to completely repair after the severe injury has stimulated further study of the regulators of the cardiomyocyte cell cycle to promote replication for the remuscularization of injured heart. In all mammals just before or after birth, single-nucleated hyperplastically growing cardiomyocytes, 1X2N, undergo ≥1 additional DNA replications not followed by cytokinesis, resulting in cells with ≥2 nuclei or as in primates, multiple DNA replications (polyploidy) of 1 nucleus, 2X2(+)N or 1X4(+)N. All further growth of the heart is attributable to hypertrophy of cardiomyocytes. Animal studies ranging from zebrafish with 100% 1X2N cells in the adult to some strains of mice with up to 98% 2X2N cells in the adult and other species with variable ratios of 1X2N and 2X2N cells are reviewed relative to the time of conversion. Various structural, physiologic, metabolic, genetic, hormonal, oxygenation, and other factors that play a key role in the inability of post-neonatal and adult myocytes to undergo additional cytokinesis are also reviewed.



J Am Heart Assoc: 04 Jan 2021:e017839; epub ahead of print
Bishop SP, Zhou Y, Nakada Y, Zhang J
J Am Heart Assoc: 04 Jan 2021:e017839; epub ahead of print | PMID: 33399005
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model.

Nishinarita R, Niwano S, Niwano H, Nakamura H, ... Sakagami H, Ako J


Background:
Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium-glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate. Methods and Results The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model. The study included 12 beagle dogs, with 10 receiving continuous rapid atrial pacing and 2 acting as the nonpacing group. The 10 dogs that received continuous rapid atrial pacing for 3 weeks were subdivided as follows: pacing control group (n=5) and pacing+CAN (3 mg/kg per day) group (n=5). The atrial effective refractory period, conduction velocity, and AF inducibility were evaluated weekly through atrial epicardial wires. After the protocol, atrial tissues were sampled for histological examination. The degree of reactive oxygen species expression was evaluated by dihydroethidium staining. The atrial effective refractory period reduction was smaller (=0.06) and the degree of conduction velocity decrease was smaller in the pacing+CAN group compared with the pacing control group (=0.009). The AF inducibility gradually increased in the pacing control group, but such an increase was suppressed in the pacing+CAN group (=0.011). The pacing control group exhibited interstitial fibrosis and enhanced oxidative stress, which were suppressed in the pacing+CAN group.
Conclusions:
CAN and possibly other SGLT2 inhibitors might be useful for preventing AF and suppressing the promotion of atrial remodeling as an AF substrate.



J Am Heart Assoc: 04 Jan 2021:e017483; epub ahead of print
Nishinarita R, Niwano S, Niwano H, Nakamura H, ... Sakagami H, Ako J
J Am Heart Assoc: 04 Jan 2021:e017483; epub ahead of print | PMID: 33399004
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Multicohort Metabolomics Analysis Discloses 9-Decenoylcarnitine to Be Associated With Incident Atrial Fibrillation.

Lind L, Salihovic S, Sundström J, Broeckling CD, ... Fall T, Ärnlöv J


Background:
The molecular mechanisms involved in atrial fibrillation are not well known. We used plasma metabolomics to investigate if we could identify novel biomarkers and pathophysiological pathways of incident atrial fibrillation. Methods and Results We identified 200 endogenous metabolites in plasma/serum by nontargeted ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry in 3 independent population-based samples (TwinGene, n=1935, mean age 68, 43% females; PIVUS [Prospective Investigation of the Vasculature in Uppsala Seniors], n=897, mean age 70, 51% females; and ULSAM [Uppsala Longitudinal Study of Adult Men], n=1118, mean age 71, all males), with available data on incident atrial fibrillation during 10 to 12 years of follow-up. A meta-analysis of ULSAM and PIVUS was used as a discovery sample and TwinGene was used for validation. In PIVUS, we also investigated associations between metabolites of interest and echocardiographic indices of myocardial geometry and function. Genome-wide association studies were performed in all 3 cohorts for metabolites of interest. In the meta-analysis of PIVUS and ULSAM with 430 incident cases, 4 metabolites were associated with incident atrial fibrillation at a false discovery rate <5%. Of those, only 9-decenoylcarnitine was associated with incident atrial fibrillation and replicated in the TwinGene sample (288 cases) following adjustment for traditional risk factors (hazard ratio, 1.24 per unit; 95% CI, 1.06-1.45, =0.0061). A meta-analysis of all 3 cohorts disclosed another 4 significant metabolites. In PIVUS, 9-decenoylcarnitine was related to left atrium size and left ventricular mass. A Mendelian randomization analysis did not suggest a causal role of 9-decenoylcarnitine in atrial fibrillation.
Conclusions:
A nontargeted metabolomics analysis disclosed 1 novel replicated biomarker for atrial fibrillation, 9-Decenoylcarnitine, but this acetylcarnitine is likely not causally related to atrial fibrillation.



J Am Heart Assoc: 04 Jan 2021:e017579; epub ahead of print
Lind L, Salihovic S, Sundström J, Broeckling CD, ... Fall T, Ärnlöv J
J Am Heart Assoc: 04 Jan 2021:e017579; epub ahead of print | PMID: 33399003
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Race, Body Mass Index, and the Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

Singleton MJ, German CA, Carnethon M, Soliman EZ, Bertoni AG, Yeboah J


Background:
Higher body mass index (BMI) is associated with increased risk of incident atrial fibrillation (AF), but it is not known whether this relationship varies by race/ethnicity. Methods and Results Eligible participants (6739) from MESA (Multi-Ethnic Study of Atherosclerosis) were surveilled for incident AF using MESA hospital surveillance, scheduled MESA study ECG, and Medicare claims data. After a median 13.8 years of follow-up, 970 participants (14.4%) had incident AF. With BMI modeled categorically in a Cox proportional hazards model, only those with grade II and grade III obesity had increased risks of AF (hazard ratio [HR], 1.50; 95% CI, 1.14-1.98, =0.004 for grade II obesity and HR, 2.13; 95% CI, 1.48-3.05, <0.0001 for grade III obesity). The relationship between BMI and AF risk was J-shaped. However, the risk of AF as a function of BMI varied substantially by race/ethnicity ( value for interaction=0.02), with Chinese-American participants having a much higher risk of AF with higher BMI and Black participants having minimal increased risk of AF with higher BMI.
Conclusions:
Obesity is associated with an increased risk of incident AF, but the relationship between BMI and the risk of AF is J-shaped and this relationship differs by race/ethnicity, such that Chinese-American participants have a more pronounced increased risk of AF with higher BMI, while Black participants have minimal increased risk. Further exploration of the differential effects of BMI by race/ethnicity on cardiovascular outcomes is needed.



J Am Heart Assoc: 30 Dec 2020:e018592; epub ahead of print
Singleton MJ, German CA, Carnethon M, Soliman EZ, Bertoni AG, Yeboah J
J Am Heart Assoc: 30 Dec 2020:e018592; epub ahead of print | PMID: 33382342
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Predictors of Left Ventricular Scar Using Cardiac Magnetic Resonance in Athletes With Apparently Idiopathic Ventricular Arrhythmias.

Crescenzi C, Zorzi A, Vessella T, Martino A, ... Calò L, Corrado D


Background:
In athletes with ventricular arrhythmias (VA) and otherwise unremarkable clinical findings, cardiac magnetic resonance (CMR) may reveal concealed pathological substrates. The aim of this multicenter study was to evaluate which VA characteristics predicted CMR abnormalities. Methods and Results We enrolled 251 consecutive competitive athletes (74% males, median age 25 [17-39] years) who underwent CMR for evaluation of VA. We included athletes with >100 premature ventricular beats/24 h or ≥1 repetitive VA (couplets, triplets, or nonsustained ventricular tachycardia) on 12-lead 24-hour ambulatory ECG monitoring and negative family history, ECG, and echocardiogram. Features of VA that were evaluated included number, morphology, repetitivity, and response to exercise testing. Left-ventricular late gadolinium-enhancement was documented by CMR in 28 (11%) athletes, mostly (n=25) with a subepicardial/midmyocardial stria pattern. On 24-hour ECG monitoring, premature ventricular beats with multiple morphologies or with right-bundle-branch-block and intermediate/superior axis configuration were documented in 25 (89%) athletes with versus 58 (26%) without late gadolinium-enhancement (<0.001). More than 3300 premature ventricular beats were recorded in 4 (14%) athletes with versus 117 (53%) without positive CMR (<0.001). At exercise testing, nonsustained ventricular tachycardia occurred at peak of exercise in 8 (29%) athletes with late gadolinium-enhancement (polymorphic in 6/8, 75%) versus 17 athletes (8%) without late gadolinium-enhancement (=0.002), (<0.0001). At multivariable analysis, all 3 parameters independently correlated with CMR abnormalities.
Conclusions:
In athletes with apparently idiopathic VA, simple characteristics such as number and morphology of premature ventricular beats on 12-lead 24-hour ambulatory ECG monitoring and response to exercise testing predicted the presence of concealed myocardial abnormalities on CMR. These findings may help cost-effective CMR prescription.



J Am Heart Assoc: 30 Dec 2020:e018206; epub ahead of print
Crescenzi C, Zorzi A, Vessella T, Martino A, ... Calò L, Corrado D
J Am Heart Assoc: 30 Dec 2020:e018206; epub ahead of print | PMID: 33381977
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Differences in Healthcare Use Between Patients With Persistent and Paroxysmal Atrial Fibrillation Undergoing Catheter-Based Atrial Fibrillation Ablation: A Population-Based Cohort Study From Ontario, Canada.

Ha ACT, Wijeysundera HC, Qiu F, Henning K, ... Skanes AC, Verma A


Background:
Patients with persistent atrial fibrillation (AF) undergoing catheter-based AF ablation have lower success rates than those with paroxysmal AF. We compared healthcare use and clinical outcomes between patients according to their AF subtypes. Methods and Results Consecutive patients undergoing AF ablation were prospectively identified from a population-based registry in Ontario, Canada. Via linkage with administrative databases, we performed a retrospective analysis comparing the following outcomes between patients with persistent and paroxysmal AF: healthcare use (defined as AF-related hospitalizations/emergency room visits), periprocedural complications, and mortality. Multivariable Poisson modeling was performed to compare the rates of AF-related and all-cause hospitalizations/emergency room visits in the year before versus after ablation. Between April 2012 and March 2016, there were 3768 consecutive patients who underwent first-time AF ablation, of whom 1040 (27.6%) had persistent AF. The mean follow-up was 1329 days. Patients with persistent AF had higher risk of AF-related hospitalization/emergency room visits (hazard ratio [HR], 1.21; 95% CI, 1.09-1.34), mortality (HR, 1.74; 95% CI, 1.15-2.63), and periprocedural complications (odds ratio, 1.36; 95% CI, 1.02-1.75) than those with paroxysmal AF. In the overall cohort, there was a 48% reduction in the rate of AF-related hospitalization/emergency room visits in the year after versus before ablation (rate ratio [RR], 0.52; 95% CI, 0.48-0.56). This reduction was observed for patients with paroxysmal (RR, 0.45; 95% CI, 0.41-0.50) and persistent (RR, 0.74; 95% CI, 0.63-0.87) AF.
Conclusions:
Although patients with persistent AF had higher risk of adverse outcomes than those with paroxysmal AF, ablation was associated with a favorable reduction in downstream AF-related healthcare use, irrespective of AF type.



J Am Heart Assoc: 30 Dec 2020:e016071; epub ahead of print
Ha ACT, Wijeysundera HC, Qiu F, Henning K, ... Skanes AC, Verma A
J Am Heart Assoc: 30 Dec 2020:e016071; epub ahead of print | PMID: 33381975
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Left Atrial Reservoir Strain by Speckle Tracking Echocardiography: Association With Exercise Capacity in Chronic Kidney Disease.

Gan GCH, Bhat A, Chen HHL, Gu KH, ... Eshoo S, Thomas L


Background:
Left atrial (LA) function plays a pivotal role in modulating left ventricular performance. The aim of our study was to evaluate the relationship between resting LA function by strain analysis and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its utility compared with exercise E/e\'. Methods and Results Consecutive patients with stage 3 and 4 CKD without prior cardiac history were prospectively recruited from outpatient nephrology clinics and underwent clinical evaluation and resting and exercise stress echocardiography. Resting echocardiographic parameters including E/e\' and phasic LA strain (LA reservoir [LASr], conduit, and contractile strain) were measured and compared with exercise E/e\'. A total of 218 (63.9±11.7 years, 64% men) patients with CKD were recruited. Independent clinical parameters associated with exercise capacity were age, estimated glomerular filtration rate, body mass index, and sex (<0.01 for all), while independent resting echocardiographic parameters included E/e\', LASr, and LA contractile strain (<0.01 for all). Among resting echocardiographic parameters, LASr demonstrated the strongest positive correlation to metabolic equivalents achieved (r=0.70; <0.01). Receiver operating characteristic curves demonstrated that LASr (area under the curve, 0.83) had similar diagnostic performance as exercise E/e\' (area under the curve, 0.79; =0.20 on DeLong test). A model combining LASr and clinical metrics showed robust association with metabolic equivalents achieved in patients with CKD.
Conclusions:
LASr, a marker of decreased LA compliance is an independent correlate of exercise capacity in patients with stage 3 and 4 CKD, with similar diagnostic value to exercise E/e\'. Thus, LASr may serve as a resting biomarker of functional capacity in this population.



J Am Heart Assoc: 28 Dec 2020:e017840; epub ahead of print
Gan GCH, Bhat A, Chen HHL, Gu KH, ... Eshoo S, Thomas L
J Am Heart Assoc: 28 Dec 2020:e017840; epub ahead of print | PMID: 33372523
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Circulating Vascular Cell Adhesion Molecule-1 and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis (MESA).

Patel RB, Colangelo LA, Bielinski SJ, Larson NB, ... Shah SJ, Lloyd-Jones DM


Background:
Serum levels of vascular cell adhesion molecule-1 (VCAM-1) are reflective of endothelial activation. Although VCAM-1 has been implicated in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), the prospective association of VCAM-1 with development of clinically overt heart failure (HF) across ejection fraction categories is unclear. Methods and Results In MESA (the Multi-Ethnic Study of Atherosclerosis), we evaluated the association of VCAM-1 at examination 2 (2002-2004) with incident HF (HFpEF and HF with reduced ejection fraction) after adjustment for cardiovascular risk factors. Incident HF was independently adjudicated as first hospitalization for symptomatic HF. Among 2297 participants (mean age, 63 years; women, 53%), those with higher VCAM-1 were more likely to be White race, had higher blood pressure, and had lower kidney function. Over a median of 14.4 years, there were 102 HF events (HFpEF=65; HF with reduced ejection fraction=37). After covariate adjustment, each doubling of VCAM-1 was associated with incident HF (hazard ratio [HR], 1.94; 95% CI, 1.17-3.23; =0.01). This association appeared stronger among current/former smokers compared with never smokers. On evaluation of HF subtypes, VCAM-1 was associated with incident HFpEF (HR, 1.97; 95% CI, 1.04-3.72; =0.04) but not with incident HF with reduced ejection fraction, although risk estimates were consistent (HR, 1.82; 95% CI, 0.79-4.21; =0.16).
Conclusions:
In a multiethnic cohort, VCAM-1 was significantly associated with incident HF over long-term follow-up. These findings suggest a potential role for endothelial activation in driving clinical HF, and specifically HFpEF. Therapies that decrease endothelial activation may prevent the progression from cardiovascular risk factors to clinical HF.



J Am Heart Assoc: 16 Dec 2020; 9:e019390
Patel RB, Colangelo LA, Bielinski SJ, Larson NB, ... Shah SJ, Lloyd-Jones DM
J Am Heart Assoc: 16 Dec 2020; 9:e019390 | PMID: 33161805
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Temporal Trends and Sex Differences in Intensity of Healthcare at the End of Life in Adults With Heart Failure.

Van Spall HGC, Hill AD, Fu L, Ross HJ, Fowler RA


Background:
Patients with chronic disease prefer an adequately supported death at home, but often die in the hospital. We assessed temporal trends and sex differences in healthcare intensity and location of death among decedents with heart failure. Methods and Results This was a retrospective cohort study of adults with heart failure who died between April 1, 2004 and March 31, 2017 in Ontario, Canada. We used population-based administrative databases to assess healthcare utilization during the last 6 months of life and applied multilevel multivariable logistic regression to assess whether sex was independently associated with location of death. Among 396 024 decedents with heart failure, mean (SD) age was 81.8 (10.7) years, 51.5% were women, and 53.4% had in-hospital deaths. From 2004 to 2016, there was an increase in patients receiving mechanical ventilation (15.1%-19.6%), hemodialysis (5.2%-6.8%), and cardiac revascularization (1.7%-2.3%). Relative to men, women spent fewer days in a hospital (mean, 16.4 versus 18.3; mean difference, 1.9; 95% CI, 1.7-2.0; <0.001) and in an intensive care unit (mean, 2.1 versus 3.0; mean difference, 0.9; 95% CI, 0.8-0.9; <0.001); and less commonly received mechanical ventilation (15.5% versus 20.8%; <0.001); hemodialysis (4.8% versus 7.7%; <0.001); or cardiac catheterization (2.8% versus 4.6%; <0.001). Female sex was independently associated with lower odds of in-hospital death (odds ratio, 0.88; 95% CI, 0.87-0.89). Mean (SD) 6-month direct healthcare cost was greater for in-hospital ($52 349 [$55 649]) than out-of-hospital ($35 998 [$31 900]) death.
Conclusions:
Among decedents with heart failure, invasive care in the last 6 months increased in prevalence over time but was less common in women, who had lower odds of dying in a hospital.



J Am Heart Assoc: 15 Dec 2020:e018495; epub ahead of print
Van Spall HGC, Hill AD, Fu L, Ross HJ, Fowler RA
J Am Heart Assoc: 15 Dec 2020:e018495; epub ahead of print | PMID: 33325249
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex Differences in the Age of Diagnosis for Cardiovascular Disease and Its Risk Factors Among US Adults: Trends From 2008 to 2017, the Medical Expenditure Panel Survey.

Okunrintemi V, Tibuakuu M, Virani SS, Sperling LS, ... Blumenthal RS, Michos ED


Background:
Sex differences in the trends for control of cardiovascular disease (CVD) risk factors have been described, but temporal trends in the age at which CVD and its risk factors are diagnosed and sex-specific differences in these trends are unknown. Methods and Results We used the Medical Expenditure Panel Survey 2008 to 2017, a nationally representative sample of the US population. Individuals ≥18 years, with a diagnosis of hypercholesterolemia, hypertension, coronary heart disease, or stroke, and who reported the age when these conditions were diagnosed, were included. We included 100 709 participants (50.2% women), representing 91.9 million US adults with above conditions. For coronary heart disease and hypercholesterolemia, mean age at diagnosis was 1.06 and 0.92 years older for women, compared with men, respectively (both <0.001). For stroke, mean age at diagnosis for women was 1.20 years younger than men (<0.001). The mean age at diagnosis of CVD risk factors became younger over time, with steeper declines among women (annual decrease, hypercholesterolemia [women, 0.31 years; men 0.24 years] and hypertension [women, 0.23 years; men, 0.20 years]; <0.001). Coronary heart disease was not statistically significant. For stroke, while age at diagnosis decreased by 0.19 years annually for women (=0.03), it increased by 0.22 years for men (=0.02).
Conclusions:
The trend in decreasing age at diagnosis for CVD and its risk factors in the United States appears to be more pronounced among women. While earlier identification of CVD risk factors may provide opportunity to initiate preventive treatment, younger age at diagnosis of CVD highlights the need for the prevention of CVD earlier in life, and sex-specific interventions may be needed.



J Am Heart Assoc: 14 Dec 2020; 9:e018764
Okunrintemi V, Tibuakuu M, Virani SS, Sperling LS, ... Blumenthal RS, Michos ED
J Am Heart Assoc: 14 Dec 2020; 9:e018764 | PMID: 33161825
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Use of Oral Anticoagulation in a Real-World Population With Device Detected Atrial Fibrillation.

Kaplan RM, Ziegler PD, Koehler J, Landman S, Sarkar S, Passman RS


Background:
Guideline recommendations for oral anticoagulation (OAC) in patients with atrial fibrillation (AF) are based on CHADS-VASc score alone. Patients with cardiac implantable electronic devices provide an opportunity to assess how the interaction between AF duration and CHADS-VASc score influences OAC prescription rates. Methods and Results Data from the Optum de-identified Electronic Health Record data set were linked to the Medtronic CareLink database of cardiac implantable electronic devices. An index date was assigned as the later of 6 months after device implant or 1 year after Electronic Health Record data availability. Maximum daily AF duration (no AF, 6 minutes-23.5 hours, and >23.5 hours) was assessed for 6 months before index date. OAC prescription rates were computed as a function of both AF duration and CHADS-VASc score. A total of 35 779 patients with CHADS-VASc scores ≥1 were identified, including 27 198 not prescribed OAC. Overall OAC prescription rate among the 12 938 patients with device-detected AF >6 minutes was 36.7% and significantly higher in those with a maximum daily AF duration >23.5 hours (45.4%) compared with those with 6 minutes to 23.5 hours (28.7%). OAC prescription rates increased monotonically with both increasing AF duration and CHADS-VASc score, reaching a maximum of 67.2% for patients with AF >23.5 hours and a CHADS-VASc score ≥5.
Conclusions:
Real-world prescription of OAC increased with both increasing duration of AF and CHADS-VASc score. This highlights the need for further research into the role of AF duration, stroke risk, and the need for anticoagulation in patients with devices capable of long-term AF monitoring.



J Am Heart Assoc: 14 Dec 2020; 9:e018378
Kaplan RM, Ziegler PD, Koehler J, Landman S, Sarkar S, Passman RS
J Am Heart Assoc: 14 Dec 2020; 9:e018378 | PMID: 33252286
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Laser-Assisted Removal of Embedded Vena Cava Filters: A First-In-Human Escalation Trial in 500 Patients Refractory to High-Force Retrieval.

Kuo WT, Doshi AA, Ponting JM, Rosenberg JK, Liang T, Hofmann LV


Background:
Many patients are subject to potential risks and filter-related morbidity when standard retrieval methods fail. We evaluated the safety and efficacy of the laser sheath technique for removing embedded inferior vena cava filters. Methods and Results Over an 8.5-year period, 500 patients were prospectively enrolled in an institutional review board-approved study. There were 225 men and 275 women (mean age, 49 years; range, 15-90 years). Indications for retrieval included symptomatic acute inferior vena cava thrombosis, chronic inferior vena cava occlusion, and/or pain from filter penetration. Retrieval was also offered to prevent risks from prolonged implantation and potentially to eliminate need for lifelong anticoagulation. After retrieval failed using 3X standard retrieval force (6-7 lb via digital gauge), treatment escalation was attempted using laser sheath powered by 308-nm XeCl excimer laser system (CVX-300; Spectranetics). We hypothesized that the laser-assisted technique would allow retrieval of >95% of embedded filters with <5% risk of major complications and with lower force. Primary outcome was successful retrieval. Primary safety outcome was any major procedure-related complication. Laser-assisted retrieval was successful in 99.4% of cases (497/500) (95% CI, 98.3%-99.9%) and significantly >95% (<0.0001). The mean filter dwell time was 1528 days (range, 37-10 047; >27.5 years]), among retrievable-type (n=414) and permanent-type (n=86) filters. The average force during failed attempts without laser was 6.4 versus 3.6 lb during laser-assisted retrievals (<0.0001). The major complication rate was 2.0% (10/500) (95% CI, 1.0%-3.6%), significantly <5% (<0.0005), 0.6% (3/500) (95% CI, 0%-1.3%) from laser, and all were successfully treated. Successful retrieval allowed cessation of anticoagulation in 98.7% (77/78) (95% CI, 93.1%-100.0%) and alleviated filter-related morbidity in 98.5% (138/140) (95% CI, 96.5%-100.0%).
Conclusions:
The excimer laser sheath technique is safe and effective for removing embedded inferior vena cava filters refractory to high-force retrieval. This technique may allow cessation of filter-related anticoagulation and can be used to prevent and alleviate filter-related morbidity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01158482.



J Am Heart Assoc: 14 Dec 2020; 9:e017916
Kuo WT, Doshi AA, Ponting JM, Rosenberg JK, Liang T, Hofmann LV
J Am Heart Assoc: 14 Dec 2020; 9:e017916 | PMID: 33252283
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Single-Cell Immune Profiling in Coronary Artery Disease: The Role of State-of-the-Art Immunophenotyping With Mass Cytometry in the Diagnosis of Atherosclerosis.

Kott KA, Vernon ST, Hansen T, de Dreu M, ... McGuire HM, Figtree GA

Coronary artery disease remains the leading cause of death globally and is a major burden to every health system in the world. There have been significant improvements in risk modification, treatments, and mortality; however, our ability to detect asymptomatic disease for early intervention remains limited. Recent discoveries regarding the inflammatory nature of atherosclerosis have prompted investigation into new methods of diagnosis and treatment of coronary artery disease. This article reviews some of the highlights of the important developments in cardioimmunology and summarizes the clinical evidence linking the immune system and atherosclerosis. It provides an overview of the major serological biomarkers that have been associated with atherosclerosis, noting the limitations of these markers attributable to low specificity, and then contrasts these serological markers with the circulating immune cell subtypes that have been found to be altered in coronary artery disease. This review then outlines the technique of mass cytometry and its ability to provide high-dimensional single-cell data and explores how this high-resolution quantification of specific immune cell subpopulations may assist in the diagnosis of early atherosclerosis in combination with other complimentary techniques such as single-cell RNA sequencing. We propose that this improved specificity has the potential to transform the detection of coronary artery disease in its early phases, facilitating targeted preventative approaches in the precision medicine era.



J Am Heart Assoc: 14 Dec 2020; 9:e017759
Kott KA, Vernon ST, Hansen T, de Dreu M, ... McGuire HM, Figtree GA
J Am Heart Assoc: 14 Dec 2020; 9:e017759 | PMID: 33251927
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prevalence, Features, and Prognosis of Artery-to-Artery Embolic ST-Segment-Elevation Myocardial Infarction: An Optical Coherence Tomography Study.

Takahata M, Ino Y, Kubo T, Tanimoto T, ... Hozumi T, Akasaka T


Background:
The major underlying mechanisms contributing to acute coronary syndrome are plaque rupture, plaque erosion, and calcified nodule. Artery-to-artery embolic myocardial infarction (AAEMI) was defined as ST-segment-elevation myocardial infarction caused by migrating thrombus formed at the proximal ruptured plaque. The aim of this study was to investigate the prevalence and clinical features of AAEMI by using optical coherence tomography. Methods and Results This study retrospectively enrolled 297 patients with ST-segment-elevation myocardial infarction who underwent optical coherence tomography before percutaneous coronary intervention. Patients were divided into 4 groups consisting of plaque rupture, plaque erosion, calcified nodule, and AAEMI according to optical coherence tomography findings. The prevalence of AAEMI was 3.4%. The culprit vessel in 60% of patients with AAEMI was right coronary artery. Minimum lumen area at the culprit site was larger in AAEMI compared with plaque rupture, plaque erosion, and calcified nodule (4.0 mm [interquartile range (IQR), 2.2-4.9] versus 1.0 mm [IQR, 0.8-1.3] versus 1.0 mm [IQR, 0.8-1.2] versus 1.1 mm [IQR, 0.7-1.6], <0.001). Lumen area at the rupture site was larger in patients with AAEMI compared with patients with plaque rupture (4.4 mm [IQR, 2.5-6.7] versus 1.5 mm [IQR, 1.0-2.4], <0.001). In patients with AAEMI, the median minimum lumen area at the occlusion site was 1.2 mm (IQR, 1.0-2.1), 40% of them had nonstent strategy, and the 3-year major adverse cardiac event rate was 0%.
Conclusions:
AAEMI is a rare cause for ST-segment-elevation myocardial infarction and has unique morphological features of plaque including larger lumen area at rupture site and smaller lumen area at the occlusion site.



J Am Heart Assoc: 14 Dec 2020; 9:e017661
Takahata M, Ino Y, Kubo T, Tanimoto T, ... Hozumi T, Akasaka T
J Am Heart Assoc: 14 Dec 2020; 9:e017661 | PMID: 33251922
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Older ...

This program is still in alpha version.