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AimsAtrial fibrillation (AF) and heart failure (HF) often coexist. However, whether AF onset before HF or vice versa is associated with the worst outcome remains unclear. A consensus of large studies can guide future research and preventive strategies to better target high-risk patients.Methods and resultsWe included all Danish cases with the coexistence of AF and HF (2005–17) using nationwide registries. Patients were divided into three separate groups (i) AF before HF, (ii) HF before AF, or (iii) AF and HF diagnosed concurrently (±30 days). Adjusting landmark Cox analyses (index date was the time of the latter diagnosis of AF or HF) were used for evaluating the association of the three groups with a composite outcome of ischaemic stroke or death. Among a total of 49 042 patients included, 40% had AF before HF, 27% had HF before AF, and 33% had AF and HF diagnosed concurrently. The composite endpoint accrued more often in patients with HF before AF compared to the two other groups (ConclusionsIn this large Danish national cohort, diagnosis of HF before AF was associated with an increased absolute risk of death compared to AF before HF and AF and HF diagnosed concurrently. Antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation may improve prognosis.

ObjectiveTo test the hypothesis that silent myocardial infarction (MI) is a risk factor for ischemic stroke, we evaluated the association between silent MI and subsequent ischemic stroke in the Cardiovascular Health Study.MethodsThe Cardiovascular Health Study prospectively enrolled community-dwelling individuals ≥65 years of age. We included participants without prevalent stroke or baseline evidence of MI. Our exposures were silent and clinically apparent, overt MI. Silent MI was defined as new evidence of Q-wave MI, without clinical symptoms of MI, on ECGs performed during annual study visits from 1989 to 1999. The primary outcome was incident ischemic stroke. Secondary outcomes were ischemic stroke subtypes: nonlacunar, lacunar, and other/unknown. Cox proportional hazards analysis was used to model the association between time-varying MI status (silent, overt, or no MI) and stroke after adjustment for baseline demographics and vascular risk factors.ResultsAmong 4,224 participants, 362 (8.6%) had an incident silent MI, 421 (10.0%) an incident overt MI, and 377 (8.9%) an incident ischemic stroke during a median follow-up of 9.8 years. After adjustment for demographics and comorbidities, silent MI was independently associated with subsequent ischemic stroke (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.03–2.21). Overt MI was associated with ischemic stroke both in the short term (HR, 80; 95% CI, 53–119) and long term (HR, 1.60; 95% CI, 1.04–2.44). In secondary analyses, the association between silent MI and stroke was limited to nonlacunar ischemic stroke (HR, 2.40; 95% CI, 1.36–4.22).ConclusionIn a community-based sample, we found an association between silent MI and ischemic stroke.

BackgroundMicrosize myocardial infarction (MI) is a recently described phenomenon that meets rigorous criteria for MI with very low peak troponin elevations. We aim to compare the risk for cardiovascular events and mortality following microsize versus usual MIs.Methods and resultsProspective cohort analysis of REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a history of coronary heart disease (CHD) who had an incident MI between 2003 and 2015. Incident MIs were classified as microsize MI (peak troponin ConclusionMicrosize MIs have a prognostic value for future cardiovascular events and mortality comparable to usual MIs. These findings should encourage clinicians to initiate secondary prevention strategies in patients with microsize MI until this emerging clinical entity is better understood.

Objective: To assess rates of postoperative stroke after elective noncardiac surgery in patients with atrial fibrillation (AF). Methods: We conducted a retrospective cohort study using all-payer administrative claims data on all non-federal hospitalizations and emergency department visits in 11 states between 2016 and 2018. We included patients hospitalized for elective noncardiac surgery, as defined by a surgical diagnosis related group and major diagnostic category codes. The exposure variable was preoperative AF. The outcome variable was ischemic stroke within 30 days of surgery. We performed survival analyses using Kaplan-Meier cumulative rates and Cox proportional hazards models. We stratified AF patients by their CHA 2 DS 2 -VASc score and tested its discrimination using the c-statistic. Results: We identified 1,301,709 patients undergoing elective noncardiac surgery, of whom 94,363 (7.3%) had preoperative AF. Patients with AF were older (mean age, 73 versus 62 years) and had higher CHA 2 DS 2 -VASc scores (mean score, 3.2 vs 2.2). We identified 2,893 patients with postoperative stroke. The cumulative rate of postoperative stroke was 0.65% (95% CI, 0.60-0.70%) in patients with AF vs 0.19% (95% CI, 0.18-0.20%) in patients without AF. After adjustment for demographics and vascular risk factors, AF was associated with a higher risk of postoperative stroke (HR, 1.7; 95% CI, 1.5-1.8). Among AF patients, the CHA 2 DS 2 -VASc score was a good predictor of postoperative stroke (AUC, 0.81; 95% CI, 0.79-0.83). Rates of postoperative stroke among AF patients ranged from 2 DS 2 -VASc score of 0-2 to 14% in those with a score of 8 (Figure). Conclusions: Patients with AF faced a heightened risk of postoperative stroke and this risk varied in proportion to the CHA 2 DS 2 -VASc score.

Background: Available nomograms to predict aortic root (AoR) diameter for body surface area have limitations. The purpose of this study was to evaluate the use of a new multivariate predictive model to identify AoR dilatation in hypertensive patients with left ventricular hypertrophy. Methods: 943 of 961 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic sub-study had the necessary baseline characteristics and echocardiographic 2D measurements of AoR size to be included. Results: Predicted AoR (Sinus of Valsalva) diameter was 1.519 + (age [years] × 0.010) + (height [cm] × 0.010) – (gender [1 = M, 2 = F] × 0.247), and a measured AoR diameter exceeding the 97.5-percentile of this estimate was considered dilated. Measured AoR diameter was larger in men than in women (3.75 vs. 3.48 cm, p < 0.001) and AoR diameter predicted by the model was larger than predicted by nomogram (3.52 vs. 3.28 cm, p < 0.001). Using the multivariate model to identify patients with AoR dilatation, the prevalence was 13.7% in men and 12.3% in women (p = 0.537). There was consensus of AoR phenotype (normal/dilated) between model and nomogram in 92.8% of the patients. In multivariate logistic regression, AoR dilatation by model definition was predicted by presence of aortic regurgitation (OR 2.67, p < 0.001) and SD increase in age (OR 0.75, p = 0.023), pulse pressure (OR 0.64, p < 0.001), left ventricular mass index (OR 1.36, p = 0.08) and stroke volume (OR 1.45, p = 0.002), but not by body weight. Conclusions: Using the proposed model the prevalence of AoR dilatation was equal in men and women and the model seems to address the effects of gender, age and body size on AoR size. Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00338260.

Background: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). Methods: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association’s COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. Results: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03–1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10–1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65–1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84–1.33]). Conclusions: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.

Objective Atrial cardiopathy without atrial fibrillation (AF) may be a potential cardiac source of embolic strokes of undetermined source (ESUS). Atrial volume is a feature of atrial cardiopathy, but the relationship between atrial volume and ESUS remains unclear. Methods We compared left atrial volume among ischemic stroke subtypes in the Cornell Acute Stroke Academic Registry (CAESAR), which includes all patients with acute ischemic stroke at our hospital since 2011. Stroke subtype was determined by neurologists per the TOAST classification and consensus ESUS definition. Left atrial volume index (LAVI) was obtained directly from our echocardiography image system (Xcelera, Philips Healthcare). We used t‐tests and analysis of variance for unadjusted comparisons and targeted minimum loss‐based estimation for comparisons adjusted for demographics and comorbidities. Results Among 2116 patients in CAESAR from 2011 to 2016, 1293 had LAVI measurements. LAVI varied across subtypes (P

Background Retrospective studies have reported an association between cancer and arterial thromboembolic event (ATE) risk. Objectives We sought to confirm this in a prospective cohort with adjudicated outcomes. Methods We evaluated participants enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study with Medicare coverage for 365 days before their baseline visit (2003-2007). Medicare claims were used to identify new cancer diagnoses during follow-up. Using incidence-density sampling, participants who developed cancer were matched by age, sex, race, and education 1:4 to control participants who had not developed cancer. Participants were prospectively followed through 2015 for an expert-adjudicated ATE, defined as acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent ATE. Results In this analysis, 836 REGARDS participants with incident cancer were matched to 3339 control participants without cancer. In the 30 days after cancer diagnosis, 0.60% (n = 5) of the participants had an ATE; most of these events occurred near the time of cancer diagnosis. After adjustment for demographics, geographic region, and cardiovascular risk factors, compared to the noncancer controls, participants with incident cancer had an increased risk of ATE in the first 30 days after diagnosis (hazard ratio, 5.8; 95% confidence interval, 2.1-15.9). There was no association between cancer diagnosis and ATE beyond 30 days. Cancers with known metastases and types considered high risk for venous thromboembolism had the strongest associations with ATE. Conclusions Incident cancer is associated with an increased short-term risk of ATE independent of vascular risk factors.

Cancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.

Introduction: COVID-19 is a respiratory syndrome with high rates of mortality, and findings from the ECG on hospital presentation have been shown to increase the odds of death. We thus hypothesized that findings from the presenting ECG could discriminate the risk of death in high risk subgroups, and sought to create an ECG risk score for death in COVID-19. Methods: We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics were manually abstracted from the electronic health record; ECG data were digitally extracted from the first ECG in each patient, and Bazett-corrected QT interval and ST segment deviation at the M-point (STm, in μV) were quantified in all 12 leads. Our primary outcome was death. Results: 710 patients who presented to a large teaching hospital with COVID-19 underwent an ECG. The mean age was 63 ± 16 years, 37% were women, 62% of patients were non-white, and 56% had hypertension; 78 (11%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (OR=3.56, 95% CI 1.80-7.02, p80, Figure ). Conclusions: A simple ECG risk score (including APCs, RBBB/IVB, STmV5V6 ≤ -50 μV, STmV2

Background Cornell voltage criteria (CL) and Sokolow-Lyon criteria (SL) for electrocardiographic left ventricular hypertrophy (ECG-LVH) are well known predictors of cardiovascular outcome. However, their predictive value may differ according to patient type and remains to be further tested in diabetic mellitus (DM) patients. Purpose The present study aims to determine the prevalence of each ECG-LVH criteria and their respective predictive value in DM patients. Method A retrospective cohort study of individuals age >40 years with digital ECGs from primary care were collected during 2001 to 2011. Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. DM was defined if individuals were prescribed oral antidiabetics or insulin, if they were diagnosed with DM type I or II, or had a HbA1c>48 mmol/l. Cox multivariable analysis was used for estimating hazard ratio (HR) and 95% confidence intervals (95% CI) for all-cause mortality during follow-up of up to 17 years. Results Included were 183,749 individuals with a digital ECG collected in primary care. A total of 13,003 (7.1%) individuals had DM, they were older (65.8 vs. 61.3 years), had more myocardial infarction (16.1% vs. 5.2%), stroke (14.4% vs. 6.2%), hypertension (35.1% vs. 13.2%), CL LVH (8.0% vs. 5.6%) and more were males (53.3% vs. 45.3%) compared to the non-DM individuals (all p0.45). Conclusion Cornell Voltage Left Ventricular Hypertrophy is a strong predictor of mortality in patients with and without diabetes and an independent risk factor compared to hypertension and diabetes. The predictive value was substantially stronger than Sokolow-Lyon Voltage criteria for hypertrophy. Figure 1. LVH and all-cause mortality Funding Acknowledgement Type of funding source: None

Background and Purpose: One-fifth of ischemic strokes are embolic strokes of undetermined source (ESUS). Their theoretical causes can be classified as cardioembolic versus noncardioembolic. This distinction has important implications, but the categories’ proportions are unknown. Methods: Using data from the Cornell Acute Stroke Academic Registry, we trained a machine-learning algorithm to distinguish cardioembolic versus non-cardioembolic strokes, then applied the algorithm to ESUS cases to determine the predicted proportion with an occult cardioembolic source. A panel of neurologists adjudicated stroke etiologies using standard criteria. We trained a machine learning classifier using data on demographics, comorbidities, vitals, laboratory results, and echocardiograms. An ensemble predictive method including L1 regularization, gradient-boosted decision tree ensemble (XGBoost), random forests, and multivariate adaptive splines was used. Random search and cross-validation were used to tune hyperparameters. Model performance was assessed using cross-validation among cases of known etiology. We applied the final algorithm to an independent set of ESUS cases to determine the predicted mechanism (cardioembolic or not). To assess our classifier’s validity, we correlated the predicted probability of a cardioembolic source with the eventual post-ESUS diagnosis of atrial fibrillation. Results: Among 1083 strokes with known etiologies, our classifier distinguished cardioembolic versus noncardioembolic cases with excellent accuracy (area under the curve, 0.85). Applied to 580 ESUS cases, the classifier predicted that 44% (95% credibility interval, 39%–49%) resulted from cardiac embolism. Individual ESUS patients’ predicted likelihood of cardiac embolism was associated with eventual atrial fibrillation detection (OR per 10% increase, 1.27 [95% CI, 1.03–1.57]; c-statistic, 0.68 [95% CI, 0.58–0.78]). ESUS patients with high predicted probability of cardiac embolism were older and had more coronary and peripheral vascular disease, lower ejection fractions, larger left atria, lower blood pressures, and higher creatinine levels. Conclusions: A machine learning estimator that distinguished known cardioembolic versus noncardioembolic strokes indirectly estimated that 44% of ESUS cases were cardioembolic.

Highlights • Findings of left and right sided heart disease on the presentation electrocardiogram are associated with death in COVID-19 • Right bundle branch block in COVID-19 is likely secondary to acute right ventricular distension, and could represent the at-risk right ventricle. • Markers of left ventricular stiffness (atrial premature contractions, prolonged intraventricular conduction, and ischemic repolarization abnormalities) are associated with death., Background Coronavirus disease 2019 (COVID-19) is a respiratory syndrome with high rates of mortality, and there is a need for easily obtainable markers to provide prognostic information. We sought to determine whether the electrocardiogram (ECG) on hospital presentation provides prognostic information, specifically related to death. Methods and Results We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics and ECG variables were manually abstracted from the electronic health record and first ECG. Our primary outcome was death. There were 756 patients who presented to a large New York City teaching hospital with COVID-19 who underwent an ECG. The mean age was 63.3 ± 16 years, 37% were women, 61% of patients were nonwhite, and 57% had hypertension; 90 (11.9%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.23–5.36, P = .01), a right bundle branch block or intraventricular block (OR 2.61, 95% CI 1.32–5.18, P = .002), ischemic T-wave inversion (OR 3.49, 95% CI 1.56–7.80, P = .002), and nonspecific repolarization (OR 2.31, 95% CI 1.27–4.21, P = .006) increased the odds of death. ST elevation was rare (n = 5 [0.7%]). Conclusions We found that patients with ECG findings of both left-sided heart disease (atrial premature contractions, intraventricular block, repolarization abnormalities) and right-sided disease (right bundle branch block) have higher odds of death. ST elevation at presentation was rare., Graphical Abstract Image, graphical abstract

Introduction: Myocardial infarction (MI) is associated with cerebral infarction. We assessed whether MI size and location is related to the risk of cerebral infarction. Methods: We performed a cross-sectional study of patients evaluated between 2014-2017 at New York-Presbyterian Hospital/Weill Cornell Medicine. We included all adults who underwent both brain MRI and delayed-enhancement cardiac MRI (DE-CMR) within 365 days of each other and had evidence of MI on DE-CMR. We evaluated associations between MI size and any cerebral infarction, apical MI and any cerebral infarction, and between MI size/location and cortical versus subcortical cerebral infarction. We used multiple logistic regression models adjusted for age, sex, race, and the total number of vascular risk factors. Results: We identified 234 patients who underwent DE-CMR and brain MRI within 365 days, among whom 76 had evidence of MI on DE-CMR. Of these 76 patients, 51 (67.1%) had evidence of cerebral infarction. There was no association between the size of MI (global MI burden) and any cerebral infarction (OR per 1% increase in MI size, 1.02; 95% CI, 1.0-1.1; P = 0.43), but there was an association between MI size and cortical cerebral infarction (OR per 1% increase in MI size, 1.05; 95% CI, 1.0-1.1; P = 0.047). We found no association between apical MI location and any cerebral infarction (OR 3.2, 95% CI, 0.9-12.2, P = 0.08), but there was an association between apical MI location and cortical cerebral infarction (OR, 3.7; 95% CI, 1.2-11.3; P = 0.02). Conclusion: Among patients with MI on cardiac imaging, MI size and apical MI location were associated with cortical cerebral infarction. Our results may help stratify cardioembolic risk and lead to improved antithrombotic treatment algorithms among patients with MI.

Purpose: Hypertensive patients are at increased risk of atrial fibrillation (AF). Although low baseline high density lipoprotein (HDL) cholesterol has been associated with a higher risk of AF, this has not been verified in recent population-based studies. Whether changing levels of HDL over time are more strongly related to the risk of new AF in hypertensive patients has not been examined. Material and methods: Incident AF was examined in relation to baseline and on-treatment HDL levels in 8267 hypertensive patients with no history of AF, in sinus rhythm on their baseline electrocardiogram, randomly assigned to losartan- or atenolol-based treatment. HDL levels at baseline and each year of testing were categorised into quartiles according to baseline HDL levels. Results: During 4.7 ± 1.10 years of follow-up, 645 patients (7.8%) developed new AF. In univariate Cox analyses, compared with the highest quartile of HDL levels (>1.78 mmol/l), patients with on-treatment HDL in the lowest quartile (≤ 1.21 mmol/l) had a 53% greater risk of new AF. Patients with on-treatment HDL in the second and third quartiles had intermediate increased risks of AF. Baseline HDL in the lowest quartile was not a significant predictor of new AF (hazard ratio (HR): 1.14, 95% confidence interval (CI): 0.90–1.43). In multivariable Cox analyses adjusting for multiple baseline and time-varying covariates, the lowest quartile of on-treatment HDL remained associated with a nearly 54% increased risk of new AF (HR: 1.54, 95% CI: 1.16–2.05) whereas a baseline HDL≤ ⩽1.21 mmol/l was not predictive of new AF (HR: 1.01, 95% CI: 0.78–1.31). Conclusion: Lower on-treatment HDL is strongly associated with risk of new AF. These findings suggest that serial assessment of HDL can estimate AF risk better than baseline HDL in hypertensive patients with left ventricular hypertrophy. Future studies may investigate whether therapies that increase HDL can lower risk of developing AF. Clinical Trials Registration: http://clinicaltrials.gov/ct/show/NCT00338260?order=1

Epidemiologic studies suggest that chronic exposure to arsenic is related to cardiovascular disease (CVD), but the pathophysiological link remains uncertain. We evaluated the association of chronic low-moderate arsenic exposure and arsenic metabolism with baseline difference and annual change in ECG measures (QT interval, JT interval, PR interval, QRS duration, and QT dispersion) using linear mixed models in the Strong Heart Study main cohort (N = 1174, median age 55 years) and family study (N = 1695 diabetes-free, median age 36 years). At baseline, arsenic exposure was measured as the sum of inorganic and methylated species in urine (ΣAs) and arsenic metabolism was measured as the relative percentage of arsenic species. Median ΣAs and Bazett heart rate-corrected QT interval (QTc) were 8.6 μg/g creatinine and 424 ms in the main cohort and 4.3 μg/g and 414 ms in the family study, respectively. In the main cohort, a comparison of the highest to lowest ΣAs quartile (14.4 vs.5.2 μg/g creatinine) was associated with a 5.3 (95% CI: 1.2, 9.5) ms higher mean baseline QTc interval but no difference in annual change in QTc interval. In the family study, a comparison of the highest to lowest quartile (7.1 vs.2.9 μg/g creatinine) was associated with a 3.2 (95% CI: 0.6, 5.7) ms higher baseline QTc interval and a 0.6 (95% CI: 0.04, 1.2) ms larger annual increase in QTc interval. Associations with JTc interval were similar but stronger in magnitude compared to QTc interval. Arsenic exposure was largely not associated with PR interval, QRS duration or QT dispersion. Similar to arsenic exposure, a pattern of lower %MMA and higher %DMA was associated with longer baseline QTc interval in both cohorts and with a larger annual change in QTc interval in the family study. Chronic low-moderate arsenic exposure and arsenic metabolism were associated with prolonged ventricular repolarization.

ObjectiveWe aimed to evaluate the association between cancer and cerebrovascular disease in a prospective cohort study with adjudicated cerebrovascular diagnoses.MethodsWe analyzed participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were 45 years and older and had Medicare coverage for 365 days before their baseline study visit. Participants with a history of cancer or cerebrovascular events were excluded. The time-dependent exposure was a new diagnosis of malignant cancer identified through Medicare claims algorithms. Participants were prospectively followed from their baseline study visit (2003–2007) through 2014 for the outcome of a neurologist-adjudicated cerebrovascular event defined as a composite of stroke (ischemic or hemorrhagic) or TIA. Cox regression was used to evaluate the association between a new cancer diagnosis and subsequent cerebrovascular events. Follow-up time was modeled in discrete time periods to fulfill the proportional hazard assumption.ResultsAmong 6,602 REGARDS participants who met eligibility criteria, 1,149 were diagnosed with cancer during follow-up. Compared to no cancer, a new cancer diagnosis was associated with subsequent cerebrovascular events in the first 30 days after diagnosis (hazard ratio 6.1, 95% confidence interval 2.7–13.7). This association persisted after adjustment for demographics, region of residence, and vascular risk factors (hazard ratio 6.6, 95% confidence interval 2.7–16.0). There was no association between cancer diagnosis and incident cerebrovascular events beyond 30 days. Cancers considered high risk for venous thromboembolism demonstrated the strongest associations with cerebrovascular event risk.ConclusionA new diagnosis of cancer is associated with a substantially increased short-term risk of cerebrovascular events.

Background and Purpose— Emerging evidence suggests that an underlying atrial cardiopathy may result in thromboembolism before atrial fibrillation (AF) develops. We examined the association between various markers of atrial cardiopathy and the risk of ischemic stroke. Methods— The CHS (Cardiovascular Health Study) prospectively enrolled community-dwelling adults ≥65 years of age. For this study, we excluded participants diagnosed with stroke or AF before baseline. Exposures were several markers of atrial cardiopathy: baseline P-wave terminal force in ECG lead V 1 , left atrial dimension on echocardiogram, and N terminal pro B type natriuretic peptide (NT-proBNP), as well as incident AF. Incident AF was ascertained from 12-lead electrocardiograms at annual study visits for the first decade after study enrollment and from inpatient and outpatient Medicare data throughout follow-up. The primary outcome was incident ischemic stroke. We used Cox proportional hazards models that included all 4 atrial cardiopathy markers along with adjustment for demographic characteristics and established vascular risk factors. Results— Among 3723 participants who were free of stroke and AF at baseline and who had data on all atrial cardiopathy markers, 585 participants (15.7%) experienced an incident ischemic stroke during a median 12.9 years of follow-up. When all atrial cardiopathy markers were combined in 1 Cox model, we found significant associations with stroke for P-wave terminal force in ECG lead V 1 (hazard ratio per 1000 μV*ms 1.04; 95% confidence interval, 1.001–1.08), log-transformed NT-proBNP (hazard ratio per doubling of NT-proBNP, 1.09; 95% confidence interval, 1.03–1.16), and incident AF (hazard ratio, 2.04; 95% confidence interval, 1.67–2.48) but not left atrial dimension (hazard ratio per cm, 0.96; 95% confidence interval, 0.84–1.10). Conclusions— In addition to clinically apparent AF, other evidence of abnormal atrial substrate is associated with subsequent ischemic stroke. This finding is consistent with the hypothesis that thromboembolism from the left atrium may occur in the setting of several different manifestations of atrial disease.

The SPRINT study demonstrated that targeting systolic blood pressure (SBP) less than 120 mmHg was associated with lower cardiovascular event and mortality rates. In the LIFE study, however, a lower achieved SBP was associated with increased mortality. Mean baseline SBP in SPRINT was 140 mmHg and a third of the population had a baseline SBP 132 mmHg or less, raising the question of whether the lower baseline SBP in SPRINT could in part account for these differences.All-cause mortality during 4.8 ± 0.9 years follow-up was examined in relation to tertiles of achieved on-treatment average SBP in patients with baseline SBP of 25th percentile or less versus greater than 25th percentile value of 164 mmHg in 7998 nondiabetic hypertensive patients with ECG left ventricular hypertrophy randomly assigned to losartan-based or atenolol-based treatment. Average on-treatment SBP less than 142 mmHg (lowest tertile) and average SBP 142 mmHg to less than 152 mmHg (middle tertile) were compared with average SBP at least 152 mmHg (highest tertile and reference group).In the overall population, there was a significant interaction between baseline SBP 164 mmHg or less and average on-treatment SBP less than 142 mmHg in Cox analysis (χ = 15.48, P 0.001). Among patients with baseline SBP greater than 164 mmHg, in multivariate Cox analyses adjusting for other potential predictors of mortality and a propensity score for having baseline SBP 164 mmHg or less and compared with average on-treatment SBP at least 152 mmHg, average on-treatment SBP less than 142 mmHg was associated with 32% higher mortality (hazard ratio 1.32, 95% CI 1.01-1.65), whereas average SBP of 142 mmHg to less than 152 mmHg was associated with 24% lower mortality (hazard ratio 0.76, 95% CI 0.59-0.98). In contrast, among patients with baseline SBP 164 mmHg or less, both average on-treatment SBP less than 142 mmHg (hazard ratio 0.60, 95% CI 0.36-0.99) and average SBP of 142 mmHg to less than 152 mmHg (hazard ratio 0.51, 95% CI 0.30-0.89) were associated with significantly lower mortality compared with average SBP of at least 152 mmHg.Achievement of an average SBP less than 142 mmHg was associated with reduced mortality in patients with baseline SBP 164 mmHg or less but with increased mortality in those with higher baseline SBP in LIFE. These findings suggest that the lower mortality associated with a lower targeted SBP in SPRINT may not be applicable to patients with considerably higher baseline SBP than SPRINT patients. Further study is necessary to better understand these findings.http://clinicaltrials.gov/ct/show/NCT00338260?order=1.

AIM To test the efficacy of achieving target SBP less than 120 mmHg, or less than 140 mmHg, for lowering the risk of major adverse cardiovascular events (MACE) in persons with diabetes mellitus. METHOD The study comprised 4732 [mean ± SD age: 63 ± 7 years; 2258 (48%) women] persons with advanced diabetes mellitus. Participants randomly assigned to achieve intensive (

Background and Purpose— We sought to evaluate the real-world rate of safety outcomes after patent foramen ovale (PFO) closure in patients with ischemic stroke or transient ischemic attack (TIA). Methods— We performed a retrospective cohort study using administrative claims data on all hospitalizations from 2005 to 2013 in New York, California, and Florida. Using International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified patients who underwent percutaneous transcatheter PFO closure within 1 year of ischemic stroke or TIA. Our outcome was an adverse event occurring during the hospitalization for PFO closure, defined as in prior studies as atrial fibrillation or flutter, cardiac tamponade, pneumothorax, hemothorax, a vascular access complication, or death. Crude rates were reported with exact confidence intervals. Results— We identified 1887 patients who underwent PFO closure after ischemic stroke or TIA. The rate of any adverse outcome during the hospitalization for PFO closure was 7.0% (95% confidence interval [CI], 5.9%–8.2%). Rates of adverse outcomes varied by age and type of preceding cerebrovascular event. In patients >60 years of age, the rate of adverse outcomes was 10.9% (95% CI, 8.6%–13.6%) versus 4.9% (95% CI, 3.8%–6.3%) in patients ≤60 years of age. The rate of adverse outcomes was 9.9% (95% CI, 7.3%–12.5%) in patients with preceding ischemic stroke versus 5.9% (95% CI, 4.7%–7.1%) after TIA. Conclusions— Approximately 1 in 14 patients who underwent percutaneous transcatheter PFO closure after ischemic stroke or TIA experienced a serious periprocedural adverse outcome or death. The risk of adverse outcomes was highest in older patients and in those with preceding ischemic stroke.

Electrocardiographic QRS duration at rest is associated with sudden cardiac death and death from coronary heart disease in the general population. However, its relation to cardiovascular events in American Indians, a population with persistently high cardiovascular disease mortality, is unknown. The relation of QRS duration to incident cardiovascular disease during 17.2 years of follow-up was assessed in 1,851 male and female Strong Heart Study participants aged 45 to 74 years without known cardiovascular disease at baseline. Cox regression with robust standard error estimates was used to determine the association between quintiles of QRS duration and incident cardiovascular disease in gender-stratified analyses, adjusted for age, systolic blood pressure, hypertension, antihypertensive medication use, body mass index, current smoking, diabetes, total cholesterol, high-density lipoprotein cholesterol, and albuminuria. In women only, QRS duration in the highest quintile (≥105 ms) conferred significantly higher risk of cardiovascular disease than QRS duration in the lowest quintile (64 to 84 ms) (hazard ratio 1.6, 95% CI 1.1 to 2.4) likely because of higher risks of coronary heart disease (hazard ratio 1.8, 95% CI 1.1 to 3.1) and myocardial infarction (hazard ratio 2.1, 95% CI 1.0 to 4.7). Furthermore, when added to the Strong Heart Study Coronary Heart Disease Risk Calculator, QRS duration significantly improved prediction of future coronary heart disease events in women (Net Reclassification Index 0.17, 95% CI 0.06 to 0.47). In conclusion, QRS duration is an independent predictor of cardiovascular disease in women in the Strong Heart Study cohort and may have value in estimating risk in populations with similar risk profiles and a high lifetime incidence of cardiovascular disease.

Tasmanian Community Fund; Diabetes Australia; Siemens Healthcare Australia; NHMRC: 100307; Select Foundation

Objectives The aim of this study was to compare trends and outcomes of 3 approaches to carotid revascularization in the coronary artery bypass graft (CABG) population when performed during the same hospitalization. Background The optimal approach to managing coexisting severe carotid and coronary disease remains controversial. Carotid endarterectomy (CEA) or carotid artery stenting (CAS) are used to decrease the risk of stroke in patients with carotid disease undergoing CABG surgery. Methods The authors conducted a serial, cross-sectional study with time trends of 3 revascularization groups during the same hospital admission: 1) combined CEA+CABG; 2) staged CEA+CABG; and 3) staged CAS+CABG from the Nationwide Inpatient Sample database 2004 to 2012. The primary composite endpoints were in-hospital all-cause death, stroke, and death/stroke. Results During the 9-year period, 22,501 concurrent carotid revascularizations and CABG surgeries during the same hospitalization were performed. Of these, 15,402 (68.4%) underwent combined CEA+CABG, 6,297 (28.0%) underwent staged CEA+CABG, and 802 (3.6%) underwent staged CAS+CABG. The overall rate of CEA+CABG decreased by 16.1% (ptrend = 0.03) from 2004 to 2012, whereas the rate of CAS+CABG did not significantly change during these years (ptrend = 0.10). The adjusted risk of death was greater, whereas risk of stroke was lower with both combined CEA+CABG (death odds ratio [OR]: 2.08, 95% confidence interval [CI]: 1.08 to 3.97; p = 0.03; stroke OR: 0.65, 95% CI: 0.42 to 1.01; p = 0.06) and staged CEA+CABG (death OR: 2.40, 95% CI: 1.43 to 4.05; p = 0.001; stroke OR: 0.50, 95% CI: 0.31 to 0.80; p = 0.004) approaches compared with CAS+CABG. The adjusted risk of death or stroke was similar in the 3 groups. Conclusions In patients with concomitant carotid and coronary disease undergoing combined revascularization, combined CEA+CABG is utilized most frequently, followed by staged CEA+CABG and staged CAS+CABG strategies. The staged CAS+CABG strategy was associated with lower risk of mortality, but higher risk of stroke. Future studies are needed to examine the risks/benefits of different carotid revascularization strategies for high-risk patients requiring concurrent CABG.

We agree with Dr. Sorigue and colleagues that besides cancer stage, cancer histology might also affect arterial thromboembolism risk, particularly in patients with non-Hodgkin lymphoma (NHL). To investigate this hypothesis, we performed the subgroup analyses suggested by the correspondents. Using

Background It is uncertain whether there is an association between left ventricular (LV) ejection fraction ( LVEF ) or LV wall motion abnormality and embolic stroke of undetermined source ( ESUS ). Methods and Results We performed a retrospective, cross‐sectional study of patients with acute ischemic stroke enrolled in the CAESAR (Cornell Acute Stroke Academic Registry) from 2011 to 2016. We restricted this study to patients with ESUS and, as controls, those with small‐ and large‐artery ischemic strokes. LVEF had to be above 35% to be considered ESUS . In a secondary analysis, we excluded patients with ESUS who had any evidence of ipsilateral carotid atherosclerosis. Multiple logistic regression was used to evaluate whether LVEF or LV wall motion abnormality was associated with ESUS . We performed a confirmatory study at another tertiary‐care center. We identified 885 patients with ESUS (n=503) or small‐ or large‐artery strokes (n=382). Among the entire cohort, LVEF was not associated with ESUS (odds ratio per 5% decrement in LVEF , 1.0; 95% CI, 1.0–1.1) and LV wall motion abnormality was not associated with ESUS (odds ratio, 0.9; 95% CI, 0.5–1.6). The results were identical in our confirmatory study. In our secondary analysis excluding ESUS patients with any evidence of ipsilateral carotid atherosclerosis, there was an association between LVEF and ESUS (odds ratio per 5% decrement in LVEF , 1.2; 95% CI, 1.0–1.5; P =0.04). Conclusions Among the entire cohort, no association existed between LVEF or LV wall motion abnormality and ESUS ; however, after excluding ESUS patients with any evidence of ipsilateral carotid atherosclerosis, lower LVEF appeared to be associated with ESUS .

Background and Purpose— It is uncertain whether heart transplantation decreases the risk of stroke. The objective of our study was to determine whether heart transplantation is associated with a decreased risk of subsequent stroke among patients with heart failure awaiting transplantation. Methods— We performed a retrospective cohort study using administrative data from New York, California, and Florida between 2005 and 2015. Individuals with heart failure awaiting heart transplantation were identified using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for heart failure in combination with code V49.83 for awaiting organ transplant status. Individuals with prior stroke were excluded. Our primary exposure variable was heart transplantation, modeled as a time-varying covariate and defined by procedure code 37.51. The primary outcome was stroke, defined as the composite of ischemic and hemorrhagic stroke. Survival statistics were used to calculate stroke incidence, and Cox proportional hazards analysis was used to determine the association between heart transplantation and stroke while adjusting for demographics, stroke risk factors, Elixhauser comorbidities, and implantation of a left ventricular assist device. Results— We identified 7848 patients with heart failure awaiting heart transplantation, of whom 1068 (13.6%) underwent heart transplantation. During a mean follow-up of 2.7 years, we identified 428 strokes. The annual incidence of stroke was 0.7% (95% CI, 0.5%–1.0%) after heart transplantation versus 2.4% (95% CI, 2.2%–2.6%) among those awaiting heart transplantation. After adjustment for potential confounders, heart transplantation was associated with a lower risk of stroke (hazard ratio, 0.4; 95% CI, 0.2–0.6). Conclusions— Heart transplantation is associated with a decreased risk of stroke among patients with heart failure awaiting transplantation.