Atrial fibrillation onset before heart failure or vice versa: what is worst? A nationwide register study.

AIMS: Atrial 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 RESULTS: We 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 (<0.001), and this remained significant in the adjusted analyses with hazard ratios (95% confidence intervals) of 1.26 (1.22-1.30) compared to AF before HF. Finally, antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation were associated with a lower hazard ratio of the composite endpoint (all < 0.001). CONCLUSIONS: In 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.

Aortic Root Dilatation in Hypertensive Patients with Left Ventricular Hypertrophy-Application of A New Multivariate Predictive Model. The Life Study.

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.

Clinical Characteristics and Outcomes of Adults With a History of Heart Failure Hospitalized for COVID-19.

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.

Silent Myocardial Infarction and Subsequent Ischemic Stroke in the Cardiovascular Health Study.

OBJECTIVE: To 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. METHODS: The 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. RESULTS: Among 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). CONCLUSION: In a community-based sample, we found an association between silent MI and ischemic stroke.

Risk for cardiovascular events following 'microsize' versus usual myocardial infarctions.

BACKGROUND: Microsize 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 RESULTS: Prospective 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 <0.5 ng/mL) or usual MI (peak troponin ≥0.5 ng/mL). Participants were followed for a composite of cardiovascular events that included recurrent MI, coronary revascularisation, fatal CHD and heart failure, and all-cause mortality. Overall, 1024 participants with an incident MI were included in the analysis (328 with microsize MI and 696 with usual MI). Participants with microsize MI were more likely to be older and black. The multivariable-adjusted adjustment HR for cardiovascular events among participants with microsize versus usual MI after a median follow-up of 1.7 years was 1.11 (95% CI 0.86 to 1.44). The multivariable-adjusted HR for all-cause mortality after 28 days from incident MI among participants with microsize versus usual MI after a median follow-up of 3.6 years was 1.09 (95% CI 0.81 to 1.45). CONCLUSION: Microsize 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.

Associations between the size and location of myocardial infarction and cerebral infarction.

BACKGROUND: Myocardial infarction (MI) is a known cause of cerebral infarction. We assessed whether the size and location of MI is associated with the risk of cerebral infarction. METHODS AND RESULTS: We performed a cross-sectional study of adults who underwent both brain MRI and delayed-enhancement cardiac MRI (DE-CMR) within 365 days of each other at Weill Cornell Medicine between 2014 and 2017 and had evidence of MI on DE-CMR. We used multiple logistic regression to evaluate associations between MI size and any cerebral infarction, apical MI location and any cerebral infarction, and MI size/location and cortical versus subcortical cerebral infarction. Models were adjusted for demographics, and the total number of vascular risk factors. Among 234 patients who underwent both DE-CMR and brain MRI within 365 days, 76 had evidence for MI on DE-CMR. Among these 76 patients, 51 (67.1%) had evidence of cerebral infarction. The size of MI (global MI burden) was not associated with any cerebral infarction (OR per 5% increase in MI size, 1.12; 95% CI, 0.85-1.47), but was associated with cortical cerebral infarction (OR per 5% increase in MI size, 1.30; 95% CI, 1.00.-1.68). Similarly, apical MI location was not associated with any cerebral infarction (OR 2.63, 95% CI, 0.78-8.87), but was associated with cortical cerebral infarction (OR, 3.67; 95% CI, 1.19-11.33). CONCLUSION: Among patients with MI on cardiac MRI, both size and apical location of MI were associated with cortical cerebral infarction. Our results may help stratify cardioembolic risk and inform antithrombotic treatment algorithms among patients with MI.

Machine Learning Prediction of Stroke Mechanism in Embolic Strokes of Undetermined Source.

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.

On-treatment HDL cholesterol predicts incident atrial fibrillation in hypertensive patients with left ventricular hypertrophy.

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.

Electrocardiographic Findings in Coronavirus Disease-19: Insights on Mortality and Underlying Myocardial Processes.

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.

Association Between Troponin Levels and Visceral Infarction in Patients with Acute Ischemic Stroke.

BACKGROUND: Visceral infarctions appear to be more common in patients with embolic stroke subtypes, but their relation to troponin elevation remains uncertain. METHODS: Among patients with acute ischemic stroke enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) from 2011 to 2016, we included those with troponin measured within 24 hours from stroke onset and a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. A troponin elevation was defined as a value exceeding our laboratory's upper limit of normal (.04 ng/ mL) in the absence of a clinically recognized acute ST-segment elevation myocardial infarction. Visceral infarction was defined as a renal or splenic infarction as ascertained by a single radiologist blinded to patients' other characteristics. Multivariable logistic regression was used to evaluate the association between elevated troponin and visceral infarction. RESULTS: Among 2116 patients registered in CAESAR from 2011 to 2016, 153 patients had both a troponin assay and a contrast-enhanced abdominal computed tomographic scan, of whom 33 (21%) had an elevated troponin and 22 (14%) had a visceral infarction. The prevalence of visceral infarction was higher among patients with an elevated troponin (30%; 95% confidence interval [CI], 16%-49%) than among patients without an elevated troponin (10%; 95% CI, 5%-17%) (P = .003). After adjustment for demographics and comorbidities, we found a significant association between elevated troponin and visceral infarction (odds ratio, 3.9; 95% CI, 1.5-10.4). CONCLUSIONS: Among patients with acute ischemic stroke, elevated troponin was associated with visceral infarction. Our results demonstrate that poststroke troponin elevation may indicate the presence of underlying embolic sources.

The risk of arterial thromboembolic events after cancer diagnosis.

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.

Relationship between left atrial volume and ischemic stroke subtype.

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 < 0.001) from 48.8 (±30.0) mL/m2 in cardioembolic strokes to 30.3 (±10.5) mL/m2 in small-vessel strokes. LAVI was larger in ESUS (33.3 ± 13.6 mL/m2 ) than in small- or large-vessel stroke (30.9 ± 10.7 mL/m2 ) (P = 0.01). The association between LAVI and ESUS persisted after the adjustment for demographics and comorbidities: a 10 mL/m2 increase in LAVI was associated with a 4.4% increase in ESUS probability (95% CI, 2.3%-6.4%). Results were similar after excluding patients with AF during post-discharge heart-rhythm monitoring. INTERPRETATION: We found larger left atria among patients with ESUS versus non-cardioembolic stroke. There was significant overlap in left atrial size between ESUS and non-cardioembolic stroke, highlighting that many ESUS cases are not cardioembolic.

Antihypertensive therapy prevents new-onset atrial fibrillation in patients with isolated systolic hypertension: the LIFE study.

Aims: Atrial fibrillation (AF) is associated with increased cardiovascular risk and the incidence increases with age, hypertension and left ventricular hypertrophy (LVH). Reducing in-treatment systolic blood pressure (SBP) prevents new-onset AF but has previously not been studied in patients with isolated systolic hypertension (ISH). We aimed to investigate the effect on preventing new-onset AF by decreased in-treatment SBP in patients with ISH compared to patients with non-ISH. Methods and results: Double-blind, randomized, parallel-group study of 1320 patients with ISH and electrocardiographic (ECG) LVH, included among the 9193 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Annual ECGs were Minnesota coded centrally, and new-onset AF was evaluated in 1248 ISH patients and compared with 7583 non-ISH patients during mean 4.8 ± 0.9 years follow-up. Cox regression analyses were used to assess the effect of reduced in-treatment SBP. New-onset AF occurred in 61 (4.9%) ISH patients and 292 (3.9%) non-ISH patients. In multivariate analysis lower in-treatment SBP was associated with 17% risk reduction (p = 0.008) for new-onset AF in ISH patients and 9% risk reduction (p = 0.006) in non-ISH patients per 10 mmHg decrease in in-treatment SBP, independent of treatment modality, baseline risk factors, baseline SBP and in-treatment heart rate and ECG-LVH. There was a significant interaction (p = 0.041) in favor of SBP reduction and AF prevention in ISH vs. non-ISH patients. Conclusion: Our data suggest that the effect of in-treatment SBP reduction in preventing new-onset AF is stronger in ISH compared to non-ISH patients with hypertension and ECG-LVH. However, the principal findings were the same in ISH and non-ISH patients.

Association Between Left Ventricular Ejection Fraction, Wall Motion Abnormality, and Embolic Stroke of Undetermined Source.

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 .

Risk factors for 'microsize' vs. usual myocardial infarctions in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

AIMS: A recently described phenomenon is that of myocardial infarction (MI) events that meet criteria for MI, but that have very low peak troponin elevations, so-called 'microsize MI'. These events are very common and associated with increased risk of all-cause mortality. Our aim is to compare risk factors for microsize MI vs. usual MI events. METHODS AND RESULTS: Among 24 470 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort free of coronary heart disease at baseline, heart-related hospitalizations were expert adjudicated for MI using published guidelines. Myocardial infarctions were classified as microsize MI (peak troponin <0.5 ng/mL) or usual MI (peak troponin ≥0.5 ng/mL). Competing risk analyses assessed associations between baseline risk factors and incident microsize vs. usual MI. Between 2003 and 2013 there were 891 MIs; 279 were microsize MI and 612 were usual MI. Risk factors for both usual MI and microsize MI include age, gender, diabetes, and urinary albumin to creatinine ratio. Risk factors for only usual MI include Residence in the Stroke Belt and Buckle regions and current smoking. Black race was associated with a uniquely lower risk of usual MI. CONCLUSION: The similarities in risk profiles suggest a possible common aetiology and should encourage clinicians to both treat reversible risk factors for microsize MI and to initiate secondary prevention strategies following these events until this emerging clinical entity is better understood. Future studies should further assess the clinical outcomes of these two entities and their effect on future management.

Association Between Heart Transplantation and Subsequent Risk of Stroke Among Patients With Heart Failure.

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.

Association of left bundle branch block with new onset abnormal wall motion in treated hypertensive patients with left ventricle hypertrophy: the LIFE Echo Sub-study.

AIMS: We aimed to investigate whether left bundle branch block (LBBB) is related to new-onset left ventricle (LV) wall motion abnormalities during treatment in hypertensive patients with electrocardiographic (ECG) defined left ventricular hypertrophy (LVH). METHODS AND RESULTS: 960 patients with essential hypertension and ECG-LVH participating in the LIFE Echo Sub-study were investigated at baseline and annually with echocardiography, during randomized antihypertensive therapy. After excluding patients with LV wall motion abnormalities at baseline and patients developing new-onset LBBB during study time, we investigated 784 patients. The participants with (n = 32) and without (n = 752) LBBB were similar regarding most baseline variables. Logistic regression models controlling for LV mass index, Framingham risk score, and randomized treatment assignment were used to assess the odds ratio of developing new-onset abnormal LV wall motion on annual follow-up echocardiograms. The likelihood of developing new global LV wall motion abnormalities in patients with LBBB was not higher compared to those without LBBB except at year 5 (p = .002). The likelihood of developing new segmental LV wall motion abnormalities in patients with LBBB was however higher compared to patients without LBBB after 1 year (OR = 3.1, 95% CI = 0.7-14.2, p = .173); 2 years (OR = 6.9, 2.1-22.4, p = .003); 3 years (OR = 5.3, 2.0-14.3, p < .001), 4 years (OR = 4.0, 1.6-10.3, p = .003 and 5 years (OR = 4.1, 1.0-16.2, p = .394) of treatment. CONCLUSION: Among patients with ECG-LVH, undergoing antihypertensive treatment, the presence of LBBB independently identifies individuals with ∼3- to 7-fold greater odds of developing new segmental abnormal LV wall motion. These findings suggest that LBBB may be a marker for progressive myocardial disease.

Effect of antihypertensive therapy on development of incident conduction system disease in hypertensive patients.

BACKGROUND: Previous work has demonstrated that treatment of hypertensive patients with the angiotensin-converting enzyme inhibitor lisinopril was associated with a reduced incidence of a composite conduction system disease endpoint and also left bundle branch block (LBBB) compared with chlorthalidone therapy. The relationship of incident conduction system disease to angiotensin receptor blocker therapy has not been examined. METHODS: Risk of new right (RBBB) or LBBB in relation to losartan-based vs. atenolol-based treatment was assessed in 8342 hypertensive patients without baseline RBBB or LBBB. Risk of incident intraventricular conduction delay (IVCD), defined as new QRS duration at least 110 ms was assessed in the 7110 patient subset who also had baseline QRS duration less than 110 ms. QRS duration and BBB were determined on in-study ECGs done at 6 months, 1 year and then yearly. RESULTS: During 4.8 ±â€Š1.0 years follow-up, 459 patients developed new LBBB (5.5%), 184 (2.2) new RBBB and 1173 (16.5%) a new IVCD. In univariate Cox analyses, losartan-based treatment was not associated with a significantly reduced risk of either new LBBB (hazard ratio 0.95, 95% CI 0.79-1.14, P = 0.583) or RBBB (hazard ratio 1.02, 95% CI 0.76-1.36, P = 0.903), but resulted in a 15% lower risk of new IVCD (hazard ratio 0.85, 95% CI 0.76-0.95, P = 0.005). In a multivariable Cox model that adjusted for other statistically significant predictors of incident IVCD in this population (age, sex, race, history of ischemic heart disease, MI, heart failure, diabetes or atrial fibrillation, prior antihypertensive treatment, baseline total and HDL cholesterol, serum glucose and creatinine and baseline QRS duration as standard covariates and incident MI and on-treatment systolic and diastolic pressure, BMI and Cornell voltage as time-dependent covariates), losartan treatment remained associated with a 13% lower risk of new IVCD (hazard ratio 0.87, 95% CI 0.77-0.98, P = 0.021). CONCLUSION: Incident IVCD, but not BBB, is significantly reduced by losartan-based treatment. Further study is warranted to assess the potential differential impact of this therapy on QRS prolongation vs. development of more discrete conduction system block. CLINICAL TRIALS REGISTRATION: .

Arterial thromboembolic events preceding the diagnosis of cancer in older persons.

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.