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Aims There is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment. Methods and results We investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. LV enlargement, whether by diameter [LV end‐diastolic diameter index (LVEDDI) and LV end‐systolic diameter index (LVESDI)] or volume [LV end‐diastolic volume index (LVEDVI) and LV end‐systolic volume index (LVESVI)], was independently associated with all‐cause death [LVEDDI: hazard ratio (HR) per cm/m2 1.53, LVESDI: HR per cm/m2 1.65, LVEDVI: HR per 10 mL/m2 1.07, and LVESVI: HR per 10 mL/m2 1.10; all P values

BACKGROUND: Prolonged monitoring of cardiac rhythm has been used to screen for subclinical atrial fibrillation (AF); little is known about other arrhythmias in the general population, especially in the elderly, who are at higher risk of arrhythmias. METHODS: We evaluated the frequency of arrhythmias in the tri-ethnic (white, Black, Hispanic), community-based Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study using a patch-based recorder for up to 14 days in 527 participants free of AF, congestive heart failure (CHF) or history of stroke. Differences according to gender, age, ethnicity and presence of hypertension, diabetes and pertinent ECG and echocardiographic variables were examined. RESULTS: Mean age was 77.2±6.8 years (37.2% men, 62.8% women). AF was present in 10 participants (1.9%), only 2 of them symptomatic. Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) episodes were observed in 84.4% and 25.0% but only 13.5% and 10.6% of participants reported symptoms, respectively. Severe bradycardia (75 years; ventricular arrhythmias and severe bradycardia were more common in men. Whites had significantly more episodes of AF than Hispanics, SVT than Blacks and VT≥10 beats than Hispanics and Blacks. Hypertensives had more episodes of severe bradycardia. LV hypertrophy or LVEF

Aims This study aimed to investigate the impact of baseline 6 min walk test distance (6MWTD) on time to major cardiovascular (CV) events in heart failure with reduced ejection fraction (HFrEF) and its impact in clinically relevant subgroups. Methods and results In the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, 6MWTD at baseline was available in 2102 HFrEF patients. Median follow‐up was 3.4 years. All‐cause death and heart failure hospitalization (HFH) exhibited a significant non‐linear relationship with 6MWTD (P = 0.023 and 0.032, respectively), whereas a significant association between 6MWTD and CV death was shown in a linear model [hazard ratio (HR) per 10 m increase, 0.989; P = 0.011]. In linear splines with the best cut‐off point at 200 m, the positive effect of a longer 6MWTD on all‐cause death and HFH was only observed for 6MWTD > 200 m (HR per 10 m increase, 0.987; P = 0.0036 and 0.986; P = 0.0022, respectively). The associations between 6MWTD and CV outcomes were consistent across clinical subgroups; for age, a significant relationship between 6MWTD and HFH was observed in patients ≥60 years (HR per 10 m increase, 0.98; P

Purpose Although subclinical hypothyroidism (SCH) is a common clinical entity and carries independent risk for incident heart failure (HF), its possible association with subclinical cardiac dysfunction is unclear. Left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic strain can unmask subclinical left heart abnormalities and are excellent predictors for HF. This study aimed to investigate the association between the presence of SCH and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease. Methods We examined 1078 participants who voluntarily underwent extensive cardiovascular health check-ups, including laboratory tests and 2-dimensional speckle-tracking echocardiography to assess LVGLS and LA reservoir, conduit, and pump strain. SCH was defined as an elevated serum thyroid-stimulating hormone level with normal concentration of free thyroxine. Results Mean age was 62 ± 12 years, and 56% were men. Seventy-eight (7.2%) participants exhibited SCH. Individuals with SCH had significantly reduced LA reservoir (37.1 ± 6.6% vs 39.1 ± 6.6%; P = 0.011) and conduit strain (17.3 ± 6.3% vs 19.3 ± 6.6%; P = 0.012) compared with those with euthyroidism, whereas there was no significant difference in left ventricular ejection fraction, LA volume index, LVGLS, and LA pump strain between the 2 groups. In multivariable analyses, SCH remained associated with impaired LA reservoir strain, independent of age, traditional cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters. including LVGLS (standardized β −0.054; P = 0.032). Conclusions In an unselected community-based cohort, individuals with SCH had significantly impaired LA phasic function. This association may be involved in the higher incidence of HF in subjects with SCH.

Objectives Recently, more sophisticated blood pressure (BP) measurements, such as central and ambulatory BP (ABP), have proven to be stronger predictors of future cardiovascular disease than conventional office BP. Their predictive value for atrial fibrillation development is not established. We investigated the prognostic impact for incident atrial fibrillation of office, central and ambulatory BP measurements in a predominantly older population-based cohort. Methods Of 1004 participants in the Cardiovascular Abnormalities and Brain Lesions (CABL) study, 769 in sinus rhythm with no history of atrial fibrillation or stroke (mean age 70.5 years) underwent ABP and arterial wave reflection analysis for central BP determination. Fine and Gray's proportional subdistribution hazards models were used to assess the association of BP parameters with incident atrial fibrillation. Results During 9.5 years, atrial fibrillation occurred in 83 participants. No office BP variable showed a significant association with incident atrial fibrillation. Central SBP and central pulse pressure were marginally associated with incident atrial fibrillation in multivariate analysis. Among ABP variables, 24-h SBP [adjusted hazard ratio per 10 mmHg, 1.24; 95% confidence interval (CI) 1.07--1.44; P = 0.004], daytime SBP (adjusted hazard ratio per 10 mmHg, 1.21; 95% CI 1.04--1.40; P = 0.011) and night-time SBP (adjusted hazard ratio per 10 mmHg, 1.22; 95% CI 1.07--1.39; P = 0.002) were significantly associated with incident atrial fibillation. Conclusion In a predominantly older, stroke-free community-based cohort, ABP was a better independent predictor of incident atrial fibrillation than central BP, whereas office BP was inadequate for this purpose.

Background Mitochondrial permeability transition pore (mPTP) closure triggers cardiomyocyte differentiation during development while pathological opening causes cell death during myocardial ischemia-reperfusion and heart failure. Ubiquinone modulates the mPTP; however, little is known about its mechanistic role in health and disease. We previously found excessive proton leak in newborn Fmr1 KO mouse forebrain caused by ubiquinone deficiency and increased open mPTP probability. Because of the physiological differences between the heart and brain during maturation, we hypothesized that developing Fmr1 KO cardiomyocyte mitochondria would demonstrate dissimilar features. Methods Newborn male Fmr1 KO mice and controls were assessed. Respiratory chain enzyme activity, ubiquinone content, proton leak, and oxygen consumption were measured in cardiomyocyte mitochondria. Cardiac function was evaluated via echocardiography. Results In contrast to controls, Fmr1 KO cardiomyocyte mitochondria demonstrated increased ubiquinone content and decreased proton leak. Leak was cyclosporine (CsA)-sensitive in controls and CsA-insensitive in Fmr1 KOs. There was no difference in absolute mitochondrial respiration or cardiac function between strains. Conclusion These findings establish the newborn Fmr1 KO mouse as a novel model of excess ubiquinone and closed mPTP in the developing heart. Such a model may help provide insight into the biology of cardiac development and pathophysiology of neonatal heart failure. Impact Ubiquinone is in excess and the mPTP is closed in the developing FXS heart. Strengthens evidence of open mPTP probability in the normally developing postnatal murine heart and provides new evidence for premature closure of the mPTP in Fmr1 mutants. Establishes a novel model of excess CoQ and a closed pore in the developing heart. Such a model will be a valuable tool used to better understand the role of ubiquinone and the mPTP in the neonatal heart in health and disease.

Background Increased arterial stiffness has been proposed as one of the key mechanisms of incident heart failure with preserved ejection fraction (HFpEF). However, the possible association between arterial stiffness and subclinical left ventricular (LV) dysfunction and possible sex-specific differences remain unclarified. LV strain is emerging as a highly sensitive tool to unmask early LV abnormalities. Purpose We investigated whether increased arterial stiffness is independently associated with subclinical LV dysfunction in a large community-based cohort without overt cardiovascular disease. Methods We examined 1,155 participants who underwent extensive cardiovascular examination. Speckle-tracking echocardiography was employed to assess LV global longitudinal strain (LVGLS) and circumferential strain (GCS), and arterial stiffness was assessed by cardio-ankle vascular index (CAVI). Results Mean age was 62±12 years, and 56% were male. CAVI as continuous variable was associated with abnormal LVGLS (>−18.6%), independent of cardiovascular risk factors and pertinent laboratory and echocardiographic parameters (adjusted odds ratio [OR] 1.23, p=0.034), whereas there was no relationship with LVGCS. In sex-stratified analysis, more pronounced association between quartiles of CAVI and abnormal LVGLS was observed in women than in men (unadjusted OR = 6.43 in women and 2.46 in men for upper quartile vs. lower quartile, both p Conclusion Increased arterial stiffness was independently associated with decreased LVGLS even in the absence of overt cardiovascular disease; a sex-specific pattern exists in the alteration of vascular-ventricular coupling, which might partially explain the greater susceptibility to HFpEF in women. Funding Acknowledgement Type of funding source: None

Aims Although serum uric acid (SUA) level is correlated with oxidative stress and serves as a marker of poor prognosis in heart failure patients, its possible association with subclinical left ventricular (LV) dysfunction has not been evaluated. This study aimed to investigate the association between SUA and subclinical LV dysfunction in a sample of a general population without overt cardiac disease. Methods and results We examined 1175 participants who underwent extensive cardiovascular health check‐up including laboratory tests and speckle‐tracking echocardiography to assess LV global longitudinal strain (GLS). The association of SUA concentration, as a continuous variable and a categorical variable using quartiles, with the presence of abnormal LVGLS was assessed. Mean age was 62 ± 12 years, and 656 (56%) were male participants. Mean SUA was 5.6 ± 1.3 mg/dL (25th–75th percentile, 4.6–6.5 mg/dL). The prevalence of abnormal LVGLS (greater than –18.6%) was greatest in the upper quartile of SUA. In multivariable analysis, SUA as a continuous variable was significantly associated with abnormal LVGLS [adjusted odds ratio (OR), 1.26 per 1 mg/dL; P = 0.008] independent of traditional cardiovascular risk factors, pertinent laboratory parameters and echocardiographic measures, and medications. In the categorical analysis, the upper quartile of SUA was independently associated with abnormal LVGLS in a fully adjusted model (adjusted OR, 2.28 vs. lowest quartile; P = 0.020). Conclusions In a sample of the general population, an elevated SUA was independently associated with subclinical LV dysfunction. Assessment of LVGLS may add important prognostic information in individuals with elevated SUA, even in the absence of overt cardiac disease.

Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that subclinical left ventricular dysfunction adversely affects LA/RV geometry and function even in a preclinical setting. This study aimed to investigate the atrioventricular and ventricular functional interdependence in a community‐based cohort without overt cardiovascular disease. Methods and Results Left ventricular global longitudinal strain (LVGLS), RV free‐wall longitudinal strain and LA phasic strain were assessed by speckle‐tracking echocardiography in 1080 participants (600 men; 62±12 years) between 2014 and 2018. One hundred and forty‐three participants (13.2%) had an abnormal LVGLS (>−18.6%). LA reservoir strain, conduit strain, and RV free‐wall longitudinal strain were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (all P −19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS. Decreased LVGLS was associated with worse LA reservoir strain, conduit strain and RV free‐wall longitudinal strain (standardized β=−0.20, −0.19 and 0.11 respectively, all P 28.6 pg/mL for men and >44.4 pg/mL for women) compared with normal LVGLS (odds ratio, 2.01; P =0.030). Conclusions LA/RV dysfunction was present in 20% individuals with abnormal LVGLS and multi‐chamber impairment was associated with elevated B‐type natriuretic peptide level, which may provide valuable insights for a better understanding of atrioventricular and ventricular interdependence and possibly heart failure preventive strategies.

RATIONALE AND OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP 30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI −3.01, 6.82), 0.003 cm(3) (asinh transformed, 95% CI −0.13, 0.13), and −7.0 cm(3) (95% CI −13.3, −0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04). LIMITATIONS: Measurement variability due to multi-site design. CONCLUSIONS: Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease. FUNDING: The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with the study number NCT01206062.

BACKGROUND: LV hypertrophy is an independent risk factor for cardiovascular outcomes. There are limited data about modifiable factors associated with progression of LV hypertrophy in the older adults. Our objective is to describe the changes in left ventricular (LV) mass and geometry over time in a predominantly older multi-ethnic cohort and to identify possible predictors of changes over time. METHODS: We analyzed data from participants in the Northern Manhattan Study (NOMAS) who underwent serial echocardiographic studies, comparing the baseline and the most recent echocardiograms. We recorded changes in LV mass and geometry and correlated them with baseline characteristics using linear regression models. RESULTS: There were 826 participants (mean age 64.2 ± 8.0 years) included in the analysis (time between measurements: 8.5 ± 2.7 years). Overall, LV mass index increased from 45.0 ± 12.7 to 50.3 ± 14.6 g/m(2.7) (p < 0.001). There were 548 participants (66.3%) with LV mass increase; 258 subjects (31.2%) showed worsening LV geometry. Multivariable analysis showed that change in LV mass index was independently associated with baseline LV mass index (β estimate: −17.000, [standard error: 1.508], p < 0.001), hypertension (2.094 [0.816], p=0.011), body mass index (0.503 [0.088], p < 0.001) and waist-to-hip ratio (1.031 [0.385], p=0.008).Both waist-to-hip ratio or waist-to-height ratio remained significantly associated with LV mass increase even after adjusting for body mass index (p= 0.008 and p=0.036, respectively) CONCLUSIONS: Regardless of race/ethnicity, LV mass progressed over time in the older adults. We also observed worsening geometry was frequent. Assessment of central obesity in the older population is important because indicators of central obesity add prognostic value over body mass index for the risk of LV mass increase.

Hypertension is the most prevalent modifiable risk factor for stroke. Office blood pressure (BP) measurements may have limitations in defining the impact of hypertension on stroke. Our aim was to compare the stroke risk for office, central, and ambulatory BP measurements in a predominantly older population-based prospective cohort. Participants in the CABL study (Cardiovascular Abnormalities and Brain Lesions; n=816; mean age, 70.8±9.0 years; 39.8% men) underwent applanation tonometry of the radial artery for central BP and 24-hour ambulatory BP monitoring. During a follow-up of 9.6±3.1 years, stroke occurred in 76 participants (9.3%). Among office BP variables, only diastolic BP was associated with stroke in multivariable competing risk model ( P =0.016). None of the central BP variables showed a significant association with stroke. Conversely, all ambulatory systolic and diastolic BP variables were significantly associated with stroke after adjustment for clinical confounders (all P P

Obesity increases the risk for atrial fibrillation (AF), although the impact of abdominal fat distribution on left atrial (LA) morphology and functional remodeling remains unclear. This study aimed to investigate whether increased abdominal adiposity is independently associated with impaired LA function and/or LA enlargement in a sample of the general population and to evaluate the role of adipokines in this association.The study cohort consisted of 527 participants (362 men; 57 ± 10 years) without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination and echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess LA phasic function including reservoir, conduit and pump strain. LA reservoir and conduit strain decreased with increasing VFA quartiles (both p 0.05), whereas no significant differences were observed in LA volume index and pump strain. When stratified by SFA, there were no significant differences in LA size and function across the quartiles. In multivariable analysis, VFA was significantly associated with LA conduit strain independent of cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters (standardized β = -0.136, p = 0.019). VFA was correlated with serum adiponectin level (r = -0.51, p 0.001), but there was no association between adiponectin level and three LA phasic strains.In a sample of the general population, VFA accumulation was independently associated with worse LA conduit strain, which may be involved in the pathophysiological mechanism of obesity-related AF.

Background and Purpose: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. Methods: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS ( Results: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P =0.78), death (4.9% versus 8.5%, P =0.68), fatal strokes (2.4% versus 8.5%, P =0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P =0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. Conclusions: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT02283294.

Background Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease. Methods We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR − 16.65%). Results Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e′ ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (− 17.6 ± 2.6% vs. − 19.7 ± 3.1%, p Conclusions In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.

Introduction: Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure (HF). However, the alteration of atrioventricular and ventricular functional interdependence in a preclinical setting is unclear. We aimed to investigate the association between LA/RV functional remodeling and subclinical left ventricular (LV) dysfunction. Methods: LV global longitudinal strain (LVGLS), RV free wall longitudinal strain (RVLS) and LA reservoir strain were assessed by speckle-tracking echocardiography in 1,080 participants (600 men; 62±12 years) without cardiac disease. Results: A hundred and forty-three participants (13.2%) had an abnormal LVGLS (>-18.6%). LA reservoir strain and RVLS were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (both p -19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS, respectively (Figure). Decreased LVGLS was significantly associated with worse LA reservoir strain and RVLS (standardized β=-0.20 and 0.11 respectively, both p Conclusions: In the general population without overt cardiac disease, approximately 20% subjects with impaired LVGLS exhibited LA/RV dysfunction, and LVGLS was independently associated with both LA and RV strain. Our findings may provide valuable insights for a better understanding of HF pathophysiology and possibly preventive strategies.

Background: Although subclinical hypothyroidism (SCH) is a common clinical entity and carries independent risk for incident heart failure (HF), its possible association with subclinical cardiac dysfunction has not been extensively evaluated. Left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic strain can unmask subclinical left heart dysfunction and are excellent predictors for HF. This study aimed to investigate the association between the presence of SCH and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease. Methods: We examined 1,078 participants who underwent extensive cardiovascular health check-up including laboratory tests and 2-dimensional speckle-tracking echocardiography to assess LVGLS and LA reservoir, conduit and pump strain. SCH was defined as an elevated serum thyroid stimulating hormone level with normal concentration of free thyroxine. Results: Mean age was 62±12 years, and 56% were men. Seventy-eight (7.2%) participants exhibited SCH. Individuals with SCH had significantly reduced LA reservoir and conduit strain (both p Conclusions: In an unselected community-based cohort, individuals with SCH had significantly impaired LA function. This association may be involved in the higher incidence of HF in subjects with SCH.

Background Obesity carries independent risk for incident atrial fibrillation (AF), although the impact of abdominal fat distribution on LA morphological and functional remodeling is not fully elucidated. Speckle-tracking echocardiography is a novel and sensitive tool that allows quantification and detection of subtle alterations in left atrial (LA) phasic function. Purpose This study aimed to investigate whether increased visceral adiposity is independently associated with impaired LA phasic function in a community-based cohort. Methods We included 527 participants without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination and speckle-tracking echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess LA phasic function including reservoir, conduit and pump strain as well as left ventricular global longitudinal strain (LVGLS). Results Mean age was 57±10 years and 362 of the participants (69%) were men. LA reservoir and conduit strain were decreased according to the VFA quartiles (both p Conclusion In a sample of the general population, VFA accumulation was independently associated with worse LA conduit strain, which may be involved in the pathophysiological mechanism of obesity-related AF. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Yamauchi Susumu Scholarship for Cardiovascular Research

Background Prolonged monitoring of cardiac rhythm has been used in patients with symptomatic arrhythmias and to assess for atrial fibrillation (AF) after cryptogenic stroke, but not in the general population and especially in older adults. Purpose To evaluate the frequency of arrhythmias in a community-based cohort of older adults through 14-days continuous cardiac monitoring using a patch-based device. Methods Cardiac rhythm was analyzed in 533 participants free of AF and congestive heart failure (CHF) from the tri-ethnic (white, black, Hispanic) Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study. AF, supraventricular tachycardia (SVT, defined as 4 beats or more), premature atrial (PACs) and ventricular (PVCs) contractions, ventricular tachycardia (VT, defined as 4 beats or more), sinus pauses (SP) and atrio-ventricular blocks (AVB) were analyzed. Gender, age and race-ethnic differences were examined. Results Mean age was 77.2±6.8 years (198 men, 335 women). Recording duration was over 10 days in 91%, and over 13 days in 84%. AF was present in 10 participants (1.9%), atrial flutter in 1 (0.2%). Other arrhythmias are reported in the Table. SP (1.9%) and high-degree AVB (Mobitz II: 0.6%; 3rd degree: 0.9%) were rare. No significant race-ethnic differences were observed. Conclusion In older adults without history of stroke or CHF, prolonged rhythm monitoring revealed moderate frequency of AF, but higher than expected frequencies of AF-predisposing conditions such as SVT and frequent PACs. VT episodes were relatively frequent, whereas SP and AVB were less frequent than commonly believed. Most arrhythmias were more frequent in the oldest; ventricular arrhythmias were more common in men than in women. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NINDS R01 NS083874

Silent brain infarctions (SBI) and white matter hyperintensities (WMH) are associated with increased risk for stroke ([1][1]). Left atrial (LA) functional impairment is associated with increased cardiovascular events including stroke ([2][2]). Although LA volume measurement is the gold standard for

Background Despite growing evidence of cardiovascular complications associated with novel 2019 coronavirus disease (COVID-19), there is little data regarding the performance of transthoracic echocardiography (TTE) and spectrum of echocardiographic findings in this disease. Methods We performed a retrospective analysis of adult patients admitted to a quaternary care center in New York City between March 1st and April 3rd, 2020. Patients were included if they had a TTE performed during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record. Results Of 749 patients, 72 (9.6%) had a TTE following a positive SARS-CoV-2 PCR test. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). While most patients had preserved biventricular function, 34.7% were found to have a left ventricular ejection fraction (LVEF) ≤ 50% and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation there was an inverse relationship between high sensitivity Troponin T and LVEF (rho = -0.34, p=0.006). Among 20 patients with prior echocardiograms, only two (10%) patients had a new reduction in LVEF of more than 10%. Clinical management was changed in eight (24.2%) of individuals who had a TTE ordered for concern for acute major cardiovascular event; and three (14.3%) in whom TTE was ordered for hemodynamic evaluation. Conclusions This study describes the clinical indications for usage and diagnostic performance, as well as findings seen on TTE in hospitalized patients with COVID-19. In appropriately selected patients TTE can be an invaluable tool for guiding COVID-19 clinical management., Highlights • TTEs are performed in a minority of COVID-19 patients • Focused studies could be performed quickly and the majority of tests were diagnostic • Patients with elevated cardiac biomarkers were more likely to exhibit reduced LV function • In appropriately selected patients TTE can guide COVID-19 clinical management

OBJECTIVES Increased arterial stiffness is currently recognized as an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study aimed to investigate the association of arterial stiffness with left atrial (LA) volume and phasic function in a community-based cohort. METHODS We included 1156 participants without overt cardiovascular disease who underwent extensive cardiovascular examination. Arterial stiffness was evaluated by cardio-ankle vascular index (CAVI). Speckle-tracking echocardiography was employed to evaluate LA phasic function including reservoir, conduit, and pump strain as well as left ventricular global longitudinal strain (LVGLS). RESULTS CAVI was negatively correlated with reservoir and conduit strain (r = -0.37 and -0.45, both P

X-linked scapuloperoneal myopathy (X-SM), one of Four-and-a-half LIM 1 (FHL1) related diseases, is an adult-onset slowly progressive myopathy, often associated with cardiomyopathy. We previously generated a knock-in mouse model that has the same mutation (c.365 G > C, p.W122S) as human X-SM patients. The mutant male mouse developed late-onset slowly progressive myopathy without cardiomyopathy. In this study, we observed that heterozygous (Het) and homozygous (Homo) female mice did not show alterations of skeletal muscle function or histology. In contrast, 20-month-old mutant female mice showed signs of cardiomyopathy on echocardiograms with increased systolic diameter [wild-type (WT): 2.74 ± 0.22 mm, mean ± standard deviation (SD); Het: 3.13 ± 0.11 mm, P

Previous studies in patients with atrial fibrillation showed that a history of heart failure (HF) could negatively impact anticoagulation quality, as measured by the average time in therapeutic range (TTR). Whether additional markers of HF severity are associated with TTR has not been investigated thoroughly. We aimed to examine the potential role of HF severity in the quality of warfarin control in patients with HF with reduced ejection fraction. Data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial were used to investigate the association between TTR and HF severity. Multivariable logistic regression models were used to examine the association of markers of HF severity, including New York Heart Association (NYHA) class, Minnesota Living with HF (MLWHF) score, and frequency of HF hospitalization, with TTR ≥70% (high TTR). We included 1,067 participants (high TTR, N = 413; low TTR, N = 654) in the analysis. In unadjusted analysis, patients with a high TTR were older and less likely to have had strokes or receive other antiplatelet agents. Those patients also had lower NYHA class, better MLWHF scores, greater 6-minute walk distance, and lower frequency of HF hospitalizations. Multivariable analysis showed that NYHA class III and/or IV (Odds ratio [OR] 0.68 [95% confidence intervals [CIs] 0.49 to 0.94]), each 10-point increase in MLWHF score (i.e., worse health-related quality of life) (OR 0.92 [0.86 to 0.99]), and higher number of HF hospitalization per year (OR0.45 [0.30 to 0.67]) were associated with decreased likelihood of having high TTR. In HF patients with systolic dysfunction, NYHA class III and/or IV, poor health-related quality of life, and a higher rate of HF hospitalization were independently associated with suboptimal quality of warfarin anticoagulation control. These results affirm the need to assess the new approaches, such as direct oral anticoagulants, to prevent thromboembolism in this patient population.

Author(s): Di Tullio, Marco R; Qian, Min; Thompson, John LP; Labovitz, Arthur J; Mann, Douglas L; Sacco, Ralph L; Pullicino, Patrick M; Freudenberger, Ronald S; Teerlink, John R; Graham, Susan; Lip, Gregory YH; Levin, Bruce; Mohr, Jay P; Buchsbaum, Richard; Estol, Conrado J; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Homma, Shunichi; WARCEF Investigators | Abstract: AimsLeft atrium (LA) dilation is associated with adverse cardiovascular (CV) outcomes. Blood stasis, thrombus formation and atrial fibrillation may occur, especially in heart failure (HF) patients. It is not known whether preventive antithrombotic treatment may decrease the incidence of CV events in HF patients with LA enlargement. We investigated the relationship between LA enlargement and CV outcomes in HF patients and the effect of different antithrombotic treatments.Methods and resultsTwo-dimensional echocardiography with LA volume index (LAVi) measurement was performed in 1148 patients with systolic HF from the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. Patients were randomized to warfarin or aspirin and followed for 3.4 ± 1.7 years. While the primary aim of the trial was a composite of ischaemic stroke, death, and intracerebral haemorrhage, the present report focuses on the individual CV events, whose incidence was compared across different LAVi and treatment subgroups. After adjustment for demographics and clinical covariates, moderate or severe LA enlargement was significantly associated with total death (hazard ratio 1.6 and 2.7, respectively), CV death (HR 1.7 and 3.3), and HF hospitalization (HR 2.3 and 2.6) but not myocardial infarction (HR 1.0 and 1.4) or ischaemic stroke (1.1 and 1.5). The increased risk was observed in both patients treated with warfarin or aspirin. In warfarin-treated patients, a time in therapeutic range g60% was associated with lower event rates, and an interaction between LAVi and time in therapeutic range was observed for death (P = 0.034).ConclusionsIn patients with systolic HF, moderate or severe LA enlargement is associated with death and HF hospitalization despite treatment with antithrombotic medications. The possibility that achieving a more consistent therapeutic level of anticoagulation may decrease the risk of death requires further investigation.

Aims Left ventricular (LV) diastolic dysfunction may lead to heart failure. A high body mass index (BMI) is associated with worse LV diastolic function. However, knowledge of the longitudinal relation between changes in BMI and LV diastolic function is limited. Methods and results We retrospectively identified 165 asymptomatic individuals (aged 60 ± 10 years, 55% male) with preserved LV ejection fraction, who underwent repeated health check-ups (median interval: 365 days) at our hospital between 2009 and 2012. The longitudinal data were analysed using a linear mixed-effects model adjusted for important clinical variables at baseline to evaluate the associations between changes in BMI and LV diastolic function from one visit to the next. Baseline characteristics were BMI, 23 ± 3 kg/m2; E/E' ratio, 9 ± 2; E' velocity, 8 ± 2 cm/s; and left atrial (LA) volume index, 26 ± 8 mL/m2. Eighty-two of our participants had baseline LV diastolic dysfunction. In multivariable analyses, a BMI change was associated with a change in LV diastolic function. A one-unit decrease in BMI between consecutive visits corresponded to an average decrease in LA volume index of 0.80 mL/m2 (95% confidence interval: 0.38, 1.23; P

Echocardiography is often used in the clinic for detection and characterization of myocardial infarction. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique based on time-domain incremental motion and strain estimation that can evaluate changes in contractility in the heart. In this study, electromechanical activation is assessed in infarcted heart to determine whether EWI is capable of detecting and monitoring infarct formation. Additionally, methods for estimating electromechanical wave (EW) velocity are presented, and changes in the EW propagation velocity after infarct formation are studied. Five (n = 5) adult mongrels were used in this study. Successful infarct formation was achieved in three animals by ligation of the left anterior descending (LAD) coronary artery. Dogs were survived for a few days after LAD ligation and monitored daily with EWI. At the end of the survival period, dogs were sacrificed and TTC (tetrazolium chloride) staining confirmed the formation and location of the infarct. In all three dogs, as soon as day 1 EWI was capable of detecting late-activated and non-activated regions, which grew over the next few days. On final day images, the extent of these regions corresponded to the location of infarct as confirmed by staining. EW velocities in border zones of infarct were significantly lower post-infarct formation when compared to baseline, whereas velocities in healthy tissues were not. These results indicate that EWI and EW velocity might help with the detection of infarcts and their border zones, which may be useful for characterizing arrhythmogenic substrate.

The presence of a patent foramen ovale (PFO) has been found to be associated with an increased risk of cryptogenic stroke in many case-control studies. This paper reviews the current understanding of the pathophysiology and diagnosis of PFO, and therapeutic options of patients with PFO and cryptogenic stroke.

Aims General obesity, defined by increased body mass index (BMI), is associated with left atrial (LA) enlargement, a marker of cardiovascular risk in the general population. The association between abdominal adiposity, defined by increased waist circumference (WC) or waist-to-hip ratio (WHR), and LA phasic volumes and reservoir function is not well known. The aim of this study was to evaluate the association between different body size metrics and LA phasic volumes and reservoir function in the elderly. Methods and results Participants from the CABL (Cardiovascular Abnormalities and Brain Lesions) study underwent measurement of BMI, WC, and WHR. The LA maximum (LAVmax) and minimum (LAVmin) volumes, and LA reservoir function, measured as total emptying volume index (LAEVI), total emptying fraction (LAEF), and expansion index (LAEI), were assessed by real-time 3D echocardiography. The study population included 629 participants (mean age 71 ± 9 years, 61% women). Mean BMI was 27.9 ± 4.6 kg/m2, WC was 95.0 ± 11.7 cm, WHR was 0.91 ± 0.08. After adjusting for multiple potential confounders (demographics, cardiovascular risk factors, left ventricular mass index, and diastolic function), higher WC was significantly associated with higher LA phasic volumes (LAVmax, β = 0.10, P = 0.007 and LAVmin, β = 0.12, P = 0.002) and reduced reservoir function (LAEVI, β = -0.15, P = 0.001 and LAEI, β = -0.09, P = 0.027). WHR was significantly associated only with reduced reservoir function (LAEVI, β = -0.11, P = 0.012), whereas BMI was not associated with either LA phasic volumes or reservoir function. Conclusion In the elderly, WC may have more impact on LA phasic volumes and reservoir function, and therefore risk for cardiovascular events, than WHR and BMI.

Objectives This study sought to assess the prevalence and prognostic value of abnormalities in left atrial (LA) phasic volumes and reservoir function in a community cohort. Background LA enlargement is associated with adverse cardiovascular outcomes. Real-time 3-dimensional (RT3D) echocardiography allows assessment of LA phasic volumes and reservoir function. However, there is a paucity of data regarding normal values, clinical correlates, and prognostic value of RT3D echocardiography-derived LA phasic volumes and reservoir function, especially in the elderly, a subgroup at high risk for cardiovascular events. Methods Left atrial maximum volume (LAVimax), minimum volume (LAVimin), and reservoir function assessed as emptying volume (LAEV), emptying fraction (LAEF), and expansion index (LAEI), were measured by RT3D echocardiography in participants from a community-based cohort study. Cut-off values for LA phasic volumes were derived from a healthy subgroup of participants free of cardiovascular disease and risk factors (n = 142; 66 ± 9 years of age; 55% women). Annual follow-up examinations were performed for cardiovascular outcomes (myocardial infarction, ischemic stroke, and vascular death). Results The cohort included 706 participants (71 ± 9 years of age; 59% women). LAVimax and LAVimin were not associated with age in the healthy subgroup but progressively increased with age in the entire cohort (p Conclusions LA phasic volumes and reservoir functions assessed by RT3D echocardiography were strong independent predictors of cardiovascular events in a community-based elderly cohort. LAVimin and reservoir function assessment may improve cardiovascular outcome prediction over LAVimax.

Objectives The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Background Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. Methods We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). Results After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. Conclusions Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938)

Elevated blood pressure (BP) level is one of the most consistently identified risk factors for silent brain disease. BP values obtained at the proximal segment of the aorta (central BP) are more directly involved than brachial BP in the pathogenesis of cardiovascular disease. However, the association between central BP and silent cerebrovascular disease has not been clearly established. Participants in the CABL (Cardiovascular Abnormalities and Brain Lesions) study (n=993; mean age, 71.7±9.3 years; 37.9% men) underwent 2-dimensional echocardiography, arterial wave reflection analysis for determination of central BPs, and brain magnetic resonance imaging. Central BPs were calculated from the radial pulse waveform. Subclinical silent cerebrovascular disease was defined as silent brain infarction and white matter hyperintensity volume. Both brachial ( P =0.014) and central pulse pressure ( P =0.026) were independently associated with silent brain infarctions after adjustment for clinical variables, but not adjusting for each other. None of the brachial BP values was associated with upper quartile of white matter hyperintensity volume in multivariable analysis. Both central systolic BP ( P P

Myostatin (MSTN) is a transforming growth factor (TGF)-β superfamily member that acts as a negative regulator of muscle growth and may play a role in cardiac remodeling. We hypothesized that inhibition of activin type II receptors (ACTRII) to reduce MSTN signaling would reduce pathological cardiac remodeling in experimental heart failure (HF). C57BL/6J mice underwent left anterior descending coronary artery ligation under anesthesia to induce myocardial infarction (MI) or no ligation (sham). MI and sham animals were each randomly divided into groups ( n ≥ 10 mice/group) receiving an ACTRII or ACTRII/TGFβ receptor-signaling inhibiting strategy: 1) myo-Fc group (weekly 10 mg/kg Myo-Fc) or 2) Fol + TGFi group (daily 12 µg/kg follistatin plus 2 mg/kg TGFβ receptor inhibitor), versus controls. ACTRII/TGFBR signaling inhibition preserved cardiac function by echocardiography and prevented an increase in brain natriuretic peptide (BNP). ACTRII/TGFBR inhibition resulted in increased phosphorylation (P) of Akt and decreased P-p38 mitogen-activated protein kinase (MAPK) in MI mice. In vitro, Akt contributed to P-SMAD2,3, P-p38, and BNP regulation in cardiomyocytes. ACTRII/TGFBR inhibition increased sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) levels and decreased unfolded protein response (UPR) markers in MI mice. ACTRII/TGFBR inhibition was associated with a decrease in cardiac fibrosis and fibrosis markers, connective tissue growth factor (CTGF), type I collagen, fibronectin, α-smooth muscle actin, and matrix metalloproteinase (MMP)-12 in MI mice. MSTN exerted a direct regulation on the UPR marker eukaryotic translation initiation factor-2α (eIf2α) in cardiomyocytes. Our study suggests that ACTRII ligand inhibition has beneficial effects on cardiac signaling and fibrosis after ischemic HF. NEW & NOTEWORTHY Activin type II receptor ligand inhibition resulted in preserved cardiac function, a decrease in cardiac fibrosis, improved SERCA2a levels, and a prevention of the unfolded protein response in mice with myocardial infarction.

Aims Obesity carries significant risk for unfavorable ventricular remodeling and subsequent heart failure (HF) development, although the association between abdominal fat distribution and subclinical ventricular dysfunction is unclear. This study aimed to compare the subcutaneous and visceral abdominal adiposity with the risk of decreased ventricular strain. Methods We included 340 participants without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination, and speckle-tracking echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess left ventricular global longitudinal strain (LVGLS) and right ventricular free-wall longitudinal strain (RVLS). Results Mean age was 56 ± 9 years, and 244 of the participants (72%) were male. The mean LVGLS and RVLS were −19.1 ± 3.0% and −25.0 ± 4.1%, respectively. Both VFA and SFA correlated with LVGLS (r = 0.46 and r = 0.15, both p Conclusion In a sample of the general population, VFA, but not SFA, accumulation was significantly associated with decreased LV and RV strain, an association that may be involved in the increased risk of HF in obese individuals.

ObjectiveTo update the 2016 American Academy of Neurology (AAN) practice advisory for patients with stroke and patent foramen ovale (PFO).MethodsThe guideline panel followed the AAN 2017 guideline development process to systematically review studies published through December 2017 and formulate recommendations.Major recommendationsIn patients being considered for PFO closure, clinicians should ensure that an appropriately thorough evaluation has been performed to rule out alternative mechanisms of stroke (level B). In patients with a higher risk alternative mechanism of stroke identified, clinicians should not routinely recommend PFO closure (level B). Clinicians should counsel patients that having a PFO is common; that it occurs in about 1 in 4 adults in the general population; that it is difficult to determine with certainty whether their PFO caused their stroke; and that PFO closure probably reduces recurrent stroke risk in select patients (level B). In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural atrial fibrillation of 0.33% per year) (level C). In patients who opt to receive medical therapy alone without PFO closure, clinicians may recommend an antiplatelet medication such as aspirin or anticoagulation (level C).

Background Increased arterial stiffness is recognized as an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. Cardio-ankle vascular index (CAVI) is emerging as an important tool to assess arterial stiffness noninvasively which is derived from the concept of stiffness β index and is less dependent on blood pressure at the time of measurement than pulse wave velocity. Purpose This study aimed to investigate the association of arterial stiffness with left atrial (LA) volume and phasic function in a community-based cohort. Methods We included 1,156 participants without overt cardiovascular disease who underwent extensive cardiovascular examination. Arterial stiffness was evaluated by CAVI. Speckle-tracking echocardiography was employed to evaluate LA phasic function including reservoir, conduit and pump strain as well as left ventricular global longitudinal strain (LVGLS). Results CAVI was negatively correlated with reservoir and conduit strain (r=−0.37 and −0.45, both p Figure 1 Conclusion Arterial stiffness was independently associated with LA reservoir and conduit function, even in the absence of overt cardiovascular disease. This association may explain the higher incidence of atrial fibrillation in individuals with increased arterial stiffness.

AIMS: Although ambulatory blood pressure (BP) is a better predictor of cardiovascular outcomes than office BP, its association with subclinical cerebrovascular disease is not clarified. We investigated the associations of office and ambulatory BP values with subclinical cerebrovascular disease in a population based, predominantly elderly cohort without prior stroke. METHODS AND RESULTS: Eight hundred and twenty-eight participants underwent 24-h ambulatory BP monitoring (ABPM), 2D echocardiography and brain magnetic resonance imaging in the Cardiac Abnormalities and Brain Lesion (CABL) study. Daytime, night-time, and 24-h BPs, nocturnal dipping pattern, morning surge (MS), and 24-h variability were assessed. Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV). The association of BP measures with the presence of SBI and upper quartile of log-WMHV (log-WMHV4) was analysed. SBIs were detected in 111 patients (13.4%). Mean log-WMHV was −0.99 ± 0.94. In multivariable analysis, only night-time systolic BP (SBP) was significantly associated with SBI [odds ratio (OR) 1.15 per 10 mmHg, P = 0.042], independent of cardiovascular risk factors, and pertinent echocardiographic parameters. Although daytime, night-time, 24-h BPs, and non-dipping pattern were all significantly associated with log-WMHV4 (all P

The impact of aging on cardiac function is not fully elucidated. Speckle-tracking echocardiography can unmask subclinical cardiac dysfunction.This study investigated the impact of healthy aging on left ventricular (LV), right ventricular (RV), and left atrial (LA) performance and their relationship with serum B-type natriuretic peptide (BNP) levels in a sample of the general population without prevalent cardiovascular risk factors and structural heart disease.Speckle-tracking echocardiography was performed to assess LV global longitudinal strain (LVGLS), RV free wall strain, and LA phasic strain in 481 normal weight healthy participants who underwent extensive cardiovascular examination. Elevated BNP was defined as BNP37.82 pg/ml for men and50.86 pg/ml for women, which was the 90th percentile of BNP value distribution in the study population.Mean age was 60 ± 12 years (range: 24 to 86 years), and 46% of the participants were men. The earliest alteration of age-related cardiac performance was observed in LA reservoir and conduit strain starting from decade 5, followed by elevated E/e' from decade 6. LVGLS decreased starting from decade 7, whereas there were no significant differences in RV strain, LV ejection fraction, or LV mass index across the decades. In the multivariable linear regression analyses, age was an independent predictor of decreased LVGLS (standardized β = 0.21; p 0.001) and decreased LA phasic strain (standardized β = -0.40 and -0.61 for reservoir and conduit strain; both p 0.001). Age and LA strain were significantly associated with elevated BNP values (adjusted odds ratios: 1.10 and 0.93; both p 0.05, respectively), independent of ventricular morphology and function.Decreases in LA reservoir and conduit strain are the earliest markers of age-related cardiac remodeling, and LA reservoir strain is an independent predictor of elevated serum BNP level, with both possibly being markers of increased risk of heart failure in older adults.

Alcohol septal ablation (ASA) and ventricular septal myectomy (VSM) are 2 options of ventricular septal reduction therapy (VSRT) for obstructive hypertrophic cardiomyopathy (HC). We hypothesized that patients with HC who underwent ASA have a higher risk of acute care use (i.e., emergency department [ED] visit or unplanned hospitalization) for cardiovascular disease (CVD) than VSM. We performed a comparative effectiveness study of ASA versus VSM (reference group) among patients with HC who underwent VSRT, using population-based ED and inpatient databases in 3 states, 2005 to 2014. The outcome was acute care use for CVD during a 2-year post-VSRT period. We constructed univariable and multivariable logistic regression models to compare the risk during sequential 6-month periods. We also performed sensitivity analysis with propensity score-matching at 1:1 ratio. We identified 850 patients with HC who underwent VSRT, including 393 with ASA and 457 with VSM. During 13 to 18 months after VSRT, there was a nonsignificantly higher risk with ASA than VSM (adjusted odds ratio [OR] 1.73; 95% confidence interval [CI] 0.83 to 3.60; p = 0.14). Patients who had ASA had a significantly higher risk in the 19 to 24 months post-VSRT period (adjusted OR 2.12; 95% CI 1.06 to 4.23; p = 0.03). Similarly, the propensity score-matched analysis demonstrated a higher risk with ASA than VSM during 13 to 18 months (OR 2.97; 95% CI 1.04 to 8.46; p = 0.04) and 19 to 24 months (OR 7.06; 95% CI 2.04 to 24.36; p = 0.002) after VSRT. In conclusion, among 850 patients with HC who underwent VSRT, the risk of acute care use for CVD was higher after ASA than VSM during the second post-VSRT year.

Author(s): Lee, Tetz C; Qian, Min; Mu, Lan; Di Tullio, Marco R; Graham, Susan; Mann, Douglas L; Nakanishi, Koki; Teerlink, John R; Lip, Gregory YH; Freudenberger, Ronald S; Sacco, Ralph L; Mohr, Jay P; Labovitz, Arthur J; Ponikowski, Piotr; Lok, Dirk J; Estol, Conrado; Anker, Stefan D; Pullicino, Patrick M; Buchsbaum, Richard; Levin, Bruce; Thompson, John LP; Homma, Shunichi; Ye, Siqin; WARCEF Investigators | Abstract: AimsThere is debate on whether the beneficial effect of implantable cardioverter-defibrillators (ICDs) is attenuated in patients with non-ischaemic cardiomyopathy (NICM). We assess whether any ICD benefit differs between patients with NICM and those with ischaemic cardiomyopathy (ICM), using data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial.Methods and resultsWe performed a post hoc analysis using WARCEF (N = 2293; ICM, n = 991 vs. NICM, n = 1302), where participants received optimal medical treatment. We developed stratified propensity scores for having an ICD at baseline using 41 demographic and clinical variables and created 1:2 propensity-matched cohorts separately for ICM patients with ICD (N = 223 with ICD; N = 446 matched) and NICM patients (N = 195 with ICD; N = 390 matched). We constructed a Cox proportional hazards model to assess the effect of ICD status on mortality for patients with ICM and those with NICM and tested the interaction between ICD status and aetiology of heart failure. During mean follow-up of 3.5 ± 1.8 years, 527 patients died. The presence of ICD was associated with a lower risk of all-cause death among those with ICM (hazard ratio: 0.640; 95% confidence interval: 0.448 to 0.915; P = 0.015) but not among those with NICM (hazard ratio: 0.984; 95% confidence interval: 0.641 to 1.509; P = 0.941). There was weak evidence of interaction between ICD status and the aetiology of heart failure (P = 0.131).ConclusionsThe presence of ICD is associated with a survival benefit in patients with ICM but not in those with NICM.

A high pulse pressure (PP) is associated with adverse cardiovascular (CV) outcomes; however, this relationship may be reversed in patients with heart failure with reduced ejection fraction (HFREF).Patients from the WARCEF trial with left ventricular ejection fraction ≤35% were included. PP was divided into tertiles: ≤42, 42-54 and54 mm Hg. Age and ejection fraction adjusted Kaplan-Meier curves were generated to evaluate the relationship between PP and outcomes [mortality, CV mortality, stroke and HF hospitalizations (HFH)]. Cox proportional hazards models were created incorporating PP as a continuous variable. The interaction of PP with New York Heart Association (NYHA) functional class was examined. Linear and restricted cubic splines were used to study nonlinear association between PP and outcomes.We included 2,299 patients with a mean(±SD) follow-up of 3.5 ± 1.8 years. The lowest tertile of PP (≤42 mm Hg) was associated with significantly higher CV mortality and HFH. Cox proportional hazards models showed a reduction in CV death and HFH with higher PP, with adjusted hazard ratios (HR) of 0.91 (P = 0.02) and 0.93 (P = 0.04) per 10 mm Hg increase in PP. This relationship was more pronounced in subjects with NYHA functional class III-IV. Spline analysis showed that the association between PP and CV mortality and HFH was only seen at PP values lower than 40 mm Hg.In patients with advanced HFREF, a low PP (40 mm Hg) portends a worse prognosis, whereas a high PP (50 mm Hg) predicts a relatively favourable prognosis.

Background Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study investigated the relationship between CKD and left atrial (LA) volume and function in a sample of the general population without overt cardiac disease. Design and methods We examined 358 participants from the Cardiovascular Abnormalities and Brain Lesions study. The LA minimum volume index (LAVI

Investigation of potential embolic source is an important diagnostic step in treating patients with ischemic stroke and transient ischemic attack. Cardiogenic embolism has been estimated to be the causative factor in 15-30% of all cases of ischemic stroke. Cardioembolic strokes are generally severe and recurrence and mortality rate high. Various cardiac disorders including atrial fibrillation, ventricular thrombus, valvular heart disease, cardiac tumors, and structural heart defects can cause cardioembolic stroke. Although the aortic arch is not a cardiac structure, it is usually considered under source of cardiac embolism (cardioaortic source) and is reviewed in this article. Echocardiography (both transthoracic and transesophageal) is a widely used and versatile technique that can provide comprehensive information of thromboembolic risk in patients with stroke. This article reviews potential cardiac sources of stroke and discusses the role of echocardiography in clinical practice.

Background Patients with systolic heart failure (HF) are at increased risk of both ischemic stroke and death. Currently, no risk scores are available to identify HF patients at high risk of stroke or death. The Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial studied 2305 HF patients, in sinus rhythm, followed for up to 6 years (3.5 ± 1.5 years). This trial showed no overall difference in those treated with warfarin vs aspirin with regard to death or stroke. The present study develops the first prognostic model to identify patients at higher risk of stroke or death based on their overall risk profile. Methods and results A scoring algorithm using 8 readily obtainable clinical characteristics as predictors, age, gender, hemoglobin, blood urea nitrogen, ejection fraction, diastolic blood pressure, diabetes status, and prior stroke or transient ischemic attack (C-index = 0.65, 95% CI: 0.613–0.681), was developed. It was validated internally using a bootstrap method. In predicting 1-year survival for death alone, our 8-predictor model had an AUC of 0.63 (95% CI: 0.579–0.678) while the 14-predictor Seattle model had an AUC of 0.72. The Seattle model did not report stroke. Conclusions This novel prognostic model predicts the overall risk of ischemic stroke or death for HF patients. This model compares favorably for death with the Seattle model and has the added utility of including stroke as an endpoint. Use of this model will help identify those patients in need of more intensive monitoring and therapy and may help identify appropriate populations for trials of new therapies. Clinical Trial Registration http://www.Clinicatrials.gov NCT00041938 .

Objective:To update the 2004 American Academy of Neurology guideline for patients with stroke and patent foramen ovale (PFO) by addressing whether (1) percutaneous closure of PFO is superior to medical therapy alone and (2) anticoagulation is superior to antiplatelet therapy for the prevention of recurrent stroke.Methods:Systematic review of the literature and structured formulation of recommendations.Conclusions:Percutaneous PFO closure with the STARFlex device possibly does not provide a benefit in preventing stroke vs medical therapy alone (risk difference [RD] 0.13%, 95% confidence interval [CI] −2.2% to 2.0%). Percutaneous PFO closure with the AMPLATZER PFO Occluder possibly decreases the risk of recurrent stroke (RD −1.68%, 95% CI −3.18% to −0.19%), possibly increases the risk of new-onset atrial fibrillation (AF) (RD 1.64%, 95% CI 0.07%–3.2%), and is highly likely to be associated with a procedural complication risk of 3.4% (95% CI 2.3%–5%). There is insufficient evidence to determine the efficacy of anticoagulation compared with antiplatelet therapy in preventing recurrent stroke (RD 2%, 95% CI −21% to 25%).Recommendations:Clinicians should not routinely offer percutaneous PFO closure to patients with cryptogenic ischemic stroke outside of a research setting (Level R). In rare circumstances, such as recurrent strokes despite adequate medical therapy with no other mechanism identified, clinicians may offer the AMPLATZER PFO Occluder if it is available (Level C). In the absence of another indication for anticoagulation, clinicians may routinely offer antiplatelet medications instead of anticoagulation to patients with cryptogenic stroke and PFO (Level C).

AIMS The aim of this study was to determine whether the CHA2 DS2 -VASc score can predict adverse outcomes such as death, ischaemic stroke, and major haemorrhage, in patients with systolic heart failure in sinus rhythm. METHODS AND RESULTS CHA2 DS2 -VASc scores were calculated for 1101 patients randomized to warfarin and 1123 patients randomized to aspirin. Adverse outcomes were defined as death or ischaemic stroke, death alone, ischaemic stroke alone, and major haemorrhage. Using proportional hazards models, we found that each 1-point increase in the CHA2 DS2 -VASc score was associated with increased hazard of death or ischaemic stroke events [hazard ratio (HR) for the warfarin arm = 1.21, 95% confidence interval (CI) 1.13-1.30, P < 0.001; for aspirin, HR = 1.20, 95% CI 1.11-1.29, P < 0.001]. Similar increased hazards for higher CHA2 DS2 -VASc scores were observed for death alone, ischaemic stroke alone, and major haemorrhage. Overall performance of the CHA2 DS2 -VASc score was assessed using c-statistics for full models containing the risk score, treatment assignment, and score-treatment interaction, with the c-statistics for the full models ranging from 0.57 for death to 0.68 for major haemorrhage. CONCLUSIONS The CHA2 DS2 -VASc score predicted adverse outcomes in patients with systolic heart failure in sinus rhythm, with modest prediction accuracy.

IMPORTANCE: There is a paucity of data detailing cardiac remodeling in female athletes compared with male athletes. The lack of reference cardiac data for elite female basketball players or female athletes of similar size makes it difficult to differentiate athletic remodeling from potential underlying cardiac disorders in this population of athletes. OBJECTIVE: To assess cardiac structure and function in elite female basketball players. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional echocardiographic study included 140 Women's National Basketball Association (WNBA) athletes on active rosters for the 2017 season. The WNBA mandates annual preseason stress echocardiograms for each athlete. The WNBA has partnered with Columbia University to annually perform a review of these studies. Data analysis was performed from June 7, 2017, to October 5, 2017. MAIN OUTCOMES AND MEASURES: Echocardiographic variables included left ventricular (LV) dimensions, wall thickness, mass, prevalence of LV hypertrophy, aortic dimensions, right ventricular (RV) dimension, and right and left atrial size. Linear regression was used to assess the associations between cardiac structure and function with body size quantified as body surface area (BSA) in the primary analysis. RESULTS: A total of 140 female athletes (mean [SD] age, 26.8 [3.9] years; 105 [75.0%] African American) participated in the study. Mean (SD) athlete height was 183.4 (9.0) cm, and mean (SD) BSA was 2.02 (0.18) m(2). Compared with guideline-defined normal values, LV enlargement was present in 36 athletes (26.0%) and 57 athletes (42.2%) had RV enlargement. There was a linear correlation between LV and RV cavity sizes and BSA extending to the uppermost biometrics (LV cavity size: r, 0.48; RV cavity size: r, 0.32; P 95 g/m(2)). Eccentric LVH was present in 16 athletes (69.6%), concentric LVH in 7 athletes (30.4%), and concentric remodeling in 27 athletes (19.3%). Mean aortic root diameter was 3.1 cm (95% CI, 3.0-3.2). Only 2 athletes (1.4%) had guideline-defined aortic enlargement compared with a range of 18% to 42% for left and right ventricular and atrial enlargement. CONCLUSIONS AND RELEVANCE: In this study, increased cardiac dimensions were frequently observed in WNBA athletes. Both BSA and physiologic remodeling affected cardiac morphologic findings. This study may provide a framework to define the range of athletic cardiac remodeling exhibited by elite female basketball players.