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Patients with chronic coronary syndrome (CCS), even when they have complete revascularization and normal left ventricular (LV) systolic function, experience subsequent cardiovascular disease (CVD), highlighting the importance of surrogate markers to prevent adverse consequences. Speckle-tracking echocardiography-derived left atrial (LA) reservoir strain has emerged as a sensitive marker for CVD in various clinical settings. The present study investigated the prevalence, determinants, and prognostic value of LA dysfunction in CCS. We included 278 consecutive patients with CCS with completed percutaneous coronary intervention and preserved LV ejection fraction who underwent follow-up echocardiography. Speckle-tracking analysis was performed to assess LA reservoir strain, and LA dysfunction was defined as LA reservoir strain ≤24%. The primary outcome comprised new-onset atrial fibrillation, heart failure hospitalization, acute coronary syndrome, stroke, or all-cause death. At baseline, 28 patients (10.1%) had LA dysfunction. Multivariable analysis identified age, hypertension, LV ejection fraction, and multivessel disease as independent determinants of LA reservoir strain (all p0.05). During a median follow-up of 4.8 years, the primary outcome occurred in 60 patients (21.6%). LA dysfunction carried a significant risk for primary outcome independent of traditional risk factors, LV parameters, and LA size (adjusted hazard ratio 3.10, p = 0.003); the risk increase remained significant even after excluding atrial fibrillation from the primary outcome (adjusted hazard ratio 2.27, p = 0.043). In conclusion, approximately 10% of patients with CCS with normal LV ejection fraction had LA dysfunction associated with adverse cardiovascular outcomes. Further studies are needed to explore whether therapeutic interventions affecting LA remodeling may help prevent CVD events.

Arterial structural and functional remodeling is recognized as a key determinant of incident heart failure, although the contribution of arterial properties on left ventricular (LV) remodeling is not fully studied. Aortic dilatation is an early manifestation of arterial remodeling and estimated pulse wave velocity (ePWV) is emerging as a simple measure of arterial stiffness. This study aimed to characterize the association of aortic size and ePWV with LV morphology and function.The study cohort consisted of 539 participants without overt cardiac disease who underwent extensive cardiovascular examination. Aortic root diameter was measured by two-dimensional echocardiography and ePWV was calculated from a regression equation using age and mean blood pressure. LV global longitudinal strain (LVGLS) was obtained by speckle-tracking echocardiography.Aortic root diameter and ePWV were correlated with LV mass index and LVGLS, while only ePWV was related to E / e' ratio. In multivariable analysis, aortic root diameter and ePWV were significantly related to LV mass index and LVGLS (all P 0.05), and the association of aortic root size and ePWV with LVGLS was independent of LV mass index and E / e' ratio. Individuals with both aortic root enlargement and increased ePWV had significantly larger LV mass index and reduced LVGLS compared with those either or those with normal aortic size and ePWV (both P 0.05).Aortic root size and ePWV were independently associated with unfavorable LV remodeling in individuals free of cardiac disease, which might provide useful information into the pathogenesis-linking arterial remodeling and heart failure.

The impact of blood pressure (BP) levels on subclinical left ventricular (LV) dysfunction and possible sex-specific difference remains unclarified. This study investigated the relationship between BP categories given in the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and subclinical LV dysfunction in subjects free of cardiac disease.We examined antihypertensive medication-naive 858 individuals who underwent extensive cardiovascular health check-up. LV global longitudinal (LVGLS) and circumferential strain (LVGCS) were assessed by two-dimensional speckle-tracking echocardiography. Participants were categorized into four groups: normal BP, elevated BP, isolated diastolic hypertension (IDH), and systolic hypertension (SH). Among the 858 participants, 422 individuals had normal BP, 113 had elevated BP, 160 had IDH, and 163 had SH. Prevalence of abnormal LVGLS (-18.6%) was greatest in SH (19.0%), followed by IDH (17.5%), elevated BP (14.2%), and normal BP (7.1%, P 0.001); no significant differences were observed for LVGCS (P = 0.671). In the multivariable analyses, IDH and SH were associated with impaired LVGLS [adjusted odds ratio (OR) 2.69 and 2.66, P 0.001], and borderline significance was observed for elevated BP (adjusted OR 1.90, P = 0.060); there was no significant association between any of the BP groups and LVGCS. In sex-stratified analysis, IDH and SH carried the significant risk of abnormal LVGLS in both sexes, while elevated BP was associated with LVGLS only in women.Isolated diastolic hypertension and SH redefined by ACC/AHA guideline carried significant risk for LVGLS, but not LVGCS. Elevated BP was associated with LVGLS only in women. Our findings provide information on cardiac correlates of the newly established BP categories.

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

The association between cervical internal carotid artery (cICA) tortuosity and atherosclerosis is a matter of debate. Additionally, some genetic syndromes characterized by connective tissue remodeling are associated with arterial tortuosity, raising the possibility that cICA tortuosity may not only be atherosclerotic. In this study, we hypothesized that cICA tortuosity is not associated with imaging biomarkers of atherosclerosis.The Northern Manhattan Study (NOMAS) was a prospective, multiethnic cohort of stroke-free individuals who underwent brain MRA, carotid ultrasound and transthoracic echocardiogram from 2003-2008. The cICA tortuosity was scored in each carotid as 0 = no tortuosity, 1 = tortuosity90°, 2 = tortuosity ≥90°. A summary cICA tortuosity score (possible range 0-4) was created by adding up the tortuosity score from each carotid. Participants were assessed for atherosclerotic markers by using B‑mode carotid sonography and transthoracic echocardiography.Of 558 participants 178 (31.9%) had any cervical ICA tortuosity (tortuosity score0). The cICA tortuosity score was higher in women and was associated with diastolic and systolic blood pressures and height (all P 0.05). In models adjusted for demographics and risk factors, only the association with diastolic blood pressure remained significant (β = 0.002, P = 0.02). Similarly, cICA tortuosity was associated with larger aortic root diameter (B = 1.03 ± 0.36, P = 0.004) but not with other markers of carotid or aortic atherosclerosis.Cervical ICA tortuosity is associated with a higher diastolic blood pressure and larger aortic root diameter but not with other measures of atherosclerosis. Determining the risks of vascular events associated with this non-atherosclerotic phenotype may help for a better risk stratification for individuals with cICA tortuosity.

Although higher body mass index (BMI) is associated with adverse left ventricular morphology and functional remodeling, its possible association with right ventricular (RV) dysfunction has not been extensively evaluated. RV free wall longitudinal strain (RVLS) is emerging as an important tool to detect early RV dysfunction. This study aimed to investigate the independent effect of increased BMI on RVLS in a large sample of the general population without overt cardiac disease. We examined 1,085 participants (603 men, mean age 62 years) who voluntarily underwent an extensive cardiovascular health check-up. This included laboratory tests and speckle-tracking echocardiography to assess RVLS. The association between BMI and RVLS was determined by logistic regression analyses. The prevalence of abnormal RVLS (-19.2%) was greatest in obese individuals (29.7%), followed by overweight (16.3%), and normal weight (10.6%, p0.001). In multivariable analyses, BMI was significantly associated with abnormal RVLS (adjusted odds ratio [OR] = 1.07 per 1 kg/m

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.

Depression is a recognized predictor of adverse outcomes in patients with heart failure (HF) and is associated with poor quality of life, functional limitation, increased morbidity and mortality, decreased adherence to treatment, and increased rehospitalization. To understand the impact of depression on HF readmission, we conducted a retrospective cohort study using the Nationwide Readmission Database (NRD) 2010-2014.We identified all patients with the primary discharge diagnosis of HF by ICD-9-CM codes. The primary outcome of the study was to identify 30-day all-cause readmission and causes of readmission in patients with and without depression. Multivariate Cox regression analysis was used to estimate the adjusted hazard ratio for the primary and secondary outcomes.Among, 3,500,570 patients admitted with HF, 9.7% had concomitant depression. Patients with depression were more likely to be readmitted within 30 days (19.7% vs. 18.5%; P 0.001). Concomitant depression was associated with higher risk of all-cause readmissions within 30 days and 90 days [P 0.001] but was not associated with increased readmissions due to cardiovascular (CV) cause at 30 days and 90 days. The hazard of psychiatric causes of readmission was higher in patients with depression, both at 30 days [P 0.001], and 90 days [P 0.001]. Most of the readmissions were due to CV causes, with HF being the most common cause.Among patients hospitalized with HF, the presence of depression is associated with increased all-cause readmission driven mainly by psychiatric causes but not CV-related readmission. Standard interventions targeted toward HF are unlikely to modify this portion of all-cause readmission.

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.

We examined the age-related differences in cardiovascular health (CVH) metrics for incident cardiovascular disease (CVD). Analyses were conducted using data from the JMDC Claims Database from 2005 to 2020 (n = 2,728,427; mean age 44.9 ± 11.0 years; 56.2% men). Participants were categorized on the basis of age: 20 to 49 years (n = 1,800,161), 50 to 59 years (n = 644,703), and 60 to 75 years (n = 283,563). Ideal CVH metrics included nonsmoking, body mass index25 kg/m

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.

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

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.

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 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.

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

Background and Purpose- To test the hypothesis that covert brain infarcts (CBIs) are more likely to be located in noneloquent brain areas compared with clinical strokes and that CBI etiological subtypes carry a differential risk of vascular events compared with people without CBI. Methods- We used brain magnetic resonance imaging from 1290 stroke-free participants in the NOMAS (Northern Manhattan Study) to evaluate for CBI. We classified CBI as cardioembolic (ie, known atrial fibrillation), large artery atherosclerosis (extracranial and intracranial), penetrating artery disease, and cryptogenic (no apparent cause). CBI localized in the nonmotor areas of the right hemisphere were considered noneloquent. We then evaluated risk of events by CBI subtype with adjusted Cox proportional models. Results- At the time of magnetic resonance imaging, 236 participants (18%) had CBI (144 [61%] distal cryptogenic, 29 [12%] distal cardioembolic, 26 [11%] large artery atherosclerosis, and 37 [16%] penetrating artery disease). Smaller (per mm, odds ratio, 0.8 [0.8-0.9]) and nonbrain stem infarcts (odds ratio, 0.2 [0.1-0.6]) were more likely to be covert. During the follow-up period (10.4±3.1 years), 398 (31%) died (162 [13%] of vascular death) and 117 (9%) had a stroke (99 [85%]) were ischemic. Risks of events varied by CBI subtype, with the highest risk of stroke (hazard ratio, 2.2 [1.3-3.7]) and vascular death (hazard ratio, 2.24 [1.29-3.88]) noted in participants with intracranial large artery atherosclerosis-related CBI. Conclusions- CBI can be classified into subtypes that have differential outcomes. Certain CBI subtypes such as those related to intracranial large artery atherosclerosis have a high risk of adverse vascular outcomes and could warrant consideration of treatment trials.

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

Rationale Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes. Aims The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy. Sample size estimate 1100 participants. Methods and design Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet. Population studied Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. Study outcomes The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. Discussion ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.

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.

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.

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

Epidemiologic studies assessing the relationship between blood pressure (BP), body mass, and cardiovascular events have primarily been based on office BP measurements, and few data are available in the elderly. The aim of the present study was to evaluate the relationship between body mass index (BMI) and BP values obtained by ambulatory blood pressure monitoring (ABPM) as compared to office BP measurements, and the effect of anti-hypertensive treatment on the relationship. The study population consisted of 813 subjects participating in the cardiovascular abnormalities and brain lesions (CABL) study who underwent 24-h ABPM. Office BP (mean of two measurements) was found to be associated with increasing BMI, for both SBP (p ≤ 0.05) and DBP (p ≤ 0.001). In contrast, there was no association seen of increasing BMI with ABPM parameters in the overall cohort, even after adjusting for age and gender. However, among subjects not on anti-hypertensive treatment, office SBP and DBP measurements were significantly correlated with increasing BMI (p ≤ 0.01) as were daytime SBP and 24-h SBP, although with a smaller spread across BMI subgroups compared with office readings. In treated hypertensives, there was only a trend toward increasing office DBP and increasing DBP variability with higher BMI. Our results suggest that body mass may have a less significant influence on BP values in the elderly when ABPM rather than office measurements are considered, particularly in patients receiving anti-hypertensive treatment.

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.

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.

Background and Purpose— Ischemic stroke (IS) secondary to atrial fibrillation (AF) is largely preventable with the use of anticoagulation. We sought to identify race-ethnicity and sex disparities with the use of direct oral anticoagulants (DOACs), aspirin, and warfarin in IS patients with AF and to identify temporal trends in the utilization of these medications. Methods— The FLiPER-AF Stroke Study (Florida Puerto Rico Atrial Fibrillation) included 24 040 IS cases enrolled in the Florida-Puerto Rico Collaboration to Reduce Stroke Registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the effect of race-ethnicity and sex on utilization of DOACs, aspirin, and warfarin for stroke prevention in AF after adjustment for sociodemographic, hospital, and clinical factors. Results— Among 24 040 IS cases, 54% were women and 10% black, 12% FL-Hispanics, 4% PR-Hispanic, and 74% whites. From 2010 to 2016, DOAC use increased from 0% to 36%, warfarin use decreased from 51% to 17%, and aspirin use remained relatively stable (42%–40%). After adjustment, blacks had higher odds of warfarin (odds ratio, 1.22; 95% CI, 1.07–1.40) prescription at discharge compared with whites. Men had higher rates of aspirin (42.1% versus 38.8%), warfarin (33.6% versus 28.9%), and DOAC (21.3% versus 19.3%) use compared with women. After adjustment, women had lower odds of being discharged on aspirin (odds ratio, 0.92; 95% CI, 0.86–0.98) or warfarin (odds ratio, 0.91; 95% CI, 0.84–0.99). There was no sex difference in use of DOACs. Conclusions— Our study confirmed the increasing use of DOACs, downtrending use of warfarin, whereas aspirin use remained similar over the years. There are sex and race-ethnicity disparities in anticoagulation use in IS patients with AF. It is critical to understand underlying drivers of these disparities to develop better practice strategies for stroke prevention in patients with AF. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03627806.

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.

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

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 .

Background Although implantation of a left ventricular assist device ( LVAD ) generally improves tricuspid regurgitation ( TR ) in short‐term follow‐up, the clinical significance of residual TR in patients with mid‐ to long‐term LVAD support is unknown. This study aimed to identify the prevalence, predictors, and prognostic value of residual TR in LVAD patients in association with tricuspid valve ( TV ) deformation. Methods and Results The study cohort consisted of 127 patients who underwent LVAD implantation without TV procedure and were supported with LVAD at least 1 year. All patients underwent echocardiographic examination preoperatively and 1 year after LVAD implantation. TR was quantitatively assessed by ratio of TR color jet area/right atrial area, and significant residual TR was defined as ≥20% of % TR at follow‐up echocardiographic examination. Detailed echocardiographic measurements were also performed, including TV annulus diameter, TV leaflet displacement, and left ventricular and right ventricular systolic function. LVAD implantation significantly improved ratio of TR color jet area/right atrial area as well as left ventricular and right ventricular systolic function and tethering distance (all P TV annulus diameter ( P =0.002). Significant residual TR was observed in 30 (23.6%) patients. Age, preoperative TV annulus diameter, and residual mitral regurgitation were significantly associated with significant residual TR (all P TV tethering was not. During a mean follow‐up of 21±17 months, patients with residual TR had significantly higher mortality than those without residual TR (log‐rank P Conclusions Significant residual TR was observed in ≈25% patients supported with LVAD over 1 year and was associated with unfavorable outcome.

Hypothesis We hypothesized that P wave terminal Force in the V1 lead (PTFV1) would be associated with leukoaraiosis and subclinical infarcts, especially cortical infarcts, in a population-based, multi-ethnic cohort. Methods PTFV1 was collected manually from baseline electrocardiograms of clinically stroke-free Northern Manhattan Study participants. Investigators read brain MRIs for superficial infarcts, deep infarcts, and white matter hyperintensity volume (WMHV). WMHV was adjusted for head size and log transformed, achieving a normal distribution. Logistic regression models investigated the association of PTFV1 with cortical and with all subclinical infarcts. Linear regression models examined logWMHV. Models were adjusted for demographics and risk factors. Results Among 1174 participants with PTFV1 measurements, the mean age at MRI was 70 ± 9 years. Participants were 14.4% white, 17.6% black, and 65.8% Hispanic. Mean PTFV1 was 3587.35 ± 2315.62 μV-ms. Of the 170 subclinical infarcts, 40 were cortical. PTFV1 ≥ 5000 μV-ms was associated with WMHV in a fully adjusted model (mean difference in logWMHV 0.15, 95% confidence interval 0.01–0.28). PTFV1 exhibited a trend toward an association with cortical infarcts (unadjusted OR per SD change logPTFV1 1.30, 95% CI 0.94–1.81), but not with all subclinical infarcts. Conclusion Electrocardiographic evidence of left atrial abnormality was associated with leukoaraiosis.

Increased left ventricular mass (LVM) is an intermediate phenotype for cardiovascular disease (CVD) and a predictor of stroke. Using families from the Dominican Republic, we have previously shown LVM to be heritable and found evidence for linkage to chromosome 12p11. Our current study aimed to further characterize the QTL by sequencing the 1 LOD unit down region in 10 families from the Dominican Republic with evidence for linkage to LVM. Within this region, we tested 5477 common variants [CVs; minor allele frequency (MAF) ≥5%] using the Quantitative Transmission-Disequilibrium Test (QTDT). Gene-based analyses were performed to test rare variants (RVs; MAF < 5%) in 181 genes using the family-based sequence kernel association test. A sample of 618 unrelated Dominicans from the Northern Manhattan Study (NOMAS) and 12 Dominican families with Exome Array data were used for replication analyses. The most strongly associated CV with evidence for replication was rs1046116 (Discovery families P = 9.0 × 10−4; NOMAS P = 0.03; replication families P = 0.46), a missense variant in PKP2. In nonsynonymous RV analyses, PKP2 was one of the most strongly associated genes (P = 0.05) with suggestive evidence for replication in NOMAS (P = 0.05). PKP2 encodes the plakophilin 2 protein and is a desmosomal gene implicated in arrythmogenic right ventricular cardiomyopathy and recently in arrhythmogenic left ventricular cardiomyopathy, which makes PKP2 an excellent candidate gene for LVM. In conclusion, sequencing of our previously reported QTL identified common and rare variants within PKP2 to be associated with LVM. Future studies are necessary to elucidate the role these variants play in influencing LVM.

Background and Purpose— Although increased heart rate (HR) is a predictor of cardiovascular events and mortality, its possible association with subclinical cerebrovascular disease, which is prevalent in the elderly, has not been evaluated. This study aimed to investigate the association of daytime, nighttime, 24-hour HR, and HR variability with subclinical cerebrovascular disease in an elderly cohort without history of stroke. Methods— The study cohort consisted of 680 participants (mean age, 73±7 years; 42% men) in sinus rhythm who underwent 24-hour ambulatory blood pressure and HR monitoring, 2-dimensional echocardiography, and brain magnetic resonance imaging as part of the CABL study (Cardiac Abnormalities and Brain Lesion). Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume (WMHV). The relationship of HR measures with the presence of silent brain infarct and upper quartile of log WMHV (log WMHV4) was analyzed. Results— Presence of silent brain infarct was detected in 93 participants (13.7%); mean log WMHV was −0.92±0.93 (median, −1.05; min, −5.88; max, 1.74). Multivariate analysis showed that only nighttime HR (adjusted odds ratio, 1.29 per 10 bpm; 95% confidence interval, 1.03–1.61; P =0.026) was significantly associated with log WMHV4, independent of traditional cardiovascular risk factors, ambulatory systolic blood pressure, and echocardiographic parameters. No similar association was observed for daytime HR and HR variability. There was no significant association between all HR measures and silent brain infarct. Conclusions— In a predominantly elderly cohort, elevated nighttime HR was associated with WMHV, suggesting an independent role of HR in subclinical cerebrovascular disease.

Although late-onset right-sided heart failure is recognized as a clinical problem in the treatment of patients with left ventricular assist devices (LVADs), the mechanism and predictors are unknown. Tricuspid valve (TV) deformation leads to the restriction of the leaflet motion and decreased coaptation, resulting in a functional tricuspid regurgitation that may act as a surrogate marker of late right-sided heart failure. This study aimed to investigate the association of preoperative TV deformation (annulus dilatation and leaflet tethering) with late right-sided heart failure development after continuous-flow LVAD implantation. The study cohort consisted of 274 patients who underwent 2-dimensional echocardiography before LVAD implantation. TV annulus diameter and tethering distance were measured in an apical 4-chamber view. Late right-sided heart failure was defined as right-sided heart failure requiring readmission and medical and/or surgical treatment after initial LVAD implantation. During a mean follow-up of 25.1 ± 19.0 months after LVAD implantation, late right-sided heart failure occurred in 33 patients (12.0%). Multivariate Cox proportional hazard analysis demonstrated that TV annulus diameter (hazard ratio 1.221 per 1 mm, p

Background and Purpose— Electrocardiographic left atrial abnormality has been associated with stroke independently of atrial fibrillation (AF), suggesting that atrial thromboembolism may occur in the absence of AF. If true, we would expect an association with cryptogenic or cardioembolic stroke rather than noncardioembolic stroke. Methods— We conducted a case-cohort analysis in the Northern Manhattan Study, a prospective cohort study of stroke risk factors. P-wave terminal force in lead V 1 was manually measured from baseline ECGs of participants in sinus rhythm who subsequently had ischemic stroke (n=241) and a randomly selected subcohort without stroke (n=798). Weighted Cox proportional hazard models were used to examine the association between P-wave terminal force in lead V 1 and stroke etiologic subtypes while adjusting for baseline demographic characteristics, history of AF, heart failure, diabetes mellitus, hypertension, tobacco use, and lipid levels. Results— Mean P-wave terminal force in lead V 1 was 4452 (±3368) μV*ms among stroke cases and 3934 (±2541) μV*ms in the subcohort. P-wave terminal force in lead V 1 was associated with ischemic stroke (adjusted hazard ratio per SD, 1.20; 95% confidence interval, 1.03–1.39) and the composite of cryptogenic or cardioembolic stroke (adjusted hazard ratio per SD, 1.31; 95% confidence interval, 1.08–1.58). There was no definite association with noncardioembolic stroke subtypes (adjusted hazard ratio per SD, 1.14; 95% confidence interval, 0.92–1.40). Results were similar after excluding participants with a history of AF at baseline or new AF during follow-up. Conclusions— ECG-defined left atrial abnormality was associated with incident cryptogenic or cardioembolic stroke independently of the presence of AF, suggesting atrial thromboembolism may occur without recognized AF.

Impaired cardiac function is considered a contraindication for lung transplantation (LT). Because right ventricular (RV) function is expected to improve after LT, poor left ventricular (LV) function is often the determinant for LT eligibility. However, the changes in cardiac function before and after LT have not yet been elucidated. Therefore, we reviewed echocardiograms obtained from 67 recipients before and after LT. In a subset of 49 patients, both RV and LV longitudinal strains based on 2-dimensional speckle tracking echocardiography were analyzed. The cardiopulmonary exercise tests were also reviewed. All patients showed significant improvements in their exercise capacity after LT. RV echo parameters improved in all patients after LT (RV fractional area change: 36.7 ± 5.6% to 41.5 ± 2.7%, RV strain: -15.5 ± 2.9% to -18.0 ± 2.1%, RV E/E': 8.4 ± 1.8 to 7.7 ± 1.8; all p0.05). Overall, the left ventricular ejection fraction (LVEF) did not change (58.7 ± 6.0% to 57.5 ± 9.7%, p = 0.385); however, 20 patients (30%) showed10% decrease in LVEF after LT (61.5 ± 6.1% to 47.3 ± 4.2%, p0.001) and an increase in LV E/E' (11.8 ± 1.8 to 12.9 ± 2.2, p = 0.049). Multivariate logistic regression analysis revealed that pre-LT LV E/E' was associated with decrease in LVEF after LT (odds ratio 1.381, 95% confidence interval 1.010 to 1.947, p = 0.043). Furthermore, patients with strain data showed that lower pre-LT LV strain was independently associated with LVEF decrease after LT (odds ratio 1.293, 95% confidence interval 1.088 to 1.614, p = 0.002). Although RV function improves after LT, LV systolic and diastolic functions deteriorate in a sizable proportion of patients. Impaired LV diastolic function before transplant appears to increase the risk of LVEF deterioration after LT.

Although it is well known that the prevalence of aortic arch plaques, one of the risk factors for ischemic stroke, is high in patients with severe aortic stenosis, the underlying mechanisms are not well understood. Increased day-by-day blood pressure (BP) variability is also known to be associated with stroke; however, little is known on the association between day-by-bay BP variability and aortic arch atherosclerosis in patients with aortic stenosis. Our objective was to clarify the association between day-by-day BP variables (average values and variability) and aortic arch atherosclerosis in patients with severe aortic stenosis.The study population consisted of 104 consecutive patients (mean age 75 ± 8 years) with severe aortic stenosis who were scheduled for aortic valve replacement. BP was measured in the morning in at least 4 consecutive days (mean 6.8 days) prior to the day of surgery. Large (≥4 mm), ulcerated, or mobile plaques were defined as complex plaques using transesophageal echocardiography.Cigarette smoking and all systolic BP variables were associated with the presence of complex plaques (p 0.05), whereas diastolic BP variables were not. Multiple regression analysis indicated that day-by-day mean systolic BP and day-by-day systolic BP variability remained independently associated with the presence of complex plaques (p 0.05) after adjustment for age, male sex, cigarette smoking, hypertension, hypercholesterolemia, and diabetes mellitus.These findings suggest that higher day-by-day mean systolic BP and day-by-day systolic BP variability are associated with complex plaques in the aortic arch and consequently stroke risk in patients with aortic stenosis.

Background Aortic valve calcification (AVC) without stenosis is common in the elderly, is associated with cardiovascular morbidity and mortality, and may progress to aortic valve stenosis. Arterial stiffness and pulse-wave reflection are important components of proximal aortic hemodynamics, but their relationship with AVC is not established. Methods To investigate the relationship of arterial wave reflection and stiffness with AVC, pulse wave analysis and AVC evaluation by echocardiography were performed in 867 participants from the Cardiovascular Abnormalities and Brain Lesions study. Participants were divided into four categories on the basis of the severity and extent of AVC: (1) none or mild focal AVC, (2) mild diffuse AVC, (3) moderate to severe focal AVC, and (4) moderate to severe diffuse AVC. Central blood pressures and pulse pressure, total arterial compliance, augmentation index, and time to wave reflection were assessed using applanation tonometry. Results Indicators of arterial stiffness and wave reflection were significantly associated with AVC severity, except for central systolic and diastolic pressures and time to reflection. After adjustment for pertinent covariates (age, sex, race/ethnicity, and estimated glomerular filtration rate), only augmentation pressure ( P = .02) and augmentation index ( P = .002) were associated with the severity of AVC. Multivariate logistic regression analysis revealed that augmentation pressure (odds ratio per mm Hg, 1.14; 95% confidence interval, 1.02–1.27; P = .02) and augmentation index (odds ratio per percentage point, 1.07; 95% confidence interval, 1.01–1.13; P = .02) were associated with an increased risk for moderate to severe diffuse AVC, even when central blood pressure value was included in the same model. Conclusions Arterial wave reflection is associated with AVC severity, independent of blood pressure values. Increased contribution of wave reflection to central blood pressure could be involved in the process leading to AVC.

One mechanism linking diet, specifically the Mediterranean-style diet (DT), with cardiovascular disease prevention may be an association between a DT and left ventricular (LV) mass. However, there are little data on this relation. We hypothesized that adherence to a DT would be inversely associated with LV mass in the multiethnic population-based Northern Manhattan Study. The study included 1,937 participants with diet assessments and LV mass measured using echocardiography (mean age 67 ± 9 years, 39% male, 58% Hispanic, 20% white, 20% black). A DT adherence score (range 0 to 9, 9 representing maximal adherence) was examined continuously and categorically (score 6 to 9 representing the top quartile vs 0 to 5). Multivariable-adjusted linear regression models were constructed to examine the cross-sectional association between a DT and LV mass. An inverse association was observed between the DT score and LV mass. In a model controlling for demographics, behavioral risk factors, diabetes, and blood pressure variables, LV mass was 1.98 g lesser for each 1-point greater DT score, and those with scores of 6 to 9 had an average LV mass that was 7.30 g less than those with scores of 0 to 5. The association was attenuated but remained statistically significant after additionally adjusting for body mass index. Results were similar when LV mass was corrected for height (LV mass). In conclusion, greater adherence to a DT is associated with decreased LV mass, an important risk factor for cardiovascular disease, and this association may be partly mediated by obesity. The association with LV mass may be involved in the protective effect of a DT on clinical vascular outcomes.

Background Left ventricular ( LV ) hypertrophy and subclinical cerebrovascular disease are early manifestations of cardiac and brain target organ damage caused by hypertension. This study aimed to investigate whether intensive office systolic blood pressure ( SBP ) control has beneficial effects on LV morphology and function and subclinical cerebrovascular disease in elderly patients with hypertension. Methods and Results We examined 420 patients treated for hypertension without history of heart failure and stroke from the CABL (Cardiovascular Abnormalities and Brain Lesions) study. All patients underwent 2‐dimensional echocardiographic examination and brain magnetic resonance imaging. Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume. Patients were divided into 3 groups: SBP SBP 120 to 139 mm Hg (less intensive control); and SBP ≥140 mm Hg (uncontrolled). Prevalence of LV hypertrophy and diastolic dysfunction were lowest in the intensive control, intermediate in the less intensive control, and highest in the uncontrolled groups (12.8%, 31.8%, and 44.7%, respectively [ P LV hypertrophy; 46.8%, 61.7%, and 72.6%, respectively [ P =0.003], for diastolic dysfunction). Patients with less intensive SBP control had greater risk of LV hypertrophy than those with intensive control (adjusted odds ratio, 3.26; P =0.013). A similar trend was observed for LV diastolic dysfunction but did not reach statistical significance (adjusted odds ratio, 1.65; P =0.144). Conversely, intensive SBP control was not significantly associated with reduced risk of silent brain infarcts and white matter hyperintensity volume compared with less intensive control. Conclusions Compared with less intensive control, intensive SBP control may have a stronger beneficial effect on cardiac than cerebral subclinical disease.

Accreditation of echocardiographic testing facilities by the Intersocietal Accreditation Commission (IAC) is supported by the American College of Cardiology and American Society of Echocardiography. However, limited information exists on the accreditation status and geographic distribution of echocardiographic facilities in the United States. Our study aimed to identify (1) the proportion of outpatient echocardiography facilities used by Medicare beneficiaries that are IAC accredited, (2) their geographic distribution, and (3) variations in procedure type and volume by accreditation status.As part of the VALUE-ECHO (Value of Accreditation, Location, and Utilization Evaluation-Echocardiography) study, we examined the proportion of IAC-accredited echocardiographic facilities performing outpatient echocardiography in the 2013 Centers for Medicare and Medicaid Services outpatient limited data set (100% sample) and their geographic distribution using geocoding in ArcGIS (ESRI, Redlands, CA).Among 4573 outpatient facilities billing Medicare for echocardiographic testing in 2013, 99.6% (n = 4554) were IAC accredited (99.7% in the 50 US states and 86.2% in Puerto Rico). The proportion IAC-accredited echocardiographic facilities varied by region, with 98.7%, 99.9%, 99.9%, 99.5%, and 86.2% of facilities accredited in the Northeast, South, Midwest, West, and Puerto Rico, respectively (P .01, Fisher exact test). Of all echocardiographic outpatient procedures conducted (n = 1,890,156), 99.8% (n = 1,885,382) were performed in IAC-accredited echocardiographic facilities. Most procedures (90.9%) were transthoracic echocardiograms, of which 99.7% were conducted in IAC-accredited echocardiographic facilities.Almost all outpatient echocardiographic facilities billed by Medicare are IAC accredited. This accreditation rate is substantially higher than previously reported for US outpatient vascular testing facilities (13% IAC accredited). The uniformity of imaging and interpretation protocols from a single accrediting body is important to facilitate optimal cardiovascular care.

Background: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. Methods: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. Results: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR 79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. Conclusions: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.