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Background Low cardiorespiratory fitness (CRF), high body mass index, and excess visceral adiposity are each associated with impairment in left ventricular (LV) peak circumferential strain (Ecc), an intermediate phenotype that precedes the development of clinical heart failure (HF). However, the association of regional fat distribution and CRF with Ecc independent of each other and other potential confounders is not known. Methods Participants from the Dallas Heart Study Phase 2 who underwent dual energy X-ray absorptiometry assessment of regional fat distribution, CRF assessment by submaximal treadmill test, and Ecc quantification by tissue-tagged cardiovascular magnetic resonance were included in the analysis. The cross-sectional associations of measures of regional adiposity, namely visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and lower-body fat (LBF) with Ecc after adjustment for CRF and other potential confounders (independent variables) were assessed using multivariable linear regression analysis. Results The study included 1089 participants (55% female, 39% black). In the unadjusted analysis, higher VAT was associated with greater impairment in Ecc. After adjustment for baseline risk factors, CRF, parameters of LV structure and function, and other fat depots such as SAT and LBF, higher VAT remained associated with greater impairment in Ecc (β: 0.19, P = 0.002). SAT and LBF were not significantly associated with Ecc, however, CRF remained associated with Ecc in the fully adjusted model including all fat depots (β: − 0.15, P Conclusions VAT and CRF are each independently associated with impairment in Ecc, suggesting that higher VAT burden and low CRF mediate pathological cardiac remodeling through distinct mechanisms.

Objectives This study analyzed changes in depressive symptoms in patients with heart failure and preserved ejection fraction (HFpEF) who were enrolled in the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Background There are limited longitudinal data for depressive symptoms in patients with HFpEF. Methods In patients enrolled in the United States and Canada (n = 1,431), depressive symptoms were measured using Patient Health Questionnaire-9 (PHQ-9). Clinically meaningful changes in PHQ-9 scores were defined as worse (≥3-point increase) or better (≥3-point decrease). Multivariate models were used to identify predictors of change in depressive symptoms. Cox proportional hazard models were used to determine the impact of symptom changes from baseline on subsequent incident cardiovascular events. Results At 12 months, 19% of patients experienced clinically worsening depressive symptoms, 31% better, and 49% unchanged. Independent predictors of clinically meaningful improvement in depressive symptoms included higher baseline PHQ-9 scores, male sex, lack of chronic obstructive pulmonary disease, and randomization to spironolactone. After data were adjusted for cardiovascular comorbidities, higher baseline PHQ-9 was associated with all-cause mortality (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.02 to 1.16; p = 0.011), whereas worsening depressive symptoms at 12 months were associated with cardiovascular death (HR: 2.47; 95% CI: 1.32 to 4.63; p = 0.005) and all-cause mortality (HR: 1.82; 95% CI: 1.13 to 2.93; p = 0.014). Randomization to spironolactone was associated with modest but statistically significant reduction in depressive symptoms over the course of the trial (p = 0.014). Conclusions Higher baseline depressive symptoms and worsening depressive symptoms were associated with all-cause mortality. Randomization to spironolactone was associated with modest reduction in depressive symptoms. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)

Supplemental Digital Content is available in the text., Background: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C. Methods: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke. Results: In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52–0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61–0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35–0.69]; for Blacks, 1.22 [95% CI, 0.76–1.98]; Pinteraction=0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36–0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08–2.83]; Pinteraction

Objectives This study sought to describe baseline health-related quality of life (HRQL) in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, the largest heart failure with preserved ejection fraction (HFpEF) trial to date. Background There are limited data characterizing HRQL in patients with HFpEF using validated metrics. Methods The PARAGON-HF trial randomized symptomatic patients with HFpEF (≥45%) ≥50 years of age to either sacubitril/valsartan or valsartan. The study reports comprehensive baseline HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period. The study then compares baseline HRQL with patients with heart failure with reduced ejection fraction (HFrEF) (≤40%) enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Forward multivariable stepwise regression modeling was performed separately in both trials to identify independent clinical correlates of KCCQ-Overall Summary (KCCQ-OS) score. PARADIGM-HF trial patients Results In the PARAGON-HF trial, 4,735 of 4,822 patients (mean age 73 ± 8 years; 48% men) completed baseline KCCQ at randomization. Mean KCCQ-OS score was 71. Women had worse mean KCCQ-OS score than men did. Patients in the PARAGON-HF trial reported lower KCCQ scores in nearly all domains when compared with the PARADIGM-HF trial (KCCQ-OS score 71 ± 19 vs. 73 ± 19; p Conclusions HRQL was largely worse in women and was similar in HFpEF and HFrEF after accounting for variation in demographics, functional status, and symptom burden. Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF [PARAGON-HF] NCT01920711; Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)

Background: Heart failure (HF) risk and the underlying risk factors vary by race. Traditional models for HF risk prediction treat race as a covariate in risk prediction and do not account for significant parameters such as cardiac biomarkers. Machine learning (ML) may offer advantages over traditional modeling techniques to develop race-specific HF risk prediction models and to elucidate important contributors of HF development across races. Methods: We performed a retrospective analysis of 4 large, community cohort studies (ARIC [Atherosclerosis Risk in Communities], DHS [Dallas Heart Study], JHS [Jackson Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) with adjudicated HF events. The study included participants who were >40 years of age and free of HF at baseline. Race-specific ML models for HF risk prediction were developed in the JHS cohort (for Black race–specific model) and White adults from ARIC (for White race–specific model). The models included 39 candidate variables across demographic, anthropometric, medical history, laboratory, and electrocardiographic domains. The ML models were externally validated and compared with prior established traditional and non–race-specific ML models in race-specific subgroups of the pooled MESA/DHS cohort and Black participants of ARIC. The Harrell C-index and Greenwood-Nam-D’Agostino χ 2 tests were used to assess discrimination and calibration, respectively. Results: The ML models had excellent discrimination in the derivation cohorts for Black (n=4141 in JHS, C-index=0.88) and White (n=7858 in ARIC, C-index=0.89) participants. In the external validation cohorts, the race-specific ML model demonstrated adequate calibration and superior discrimination (Black individuals, C-index=0.80–0.83; White individuals, C-index=0.82) compared with established HF risk models or with non–race-specific ML models derived with race included as a covariate. Among the risk factors, natriuretic peptide levels were the most important predictor of HF risk across both races, followed by troponin levels in Black and ECG-based Cornell voltage in White individuals. Other key predictors of HF risk among Black individuals were glycemic parameters and socioeconomic factors. In contrast, prevalent cardiovascular disease and traditional cardiovascular risk factors were stronger predictors of HF risk in White adults. Conclusions: Race-specific and ML-based HF risk models that integrate clinical, laboratory, and biomarker data demonstrated superior performance compared with traditional HF risk and non–race-specific ML models. This approach identifies distinct race-specific contributors of HF.

Background Professional society guidelines are emerging for cardiovascular care in cancer patients. However, it is not yet clear how effectively the cancer survivor population is screened and treated for cardiomyopathy in contemporary clinical practice. As electronic health records (EHRs) are now widely used in clinical practice, we tested the hypothesis that an EHR-based cardio-oncology registry can address these questions. Objective The aim of this study was to develop an EHR-based pragmatic cardio-oncology registry and, as proof of principle, to investigate care gaps in the cardiovascular care of cancer patients. Methods We generated a programmatically deidentified, real-time EHR-based cardio-oncology registry from all patients in our institutional Cancer Population Registry (N=8275, 2011-2017). We investigated: (1) left ventricular ejection fraction (LVEF) assessment before and after treatment with potentially cardiotoxic agents; and (2) guideline-directed medical therapy (GDMT) for left ventricular dysfunction (LVD), defined as LVEF Results Rapid development of an EHR-based cardio-oncology registry was feasible. Identification of tests and outcomes was similar using the EHR-based cardio-oncology registry and manual chart abstraction (100% sensitivity and 83% specificity for LVD). LVEF was documented prior to initiation of cancer therapy in 19.8% of patients. Prevalence of postchemotherapy LVD and HFrEF was relatively low (9.4% and 2.5%, respectively). Among patients with postchemotherapy LVD or HFrEF, those referred to cardiology had a significantly higher prescription rate of a GDMT. Conclusions EHR data can efficiently populate a real-time, pragmatic cardio-oncology registry as a byproduct of clinical care for health care delivery investigations.

Recent evidence showed that the characteristics and outcome of those with de novo heart failure (HF) and acutely decompensated chronic heart failure (ADCHF) were different. We aimed to perform a comprehensive search on the clinical characteristics and outcome of patients with de novo HF and ADCHF.We performed a comprehensive search on de novo/new onset acute HF vs ADCHF from inception up until December 2019.There were 38320 patients from 15 studies. De novo HF were younger and, had less prevalent hypertension, diabetes mellitus, ischaemic heart disease, chronic obstructive pulmonary disease, atrial fibrillation, and history of stroke/transient ischaemic attack compared to ADCHF. Five studies showed a lower NT-proBNP in de novo HF patients, while one study showed no difference. Valvular heart disease as aetiology of heart failure was less frequent in de novo HF, and upon sensitivity analysis, hypertensive heart disease was more frequent in de novo HF. As for precipitating factors, ACS (OR 2.42; IRisk factors, aetiology, and precipitating factors of HF in de novo and ADCHF differ. De novo HF also had lower 1-year mortality and 3-month mortality compared to ADCHF.

Excess visceral adipose tissue (VAT) is associated with cardiovascular disease and associated risk factors, whereas subcutaneous abdominal adipose tissue (SAT) is relatively metabolically inert in obesity [(1)][1]. Conversely, lower body subcutaneous fat (LBF) is associated with lower risk [(1)][1

Importance Impaired myocardial flow reserve (MFR) and stress myocardial blood flow (MBF) on positron emission tomography (PET) myocardial perfusion imaging may identify adverse myocardial characteristics, including myocardial stress and injury in aortic stenosis (AS). Objective To investigate whether MFR and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after aortic valve replacement (AVR). Design, setting, and participants In this single-center prospective observational study in Boston, Massachusetts, from 2018 to 2020, patients with predominantly moderate to severe AS underwent ammonia N13 PET myocardial perfusion imaging for myocardial blood flow (MBF) quantification, resting transthoracic echocardiography (TTE) for assessment of myocardial structure and function, and measurement of circulating biomarkers for myocardial injury and wall stress. Evaluation of health status and functional capacity was also performed. A subset of patients underwent repeated assessment 6 months after AVR. A control group included patients without AS matched for age, sex, and summed stress score who underwent symptom-prompted ammonia N13 PET and TTE within 90 days. Exposures MBF and MFR quantified on ammonia N13 PET myocardial perfusion imaging. Main outcomes and measures LV structure and function parameters, including echocardiographic global longitudinal strain (GLS), circulating high-sensitivity troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), health status, and functional capacity. Results There were 34 patients with AS (1 mild, 9 moderate, and 24 severe) and 34 matched control individuals. MFR was independently associated with GLS and LV ejection fraction, (β,-0.31; P = .03; β, 0.41; P = .002, respectively). Stress MBF was associated with hs-cTnT (unadjusted β, -0.48; P = .005) and log NT-pro BNP (unadjusted β, -0.37; P = .045). The combination of low stress MBF and high hs-cTnT was associated with higher interventricular septal thickness in diastole, relative wall thickness, and worse GLS compared with high stress MBF and low hs-cTnT (12.4 mm vs 10.0 mm; P = .008; 0.62 vs 0.46; P = .02; and -13.47 vs -17.11; P = .006, respectively). In 9 patients studied 6 months after AVR, mean (SD) MFR improved from 1.73 (0.57) to 2.11 (0.50) (P = .008). Conclusions and relevance In this study, in AS, MFR and stress MBF were associated with adverse myocardial characteristics, including markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation.

Aims Hypertension is a well-established heart failure (HF) risk factor, especially in the context of adverse left ventricular (LV) remodelling. We aimed to use myocardial flow reserve (MFR) and global longitudinal strain (GLS), markers of subclinical microvascular and myocardial dysfunction, to refine hypertensive HF risk assessment. Methods and results Consecutive patients undergoing symptom-prompted stress cardiac positron emission tomography (PET)-computed tomography and transthoracic echocardiogram within 90 days without reduced left ventricular ejection fraction ( Conclusion We have demonstrated important associations between coronary microvascular dysfunction and myocardial mechanics that refine disease characterization and HF risk assessment of patients with hypertension based on subclinical target organ injury.

OnBehalf The ARIC Study Background Age-related left atrial (LA) structural/functional abnormalities in elderly patients with normal sinus rhythm and preserved ejection fraction may precede the development of overt atrial fibrillation, and also may be related to stroke. Purpose To evaluate the association of 3-dimensional echocardiographic (3DE) atrial contractility parameters with subclinical cerebral infarcts (SCIs), as assessed by brain MRI, and clinically diagnosed stroke Methods We studied 407 participants (mean age 76 ± 5 years, 40.5% male) from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) without AF and who underwent a brain MRI and a 3DE examination in 2011-13. We defined 3 groups: those with no cerebral infarcts on brain MRI (NCIs, N = 315); those with MRI-diagnosed SCIs (N = 58); and those with clinically diagnosed stroke (N = 34). Results While still within the normal range, LA indexed volume significantly increased across the 3 groups (P-trend = 0.01).This was accompanied by an increase in the LA global longitudinal strain (GLS), an echocardiographic index of LA reservoir function (P-trend = 0.004). E/e’ divided by LA GLS—index of atrial stiffness—worsened across groups (P-trend = 0.005) and was independently associated with SCIs and Stroke, pooled together, [OR per 1 %-1, 1.97; 95% CI (1.24, 3.11), P = 0.004], and Stroke [OR per 1 %-1, 2.30; 95% CI (1.23, 4.30), P = 0.009]. LA GLS was marginally associated with an increased odd of SCIs [OR per 1 %, 1.07; 95% CI (1.01, 1.13), P = 0.014]. Conclusions Among elderly participants with normal sinus rhythm and preserved ejection fraction in a large cohort study, markers of LA function and stiffness are associated with increased odds of subclinical infarcts and stroke. These data suggest that even subtle LA dysfunction, which may contribute to LA stasis, may predispose to subclinical cerebral infarcts and stroke.

Objectives: This study sought to assess the effects of neurohormonal therapies in preventing cardiotoxicity in patients receiving chemotherapy. Background: Various cardioprotective approaches have been evaluated to prevent chemotherapy-related cardiotoxicity; however, their overall utility remains uncertain. Methods: This meta-analysis included randomized clinical trials of adult patients that underwent chemotherapy and neurohormonal therapies (β-blockers, mineralocorticoid receptor antagonists, or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) versus placebo with follow-up ≥4 weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of the trial. Other outcomes of interest were measures of LV size, strain, and diastolic function. Pooled estimates for each outcome were reported as standardized mean difference and weighted mean difference between the neurohormonal therapy and placebo groups using random effects models. Results: We included 17 trials, collectively enrolling 1,984 participants. In pooled analysis, neurohormonal therapy (vs. placebo) was associated with significantly higher LVEF on follow-up (standardized mean difference: +1.04 [95% confidence interval (CI): 0.57 to 1.50]) but with significant heterogeneity in the pooled estimate (I2 = 96%). Compared with placebo-treated patients, those randomized to neurohormonal therapies experienced a 3.96% (95% CI: 2.90 to 5.02) less decline in LVEF estimated by weighted mean difference, but with significant heterogeneity (I2 = 98%). There was a trend toward lower adverse clinical events with neurohormonal therapy (vs. placebo) that did not meet statistical significance (risk ratio: 0.80 [95% CI: 0.53 to 1.20]; I2 = 71%). Conclusions: Neurohormonal therapies are associated with higher LVEF in follow-up among cancer patients receiving chemotherapy, although absolute changes in LVEF are small and may be within inter-test variability. Furthermore, significant heterogeneity is observed in the treatment effects across studies highlighting the need for larger trials of cardioprotective strategies.

Aims The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular (CV) death or heart failure (HF) hospitalization in a population with atrial fibrillation (AF). Methods and results In a prospective echocardiographic substudy of the Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) study, 971 patients underwent transthoracic echocardiography. The associations between LA structure (LA volume index [LAVi]) and function (LA emptying fraction [LAEF] and LA expansion index [LAEi]) and risk for the composite endpoint of CV death or HF hospitalization, and its components, were assessed. Over a median follow-up of 2.5 years, 142 patients (14.6%) experienced CV death or HF hospitalization. Higher LAVi and lower LAEF and LAEi were each associated with a higher unadjusted risk for the composite outcome and its components. After adjustment for clinical and echocardiographic confounders, only measures of impaired LA function were predictive of the composite outcome (hazard ratio [HR] per 1 standard deviation [SD] decrease in LAEF: 1.35; 95% confidence interval [CI] 1.09-1.67 [P = 0.005]; HR per 1 SD decrease in LAEi: 1.34; 95% CI 1.06-1.69 [P = 0.012]). These findings were similar regardless of left ventricular ejection fraction, history of HF or whether patients were in AF or sinus rhythm at the time of the echocardiographic examination. Conclusions In patients with AF, LA dysfunction was significantly associated with an increased risk for CV death or HF hospitalization and was more predictive of these outcomes than LA size. These parameters may help to identify AF patients at greatest risk for the development of HF. Clinical trial registration ClinicalTrials.gov, NCT00781391.

AIMS Narrower retinal arterioles and wider retinal venules have been associated with macrovascular forms of cardiovascular disease (CVD). However, whether they are predictive of the development of heart failure (HF) independent of atherosclerotic CVD is unclear. We aimed to describe long-term associations of retinal vessel calibres with incident HF, in those with and without prevalent macrovascular disease, and how they relate to cardiac structure and function. METHODS AND RESULTS This analysis included Atherosclerosis Risk in Communities Study participants who underwent retinal photography between 1993 and 1995. HF outcomes were followed in these participants until the end of 2013. Returning participants underwent echocardiography between 2011 and 2013. Participants with retinal vessel measurements who were free of CVD at baseline (n = 10 692) were followed for a mean of 16 years (baseline mean age 60 ± 6 years). Wider central retinal venular equivalent (CRVE) and narrower central retinal arteriolar equivalent (CRAE), adjusted for age, gender, and race, were significantly linearly associated with incident HF; however, a non-linear association was detected with CRVE and incident HF (P-value for overall trend

Left ventricular non-compaction (LVNC) is a myocardial disorder, classically defined as a double-layered myocardium, consisting of a thick and spongy or hypertrabeculated endocardial segment, defined as non-compacted.

e19359 Background: EMR generated QTc prolongation alerts are ubiquitous in cancer patients. Their significance and impact on mortality is unknown. Methods: From 2006-2018, 19,223 adult cancer patients at UT-Southwestern hospitals had EMR generated QTc prolongation drug alerts. We collected information on cancer site, demographics and alert details. Deaths ≤10 days from a first QTc alert (acute mortality) were considered more attributable to QTc prolongation. We analyzed overall patient survival through multivariable Kaplan-Meier analysis and Cox regression with the two-outcomes (dead/alive) using a ≤10 days cutoff and followed patients for 365 days from their 1st alert. Results: Analysis of mortality from 1st QTc alert demonstrated statistically significant (p = < 0.05) higher risk of ≤10-day mortality in: patients age > 70 yrs, hazard ratio (HR) = 2.32; black, HR = 1.26 or other/unknown race, HR = 1.29; and increasing number of QTc alerts, particularly patients with 6-10, HR = 1.67 or > 11 HR = 1.88 alerts. Females had lower mortality compared to males, HR = 0.83. Compared to a head and neck cancer patient baseline, significantly increased ≤10-day mortality was seen in: GI, HR = 2.16; lung, HR = 1.94; blood, HR = 1.46; soft tissue, HR = 2.26; and female genital, HR = 1.55 cancers. Male genital, HR = 0.39; breast, HR = 0.57; and endocrine, HR = 0.48 cancers had significantly decreased ≤10-day mortality. In patients with EKG’s recorded: 34 males who died ≤10-days of their 1st alert had significantly longer QTc intervals compared the 5465 who survived to day 11 (469 vs 450 msec, p = < 0.0001). There was no QTc prolongation in the 24 females who died ≤10-days compared to the 4392 who survived to Day 11. Deaths ≤10 days after a QTc alert were rare (total 149/19,223; range 0.01 for male genital to 2.5% for GI), while the majority of deaths within 1 year of a patient’s 1st alert occurred between 11-180 days (range 1.03% for endocrine to 11.05% for lung). Most patients were alive > 1 year after their 1st alert: 63.77% (lung)-95.9% (endocrine). Conclusions: Patients with EKG-proven prolongation of QTc intervals after QTc alerts likely represent a segment of the population where intervention may reduce acute mortality. It is unclear whether the QTc interval prolongation is the actual cause of death or if the EMR alerts identify patients with co-morbidities associated with high risk of acute mortality.

ObjectivesTo assess differences in blood flow momentum (BFM) and kinetic energy (KE) dissipation in a model of cardiac dyssynchrony induced by electrical right ventricular apical (RVA) stimulation compared with spontaneous sinus rhythm.MethodsWe cross-sectionally enrolled 12 consecutive patients (mean age 74±8 years, 60% male, mean left ventricular ejection fraction 58%±6 %), within 48 hours from pacemaker (PMK) implantation. Inclusion criteria were: age>18 years, no PMK-dependency, sinus rhythm with a spontaneous narrow QRS at the ECG, preserved ejection fraction (>50%) and a low percentage of PMK-stimulation (ResultsCompared with sinus rhythm, BFM shifted from 27±3.3 to 34±7.6° (p=0.016), while RVA-pacing was characterised by a 35% of increment in KE dissipation, during diastole (p=0.043) and 32% during systole (p=0.016). In the same conditions, left ventricle global longitudinal strain (LV GLS) significantly decreased from 17±3.3 to 11%±2.8% (p=0.004) during RVA-stimulation. At the multivariable analysis, BFM and diastolic KE dissipation were significantly associated with LV GLS deterioration (Beta Coeff.=0.54, 95% CI 0.07 to 1.00, p=0.034 and Beta Coeff.=0.29, 95% CI 0.02 to 0.57, p=0.049, respectively).ConclusionsIn RVA-stimulation, BFM impairment and KE dissipation were found to be significantly associated with LV GLS deterioration, when controlling for potential confounders. Such changes may favour the onset of cardiac remodelling and sustain heart failure.

We thank Dr. Belkin and colleagues for their interest in our work describing the health-related quality of life in heart failure across the spectrum of left ventricular ejection fraction leveraging data from 2 similarly designed contemporary trials, the PARADIGM-HF (Prospective Comparison of ARNI

Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probability-based, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94, 95% CI 0.78 to 1.13, p interaction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (p interaction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target.

Background Obesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear. Objectives This study sought to determine the relationship between adipose tissue distribution and incident hypertension. Methods Normotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI). Results Among 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m2), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase). Conclusions Increased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association.

Background Although the use of LVADs in treating patients with advanced heart failure is growing, no current tool exists that can reliably assess health-related quality of life (HRQL) in this population. The QuaLVAD instrument has been designed to address this need. It incorporates important elements of LVAD-related care such as LVAD-specific complications, routine care of the device and other related clinical, personal and social factors. Methods The QuaLVAD instrument was designed after literature search, expert consultation, and patient discussion. It currently includes a 70-item instrument with scores ranging from 0-100 wherein a higher score signifies better HRQL. We assessed its performance by enrolling 24 patients and co-administered it with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and visual analog scale (VAS) to stable patients implanted with a LVAD. Cronbach's alpha was calculated to measure the internal consistency of the instrument. Spearman correlation coefficients (ρ) and Wilcoxon rank-sum test helped assess for various associations of the QuaLVAD scores. Results The 24 subjects included had a mean age and BMI of 60.0 ± 13.2 years and 32.3 ± 18.2 kg/m2 respectively. The Cronbach's alpha for the entire instrument was 0.95 and >0.75 for all its six domains. Other summary statistics and the Cronbach's alpha for each domain are shown in Table 1. Amongst patient characteristics, the QuaLVAD overall score had the greatest correlation (ρ = -0.60) with the total number of comorbidities and a significant association with outpatient status of the subject (p-value = 0.05). A moderate negative correlation (ρ = -0.37) was observed with the New York Heart Association (NYHA) class. Convergent validity was established with strong correlation scores with the KCCQ and VAS (ρ of 0.84 and 0.67 respectively for overall scores; p-value ≤ 0.001). Subject feedback indicated that 52% considered the QuaLVAD instrument as more relevant in assessing their LVAD-related quality of life than any previously filled questionnaires. Conclusion Our results have demonstrated promising early insights into the internal consistency and validity of the QuaLVAD instrument. To further refine the instrument, we shall focus on item reduction, testing responsiveness to change in HRQL and more widespread application of this novel instrument.

IMPORTANCE: Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). OBJECTIVE: To examine the effects of sacubitril/valsartan on physical and social activities. DESIGN, SETTING, AND PARTICIPANTS: The PARADIGM-HF trial was a randomized, double-blind, active treatment–controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. INTERVENTIONS: Sacubitril/valsartan, 200 mg twice daily, or enalapril, 10 mg twice daily. MAIN OUTCOMES AND MEASURES: Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. RESULTS: At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95% CI, 1.19-3.50; P

We thank Dr. Gomez-Ambrosi and colleagues for their insights regarding our paper [(1)][1]. We agree completely with the notion that body mass index (BMI) has limitations with regard to measuring adiposity, although it certainly remains the most clinically used measure of adiposity. For this reason

Advanced lipid testing has been suggested by some experts to identify patients with substantial residual risk for more aggressive targeting of lifestyle and pharmacologic therapies. It measures the subpopulation of lipoproteins and apolipoproteins, which include lipoprotein (a), apolipoprotein A-I, and apolipoprotein B, and measures of lipoprotein particle composition such as LDL particle (LPL-P) and HDL particle (HDL-P) number and size. Obesity is associated with smaller LDL-P and HDL-P sizes. Moderate weight loss via fasting/calorie restriction is associated with LDL-P size increase, whereas moderate weight loss via endurance exercise is associated with HDL-P size increase. Diets high in carbohydrates are associated with a more atherogenic advanced lipoprotein profile characterized by smaller LDL-P and HDL-P sizes. In summary, lifestyle changes such as weight loss, exercise, and dietary modification correlate with improvement in the profile of advanced lipoproteins. Regrettably, therapies targeting HDL and HDL composition have been disappointing to date.