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Coronary artery calcium (CAC) scoring can identify individuals who may benefit from aggressive prevention therapies. However, there is a paucity of contemporary data on the impact of CAC testing on patient management. Retrospective cohort study of adults who underwent CAC testing at Brigham and Women's Hospital between 2015 and 2019. Information on baseline medications, follow-up medications, lifestyle modification, and downstream cardiovascular testing within one-year post-CAC were obtained from electronic health records. Of the 839 patients with available baseline and follow-up data, 376 (45%) had a CAC ​= ​0, 289 (34%) had CAC ​= ​1–99, and 174 (21%) had CAC≥100. The mean age at time of CAC testing was 59 ​± ​9.7 years. Patients with higher CAC scores were more likely to be male, have diabetes and hypertension, and have higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol. A non-zero CAC score was associated with initiation of aspirin (41% increase, p ​< ​0.001), anti-hypertensives (9% increase, p ​= ​0.031), and lipid-lowering therapies (114% increase, p ​< ​0.001), whereas CAC ​= ​0 was not. Among individuals with CAC≥100, 75% were started on new or more intense lipid-lowering therapy. Higher calcium scores correlated with increased physician recommendations for diet (p ​= ​0.008) and exercise (p ​= ​0.004). The proportion of cardiovascular downstream testing following CAC was 9.1%, and the majority of patients who underwent additional testing post-CAC had CAC scores ≥100. Approximately half of individuals referred for CAC testing had evidence of calcified coronary plaque, and of those who had significant calcifications (CAC≥100), nearly 90% were prescribed lipid-lowering therapies post-CAC. Rates of downstream non-invasive testing were low and such testing was mostly performed in patients who had at least moderate CAC. Among patients with coronary artery calcium (CAC) scores ≥100, 75% were started on new or more intense lipid-lowering therapy. Patients with higher CAC scores were also more likely to be prescribed other preventive pharmacologic therapies, such as aspirin and anti-hypertensives, and be recommended lifestyle modification. Rates of downstream testing were low and such testing was mostly performed in patients who had moderate or severe coronary calcifications. [ABSTRACT FROM AUTHOR]

Background: Although heart failure (HF) risk and cardiac structure/function reportedly differ according to race and gender, limited data exist in late life when risk of HF is highest.Objectives: The goal of this study was to evaluate race/gender-based differences in HF risk factors, cardiac structure/function, and incident HF in late life.Methods: This analysis included 5,149 HF-free participants from ARIC (Atherosclerosis Risk In Communities), a prospective epidemiologic cohort study, who attended visit 5 (2011-2013) and underwent echocardiography. Participants were subsequently followed up for a median 5.5 years for incident HF/death.Results: Patients' mean age was 75 ± 5 years, 59% were women, and 20% were Black. Male gender and Black race were associated with lower mean left ventricular ejection fraction. Black race was also associated with greater left ventricular wall thickness and concentricity, differences that persisted after adjusting for cardiovascular comorbidities. After adjusting for cardiovascular comorbidities, men were at higher risk for HF and heart failure with reduced ejection fraction (HFrEF) in Black participants compared with White participants (HF: HR of 2.36 [95% CI: 1.37-4.08] vs 1.16 [95% CI: 0.89-1.51], interaction P = 0.016; HFrEF: HR of 3.70 [95% CI: 1.72-7.95] vs 1.55 [95% CI: 1.01-2.37] respectively, interaction P = 0.039). Black race was associated with a higher incidence of HF overall and HFrEF in men only (HF: 1.65 [95% CI: 1.07-2.53] vs 0.76 [95% CI: 0.49-1.17]; HFrEF: HR of 2.55 [95% CI: 1.46-4.44] vs 0.91 [95% CI: 0.46-1.83]). No race/gender-based differences were observed in risk of incident heart failure with preserved ejection fraction.Conclusions: Among older persons free of HF, men and Black participants exhibit worse systolic performance and are at heightened risk for HFrEF, whereas the risk of heart failure with preserved ejection fraction is similar across gender and race groups. [ABSTRACT FROM AUTHOR]

The authors aimed to study the sensitivity and specificity of exercise treadmill testing (ETT) in the diagnosis of coronary microvascular disease (CMD), as well as the prognostic implications of ETT results in patients with CMD. ETT is validated to evaluate for flow-limiting coronary artery disease (CAD), however, little is known about its use for evaluating CMD. We retrospectively studied 249 consecutive patients between 2006 and 2016 who underwent ETT and positron emission tomography within 12 months. Patients with obstructive CAD or left ventricular systolic dysfunction were excluded. CMD was defined as a coronary flow reserve <2. Patients were followed for the occurrence of a first major adverse event (composite of death or hospitalization for myocardial infarction or heart failure). The sensitivity and specificity of a positive ETT to detect CMD were 34.7% (95% CI: 25.4%-45.0%) and 64.9% (95% CI: 56.7%-72.5%), respectively. The specificity of a positive ETT to detect CMD increased to 86.8% (95% CI: 80.3%-91.7%) when only classifying studies with ischemic electrocardiogram changes that lasted at least 1 minute into recovery as positive, although at a cost of lower sensitivity (15.3%; 95% CI: 8.8%-24.0%). Over a median follow-up of 6.9 years (IQR: 5.1-8.2 years), 30 (12.1%) patients met the composite endpoint, including 13 (13.3%) with CMD (n = 98). In patients with CMD, ETT result was not associated with the composite endpoint (P = 0.076). Our data suggest limited sensitivity of ETT to detect CMD. However, a positive ETT with ischemic changes that persist at least 1 minute into recovery in the absence of obstructive CAD should raise suspicion for the presence of CMD given a high specificity. Further study is needed with larger patient sample sizes to assess the association between ETT results and outcomes in patients with CMD. [Display omitted] [ABSTRACT FROM AUTHOR]

• Among patients with coronary artery disease enrolled in cardiac rehabilitation, 79% were on optimal medical therapy. • Only 18% of patients with heart failure enrolled in cardiac rehabilitation were on optimal medical therapy. • Use of medications including angiotensin receptor neprilysin inhibitor, angiotensin converting enzyme inhibitors/angiotensin receptor blockers and spironolactone (although least prescribed) increased over from 2015 to 2019. Optimal medical therapy (OMT) in patients with coronary artery disease (CAD) and/or heart failure (HF) is underused despite the established benefits of these medications. Cardiac rehabilitation (CR) may be one place where OMT could be promoted. We sought to describe the prevalence and characteristics of OMT use in patients with CAD or HF undergoing CR. We included patients with CAD (myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, angina) and HF enrolled in our CR program. For patients with CAD, we defined OMT to consist of aspirin or other antiplatelets, statins, and beta-blockers (BB). For patients with HF or EF ≤ 40%, OMT included BB, spironolactone, and either Angiotensin Converting Enzyme inhibitors (ACEi)/angiotensin receptor blockers or angiotensin receptor neprilysin inhibitor (ARNI). For CAD patients with normal EF, OMT also included ACEi/ARB/ARNI if they also had diabetes type 2. From January 2015 to December 2019, 828 patients were referred to CR and 743 attended. Among 612 patients (mean age: 65, 23% female) with CAD, 483 (79%) patients were on OMT. Of the 131 HF patients (mean age: 64, 21% female) enrolled in CR, only 23 (18%) met all 3 OMT criteria, whereas most patients were on only 1 (93 %) or 2 (76%) HF specific medications. Spironolactone was the least prescribed (22%) medication. Over the study period, we observed a steady increase in the use of ARNI (2015: 0% vs 2019: 27%, p < 0.01). Among the individuals, 69 patients experienced both CAD and HF, while only 7 patients were under OMT for both CAD and HF. Most patients attending CR with CAD are receiving OMT, but most patients with HF are not. Although OMT has improved over time, there remains room for improvement, particularly among patients with HF. [ABSTRACT FROM AUTHOR]

Background: We studied the relationship between resting heart rate (HR), chronotropic response to exercise, and clinical outcomes in patients with heart failure (HF) across the spectrum of left ventricle ejection fraction (LVEF).Methods and Results: Resting HR and chronotropic index (CIx) were assessed in 718 patients with HF (53 ± 14 years of age, 66% male) referred for exercise testing. Associations with the composite outcome of left ventricular assist device implantation, transplantation, or death (151 events, 4.4 [range 3.0-5.8] years of follow-up) were assessed with the use of Cox models adjusted for age, sex, HF etiology, diabetes, LVEF, beta-blocker use, device therapy, estimated glomerular filtration rate, and peak oxygen uptake. Resting HR was 73 ± 15 beats/min, CIx was 0.60 ± 0.26, LVEF was 34% ± 15%, and 39% had an LVEF ≥40%. Resting HR correlated poorly with CIx (r = 0.08; P = .04) and did not predict (P = .84) chronotropic incompetence (CIx <0.60). Both higher resting HR (per 5 beats/min increase: adjusted hazard ratio [HR] -1.05, 95% confidence interval [CI] 1.00-1.11) and CIx (per SD change: adjusted HR -0.77, 95% CI 0.62-0.94) were independent prognostic markers. No heterogeneity of effect was noted based on LVEF (P >.05).Conclusion: Higher resting HR and lower CIx are both associated with more severe HF, but correlated poorly with each other. They provide independent and additive prognostic information in HF across the LVEF spectrum. [ABSTRACT FROM AUTHOR]

Objectives: We sought to assess the anatomical distribution of traumatic pneumothoraces (PTXs) on chest computed tomography (CT) to develop an optimized protocol for PTX screening with ultrasound in the emergency department (ED). Methods: We performed a retrospective review of all chest CTs performed in one ED between January 2005 and December 2008 according to presence, location, and size of PTX. Pneumothoraces were then measured and categorized into 14 anatomical regions for each hemithorax. Results: A total of 277 (3.8%) PTXs were identified, with 26 bilateral PTX, on 3636 chest CTs performed during the study period. Etiology was blunt (85%) or penetrating trauma (15%). Eighty-three (45%) PTXs were radiographically occult on initial chest x-ray. One hundred eighty-three (66%) PTX had no chest tube at the time of CT. For both hemithoraces, the distribution demonstrated increasing PTX frequency and size from lateral to medial and from superior to inferior. Region 12 (parasternal, intercostal spaces [ICS] 7-8) was involved in 68% of PTX on either side; region 9 (parasternal, ICS 5-6), in 67% on the left and in 52% on the right; and region 11 (lateral to midclavicular line, ICS 7-8), in 46% on the left and in 53% on the right. The largest anterior-to-posterior PTX dimension was seen in region 12. Conclusions: Our results indicate that 80.4% of right- and 83.7% of left-sided traumatic PTXs would be identified by scanning regions 9, 11, and 12. These findings suggest that a standardized protocol for PTX screening with ultrasound should include these regions. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to explore the relationship between baseline resting heart rate and outcomes in patients with chronic heart failure (HF) according to baseline left ventricular ejection fraction (LVEF) and cardiac rhythm. Background: Elevated resting heart rate is associated with worse outcomes in patients with HF and reduced LVEF. Whether this association is also found in patients with HF and preserved LVEF is uncertain, as is the predictive value of heart rate in patients in atrial fibrillation (AF). Methods: Patients enrolled in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Program were divided into groups by tertiles of baseline heart rate. Cox proportional hazard models were used to investigate the association between heart rate and pre-specified outcomes in the overall population as well as in subgroups defined according to LVEF (≤40% vs. >40%) and presence (or absence) of AF at baseline. Results: After adjusting for predictors of poor prognosis, patients in the highest heart rate tertile had worse outcomes when compared with those in the lowest heart rate group (e.g., for the composite of cardiovascular death or HF hospital stay hazard ratio: 1.23, 95% confidence interval: 1.11 to 1.36, p < 0.001). The relationship between heart rate and outcomes was similar across LVEF categories and was not influenced by beta-blocker use (p value for interaction >0.10 for both endpoints). However, amongst patients in AF at baseline, heart rate had no predictive value (p value for interaction <0.001). Conclusions: Resting heart rate is an important predictor of outcome in patients with stable chronic HF without AF, regardless of LVEF or beta-blocker use. [ABSTRACT FROM AUTHOR]

Aims: The mechanisms responsible for the increased risk of heart failure (HF) post–myocardial infarction (MI) may differ between patients with versus without diabetes. We hypothesized that after high-risk MI, patients with diabetes would demonstrate patterns of remodeling that are suggestive of reduced ventricular compliance and that are associated with an increased risk of death or HF. Methods and Results: We performed quantitative echocardiographic analysis in 153 patients with diabetes and 451 patients without diabetes enrolled in the VALIANT Echo study. Diabetes was associated with a higher risk of death or HF in age-adjusted models (hazard ratio 1.44, 95% CI 1.04-2.00, P = .028). Diabetic patients were similar to nondiabetic patients with respect to left ventricular (LV) volume and ejection fraction but had higher LV mass index (104.1 ± 27.5 vs 97.1 ± 28.6 g/m2, P = .009), relative wall thickness (0.41 ± 0.08 vs 0.38 ± 0.07, P < .0001), and left atrial volume index (LAVi) (26.2 ± 8.1 vs 24.0 ± 8.2 mL/m2, P = .008)—all parameters that were significantly related to the risk of death or HF hospitalization. Changes in LV volume and ejection fraction from baseline to 20 months were not different, although diabetic patients demonstrated greater increase in LAVi (4.4 ± 7.7 vs 2.2 ± 6.7 mL/m2, P = .01). Conclusions: After high-risk MI, diabetic patients were at higher risk of death or HF and demonstrated greater baseline LV mass index, relative wall thickness, and LAVi as well as greater left atrial enlargement at 20-month follow-up. These findings suggest greater baseline concentric remodeling and long-term elevation in LV diastolic pressure post-MI among diabetic patients, which may partially mediate this risk. [ABSTRACT FROM AUTHOR]

Background: Systematic reporting of estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) Study equation is recommended for detection of chronic kidney disease and prediction of cardiovascular (CV) risk. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is a newly developed and validated formula for eGFR that is more accurate at normal or near-normal eGFR. We aimed to assess the incremental prognostic accuracy of eGFRCKD-EPI versus eGFRMDRD in subjects at increased risk for CV disease. Methods: We performed a post hoc analysis of the VALIANT trial that enrolled 14,527 patients with acute myocardial infarction with signs and symptoms of heart failure and/or left ventricular systolic dysfunction. The eGFRMDRD and eGFRCKD-EPI were computed using age, gender, race, and baseline creatinine level. Patients were categorized according to their eGFR using each equation. To assess the incremental prognostic value of eGFRCKD-EPI, the net reclassification improvement was calculated for the composite end point of CV death, recurrent myocardial infarction, heart failure, or stroke. Results: Twenty-four percent of the subjects were reclassified into a different eGFR category using eGFRCKD-EPI. The composite end point occurred in 33% of the subjects in this cohort. Based on eGFRCKD-EPI, subjects reclassified into a higher eGFR experienced fewer events than those reclassified into a lower eGFR (21% vs 43%). In unadjusted analyses, the composite end point risk in subjects with eGFR between 75 and 90 mL/min per 1.73 m2 was comparable with the referent group (eGFR between 90 and 105) using eGFRMDRD (hazard ratio 1.1, 95% CI 0.9-1.2) but was significantly higher using eGFRCKD-EPI (hazard ratio 1.2, 95% CI 1.1-1.4). The net reclassification improvement for eGFRCKD-EPI over eGFRMDRD was 8.7%. Conclusion: The CKD-EPI equation provides more accurate risk stratification than the MDRD Study equation in patients at high risk for CV disease, including identification of increased risk at mildly decreased eGFR. [Copyright &y& Elsevier]

Background: Echocardiographic measurements of left ventricular (LV) function, predominantly LV ejection fraction (LVEF), have been used to define risk in patients after myocardial infarction. However, the extent to which measures of LV structure and function provide incremental prognostic value over clinical variables in survivors of high-risk myocardial infarction has not been well defined. Methods: Predictors of death and development of heart failure were assessed in 603 patients from the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiographic substudy. We used multivariable proportional hazards models to assess the individual predictive value of echocardiographic measures including left ventricular mass index, LVEF, LV volumes, left atrial volume index, right ventricular fractional area change, mitral regurgitation, and deceleration time. We adjusted for the 11 clinical variables found previously to be most associated with all-cause mortality in this cohort. Receiver operating characteristic curves obtained via binary response regression were used to assess the incremental predictive value of echocardiographic measures in predicting outcomes of death and hospital stay for heart failure. Results: Each echocardiographic measure was independently associated with outcome of death or development of heart failure (all P < .002). Left ventricular ejection fraction alone added minimal prognostic value to the clinical assessment, yet adding additional echocardiographic assessments to a multivariable model improved in predicting 17-month survival free of heart failure significantly, increasing the c-statistic from 0.74 to 0.84 (P < .001). Conclusion: Echocardiographic measures of cardiac structure and function beyond LVEF provide important prognostic information beyond the clinical assessment. [Copyright &y& Elsevier]

Objectives: This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction. Background: The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse cardiovascular events. Methods: Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes. Results: Mean LVMi and RWT were 98.8 ± 28.4 g/m2 and 0.38 ± 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m2 increase in LVMi; 95% CI: 1.20 to 1.30; p < 0.001) (HR: 1.60 per 0.1-U increase in RWT; 95% CI: 1.30 to 1.90; p < 0.001). Increased risk associated with RWT was independent of LVMi. Conclusions: Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an increased risk of cardiovascular complications after high-risk myocardial infarction. [Copyright &y& Elsevier]

Background: Advanced age is a well-established prognostic risk factor after acute myocardial infarction (AMI), yet approximately 10% of MIs occur in patients <45 years. We examined characteristics, cardiovascular outcomes, and the influence of risk factors on outcomes in young survivors of AMI. Methods: Fourteen thousand seven hundred three patients enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial were divided into 3 age groups: 18 to <45 (n = 803), 45 to <65 (n = 6185), ≥65 years (n = 7715). Multivariate Cox regression was used to compare cardiovascular event rates and assess the impact of risk factors on outcomes. Results: The youngest patients had less diabetes, hypertension, and history of MI and were more likely to be male (18 to <45 years, 88%; ≥65 years, 59.1%), nonwhite (18 to <45 years, 9.6%; ≥65 years, 5%), current smokers (18 to <45 years, 73.7%; ≥65 years, 15.9%), obese (18 to <45 years, 37.9%; ≥65 years, 25.1%), and dyslipidemic at randomization (18 to <45 years, 43.1%; ≥65 years, 32.7%). Adjusted relative risks of smoking (18 to <45 years, hazard ratio [HR] 1.6 [95% confidence interval {CI} 1.1-2.5]; ≥45 years, HR 0.9 [95% CI 0.9-1.1]; P =.014) and hypertension (18 to <45 years, HR 1.8 [95% CI 1.3-2.6]; ≥45 years, HR 1.2 [95% CI 1.1-1.3]; P = .044) were higher in the young, with significant interactions observed between age and these risk factors. Conclusions: After AMI, risk factors and outcomes of the young differ substantively from their older counterparts. The influence of hypertension and smoking is more profound in the young, underscoring the need for aggressive risk factor modification post-AMI. [Copyright &y& Elsevier]

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 ± 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 ± 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip’s classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI. [Copyright &y& Elsevier]

Background: In survivors of myocardial infarction (MI), new left bundle branch block (LBBB) is associated with adverse outcomes, but its impact is not well described in post-MI patients with left ventricular (LV) systolic dysfunction and/or heart failure (HF).Objectives: The aim of this study was to determine if new LBBB is an independent predictor of long-term fatal and nonfatal outcomes in high-risk survivors of MI by reviewing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial.Methods: In VALIANT, 14,703 patients with LV systolic dysfunction and/or HF were randomized to valsartan, captopril, or both a mean of 5 days after MI. Baseline ECG data were available from 14,259 patients. We assessed the predictive value of new LBBB for death and major cardiovascular outcomes after 3 years, adjusting for multiple baseline covariates including LV ejection fraction.Results: At follow-up, patients with new LBBB (608 [4.2%]) compared with patients without new LBBB had more comorbidities and increased adjusted risk of death (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.6), cardiovascular death (HR 1.4, 95% CI 1.2-1.7), HF (HR 1.3, 95% CI 1.1-1.6), MI (HR 1.5, 95% CI 1.2-1.9), and the composite of death, HF, or MI (HR 1.4, 95% CI 1.2-1.6).Conclusion: In post-MI survivors with LV systolic dysfunction and/or HF, new LBBB was an independent predictor of all major adverse cardiovascular outcomes during long-term follow-up. This readily available ECG marker should be considered a major risk factor for long-term cardiovascular complications in high-risk patients after MI. [ABSTRACT FROM AUTHOR]

Background: Prolongation of the QRS duration has been shown to be associated with adverse outcomes among heart failure (HF) patients. The association of QRS duration with clinical outcomes in the post-myocardial infarction (MI) setting is less well defined.Objectives: To assess the prognostic significance of QRS duration prolongation on initial electrocardiogram after acute MI.Methods: QRS duration was measured in 403 patients with MI complicated by left ventricular dysfunction, signs or symptoms of HF, or both, who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echo study. The cohort was divided into quartiles of QRS duration (<75 ms, 75-88 ms, 89-108 ms, >108 ms). The number of clinical events were determined and compared across the groups.Results: Increasing QRS duration is associated with a higher incidence of HF, sudden death (SD), and cardiovascular (CV) death (P-trend <0.05) but not with stroke or recurrent MI. The univariate relative risks for HF, SD, and CV death with increasing QRS duration quartiles were 1.31 (95% CI, 1.06-1.64), 1.57 (95% CI, 1.03-2.40), and 1.31 (95% CI, 1.03-1.66), respectively, but QRS duration did not remain independently predictive of adverse outcome after adjusting for the 10 most predictive baseline covariates. Baseline end-diastolic and end-systolic volumes were larger and ejection fraction was lower in the higher QRS quartile groups.Conclusions: Prolonged QRS duration, even within the normal range, is associated with larger ventricular volumes, reduced systolic function, and an increased risk for development of HF, SD, and CV death after MI but appears to be a marker, rather than an independent predictor, for increased risk. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI).Background: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF.Methods: The Survival And Ventricular Enlargement (SAVE) trial randomized 2,231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI.Results: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome.Conclusions: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor. [Copyright &y& Elsevier]

: ObjectivesThe aim of this study was to determine the prognostic value of right ventricular (RV) function in patients after a myocardial infarction (MI).: BackgroundRight ventricular function has been shown to predict exercise capacity, autonomic imbalance and survival in patients with advanced heart failure (HF).: MethodsTwo-dimensional echocardiograms were obtained in 416 patients with left ventricular (LV) dysfunction (ejection fraction [LVEF] ≤40%) from the Survival And Ventricular Enlargement (SAVE) echocardiographic substudy (mean 11.1 ± 3.2 days post infarction). Right ventricular function from the apical four-chamber view, assessed as the percent change in the cavity area from end diastole to end systole (fractional area change [FAC]), was related to clinical outcome.: ResultsRight ventricular function correlated only weakly with the LVEF (r = 0.12, p = 0.013). On univariate analyses, the RV FAC was a predictor of mortality, cardiovascular mortality and HF (p < 0.0001 for all) but not recurrent MI. After adjusting for age, gender, diabetes mellitus, hypertension, previous MI, LVEF, infarct size, cigarette smoking and treatment assignment, RV function remained an independent predictor of total mortality, cardiovascular mortality and HF. Each 5% decrease in the RV FAC was associated with a 16% increased odds of cardiovascular mortality (95% confidence interval 4.3% to 29.2%; p = 0.006).: ConclusionsRight ventricular function is an independent predictor of death and the development of HF in patients with LV dysfunction after MI. [Copyright &y& Elsevier]

Although physical activity is widely recommended for reducing cardiovascular and all-cause mortality risks, female individuals consistently lag behind male individuals in exercise engagement. The goal of this study was to evaluate whether physical activity derived health benefits may differ by sex. In a prospective study of 412,413 U.S. adults (55% female, age 44 ± 17 years) who provided survey data on leisure-time physical activity, we examined sex-specific multivariable-adjusted associations of physical activity measures (frequency, duration, intensity, type) with all-cause and cardiovascular mortality from 1997 through 2019. During 4,911,178 person-years of follow-up, there were 39,935 all-cause deaths including 11,670 cardiovascular deaths. Regular leisure-time physical activity compared with inactivity was associated with 24% (HR: 0.76; 95% CI: 0.73-0.80) and 15% (HR: 0.85; 95% CI: 0.82-0.89) lower risk of all-cause mortality in women and men, respectively (Wald F = 12.0, sex interaction P < 0.001). Men reached their maximal survival benefit of HR 0.81 from 300 min/wk of moderate-to-vigorous physical activity, whereas women achieved similar benefit at 140 min/wk and then continued to reach a maximum survival benefit of HR 0.76 also at ∼300 min/wk. Sex-specific findings were similar for cardiovascular death (Wald F = 20.1, sex interaction P < 0.001) and consistent across all measures of aerobic activity as well as muscle strengthening activity (Wald F = 6.7, sex interaction P = 0.009). Women compared with men derived greater gains in all-cause and cardiovascular mortality risk reduction from equivalent doses of leisure-time physical activity. These findings could enhance efforts to close the "gender gap" by motivating especially women to engage in any regular leisure-time physical activity. [Display omitted] [ABSTRACT FROM AUTHOR]

Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms. The aim of this study was to discover novel biomarkers with potentially causal associations with AS. We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over 6 years and with AV calcification with the use of cardiac computed tomography, replicated analysis in an independent sample, performed Mendelian randomization, and evaluated gene expression in explanted human AV tissue. Fifty-two proteins cross-sectionally were associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3. Among 3,413 participants in the Cardiovascular Health Study, 6 of those proteins were significantly associated with adjudicated moderate or severe AS, including matrix metalloproteinase 12 (MMP12), complement C1q tumor necrosis factor–related protein 1 (C1QTNF1), and growth differentiation factor-15. MMP12 was also associated with greater increase in AVmax over 6 years, greater degree of AV calcification, and greater expression in calcific compared with normal or fibrotic AV tissue. C1QTNF1 had consistent potential causal effects on both AS and AVmax according to Mendelian randomization analysis. These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression. [Display omitted] [ABSTRACT FROM AUTHOR]

Although the prognostic implications of higher pulmonary artery systolic pressure (PASP) are well established, few data exist regarding longitudinal change in pulmonary pressure in late life. The aim of this study was to quantify changes in PASP over 6 years and determine the relative contributions of cardiac and pulmonary dysfunction. Among 1,420 participants in the ARIC (Atherosclerosis Risk in Communities) study with echocardiographic measures of PASP at both the fifth (2011-2013) and seventh (2018-2019) visits, longitudinal changes in PASP over about 6.5 years were quantified. Multivariable regression was used to determine the extent to which cardiac and pulmonary dysfunction were associated with changes in PASP and to define the relationship of changes in PASP with dyspnea development. The mean age was 75 ± 5 years at visit 5 and 81 ± 5 years at visit 7, 24% of subjects were Black adults, and 68% were women. Over the 6.5 years, PASP increased by 5 ± 8 mm Hg, from 28 ± 5 to 33 ± 8 mm Hg. PASP increased more in older participants. Predictors of greater increases in PASP included worse left ventricular (LV) systolic and diastolic function, pulmonary function, and renal function. Increases in PASP were associated with concomitant increases in measures of LV filling pressure, including E/e′ ratio and left atrial volume index. Each 5 mm Hg increase was associated with 16% higher odds of developing dyspnea (OR: 1.16; 95% CI: 1.07-1.27; P < 0.001). Pulmonary pressure increased over 6.5 years in late life, was associated with concomitant increases in LV filling pressure, and predicted the development of dyspnea. Interventions targeting LV diastolic function may be effective at mitigating age-related increases in PASP. [Display omitted] [ABSTRACT FROM AUTHOR]

Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). This study sought to assess the clinical implications of RV function, the association with N-terminal pro–B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF. This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro–B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders. Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro–B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function. Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The influence of diabetes on progression from preclinical heart failure (HF) stages to overt HF is poorly understood.Objectives: The purpose of this study was to characterize the influence of diabetes on the progression from preclinical HF stages (A or B based on the 2021 Universal Definition) to overt HF.Methods: We included 4,774 adults with preclinical HF (stage A [n = 1,551] or B [n = 3,223]) who attended the ARIC (Atherosclerosis Risk In Communities) study Visit 5 (2011-2013). Within each stage (A or B), we assessed the associations of diabetes and glycemic control (hemoglobin A1C [HbA1C] <7% vs ≥7%) with progression to HF, and of cross-categories of HF stages (A vs B), diabetes, and glycemic control with incident HF.Results: Among the participants (mean age 75.4 years, 58% women, 20% Black), there were 470 HF events during 8.6 years of follow-up. Stage B participants with HbA1C ≥7% experienced clinical HF at a younger age than those with controlled diabetes or without diabetes (mean age 80 years vs 83 years vs 82 years; P < 0.001). HbA1C ≥7% was more strongly associated with HF in stage B (HR: 1.83; 95% CI: 1.33-2.51) compared with stage A (HR: 1.52; 95% CI: 0.53-4.38). In cross-categories of preclinical HF stage and HbA1C, participants with stage B and HbA1C ≥7% had increased risk of HF progression compared with stage A without diabetes (HR: 7.56; 95% CI: 4.68-12.20).Conclusions: Among older adults with preclinical HF stages, uncontrolled diabetes was associated with substantial risk of HF progression. Our results suggest that targeting diabetes early in the HF process is critical. [ABSTRACT FROM AUTHOR]

Background: Limited data exist to characterize novel measures of left atrial (LA) structure and function in older adults without prevalent heart failure (HF).Objectives: The aim was to assess reference range of LA measures, their associations with N-terminal pro-B-type natriuretic-peptide (NT-proBNP) and the related risk for incident HF or death.Methods: We analyzed LA structure (LA maximal [LAViMax] and minimal volume indexed by body surface area) and function (LA emptying fraction, LA reservoir, conduit, and contraction strain) in 4,901 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 75 ± 5 years, 40% male, and 19% Black) without prevalent HF. We assessed sex-specific 10th and 90th percentile ARIC-based reference limits in 301 participants free of prevalent cardiovascular disease, and related LA measures to NT-proBNP and incident HF or death (median follow-up of 5.5 years) in the whole ARIC cohort.Results: Approximately 20% of the overall population had LA abnormalities according to the ARIC-based reference limit. Each LA measure was associated with NT-proBNP and, except for LAViMax, with incident HF or death after multivariable adjustment (including left ventricular function and NT-proBNP). Results were consistent in participants with normal LAViMax (P for interaction > 0.05). LA measures were prognostic for both incident HF with preserved ejection fraction or death and incident HF with reduced ejection fraction or death. When added to HF risk factors and NT-proBNP (baseline C-statistics = 0.74) all LA measures, except for LAViMax, significantly enhanced the prognostic accuracy.Conclusions: Novel measures of LA structure and function, but not standard assessment by LAViMax, are associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP. [ABSTRACT FROM AUTHOR]

The troponin I values and echocardiographic data of 141 patients with acute pulmonary embolism (PE) were correlated with 30-day mortality. Patients with elevated troponin and right ventricular enlargement are at significantly greater risk for death after PE than patients with only 1 or with neither adverse prognostic marker. [Copyright &y& Elsevier]

Although exercise treadmill testing (ETT) is a useful initial test for patients with suspected cardiovascular (CV) disease, there is concern regarding the use of downstream imaging tests especially in the setting of equivocal or positive ETTs. Patients with no history of coronary artery disease who underwent ETT between 2009 and 2010 were prospectively included. Referring physicians were categorized as cardiologists and noncardiologists. Downstream tests included nuclear perfusion imaging, coronary computed tomography angiography, stress echocardiography, stress magnetic resonance, and invasive coronary angiography performed up to 6 months after the ETT. Patients were followed for CV death, myocardial infarction, and coronary revascularization for a median of 2.7 years. Among 3,656 patients, the ETT were negative in 2,876 (79%), positive in 132 (3.6%), and inconclusive in 643 (18%). Cardiologists ordered less downstream tests than noncardiologists (9.5% vs 12.2%, p [ 0.02), with less noninvasive tests (5.9% vs 10.4%, p <0.0001) and more invasive angiography (3.6% vs 1.8%, p <0.0001). After adjustment for confounding, patients evaluated by cardiologists were less likely to undergo additional testing after equivocal (odds ratio: 0.65, p[ 0.02) or positive ETT results (odds ratio: 0.39, p [ 0.02), whereas after negative ETT, the odds ratio was 1.7 (p [ 0.06). There was no difference in the rate of adverse CV events between patients referred by cardiologists versus noncardiologists. In conclusion, patients referred for ETT by cardiologists are less likely to undergo additional testing, particularly noninvasive tests, than those referred by noncardiologists. The lower rate of tests is driven by a lower rate of tests after positive or inconclusive ETT. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to estimate the frequency and results of downstream testing after exercise treadmill tests (ETTs). Background: The utility of additional diagnostic testing after ETT is not well characterized. Methods: We followed consecutive individuals without known coronary artery disease referred for clinical ETT at a large medical center. We measured the frequency and results of downstream imaging tests and invasive angiography within 6 months of ETT and the combined endpoint of survival free from cardiovascular death, myocardial infarction, and coronary revascularization. Results: Among 3,656 consecutive subjects who were followed for a mean of 2.5 ± 1.1 years, 332 (9.0%) underwent noninvasive imaging and 84 (2.3%) were referred directly to invasive angiography after ETT. The combined endpoint occurred in 76 (2.2%) patients. The annual incidence of the combined endpoint after negative, inconclusive, and positive ETT was 0.2%, 1.3%, and 12.4%, respectively (p < 0.001). Rapid recovery of electrocardiography (ECG) changes during ETT was associated with negative downstream test results and excellent prognosis, whereas typical angina despite negative ECG was associated with positive downstream tests and adverse prognosis (p < 0.001). Younger age, female sex, higher metabolic equivalents of task achieved, and rapid recovery of ECG changes were predictors of negative downstream tests. Conclusions: Among patients referred for additional testing after ETT, the lowest yield was observed among individuals with rapid recovery of ECG changes or negative ETT, whereas the highest yield was observed among those with typical angina despite negative ECG or a positive ETT. These findings may be used to identify patients who are most and least likely to benefit from additional testing. [Copyright &y& Elsevier]

Objectives: This study sought to relate imaging findings on positron emission tomography (PET) to adverse cardiac events in patients referred for evaluation of known or suspected cardiac sarcoidosis. Background: Although cardiac PET is commonly used to evaluate patients with suspected cardiac sarcoidosis, the relationship between PET findings and clinical outcomes has not been reported. Methods: We studied 118 consecutive patients with no history of coronary artery disease, who were referred for PET, using [18F]fluorodeoxyglucose (FDG) to assess for inflammation and rubidium-82 to evaluate for perfusion defects (PD), following a high-fat/low-carbohydrate diet to suppress normal myocardial glucose uptake. Blind readings of PET data categorized cardiac findings as normal, positive PD or FDG, positive PD and FDG. Images were also used to identify whether findings of extra-cardiac sarcoidosis were present. Adverse events (AE)—death or sustained ventricular tachycardia (VT)—were ascertained by electronic medical records, defibrillator interrogation, patient questionnaires, and telephone interviews. Results: Among the 118 patients (age 52 ± 11 years; 57% males; mean ejection fraction: 47 ± 16%), 47 (40%) had normal and 71 (60%) had abnormal cardiac PET findings. Over a median follow-up of 1.5 years, there were 31 (26%) adverse events (27 VT and 8 deaths). Cardiac PET findings were predictive of AE, and the presence of both a PD and abnormal FDG (29% of patients) was associated with hazard ratio of 3.9 (p < 0.01) and remained significant after adjusting for left ventricular ejection fraction (LVEF) and clinical criteria. Extra-cardiac FDG uptake (26% of patients) was not associated with AE. Conclusions: The presence of focal PD and FDG uptake on cardiac PET identifies patients at higher risk of death or VT. These findings offer prognostic value beyond Japanese Ministry of Health and Welfare clinical criteria, the presence of extra-cardiac sarcoidosis and LVEF. [ABSTRACT FROM AUTHOR]