Clinical Implications of the Amyloidogenic V122I Transthyretin Variant in the General Population.

BACKGROUND: The V122I variant in transthyretin (TTR) is the most common amyloidogenic mutation worldwide. The aim of this study is to describe the cardiac phenotype and risk for adverse cardiovascular outcomes of young V122I TTR carriers in the general population. METHODS AND RESULTS: TTR genotypes were extracted from whole-exome sequence data in participants of the Dallas Heart Study. Participants with African ancestry, available V122I TTR genotypes (N = 1818) and either cardiac magnetic resonance imaging (n = 1364) or long-term follow-up (n = 1532) were included. The prevalence of V122I TTR carriers (45 ± 10 years) was 3.2% (n/N = 59/1818). The V122I TTR carriers had higher baseline left ventricular wall thickness (8.52 ± 1.82 vs 8.21 ± 1.62 mm, adjusted P = .038) than noncarriers, but no differences in other cardiac magnetic resonance imaging measures (P > .05 for all). Although carrier status was not associated with amino terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline (P = .79), V122I TTR carriers had a greater increase in NT-proBNP on follow-up than noncarriers (median 28.5 pg/mL, interquartile range 11.4-104.1 pg/mL vs median 15.9 pg/mL, interquartile range 0.0-43.0 pg/mL, adjusted P = .018). V122I TTR carriers were at a higher adjusted risk of heart failure (hazard ratio 3.82, 95% confidence interval 1.80-8.13, P < .001), cardiovascular death (hazard ratio 2.65, 95% confidence interval 1.14-6.15, P = .023), and all-cause mortality (hazard ratio 1.95, 95% confidence interval 1.08-3.51, P = .026) in comparison with noncarriers. CONCLUSIONS: V122I TTR carrier status was associated with a greater increase in NT-proBNP, slightly greater left ventricular wall thickness, and a higher risk for heart failure, cardiovascular death, and all-cause mortality. These findings suggest the need to develop amyloidosis screening strategies for V122I TTR carriers.

Cardiac magnetic resonance imaging to assess the impact of maternal habitus on cardiac remodeling during pregnancy.

BACKGROUND: It is well known that the maternal cardiovascular system undergoes profound alterations throughout pregnancy. Interest in understanding these changes has led investigators to use evolving and increasingly sophisticated techniques to study these changes, most recently with 2-dimensional echocardiography. Despite its clinical utility, echocardiography has limitations, and cardiac magnetic resonance imaging (CMRI) has become increasingly used for evaluation of cardiac structure and function. OBJECTIVE: We used CMRI to evaluate cardiac remodeling according to maternal habitus throughout pregnancy and postpartum. STUDY DESIGN: This was a prospective, observational study of nulliparous women aged 18-30 years, without preexisting medical conditions, conducted from October 2012 through December 2014. Women were classified according to prepregnancy body mass index (BMI) as either normal (BMI 18.5-24.9 kg/m(2)) or overweight (BMI 25-35 kg/m(2)). All women underwent CMRI during 5 epochs throughout gestation: 12-16 weeks, 26-30 weeks, 32-36 weeks, at delivery, and 3 months' postpartum. Using left ventricular mass (LVM) as a marker of cardiac remodeling, the 2 cohorts were compared. RESULTS: There were 14 normal-weight (BMI 22.2 ± 1.3) and 9 overweight (BMI 29.1 ± 2.0) women who participated in the study. Beginning at 26-30 weeks and continuing to delivery, LVM of both normal-weight and overweight women was significantly increased compared with the respective first-trimester studies for each cohort (P < .001). LVM of both cohorts returned to their index values by 3 months' postpartum. The geometric ratio of LVM to left ventricular end-diastolic volume was calculated, and both normal-weight and overweight women demonstrated concentric remodeling throughout gestation, however this resolved by 12 weeks' postpartum. CONCLUSION: There is substantial cardiac remodeling during pregnancy with significant increases in LVM that are proportional to maternal size. Left ventricular geometric remodeling was concentric in both normal-weight and overweight women. All changes in cardiac remodeling resolved by 3 months' postpartum.

The Effects of Maternal Position and Habitus on Maternal Cardiovascular Parameters as Measured by Cardiac Magnetic Resonance.

OBJECTIVE: To evaluate left ventricular stroke volume (LVSV) and cardiac output (CO) according to maternal position and habitus throughout pregnancy and postpartum using serial cardiac magnetic resonance imaging (c-MRI). STUDY DESIGN: This was a prospective study of normotensive nulliparous women using 1.5-T c-MRI performed in both left lateral decubitus and supine positions during three epochs in pregnancy and at 12 weeks' postpartum. Women were stratified according to prepregnancy body mass indices (BMIs) as normal or overweight/obese and compared for LVSV and CO using repeated measures, mixed-random, and fixed-effects model. RESULTS: Between October 2012 and December 2014, 14 normal-weight (BMI 22.2 ± 1.3) and 9 overweight/obese (BMI 29.1 ± 2.0) women underwent c-MRI. During early pregnancy, position did not alter LVSV or CO for either cohort. Beginning at 26 to 30 weeks and continuing to 32 to 36 weeks, normal-weight women demonstrated significant positional differences for LVSV and CO (both p < 0.01). In contrast, positional differences did not influence these parameters in overweight/obese women. At 12 weeks' postpartum, all influence of position had dissipated for both cohorts. CONCLUSION: Maternal position has no effect on LVSV or CO during the first half of pregnancy. In the second half, however, only normal-weight women exhibit significant changes in cardiac parameters when comparing the left lateral decubitus with supine position.

Left atrial structure and function and clinical outcomes in the general population.

AIMS: Left atrial (LA) structural and functional abnormalities may be subclinical phenotypes, which identify individuals at increased risk of adverse outcomes. METHODS AND RESULTS: Maximum LA volume (LAmax) and LA emptying fraction (LAEF) were measured via cardiac magnetic resonance imaging in 1802 participants in the Dallas Heart Study. The associations of LAEF and LAmax indexed to body surface area (LAmax/BSA) with traditional risk factors, natriuretic peptide levels, and left ventricular (LV) structure [end-diastolic volume (EDV) and concentricity(0.67) (mass/EDV(0.67))] and function (ejection fraction) were assessed using linear regression analysis. The incremental prognostic value of LAmax/BSA and LAEF beyond traditional risk factors, LV ejection fraction, and LV mass was assessed using the Cox proportional-hazards model. Both increasing LAmax/BSA and decreasing LAEF were associated with hypertension and natriuretic peptide levels (P < 0.05 for all). In multivariable analysis, LAmax/BSA was most strongly associated with LV end-diastolic volume/BSA, while LAEF was strongly associated with LV ejection fraction and concentricity(0.67). During a median follow-up period of 8.1 years, there were 81 total deaths. Decreasing LAEF [hazard ratio (HR) per 1 standard deviation (SD) (8.0%): 1.56 (1.32-1.87)] but not increasing LAmax/BSA [HR per 1 SD (8.6 mL/m(2)): 1.14 (0.97-1.34)] was independently associated with mortality. Furthermore, the addition of LAEF to a model adjusting Framingham risk score, diabetes, race, LV mass, and ejection fraction improved the c-statistic (c-statistics: 0.78 vs. 0.77; P < 0.05, respectively), whereas the addition of LAmax/BSA did not (c-statistics: 0.76, P = 0.20). CONCLUSION: In the general population, both LAmax/BSA and LAEF are important subclinical phenotypes but LAEF is superior and incremental to LAmax/BSA.

Association of global longitudinal strain by feature tracking cardiac magnetic resonance imaging with adverse outcomes among community-dwelling adults without cardiovascular disease: The Dallas Heart Study.

AIM: Left ventricular (LV) global longitudinal strain (GLS) may detect subtle abnormalities in myocardial contractility among individuals with normal LV ejection fraction (LVEF). However, the prognostic implications of GLS among healthy, community-dwelling adults is not well-established. METHODS AND RESULTS: Overall, 2234 community-dwelling adults (56% women, 47% Black) with LVEF ≥50% without a history of cardiovascular disease (CVD) from the Dallas Heart Study who underwent cardiac magnetic resonance (CMR) with GLS assessed by feature tracking CMR (FT-CMR) were included. The association of GLS with the risk of incident major adverse cardiovascular events (MACE; composite of incident myocardial infarction, incident heart failure [HF], hospitalization for atrial fibrillation, coronary revascularization, and all-cause death), and incident HF or death were assessed with adjusted Cox proportional hazards models. A total of 309 participants (13.8%) had MACE during a median follow-up duration of 17 years. Participants with the worst GLS (Q4) were more likely male and of the Black race with a history of tobacco use and diabetes with lower LVEF, higher LV end-diastolic volume, and higher LV mass index. Cumulative incidence of MACE was higher among participants with worse (Q4 vs. Q1) GLS (20.4% vs. 9.0%). In multivariable-adjusted Cox models that included clinical characteristics, cardiac biomarkers and baseline LVEF, worse GLS (Q4 vs. Q1) was associated with a significantly higher risk of MACE (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.07-2.24, p = 0.02) and incident HF or death (HR 1.57, 95% CI 1.03-2.38, p = 0.04). CONCLUSIONS: Impaired LV GLS assessed by FT-CMR among adults free of cardiovascular disease is associated with a higher risk of incident MACE and incident HF or death independent of cardiovascular risk factors, cardiac biomarkers and LVEF.

Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk: Findings From Population-Based Cohort Studies.

BACKGROUND: Supranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic implication of supranormal left ventricular ejection fraction (LVEF)-assessed by cardiac magnetic resonance (CMR)-in healthy, community-dwelling individuals is unknown. OBJECTIVES: The purpose of this study is to investigate the prognostic implication of supranormal LVEF as assessed by CMR and its inter-relationship with stroke volume among community-dwelling adults without CVD. METHODS: Participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) cohorts free of CVD who underwent CMR with LVEF above the normal CMR cutoff (≥57%) were included. The association between cohort-specific LVEF categories and risk of clinically adjudicated major adverse cardiovascular events (MACE) was assessed using adjusted Cox models. Subgroup analysis was also performed to evaluate the association of LVEF and risk of MACE among individuals stratified by left ventricular stroke volume index. RESULTS: The study included 4,703 participants from MESA and 2,287 from DHS with 727 and 151 MACE events, respectively. In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs Q1) in both cohorts after accounting for potential confounders (MESA: HR = 1.27 [95% CI: 1.01-1.60], P = 0.04; DHS: HR = 1.72 [95% CI: 1.05-2.79], P = 0.03). A significant interaction was found between the continuous measures of LVEF and left ventricular stroke volume index (P interaction = 0.02) such that higher LVEF was significantly associated with an increased risk of MACE among individuals with low but not high stroke volume. CONCLUSIONS: Among community-dwelling adults without CVD, LVEF in the supranormal range is associated with a higher risk of adverse cardiovascular outcomes, particularly in those with lower stroke volume.

Risk scores versus natriuretic peptides for identifying prevalent stage B heart failure.

BACKGROUND: Identifying asymptomatic individuals with American Heart Association/American College of Cardiology stage B heart failure (HF) in the population is an important step to prevent the development of symptomatic HF. The comparative utility of 2 screening strategies (biomarkers vs risk scores) in identifying prevalent stage B HF is unknown. METHODS: Participants 30 to 65 years old without symptomatic HF in the Dallas Heart Study who had a cardiac magnetic resonance imaging were included (n = 2,277). Stage B HF (n = 284) was defined by left ventricular (LV) hypertrophy, reduced LV ejection fraction, or prior myocardial infarction. We compared the utility of 2 risk scores (Health Aging and Body Composition HF risk score and the Framingham Heart Failure risk score) with B-type natriuretic peptide (BNP) and N-terminal pro-BNP in identifying stage B HF using logistic regression. RESULTS: Depending upon the method of indexing LV mass (body surface area, fat-free mass, or height(2.7)), the c-statistic for the Health Aging and Body Composition HF risk score (0.73, 0.75, and 0.64, respectively) was greater than that for BNP (0.62, 0.70, and 0.57, respectively) and N-terminal pro-BNP (0.62, 0.69, and 0.56, respectively) (P < .01 for all). These findings were similar for the Framingham Heart Failure risk score except when LV mass was indexed to fat-free mass. Addition of natriuretic peptide levels to the risk scores resulted in a modest but significant improvement in discrimination of stage B HF (Δ c-statistic, 0.01-0.03, P < .05 for all). CONCLUSIONS: Screening for stage B HF in the population is enhanced when natriuretic peptides are measured in addition to, rather than in place of, traditional risk scores.

Academic Medicine Faculty Perceptions of Work-Life Balance Before and Since the COVID-19 Pandemic.

Importance: How the COVID-19 pandemic has affected academic medicine faculty's work-life balance is unknown. Objective: To assess the association of perceived work-life conflict with academic medicine faculty intention to leave, reducing employment to part time, or declining leadership opportunities before and since the COVID-19 pandemic. Design, Settings, and Participants: An anonymous online survey of medical, graduate, and health professions school faculty was conducted at a single large, urban academic medical center between September 1 and September 25, 2020. Main Outcomes and Measures: Self-assessed intention to leave, reducing employment to part time, or turning down leadership opportunities because of work-life conflict before and since the COVID-19 pandemic. Results: Of the 1186 of 3088 (38%) of faculty members who answered the survey, 649 (55%) were women and 682 (58%) were White individuals. Respondents were representative of the overall faculty demographic characteristics except for an overrepresentation of female faculty respondents and underrepresentation of Asian faculty respondents compared with all faculty (female faculty: 649 [55%] vs 1368 [44%]; Asian faculty: 259 [22%] vs 963 [31%]). After the start of the COVID-19 pandemic, faculty were more likely to consider leaving or reducing employment to part time compared with before the pandemic (leaving: 225 [23%] vs 133 [14%]; P < .001; reduce hours: 281 [29%] vs 206 [22%]; P < .001). Women were more likely than men to reduce employment to part time before the COVID-19 pandemic (153 [28%] vs 44 [12%]; P < .001) and to consider both leaving or reducing employment to part time since the COVID-19 pandemic (leaving: 154 [28%] vs 56 [15%]; P < .001; reduce employment: 215 [40%] vs 49 [13%]; P < .001). Faculty with children were more likely to consider leaving and reducing employment since the COVID-19 pandemic compared with before the pandemic (leaving: 159 [29%] vs 93 [17%]; P < .001; reduce employment: 213 [40%] vs 130 [24%]; P < .001). Women with children compared with women without children were also more likely to consider leaving since the COVID-19 pandemic than before (113 [35%] vs 39 [17%]; P < .001). Working parent faculty and women were more likely to decline leadership opportunities both before (faculty with children vs without children: 297 [32%] vs 84 [9%]; P < .001; women vs men: 206 [29%] vs 47 [13%]; P < .001) and since the COVID-19 pandemic (faculty with children vs faculty without children: 316 [34%] vs 93 [10 %]; P < .001; women vs men: 148 [28%] vs 51 [14%]; P < .001). Conclusions and Relevance: In this survey study, the perceived stressors associated with work-life integration were higher in women than men, were highest in women with children, and have been exacerbated by the COVID-19 pandemic. The association of both gender and parenting with increased perceived work-life stress may disproportionately decrease the long-term retention and promotion of junior and midcareer women faculty.

Association of Health Aging and Body Composition (ABC) Heart Failure score with cardiac structural and functional abnormalities in young individuals.

BACKGROUND: The Health ABC Heart Failure score has recently been shown to predict 5-year risk of incident heart failure in the elderly. We tested whether this risk score is associated with subclinical phenotypes of heart failure in a younger population. METHODS: We stratified participants in the Dallas Heart Study aged 30 to 65 years who had a cardiac magnetic resonance imaging and no self-reported history of heart failure or cardiomyopathy into 4 previously defined Health ABC Heart Failure risk groups: low (<5%), average (5%-10%), high (10%-20%), and very high (>20% risk for heart failure within 5 years). We compared left ventricular (LV) structural and functional parameters and levels of B-type natriuretic peptide (BNP) and N-terminal proBNP among the 4 groups. RESULTS: In the study cohort (N = 2,540), the percentage of subjects in the low-, average-, high-, and very high risk groups was 78%, 15%, 6%, and 1%, respectively. Indexed LV mass (80 +/- 15 vs 90 +/- 20 vs 95 +/- 25 vs 116 +/- 41 g/m(2)), concentricity (1.6 +/- 0.3 vs 1.8 +/- 0.4 vs 2.0 +/- 0.5 vs 2.2 +/- 0.7 g/mL), median BNP (2.8 vs 3.7 vs 4.9 vs 7.5 pg/mL) and N-terminal proBNP (26 vs 30 vs 40 vs 58 pg/mL), and prevalent LV systolic dysfunction and LV hypertrophy progressively increased across risk groups (P < .001 for all) independent of gender or method of indexing LV mass. CONCLUSIONS: The Health ABC Heart Failure score was associated with subclinical cardiac structural changes in the general population 30 to 65 years of age, suggesting that it may be a valid tool for identification of young individuals at increased risk for heart failure.

Long-term outcomes with ambrisentan monotherapy in pulmonary arterial hypertension.

BACKGROUND: This study evaluated long-term outcomes in patients with pulmonary arterial hypertension (PAH) undergoing treatment with ambrisentan monotherapy, a selective oral endothelin-1 receptor antagonist. METHODS AND RESULTS: Patients who participated in the Ambrisentan in Pulmonary Arterial Hypertension: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Efficacy Study (ARIES-1) clinical trial and extension phase at our institution were included. Cardiac catheterization, 6-minute walk distance (6MWD), and cardiac magnetic resonance (MRI) data were retrospectively reviewed. Twelve patients with PAH (11 idiopathic, 1 fenfluramine) had follow-up from 3 to 5.5 years from the initiation of ARIES-1. Patients received ambrisentan therapy throughout the study period and were on ambrisentan monotherapy for the first 2 years. At year 1, improvements in median mean pulmonary arterial pressure (PA), cardiac output, and pulmonary vascular resistance (PVR) were seen (P = .02, P = .03, P < .01), and the improvement in PVR persisted at 2 years. 6MWD also improved significantly between baseline (350 m) and 1 and 2 years (397 m, P < .01 and 393 m, P = .01). Cardiac MRI results were more varied, with an increase in RV ejection fraction from 29% at baseline to 46% at 2 years (P = .02), but other MRI variables did not improve. CONCLUSIONS: Ambrisentan monotherapy led to improvements in catheterization, 6MWD, and RV ejection fraction, and shows promise as a long-term treatment for pulmonary arterial hypertension.

The association between plasma caspase-3, atherosclerosis, and vascular function in the Dallas Heart Study.

BACKGROUND: Caspase-3, an apoptosis protease, is expressed in atherosclerotic plaques. We examined the relationship between plasma caspase-3 levels, aortic compliance, and atherosclerosis. METHODS: Caspase-3 was measured in 3,221 subjects from the Dallas Heart Study. Electron beam computed tomography measures of coronary calcium (CAC) (n = 2,404) and magnetic resonance imaging (MRI) measures of abdominal aortic wall thickness (AWT) (n = 2,208) and aortic compliance (AC) (n = 2,328) were obtained. Multivariate analyses were performed, adjusting for age, sex, ethnicity, body mass index (BMI), traditional cardiovascular risk factors, and cardiac medications. RESULTS: In univariable analysis, caspase-3 associated with CAC (P < 0.0001), AWT (P = 0.002), and AC (P < 0.0001). After multivariable adjustment, 4th quartile caspase-3 (compared to 1st quartile) was significantly associated with CAC (P = 0.004), AWT (P = 0.02), and AC (P < 0.0001) with similar findings for caspase-3 as a continuous variable. CONCLUSIONS: Caspase-3 independently associates with CAC, AWT, and AC, suggesting a link between apoptosis and atherosclerosis.

Association of African Ancestry With Electrocardiographic Voltage and Concentric Left Ventricular Hypertrophy: The Dallas Heart Study.

Importance: Compared with white individuals, black individuals have increased electrocardiographic voltage and an increased prevalence of concentric left ventricular (LV) hypertrophy. Whether environmental or genetic factors lead to these racial differences is unknown. Objective: To determine whether proportion of genetically determined African ancestry among self-reported black individuals is associated with increased electrocardiographic voltage and concentric LV hypertrophy (LVH). Design, Setting, and Participants: The Dallas Heart Study is a probability-based cohort study of English- or Spanish-speaking Dallas County, Texas, residents, with deliberate oversampling of black individuals. Participants underwent extensive phenotyping, which included electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), and dual-energy radiography absorptiometry (DEXA) at a single center. Participants aged 18 to 65 years who enrolled in the Dallas Heart Study between July 2000 and December 2002, self-identified as black (n = 1251) or white (n = 826), and had ECG, CMR, and DEXA data were included in this analysis. Data were analyzed from June 2017 to September 2018. Exposures: Proportion of African ancestry. Main Outcomes and Measures: Electrocardiographic voltage (12-lead and 9-lead) and markers of concentric LVH as assessed by CMR (LV concentricity0.67 [LV mass/end-diastolic volume0.67], LV wall thickness [LVWT], and prevalent LVH [defined by LV mass/height2.7]). Results: Of the 2077 participants included in the study, 1138 (54.8%) were women, and the mean (SD) age was 45.2 (9.9) years. Black race and African ancestry were individually associated with increased ECG voltage, LV concentricity0.67, LVWT, and prevalent LVH in multivariable analyses adjusting for age, sex, systolic blood pressure, antihypertensive medication use, and body composition. When African ancestry and black race were entered together into multivariable models, African ancestry but not black race remained associated with ECG voltage, LVWT, LV concentricity0.67, and prevalent LVH. Among black participants, African ancestry remained associated with these 4 phenotypes (12-lead voltage: ß, 0.05; P = .04; LVWT: ß, 0.05; P = .02; LV concentricty0.67: ß, 0.05; P = .045; prevalent LVH: odds ratio, 1.2; 95% CI, 1.03-1.4; P = .02). Conclusions and Relevance: Genetically determined African ancestry was associated with electrocardiographic voltage, measures of concentric LV remodeling, and prevalent LVH. These data support a genetic basis related to African ancestry for the increased prevalence of these cardiovascular traits in black individuals.

Dynamic Relation of Changes in Weight and Indices of Fat Distribution With Cardiac Structure and Function: The Dallas Heart Study.

BACKGROUND: Obesity may increase heart failure risk through cardiac remodeling. Cross-sectional associations between adiposity and cardiac structure and function have been elucidated, but the impact of longitudinal changes in adiposity on cardiac remodeling is less well understood. METHODS AND RESULTS: Participants in the Dallas Heart Study without cardiovascular disease or left ventricular dysfunction underwent assessment of body weight, anthropometrics, and cardiac magnetic resonance imaging at baseline and 7 years later. Associations between changes in indices of generalized and central adiposity with changes in left ventricular mass, volume, mass/volume ratio (concentricity), wall thickness, and ejection fraction were assessed using multivariable linear regression. The study cohort (n=1262) mean age was 44 years with 57% women, 44% black, and 36% obese participants. At follow-up, 41% had ≥5% weight gain, and 15% had ≥5% weight loss. Greater weight gain was associated with younger age, lower risk factor burden, and lower body mass index at baseline. In multivariable models adjusting for age, sex, race, comorbid conditions at baseline and follow-up, baseline adiposity, and cardiac measurement, increasing weight was associated with increases in left ventricular mass (ß=0.10, P<0.0001), wall thickness (ß=0.10, P<0.0001), and concentricity (ß=0.06, P=0.002), with modest effects on end-diastolic volume (ß=0.04, P=0.044) and ejection fraction (ß=0.05, P=0.046). Similar results were seen with other adiposity indices. CONCLUSIONS: Concentric left ventricular remodeling is the predominant phenotype linked to increasing adiposity in middle age. Our findings support the importance of weight management to prevent secular changes in adiposity, concentric remodeling, and eventual heart failure over time.

Factors Associated With Left Atrial Remodeling in the General Population.

BACKGROUND: Although contributors to remodeling of the left ventricle (LV) have been well studied in general population cohorts, few data are available describing factors influencing changes in left atrial (LA) structure. METHODS AND RESULTS: Maximum LA volume was determined by cardiac magnetic resonance imaging among 748 participants in the Dallas Heart Study at 2 visits a mean of 8 years apart. Associations of changes in LA volume (ΔLAV) with traditional risk factors, biomarkers, LV geometry, and remodeling by cardiac magnetic resonance imaging and detailed measurements of global and regional adiposity (by magnetic resonance imaging and dual-energy x ray absorptiometry) were assessed using multivariable linear regression. Greater ΔLAV was independently associated with black and Hispanic race/ethnicity, change in systolic blood pressure, LV mass and ΔLV mass, N-terminal probrain natriuretic peptide and change in N-terminal probrain natriuretic peptide, and body mass index (P<0.05 for each). In subanalyses, the associations of ΔLAV with LV mass parameters were driven by associations with baseline and ΔLV end diastolic volume (P<0.0001 for each) and not wall thickness (P=0.21). Associations of ΔLAV with body mass index were explained exclusively by associations with visceral fat mass (P=0.002), with no association seen between ΔLAV and subcutaneous abdominal fat (P=0.47) or lower body fat (P=0.30). CONCLUSIONS: Left atrial dilatation in the population is more common in black and Hispanic than in white individuals and is associated with parallel changes in the LV. LA dilatation may be mediated by blood pressure control and the development of visceral adiposity.

Association of Concentric Left Ventricular Hypertrophy With Subsequent Change in Left Ventricular End-Diastolic Volume: The Dallas Heart Study.

BACKGROUND: In the conventional paradigm of the progression of left ventricular hypertrophy, a thick-walled left ventricle (LV) ultimately transitions to a dilated cardiomyopathy. There are scant data in humans demonstrating whether this transition occurs commonly without an interval myocardial infarction. METHODS AND RESULTS: Participants (n=1282) from the Dallas Heart Study underwent serial cardiac magnetic resonance ≈7 years apart. Those with interval cardiovascular events and a dilated LV (increased LV end-diastolic volume [EDV] indexed to body surface area) at baseline were excluded. Multivariable linear regression models tested the association of concentric hypertrophy (increased LV mass and LV mass/volume0.67) with change in LVEDV. The study cohort had a median age of 44 years, 57% women, 43% black, and 11% (n=142) baseline concentric hypertrophy. The change in LVEDV in those with versus without concentric hypertrophy was 1 mL (-9 to 12) versus -2 mL (-11 to 7), respectively, P<0.01. In multivariable linear regression models, concentric hypertrophy was associated with larger follow-up LVEDV (P≤0.01). The progression to a dilated LV was uncommon (2%, n=25). CONCLUSIONS: In the absence of interval myocardial infarction, concentric hypertrophy was associated with a small, but significantly greater, increase in LVEDV after 7-year follow-up. However, the degree of LV enlargement was minimal, and few participants developed a dilated LV. These data suggest that if concentric hypertrophy does progress to a dilated cardiomyopathy, such a transition would occur over a much longer timeframe (eg, decades) and perhaps less common than previously thought. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00344903.

Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance.

Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis.

Quality Improvement of Staphylococcus aureus Bacteremia Management and Predictors of Relapse-free Survival.

PURPOSE: The purpose of this study is to improve the quality of care and patient outcomes for Staphylococcus aureus bacteremia. METHODS: A quasi-experimental pre- and postintervention study design was used to compare process and clinical endpoints before and after a quality-improvement initiative. All inpatients >18 years of age with a positive blood culture for S. aureus during the specified pre- and postintervention period with clinical information available in the electronic medical record were included. An institutional protocol for the care of patients with S. aureus bacteremia was developed, formalized, and distributed to providers using a pocket card, an electronic order set, and targeted lectures over a 9-month period. RESULTS: There were 167 episodes of S. aureus bacteremia (160 patients) identified in the preintervention period, and 127 episodes (123 patients) in the postintervention period. Guideline adherence improved in the postintervention period for usage of transesophageal echocardiogram (43.9% vs 20.2%, P <.01) and adequate duration of intravenous therapy (71% vs 60%, P = .05). In a multivariate Cox proportional hazard model, the variables associated with increased relapse-free survival were postintervention period (hazard ratio [HR] 0.48; confidence interval [CI], 0.24-0.95; P .035) and appropriate source control (HR 0.53; CI, 0.24-0.92; P .027). Regardless of intervention, presence of cancer was associated with an increased risk of relapse or mortality at 90 days (HR 2.88; P <.0001; CI, 1.35-5.01). CONCLUSION: A bundled educational intervention to promote adherence to published guidelines for the treatment of S. aureus bacteremia resulted in a significant improvement in provider adherence to guidelines as well as increased 90-day relapse-free survival.