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Background and Aim: Left ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, the predictive value of the LVH phenotype for incident AF remains uncertain. This study aimed to investigate the predictive value of LVH phenotype for incident AF., Methods and Results: This study utilized the Multi-Ethnic Study of Atherosclerosis (MESA) data. LVH was defined by cardiac magnetic resonance measured LV mass index. Isolated LVH was determined as LVH without elevated cardiac biomarker and malignant LVH was determined as LVH with at least 1 elevated biomarker. Receiver-operating characteristic (ROC) analysis was performed to calculate areas under the curves (AUC) for predicting AF. A total of 4983 community-dwelling participants were included, with a mean age of 61.5 years. 279 (5.6 %) had isolated LVH, and 222 (4.5 %) had malignant LVH. During a median follow-up of 8.5 years, 272 incident AF was observed. Compared to participants without LVH and elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95 % CI, 1.03-3.20) and malignant LVH (HR, 4.13; 95 % CI, 2.77-6.16) had a higher risk of incident AF. Malignant LVH carried a 1.5-fold increased risk of AF compared to isolated LVH (HR: 2.48, 95 % CI: 1.30-4.73). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (AUC increase: 0.03, p < 0.001)., Conclusions: The risks of AF incidence varied across LVH phenotypes. Malignant LVH carried the highest risk among LVH phenotypes. LVH phenotype provides incremental predictive value over the variables included in the CHARGE-AF model., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia., Objective: Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy., Methods: Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N = 27), and 3 to 5 years (N = 23) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance., Results: In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg/dL at baseline, 1 year, 3-5 years, P < .0001), A1c (9.5 ± 3.0, 6.5 ± 1.6, 6.5 ± 1.9%, P < .001), and HOMA-IR (34.1 [15.2-43.5], 8.7 [2.4-16.0], 8.9 [2.1-16.4], P < .001). Only HOMA-IR improved in PLD (P < .01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8 ± 1.7, 9.1 ± 1.3, 8.3 ± 1.7 mm, P < .01), and LV mass (140.7 ± 45.9, 128.7 ± 37.9, 110.9 ± 29.1 g, P < .01), and increased septal e' velocity (8.6 ± 1.7, 10.0 ± 2.1, 10.7 ± 2.4 cm/s, P < .01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e' velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD., Conclusion: Metreleptin attenuated cardiac hypertrophy and improved septal e' velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined., (Published by Oxford University Press on behalf of the Endocrine Society 2021.)

Aims: To compare left ventricular structure (LV) and diastolic function in young adults with youth- onset diabetes by type, determine the prevalence of abnormal diastolic function by diabetes type using published values from age similar healthy controls, and examine the risk factors associated with diastolic function., Methods: In a cross sectional analysis we compared LV structure and diastolic function from two dimensional echocardiogram in participants with type 1 (T1D) and type 2 diabetes (T2D) who participated in the SEARCH for Diabetes in Youth Study. Linear models were used to examine the risk factors associated with worse diastolic function., Results: Of 479 participants studied, 258 had T1D (mean age 21.2 ± 5.2 years, 60.5% non-Hispanic white, 53.9% female) and 221 had T2D (mean age 24.8 ± 4.3 years, 24.4% non-Hispanic white, 73.8% female). Median diabetes duration was 11.6 years. Participants with T2D had greater LV mass index and worse diastolic function that persisted after adjustment for differences in risk factors compared with participants with T1D (all p < 0.05). Abnormal diastolic function, quantified using healthy controls, was pronounced in both groups but greater in those with T2D than T1D (T2D: 57.7% vs T1D: 47.2%, respectively), p < 0.05. Risk factors associated with worse diastolic function included older age at diabetes diagnosis, female sex, higher BP, heart rate and HbA1c and longer diabetes duration., Conclusions: LV structure and diastolic function is worse in individuals with T2D compared to T1D. However, abnormal diastolic function in seen in both groups compared to published values from age similar healthy controls.

Background: Left ventricular (LV) epicardial pacing results in slowly propagating paced wavefronts. We postulated that this effect might limit cardiac resynchronization therapy efficacy in patients with LV enlargement using conventional biventricular pacing with single-site LV pacing, but be mitigated by LV stimulation from 2 widely spaced sites using MultiPoint pacing with wide anatomic separation (MPP-AS: ≥30 mm). We tested this hypothesis in the multicenter randomized MPP investigational device exemption trial., Methods: Following implant, quadripolar biventricular single-site pacing was activated in all patients (n=506). From 3 to 9 months postimplant, among patients with available baseline LV end-diastolic volume (LVEDV) measures, 188 received biventricular single-site pacing and 43 received MPP-AS. Patients were dichotomized by median baseline LVEDV indexed to height (LVEDVI Median ). Outcomes were measured by the clinical composite score (primary efficacy end point), quality of life, LV structural remodeling (↑EF >5% and ↓ESV 10%) and heart failure event/cardiovascular death., Results: LVEDVI Median was 1.1 mL/cm. Baseline characteristics differed in patients with LVEDVI >Median versus LVEDVI ≤Median . Among patients with LVEDVI >Median , biventricular single-site pacing was less efficacious compared to patients with LVEDVI ≤Median (clinical composite score, 65% versus 79%). In contrast, MPP-AS programming generated greater clinical composite score response (92% versus 65%, P =0.023) and improved quality of life (-31.0±29.7 versus -15.7±22.1, P =0.038) versus biventricular single-site pacing in patients with LVEDVI >Median . Reverse remodeling trended better with MPP-AS programming. In patients with LVEDVI >Median , heart failure event rate increased following the 3-month randomization point with biventricular single-site pacing (0.0150±0.1725 in LVEDVI >Median versus -0.0190±0.0808 in LVEDVI ≤Median , P =0.012), but no heart failure event occurred in patients with MPP-AS programming between 3 and 9 months in LVEDVI >Median . All measured outcomes did not differ in patients receiving MPP-AS and biventricular single-site pacing with LVEDVI ≤Median ., Conclusions: Conventional biventricular single-site pacing, even with a quadripolar lead, has reduced efficacy in patients with LV enlargement. However, the greatest response rate in patients with larger hearts was observed when programmed to MPP-AS pacing.

Importance: There is a paucity of data detailing cardiac remodeling in female athletes compared with male athletes. The lack of reference cardiac data for elite female basketball players or female athletes of similar size makes it difficult to differentiate athletic remodeling from potential underlying cardiac disorders in this population of athletes., Objective: To assess cardiac structure and function in elite female basketball players., Design, Setting, and Participants: This cross-sectional echocardiographic study included 140 Women's National Basketball Association (WNBA) athletes on active rosters for the 2017 season. The WNBA mandates annual preseason stress echocardiograms for each athlete. The WNBA has partnered with Columbia University to annually perform a review of these studies. Data analysis was performed from June 7, 2017, to October 5, 2017., Main Outcomes and Measures: Echocardiographic variables included left ventricular (LV) dimensions, wall thickness, mass, prevalence of LV hypertrophy, aortic dimensions, right ventricular (RV) dimension, and right and left atrial size. Linear regression was used to assess the associations between cardiac structure and function with body size quantified as body surface area (BSA) in the primary analysis., Results: A total of 140 female athletes (mean [SD] age, 26.8 [3.9] years; 105 [75.0%] African American) participated in the study. Mean (SD) athlete height was 183.4 (9.0) cm, and mean (SD) BSA was 2.02 (0.18) m2. Compared with guideline-defined normal values, LV enlargement was present in 36 athletes (26.0%) and 57 athletes (42.2%) had RV enlargement. There was a linear correlation between LV and RV cavity sizes and BSA extending to the uppermost biometrics (LV cavity size: r, 0.48; RV cavity size: r, 0.32; P < .001 for both). Maximal left ventricular wall thickness (LVWT) ranged from 0.6 to 1.4 cm, with 78 athletes (55.7%) having LVWT of 1.0 cm or greater and only 1 athlete (0.7%) having LVWT greater than 1.3 cm. Twenty-three athletes (16.4%) met the criteria for left ventricular hypertrophy (LVH) (>95 g/m2). Eccentric LVH was present in 16 athletes (69.6%), concentric LVH in 7 athletes (30.4%), and concentric remodeling in 27 athletes (19.3%). Mean aortic root diameter was 3.1 cm (95% CI, 3.0-3.2). Only 2 athletes (1.4%) had guideline-defined aortic enlargement compared with a range of 18% to 42% for left and right ventricular and atrial enlargement., Conclusions and Relevance: In this study, increased cardiac dimensions were frequently observed in WNBA athletes. Both BSA and physiologic remodeling affected cardiac morphologic findings. This study may provide a framework to define the range of athletic cardiac remodeling exhibited by elite female basketball players.

Background and Aims: Elevated serum calcium and phosphorus have been associated with increased risk of cardiovascular disorders. We evaluated whether abnormal calcium and high serum phosphorus are associated cross-sectionally with echocardiographic measures of left ventricular (LV) structure and function, as doing so may provide insight into the etiology of cardiac disorders., Methods and Results: Included in the analysis were 5213 Atherosclerosis Risk in Communities Study (ARIC) participants who in 2011-2013 had echocardiography and serum calcium and phosphorus measurements. We evaluated the association of serum calcium (corrected for albumin) and phosphorus quintiles with measures of LV structure and function, after adjusting for other cardiovascular risk factors. Participants were on average 75.3 years old; 59.1% were female and 19.8% were African American. Mean (±SD) concentrations of calcium and phosphorus were 9.33 ± 0.38 and 3.46 ± 0.45 mg/dL, respectively. Higher calcium was associated with lower LV end-diastolic diameter (LVEDD) but greater prevalence of concentric remodeling (p-trend: 0.005 and 0.004 respectively). We observed association between high phosphorus and high septal E/e' (p-trend: 0.02). Likewise, higher serum phosphorus was associated with higher left atrial volume index (p-trend: 0.001) and LV hypertrophy prevalence (p-trend: 0.04)., Conclusions: In conclusion, higher calcium was associated with more concentric remodeling but lower LVEDD, suggesting complex associations between calcium and cardiac function. Serum phosphorus was related to worse indices of LV diastolic function and LV hypertrophy, but not to LV systolic function. However, the magnitudes of association were modest, so clinical implications of these findings may be limited., (Copyright © 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Prior studies have found that sleep-disordered breathing (SDB) is common among those with left ventricular (LV) dysfunction and heart failure. Few epidemiological studies have examined this association, especially in US Hispanic/Latinos, who may be at elevated risk of SDB and heart failure., Methods: We examined associations between SDB and LV diastolic and systolic function using data from 1506 adults aged 18 to 64 years in the Hispanic Community Health Study/Study of Latinos ECHO-SOL Ancillary Study (2011-2014). Home sleep testing was used to measure the apnea-hypopnea index, a measure of SDB severity. Echocardiography was performed a median of 2.1 years later to quantify LV diastolic function, systolic function, and structure. Multivariable linear regression was used to model the association between apnea-hypopnea index and echocardiographic measures while accounting for the complex survey design, demographics, body mass, and time between sleep and echocardiographic measurements., Results: Each 10-unit increase in apnea-hypopnea index was associated with 0.2 (95% CI, 0.1-0.3) lower E', 0.3 (0.1-0.5) greater E/E' ratio, and 1.07-fold (1.03-1.11) higher prevalence of diastolic dysfunction as well as 1.3 (0.3-2.4) g/m 2 greater LV mass index. These associations persisted after adjustment for hypertension and diabetes mellitus. In contrast, no association was identified between SDB severity and subclinical markers of LV systolic function., Conclusions: Greater SDB severity was associated with LV hypertrophy and subclinical markers of LV diastolic dysfunction. These findings suggest SDB in Hispanic/Latino men and women may contribute to the burden of heart failure in this population.

Background and Objectives: Elevated BP load is part of the criteria for ambulatory hypertension in pediatric but not adult guidelines. Our objectives were to determine the prevalence of isolated BP load elevation and associated risk with adverse outcomes in children with CKD, and to ascertain whether BP load offers risk discrimination independently or in conjunction with mean ambulatory BPs., Design, Setting, Participants, & Measurements: We studied 533 children in the CKD in Children (CKiD) Study to determine the prevalence of normotension, isolated BP load elevation (≥25% of all readings elevated but mean BP normal), and ambulatory hypertension. We examined the association between these categories of BP control and adverse outcomes (left ventricular hypertrophy [LVH] or ESKD). We used c-statistics to determine risk discrimination for outcomes by BP load used either independently or in conjunction with other BP parameters., Results: Overall, 23% of the cohort had isolated BP load elevation, but isolated BP load elevation was not statistically significantly associated with LVH in cross-section (odds ratio, 1.8; 95% CI, 0.8 to 4.2) or time to ESKD (hazard ratio, 1.2; 95% CI, 0.7 to 2.0). In unadjusted cross-sectional analysis, every 10% higher systolic BP load was associated with 1.1-times higher odds of LVH (95% CI, 1.0 to 1.3), but discrimination for LVH was poor (c=0.61). In unadjusted longitudinal analysis, every 10% higher systolic BP load was associated with a 1.2-times higher risk of ESKD (95% CI, 1.1 to 1.2), but discrimination for ESKD was also poor (c=0.60). After accounting for mean systolic BP, systolic BP load was not statistically significantly associated with either LVH or ESKD. Findings were similar with diastolic BP load., Conclusions: BP load does not provide additive value in discriminating outcomes when used independently or in conjunction with mean systolic BP in children with CKD., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020&#95;03&#95;11&#95;CPOD10130819.mp3., (Copyright © 2020 by the American Society of Nephrology.)

Chronic kidney disease (CKD) is associated with incident cardiovascular morbidity and mortality. Whether subclinical cardiovascular disease and target organ damage is associated with incident CKD is unknown. We investigated the relations of echocardiographic left ventricular mass (LVM) with incident CKD. We evaluated 2258 Framingham Offspring cohort participants (mean age, 57 years; 56% women) who underwent echocardiography at a routine examination and had an estimated glomerular filtration rate ≥60 mL/min per 1.73 m 2 . We used Cox proportional hazards regression with discrete time intervals to relate sex-standardized LVM (independent variable) to the incidence of CKD, defined as estimated glomerular filtration rate <60 L/min per 1.73 m 2 , on follow-up. During a median follow-up of 14.6 years, 373 (16.5%) participants developed incident CKD. Higher LVM was associated with higher risk of CKD after adjusting for prevalent cardiovascular disease, body mass index, systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, antihypertensive medication, smoking, and diabetes mellitus (hazard ratio, 1.15 [95% CI, 1.03-1.29]; P =0.017) per 1-SD increase in LVM g/m 2 . Further adjustment for baseline estimated glomerular filtration rate (adjusted hazard ratio, 1.16 [95% CI, 1.04-1.31]; P =0.010) and baseline urine albumin/creatinine ratio (adjusted hazard ratio, 1.18 [95% CI, 1.04-1.33]; P =0.009) slightly attenuated the association. In our community-based sample, LVM was associated with incident CKD prospectively, which suggests that the relations between CKD and subclinical cardiovascular disease may be bidirectional. Further studies are needed to confirm our findings.

Left ventricular hypertrophy (LVH) and left atrial abnormality (LAA) are common correlated complications of hypertension. It is unclear how common for electrocardiographic markers of LAA (ECG-LAA) to coexist with ECG-LVH and how their coexistence impacts their prognostic significance. This analysis included 4,077 participants (61.2 ± 13.0 years, 51.2% women, 48.6% whites) with hypertension from the Third National Health and Nutrition Examination Survey. ECG-LVH was defined by Cornell voltage criteria. ECG-LAA was defined as deep terminal negativity of P wave in V1 >100 µV. Cox proportional hazard analysis was used to examine the associations between various combinations of ECG-LAA and ECG-LVH with all-cause mortality over a median follow-up of 14 years. The baseline prevalence of ECG-LVH, ECG-LAA, and the concomitant presence of both was 3.6%, 2.7%, and 0.34%, respectively. In a multivariable-adjusted model, mortality risk was highest in the group with concomitant ECG-LAA and ECG-LVH (hazard ratio [HR; 95% confidence interval {CI}] 2.69 [1.51, 4.80]), followed by isolated ECG-LAA (HR [95% CI] 1.63 [1.26, 2.12]), and then isolated ECG-LVH (HR [95% CI] 1.40 [1.08, 1.81]), compared with the group without ECG-LAA or ECG-LVH. Effect modification of these results by age and diabetes but not by gender or race was observed. In models with similar adjustment where ECG-LVH and ECG-LAA were entered as 2 separate variables and subsequently additionally adjusted for each other, the mortality risk was essentially unchanged for both variables. In conclusion, in participants with hypertension, ECG-LAA and ECG-LVH are independent markers of poor outcomes, and their concomitant presence carries a higher risk than either marker alone., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Obesity is a potent cardiovascular disease (CVD) risk factor and is associated with left ventricular hypertrophy (LVH). Obstructive sleep apnea (OSA) is common among individuals with obesity and is also associated with CVD risk. The authors sought to determine the association of OSA, a modifiable CVD risk factor, with LVH among overweight/obese youth with elevated blood pressure (EBP). This was a cross-sectional analysis of the baseline visit of 61 consecutive overweight/obese children with history of EBP who were evaluated in a pediatric obesity hypertension clinic. OSA was defined via sleep study or validated questionnaire. Children with and without OSA were compared using Fisher's exact tests, Student's t tests, and Wilcoxon rank sum test. Multivariable logistic regression evaluated the association between OSA and LVH. In this cohort, 71.7% of the children had LVH. Children with OSA were more likely to have LVH (85.7% vs 59.4%, P = 0.047). OSA was associated with 4.11 times greater odds of LVH (95% CI 1.15, 14.65; P = 0.030), remaining significant after adjustment for age, sex, race, and BMI z-score (after adjustment for hypertension, P = 0.051). A severe obstructive apnea-hypopnea index (AHI >10) was associated with 14 times greater odds of LVH (95% CI 1.14, 172.64, P = 0.039). OSA was significantly associated with LVH among overweight/obese youth with EBP, even after adjustment for age, sex, race, and BMI z-score. Those with the most severe OSA (AHI >10) had the greatest risk for LVH. Future studies exploring the impact of OSA treatment on CVD risk in children are needed., (©2019 Wiley Periodicals, Inc.)

Background: Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning., Methods: A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up., Results: Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure., Conclusions: Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

Background We developed a new left ventricular hypertrophy ( LVH ) criterion using a machine-learning technique called Bayesian Additive Regression Trees ( BART ). Methods and Results This analysis included 4714 participants from MESA (Multi-Ethnic Study of Atherosclerosis) free of clinically apparent cardiovascular disease at enrollment. We used BART to predict LV mass from ECG and participant characteristics using cardiac magnetic resonance imaging as the standard. Participants were randomly divided into a training set (n=3774) and a validation set (n=940). We compared the diagnostic/prognostic performance of our new BART - LVH criteria with traditional ECG - LVH criteria and cardiac magnetic resonance imaging- LVH . In the validation set, BART - LVH showed the highest sensitivity (29.0%; 95% CI , 18.3%-39.7%), followed by Sokolow-Lyon- LVH (21.7%; 95% CI , 12.0%-31.5%), Peguero-Lo Presti (14.5%; 95% CI , 6.2%-22.8%), Cornell voltage product (10.1%; 95% CI , 3.0%-17.3%), and Cornell voltage (5.8%; 95% CI , 0.3%-11.3%). The specificity was >93% for all criteria. During a median follow-up of 12.3 years, 591 deaths, 492 cardiovascular disease events, and 332 coronary heart disease events were observed. In adjusted Cox models, both BART - LVH and cardiac magnetic resonance imaging- LVH were associated with mortality (hazard ratio [95% CI ], 1.88 [1.45-2.44] and 2.21 [1.74-2.81], respectively), cardiovascular disease events (hazard ratio [95% CI ], 1.46 [1.08-1.98] and 1.91 [1.46-2.51], respectively), and coronary heart disease events (hazard ratio [95% CI ], 1.72 [1.20-2.47] and 1.96 [1.41-2.73], respectively). These associations were stronger than associations observed with traditional ECG - LVH criteria. Conclusions Our new BART - LVH criteria have superior diagnostic/prognostic ability to traditional ECG - LVH criteria and similar performance to cardiac magnetic resonance imaging- LVH for predicting events.

Objectives: The aim of this study was to evaluate the association between pre-procedural left ventricular hypertrophy (LVH) patterns and clinical outcomes after transcatheter aortic valve replacement (TAVR)., Background: The association between pre-procedural LVH pattern and severity and clinical outcomes after TAVR is uncertain., Methods: Patients (n = 31,199) across 422 sites who underwent TAVR from November 2011 through June 2016 as part of the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapies) Registry linked with the Centers for Medicare and Medicaid Services database were evaluated by varying LVH patterns, according to sex-specific cutoffs for left ventricular mass index and relative wall thickness. The association between LVH pattern (concentric remodeling, concentric LVH, and eccentric LVH) and outcomes (rates of mortality, myocardial infarction [MI], stroke, new dialysis requirement) at 1-year follow-up were evaluated using multivariate hazard models., Results: There were no significant associations between concentric remodeling (death: adjusted hazard ratio [HR]: 1.03; 95% confidence interval [CI]: 0.93 to 1.15; MI: HR: 1.05; 95% CI: 0.76 to 1.46; stroke: HR: 1.11; 95% CI: 0.89 to 1.39; new dialysis: HR: 0.86; 95% CI: 0.64 to 1.15), concentric LVH (death: HR: 1.04; 95% CI: 0.95 to 1.15; MI: HR: 1.12; 95% CI: 0.82 to 1.52; stroke: HR: 1.14; 95% CI: 0.92 to 1.40; new dialysis: HR: 1.17; 95% CI: 0.90 to 1.52), or eccentric LVH (death: HR: 0.98; 95% CI: 0.87 to 1.10; MI: HR: 1.07; 95% CI: 0.71 to 1.63; stroke: HR: 1.01; 95% CI: 0.78 to 1.32; new dialysis: HR: 1.25; 95% CI: 0.92 to 1.70) and outcomes at 1 year compared with patients without LVH., Conclusions: In a contemporary cohort of patients who underwent TAVR, pre-procedural LVH according to left ventricular mass index and relative wall thickness was not associated with adverse outcomes at 1-year follow-up. TAVR is likely to benefit patients with severe aortic stenosis regardless of the presence of LVH., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Associations between subtle changes in cardiac and cerebral structure and function are not well understood, with some studies suggesting that subclinical cardiac changes may be associated with markers of vascular brain insult. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) Study (5th ARIC visit; 2011-2013; N=1974) were used to explore relationships between abnormalities of cardiac structure/function and subclinical brain disease and to test specific associations between those cardiac and vascular brain changes that share a common mechanism. In adjusted models white matter hyperintensities were 0.66 cm 3 greater (95% confidence interval [CI] 0.08-1.25) for every 1-mm increase in left ventricular LV wall thickness and 0.64 cm 3 greater (95% CI 0.19-1.08) for every 10 g/m 2 increase in LV mass index, both markers of LV structure. Odds of brain infarction also increased with greater LV wall thickness (odds ratio 1.11, 95% CI 1.01-1.23 per 1 mm) and larger LV mass (odds ratio 1.08, 95% CI 1.00-1.17 per 10 g/m 2 ). Higher ejection fraction (per 5%), a marker of systolic function, was significantly associated with decreased odds of overall infarct (odds ratio 0.85, 95% CI 0.77-0.95), but not with cortical infarction (odds ratio 0.92, 95% CI 0.78-1.08). Conclusions Among elderly participants in a large cohort study, subclinical markers of LV structure and LV systolic dysfunction were associated with increased odds of brain infarction and more white matter hyperintensities, independent of other vascular risk factors. This suggests end-organ dysfunction occurs in the heart and brain in parallel, with further studies needed to determine causality.

Objective: The aim of this work was to investigate determinants of structural myocardial abnormalities in persons living with human immunodeficiency virus (PLWH)., Methods and Results: We reviewed archived transthoracic echocardiograms (TTEs) performed on PLWH at Duke University Medical Center from 2001 to 2012. The primary outcomes were presence of left ventricular hypertrophy (LVH) or diastolic dysfunction (DD). TTEs for 498 human immunodeficiency virus-infected persons were reviewed (median age 44 years, 38% female, 72% black, 34% with hypertension, 15% with diabetes). Among those with usable images, LVH was detected in 174 of 473 persons (37%) according to LV mass criteria and in 99 of 322 persons (31%) according to American Society of Echocardiography LV mass index criteria. Definite DD was detected in 18 of 224 persons (8%). LVH was more common in PLWH with a CD4 count ≤ 200 cells/mm 3 proximal to TTE (adjusted OR 1.68, 95% CI 1.08-2.62), CD4 nadir ≤ 200 cells/mm 3 (adjusted OR 1.63, 95% CI 1.04-2.54) and less common in persons with viral suppression (OR 0.46, 95% CI 0.27-0.80). Lower CD4 nadirs (P = .002) and proximal CD4 counts (P = .002) were also associated with DD., Conclusions: Persons with a history of advanced human immunodeficiency virus-associated immune suppression are at higher risk of LVH and DD than infected persons with preserved immune function., (Copyright © 2018. Published by Elsevier Inc.)

Background: Although diabetes mellitus (DM) and insulin resistance associate with adverse cardiac events, the associations of left ventricular (LV) remodeling and function with compromised glucose metabolism have not been fully evaluated in a general population. We used cardiovascular magnetic resonance (CMR) to evaluate how CMR indices are associated with DM or insulin resistance among participants before developing cardiac events., Methods: We studied 1476 participants who were free of clinical cardiovascular disease and who underwent tagged CMR in the Multi-Ethnic Study of Atherosclerosis (MESA). LV shape and longitudinal myocardial shortening and torsion were assessed by CMR. A higher sphericity index represents a more spherical LV shape. Multivariable linear regression was used to evaluate the associations of DM or homeostasis model assessment-estimated insulin resistance (HOMA-IR) with CMR indices., Results: In multiple linear regression, longitudinal shortening was lower in impaired fasting glucose than normal fasting glucose (NFG) (0.36% lower vs. NFG, p < 0.05); torsion was greater in treated DM (0.24 °/cm greater vs. NFG, p < 0.05) after full adjustments. Among participants without DM, greater log-HOMA-IR was correlated with greater LV mass (3.92 g/index, p < 0.05) and LV mass-to-volume ratio (0.05 /index, p < 0.01), and lower sphericity index (- 1.26/index, p < 0.01). Greater log-HOMA IR was associated with lower longitudinal shortening (- 0.26%/index, p < 0.05) and circumferential shortening (- 0.30%/index, p < 0.05). Torsion was positively correlated with log-HOMA-IR until 1.5 of log-HOMA-IR (0.16 °/cm/index, p = 0.030).), and tended to fall once above 1.5 of log-HOMA-IR (- 0.50 °/cm/index, p = 0.203). The sphericity index was associated negatively with LV mass-to-volume ratio (- 0.02/%, p < 0.001) and torsion (- 0.03°/cm/%, p < 0.001)., Conclusions: Glucose metabolism disorders are associated with LV concentric remodeling, less spherical shape, and reduced systolic myocardial shortening in the general population. Although torsion is higher in participants who are treated for DM and impaired insulin resistance, myocardial shortening was progressively decreased with higher HOMA-IR and torsion was increased only with less severe insulin resistance., Clinical Trial Registration: Multi-Ethnic Study of Atherosclerosis (MESA): A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org/ . Study Start Date: January 1999 ( NCT00005487 ).

Background: Evidence exists for racial/ethnic differences in left ventricular mass index (LVMI). How this translates to future cardiovascular disease (CVD) events is unknown., Hypothesis: The impact of racial/ethnic differences in LVMI on incident cardiovascular outcomes could have potential implications for the optimization of risk stratification strategies., Methods: Using the prospectively collected database of the Multi-Ethnic Study of Atherosclerosis (MESA) involving 4 racial/ethnic groups (non-Hispanic Whites, Chinese, Blacks, and Hispanics) free of CVD at baseline, we assessed for racial/ethnic differences in the relationship between LVMI and incident CVD using a Cox model., Results: 5004 participants (mean age, 62 ± 10 years; 48% male) were included in this study. After an average follow-up of 10.2 years, 369 (7.4%) CVD events occurred. Significant racial/ethnic differences existed in the relationship between LVMI and incident CVD (P for interaction = 0.04). Notably, the relationship was strongest for Chinese (HR per 10-unit increase in LVMI: 1.7, 95% CI: 1.1-2.8) and Hispanics (HR per 10-unit increase in LVMI: 1.9, 95% CI: 1.5-2.2). Non-Hispanic Whites demonstrated the lowest relationship (HR: 1.3, 95% CI: 1.1-1.5). LVMI values of 36.9 g/m 2.7 , 31.8 g/m 2.7 , 39.9 g/m 2.7 , and 41.7 g/m 2.7 were identified as optimal cutpoints for defining left ventricular hypertrophy (LVH) for non-Hispanic Whites, Chinese, Blacks, and Hispanics, respectively. In secondary analysis of LVH (vs no LVH) using these optimal cutpoints, we found a similar pattern of association as above (P for interaction = 0.04). For example, compared with those without LVH, Chinese with LVH had HR: 5.3, 95% CI: 1.6-17, whereas non-Hispanic Whites with LVH had HR: 1.6, 95% CI: 1.2-2.1 for CVD events., Conclusions: Among 4 races/ethnicities studied, LVMI has more prognostic utility predicting future CVD events for Chinese and Hispanics and is least significant for non-Hispanic Whites., (© 2018 Wiley Periodicals, Inc.)

Background: As heart failure (HF)-associated morbidity and mortality continue to escalate, enhanced focus on prevention is increasingly important. "Malignant" left ventricular (LV) hypertrophy (LVH): LVH combined with an elevated cardiac biomarker reflecting either injury (high-sensitivity cardiac troponin T), or strain (amino-terminal pro-B-type natriuretic peptide) has predicted accelerated progression to HF. We sought to determine whether malignant LVH identified community-dwelling adults initially free of cardiovascular disease at high risk of asymptomatic decline in LV ejection fraction or a clinical cardiovascular event., Methods and Results: A total of 4985 of 6814 individuals without prevalent cardiovascular disease underwent baseline cardiac magnetic resonance for LVH in combination with measurement of plasma high-sensitivity cardiac troponin T and amino-terminal pro-B-type natriuretic peptide as part of MESA (Multi-Ethnic Study of Atherosclerosis) and were subsequently divided into 4 groups: (1) No LVH, no elevated biomarkers (n=2206; 44.3%); (2) No LVH, ≥1 elevated biomarkers (n=2275; 45.7%); (3) LVH, no elevated biomarkers (n=153; 3.0%); and (4) LVH, ≥1 elevated biomarkers (malignant LVH; n=351; 7.0%). Cardiac magnetic resonance was repeated 10 years later (n=2831) for assessment of LV ejection fraction <50%. Median follow-up was 12.2 years. Malignant LVH was associated with 7.0-, 3.5-, and 2.6-fold adjusted increases in incidence of HF, cardiovascular death, and asymptomatic LV dysfunction, respectively, versus group 1. New-onset HF was predominately HF with reduced ejection fraction (9.5-fold increase)., Conclusions: Malignant LVH is predictive of progression to asymptomatic LV dysfunction, HF (particularly HF with reduced ejection fraction), and cardiovascular death. Consequently, malignant LVH represents a high-risk phenotype among individuals without known cardiovascular disease, which should be targeted for increased surveillance and more-aggressive therapies., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Left atrial (LA) size is a marker of diastolic function and is associated with atrial fibrillation and cardiovascular outcomes. However, there are no large population studies measuring LA structure. The relationship of demographics and cardiovascular risk factors to LA size is largely unknown. This study aimed to determine associations of LA size with demographic factors, cardiac structure and function, and cardiovascular risk factors., Methods and Results: LA volume indexed to body surface area was measured by cardiovascular magnetic resonance steady-state free precession and fast gradient echo cine long- and short-axis images in 2576 asymptomatic participants of MESA ([Multi-Ethnic Study of Atherosclerosis] 68.7 years, 53.0% women, white 42.2%, Chinese American 12.0%, black 24.5%, and Hispanic 21.2%) using biplane and short-axis images. The mean LA volume index was 36.5±11.4 mL/m 2 in the entire cohort and 35.5±10.1 mL/m 2 in subjects free of cardiovascular risk factors (n=283). Multivariable analysis included adjustment for demographics, ethnicity, cardiovascular risk factors, serological studies, socioeconomic status, left ventricular structure, and medications. In the adjusted analysis, age (β=0.2 mL/m 2 per year, P <0.0001), male sex (β=-4.2 mL/m 2 , P <0.0001), obesity (β=1.3 mL/m 2 , P <0.01), end-diastolic volume index (β=0.4 mL/m 2 , P <0.0001), Chinese American (β=-2.6 mL/m 2 , P <0.0001), and Hispanic (β=1.1 mL/m 2 , P <0.05) ethnicities were associated with LA volume index. Diabetes mellitus and smoking were not associated with LA volume index. LA volumes measured by steady-state free precession were 3% larger than by fast gradient echo cine cardiovascular magnetic resonance ( P <0.001)., Conclusions: Age, sex, ethnicity and left ventricular structural parameters were associated with LA size. Importantly, the study provides reference values of normal LA volume index., (© 2017 American Heart Association, Inc.)

Background: Obesity increases cardiovascular risk. However, the extent to which various measures of body composition are associated with abnormalities in cardiac structure and function, independent of comorbidities commonly affecting obese individuals, is not clear. This study sought to examine the relationship between body mass index, waist circumference, and percent body fat with conventional and advanced measures of cardiac structure and function., Methods and Results: We studied 4343 participants of the ARIC study (Atherosclerosis Risk in Communities) who were aged 69 to 82 years, free of coronary heart disease and heart failure, and underwent comprehensive echocardiography. Increasing body mass index, waist circumference, and body fat were associated with greater left ventricular (LV) mass and left atrial volume indexed to height(2.7) in both men and women (P<0.001). In women, all 3 measures were associated with abnormal LV geometry, and increasing waist circumference and body fat were associated with worse global longitudinal strain, a measure of LV systolic function. In both sexes, increasing body mass index was associated with greater right ventricular end-diastolic area and worse right ventricular fractional area change (P≤0.001). We observed similar associations for both waist circumference and percent body fat., Conclusions: In a large, biracial cohort of older adults free of clinically overt coronary heart disease or heart failure, obesity was associated with subclinical abnormalities in cardiac structure in both men and women and with adverse LV remodeling and impaired LV systolic function in women. These data highlight the association of obesity and subclinical abnormalities of cardiac structure and function, particularly in women., (© 2016 American Heart Association, Inc.)

Objective: To describe the prevalence of left atrial (LA) enlargement (LAE) and its association with all-cause mortality in 10,719 patients with an early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') ratio-determined normal left ventricular (LV) filling pressure and preserved LV ejection fraction (LVEF)., Methods: We evaluated 10,719 patients (deceased patients: n = 479; mean [SD] age, 65 [14] years; 60% male; surviving patients: n = 10,240; mean (SD) age, 54 (16) years; 48% male) with estimated normal LV filling pressure (E/e' ratio ≤ 8) and preserved LVEF (≥ 50%) to determine the impact of LA volume index (LAVi) on all-cause mortality during a mean (SD) follow-up of 2.2 (1.0) years., Results: In the univariate analysis, with every milliliter per square meter increase in LAVi, all-cause mortality risk increased by 3% (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04; P < .001). After adjusting for covariates, LAVi (as a continuous variable) was an independent predictor of all-cause mortality (HR, 1.015; 95% CI, 1.005-1.026; P = .01). When LAVi was assessed as a categorical variable with normal LAVi (≤ 28 mL/m(2)) as the reference group, moderate LAVi (34-39 mL/m(2)) and severe LAVi (≥ 40 mL/m(2)) were independent predictors of all-cause mortality (HR, 1.34; 95% CI, 1.01-1.79; P = .04; and HR, 1.65; 95% CI, 1.18-2.29; P = .003, respectively)., Conclusion: LAE was independently associated with an increased risk of all-cause mortality in our large cohort of 10,719 patients with normal LV filling pressure and preserved LVEF., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Impact of weight loss on cardiac structure has not been extensively investigated in large, multi-ethnic, community-based populations. We investigated the longitudinal impact of weight loss on cardiac structure by cardiac magnetic resonance (CMR)., Methods and Results: 2351 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent CMR at Exam 1 (2002) and Exam 5 (2011) were included. Primary outcomes were percentage change in LV mass (indexed to height) and LV mass-to-volume ratio (concentric LV remodelling). Multivariable linear regression was used to measure the association between outcomes and weight change. At median 9.4 years' follow-up, 639 individuals (27%) experienced >5% weight loss (median 6.9 kg) and 511 (22%) had >5% weight gain (median 6.4 kg). A >5% weight gain was associated with the greatest increase in LV mass (+5.4% median) and LV mass-to-volume ratio (+12.2% median). Adjusting for medications, hypertension/diabetes (and change in these risk factors), age, race and other risk factors, every 5% weight loss was associated with a 1.3% decrease in height-indexed LV mass and 1.3% decrease in LV mass-to-volume ratio (p<0.0001). There was no effect modification/confounding by age, race, gender or baseline BMI. Change in LV mass-to-volume ratio was roughly linear, specifically for modest degrees of weight loss (-10% to +10%). Change in LV mass was linear with weight loss, suggesting no threshold of weight loss is needed for LV mass regression., Conclusions: In a large multi-ethnic population, weight loss is associated with beneficial effects on cardiac structure, independent of age, race, gender, BMI and obesity-related cardiometabolic risk. There is no threshold of weight loss required to produce these effects., (© The European Society of Cardiology 2014.)

Objective: Cardiac changes of hypertensive pregnancy include left ventricular hypertrophy (LVH) and diastolic dysfunction. These are thought to regress postpartum. We hypothesised that women with a history of hypertensive pregnancy would have altered LV geometry and function when compared with women with only normotensive pregnancies., Methods: In this cohort study, we analysed echocardiograms of 2637 women who participated in the Family Blood Pressure Program. We compared LV mass and function in women with hypertensive pregnancies with those with normotensive pregnancies., Results: Women were evaluated at a mean age of 56 years: 427 (16%) had at least one hypertensive pregnancy; 2210 (84%) had normotensive pregnancies. Compared with women with normotensive pregnancies, women with hypertensive pregnancy had a greater risk of LVH (OR: 1.42; 95% CI 1.01 to 1.99, p=0.05), after adjusting for age, race, research network of the Family Blood Pressure Program, education, parity, BMI, hypertension and diabetes. When duration of hypertension was taken into account, this relationship was no longer significant (OR: 1.19; CI 0.08 to 1.78, p=0.38). Women with hypertensive pregnancies also had greater left atrial size and lower mitral E/A ratio after adjusting for demographic variables. The prevalence of systolic dysfunction was similar between the groups., Conclusions: A history of hypertensive pregnancy is associated with LVH after adjusting for risk factors; this might be explained by longer duration of hypertension. This finding supports current guidelines recommending surveillance of women following a hypertensive pregnancy, and sets the stage for longitudinal echocardiographic studies to further elucidate progression of LV geometry and function after pregnancy., Clinical Trial Registrations: GENOA- NCT00005269; HyperGEN- NCT00005267; Sapphire- NCT00005270; GenNet- NCT00005268., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: It is unclear whether antihypertensive treatment can restore cardiovascular disease risk to the risk level of persons with ideal blood pressure (BP) levels., Methods and Results: Data from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study were analyzed. Outcomes were compared among participants without or with antihypertensive treatment at 3 BP levels: <120/<80 mm Hg, systolic BP 120 to 139 mm Hg or diastolic BP 80 to 89 mm Hg (120 to 129/≤80 mm Hg for participants with diabetes), and systolic BP ≥140 or diastolic BP ≥90 mm Hg (systolic BP ≥130 or diastolic BP ≥80 mm Hg for participants with diabetes). Among MESA participants aged ≥50 years at baseline, those with BP <120/<80 mm Hg on treatment had higher left ventricular mass index, prevalence of estimated glomerular filtration rate <60 mL/min per 1.73 m(2), prevalence of coronary calcium score >100, and twice the incident cardiovascular disease rate over 9.5 years of follow-up than those with BP <120/<80 mm Hg without treatment. In CARDIA at year 25, persons with BP <120/<80 mm Hg with treatment had much longer exposure to higher BP and higher risk of end-organ damage and subclinical atherosclerosis than those with BP <120/<80 mm Hg without treatment. An exploratory analysis suggested that when cumulative systolic BP was high (eg, >3000 mm Hg-years in 25 years), the increase in left ventricular mass index accelerated., Conclusions: The data suggest that based on the current approach, antihypertensive treatment cannot restore cardiovascular disease risk to ideal levels. Emphasis should be placed on primordial prevention of BP increases to further reduce cardiovascular disease morbidity and mortality., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Reduced left ventricular (LV) ejection fraction increases the risk of ventricular arrhythmias; however, LV ejection fraction has a low sensitivity to predict ventricular arrhythmias. LV dilatation and mass may be useful to further risk-stratify for ventricular arrhythmias., Methods and Results: Patients from the Genetic Risk of Assessment of Defibrillator Events (GRADE) study (N=930), a study of heart failure subjects with defibrillators, were assessed for appropriate implantable cardioverter-defibrillator shock and death, heart transplant, or ventricular assist device placement by LV diameter and mass. LV mass was divided into normal, mild, moderate, and severe classifications. Severe LV end-diastolic diameter had worse shock-free survival than normal and mild LV end-diastolic diameter (P=0.0002 and 0.0063, respectively; 2-year shock free, severe 74%, moderate 80%, mild 91%, normal 88%; 4-year shock free, severe 62%, moderate 69%, mild 72%, normal 81%) and freedom from death, transplant, or ventricular assist device compared with normal and moderate LV end-diastolic diameter (P<0.0001 and 0.0441, respectively; 2-year survival: severe 78%, moderate 85%, mild 82%, normal 89%; 4-year survival: severe 55%, moderate 64%, mild 63%, normal 74%). Severe LV mass had worse shock-free survival than normal and mild LV mass (P=0.0370 and 0.0280, respectively; 2-year shock free: severe 80%, moderate 81%, mild 91%, normal 87%; 4-year shock free: severe 68%, moderate 73%, mild 76%, normal 76%) but no association with death, transplant, or ventricular assist device (P=0.1319). In a multivariable Cox proportional hazards analysis adjusted for LV ejection fraction, LV end-diastolic diameter was associated with appropriate implantable cardioverter-defibrillator shocks (hazard ratio 1.22, P=0.020). LV end-diastolic diameter was associated with time to death, transplant, or ventricular assist device (hazard ratio 1.29, P=0.0009)., Conclusions: LV dilatation may complement ejection fraction to predict ventricular arrhythmias., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02045043., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: High reproducibility of LV mass and volume measurement from cine cardiovascular magnetic resonance (CMR) has been shown within single centers. However, the extent to which contours may vary from center to center, due to different training protocols, is unknown. We aimed to quantify sources of variation between many centers, and provide a multi-center consensus ground truth dataset for benchmarking automated processing tools and facilitating training for new readers in CMR analysis., Methods: Seven independent expert readers, representing seven experienced CMR core laboratories, analyzed fifteen cine CMR data sets in accordance with their standard operating protocols and SCMR guidelines. Consensus contours were generated for each image according to a statistical optimization scheme that maximized contour placement agreement between readers., Results: Reader-consensus agreement was better than inter-reader agreement (end-diastolic volume 14.7 ml vs 15.2-28.4 ml; end-systolic volume 13.2 ml vs 14.0-21.5 ml; LV mass 17.5 g vs 20.2-34.5 g; ejection fraction 4.2 % vs 4.6-7.5 %). Compared with consensus contours, readers were very consistent (small variability across cases within each reader), but bias varied between readers due to differences in contouring protocols at each center. Although larger contour differences were found at the apex and base, the main effect on volume was due to small but consistent differences in the position of the contours in all regions of the LV., Conclusions: A multi-center consensus dataset was established for the purposes of benchmarking and training. Achieving consensus on contour drawing protocol between centers before analysis, or bias correction after analysis, is required when collating multi-center results.

Background: Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF., Methods and Results: We studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (±SD) follow-up period of 4.3±1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4)., Conclusions: Symptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors., (© 2015 American Heart Association, Inc.)

Despite the low sensitivity of the electrocardiogram (ECG) in detecting left ventricular hypertrophy (LVH), ECG-LVH is known to be a strong predictor of cardiovascular risk. Understanding reasons for the discrepancies in detection of LVH by ECG versus imaging could help improve the diagnostic ability of ECG. We examined factors associated with false-positive and false-negative ECG-LVH, using cardiac magnetic resonance imaging (MRI) as the gold standard. We also compared the prognostic significance of ECG-LVH and MRI-LVH as predictors of cardiovascular events. This analysis included 4,748 participants (mean age 61.9 years, 53.5% females, 61.7% nonwhites). Logistic regression with stepwise selection was used to identify factors associated with false-positive (n = 208) and false-negative (n = 387), compared with true-positive (n = 208) and true-negative (n = 4,041) ECG-LVH, respectively. A false-negative ECG-LVH status was associated with increased odds of Hispanic race/ethnicity, current smoking, hypertension, increased systolic blood pressure, prolongation of QRS duration, and higher body mass index and with lower odds of increased ejection fraction (model-generalized R(2) = 0.20). A false-positive ECG-LVH status was associated with lower odds of black race, Hispanic race/ethnicity, minor ST-T abnormalities, increased systolic blood pressure, and presence of any major electrocardiographic abnormalities (model-generalized R(2) = 0.29). Both ECG-LVH and MRI-LVH were associated with an increased risk of cardiovascular disease events (hazard ratio 1.51, 95% confidence interval 1.03 to 2.20 and hazard ratio 1.81, 95% confidence interval 1.33 to 2.46, respectively). In conclusion, discrepancy in LVH detection by ECG and MRI can be relatively improved by considering certain participant characteristics. Discrepancy in diagnostic performance, yet agreement on predictive ability, suggests that LVH by ECG and LVH by imaging are likely to be two distinct but somehow related phenotypes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Fibroblast growth factor-23 (FGF-23) is a phosphaturic factor previously associated with left ventricular hypertrophy and systolic dysfunction among individuals with chronic kidney disease. Whether FGF-23 acts directly to induce left ventricular hypertrophy, potentially independent of its klotho coreceptor, remains uncertain. We investigated associations of FGF-23 with cardiac structural abnormalities among individuals with a broad range of kidney function and explored potential biological mechanisms using cardiac magnetic resonance imaging and histology in klotho-null mice, an established model of constitutively elevated FGF-23., Methods and Results: Among 887 participants with coronary artery disease in the Heart and Soul Study, FGF-23 was modestly associated with worse left ventricular ejection fraction (-1.0% per standard deviation increase in lnFGF-23; standard error, 0.4%), but was not associated with the overall prevalence of concentric hypertrophy (odds ratio, 1.5; CI, 0.9 to 2.4) or eccentric hypertrophy (odds ratio, 1.1; CI, 0.9 to 1.3). FGF-23 was only associated with concentric hypertrophy among individuals with diminished kidney function (eGFR <60 mL/min per 1.73 m(2); odds ratio, 2.3; CI, 1.0 to 5.3; P-interaction=0.28). Comparing klotho-null with wild-type mice, null mice did not have greater left ventricular mass (P=0.37) or a lower ejection fraction (P=0.94)., Conclusions: Together, our results suggest that FGF-23 is unlikely to have major effects on cardiovascular structure and function among patients free of substantial chronic kidney disease, and these effects may not be independent of the klotho coreceptor.

Background and Objectives: Higher left ventricular volume is associated with death in patients with ESRD. This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling., Design, Setting, Participants, & Measurements: The Frequent Hemodialysis Network daily trial randomized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis; the Frequent Hemodialysis Network nocturnal trial randomized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis. Left and right ventricular end systolic and diastolic volumes, left ventricular mass, and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling. In each trial, the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups., Results: In the daily trial, frequent hemodialysis resulted in significant reductions in left ventricular end diastolic volume (-11.0% [95% confidence interval, -16.1% to -5.5%]), left ventricular end systolic volume (-14.8% [-22.7% to -6.2%]), right ventricular end diastolic volume (-11.6% [-19.0% to -3.6%]), and a trend for right ventricular end systolic volume (-11.3% [-21.4% to 0.1%]) compared with conventional therapy. The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d (P value [interaction]=0.02). In the nocturnal trial, there were no significant changes in left or right ventricular volumes. The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial., Conclusions: Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass, but it does not affect left ventricular remodeling.

Background: Like left ventricular hypertrophy (LVH), abnormal left ventricular (LV) geometry increases cardiovascular risk, but little data utilizing age and sex-specific norms are currently available on LV geometry in hypertensive children., Methods: This was a cross-sectional study of 141 hypertensive children aimed at determining the prevalence of LVH and abnormal LV geometry in the patient population and whether clinical characteristics associated with these findings differ by race. LVH was defined as an LV mass index of ≥95th percentile or cardiologist diagnosis. Abnormal geometry was defined as the presence of LVH or a relative wall thickness of >0.41., Results: The prevalence of LVH was 35 % overall. According to race, LVH prevalence was 49 % among African-Americans (AA) versus 30 % among non-AA (p < 0.05). Overweight/obesity was also highly prevalent among AA compared to non-AA (87 vs. 71 %, respectively; p = 0.03). After multivariable adjustment, the body mass index (BMI) z-score and 95 % diastolic blood pressure (BP) index were the sole independent predictors of LVH. Of the 141 hypertensive children, 40 % had abnormal LV geometry; 63 % among AA vs. 32 % among non-AA (p = 0.001). Multivariable analyses revealed a 3.8-fold increased odds of abnormal geometry among AA (p = 0.002)., Conclusions: While LVH, abnormal geometry and overweight/obesity are more prevalent among AA hypertensive children, after multivariable adjustment, BMI and race were independently associated with LVH and abnormal geometry, respectively. This result suggests that both race and obesity have important roles in the development of end-organ damage among children with primary hypertension.

Background: Hypertension, a strong determinant of cardiovascular disease risk, has been documented among elite, professional American-style football (ASF) players. The risk of increased blood pressure (BP) and early adulthood hypertension among the substantially larger population of collegiate ASF athletes is not known., Methods and Results: We conducted a prospective, longitudinal study to examine BP, the incidence of hypertension, and left ventricular remodeling among collegiate ASF athletes. Resting BP and left ventricular structure were assessed before and after a single season of competitive ASF participation in 6 consecutive groups of first-year university athletes (n=113). ASF participation was associated with significant increases in systolic BP (116±8 versus 125±13 mm Hg; P<0.001) and diastolic BP (64±8 mm Hg versus 66±10 mm Hg; P<0.001). At the postseason assessment, the majority of athletes met criteria for Joint National Commission (seventh report) prehypertension (53 of 113, 47%) or stage 1 hypertension (16 of 113, 14%). Among measured characteristics, lineman field position, intraseason weight gain, and family history of hypertension were the strongest independent predictors of postseason BP. Among linemen, there was a significant increase in the prevalence of concentric left ventricular hypertrophy (2 of 64 [3%] versus 20 of 64 [31%]; P<0.001) and change in left ventricular mass correlated with intraseason change in systolic BP (R=0.46, P<0.001)., Conclusions: Collegiate ASF athletes may be at risk for clinically relevant increases in BP and the development of hypertension. Enhanced surveillance and carefully selected interventions may represent important opportunities to improve later-life cardiovascular health outcomes in this population.

Background: Prevalent atrial fibrillation (AF) is associated with a higher sudden cardiac death (SCD) rate in some populations, and incident AF predicts increased mortality risk in the general population and after myocardial infarction. However, the relationship of SCD to new-onset AF is unclear., Methods and Results: The relationship of SCD to new-onset AF was evaluated in 8831 hypertensive patients with electrocardiographic left ventricular hypertrophy with no history of AF, in sinus rhythm on their baseline electrocardiogram, randomly assigned to losartan- or atenolol-based treatment. During 4.7±1.1 years mean follow-up, new-onset AF occurred in 701 patients (7.9%) and SCD in 151 patients (1.7%). In univariate Cox analyses, new-onset AF was associated with a >4-fold higher risk of SCD (hazard ratio, 4.69; 95% CI interval, 2.96-7.45; P<0.001). In multivariate Cox analyses adjusting for age, sex, race, diabetes mellitus, history of heart failure, myocardial infarction, ischemic heart disease, stroke, smoking, serum high-density lipoprotein cholesterol, creatinine, glucose, and urine albumin/creatinine ratio as standard risk factors, and for incident myocardial infarction, in-treatment use of digoxin, systolic and diastolic pressure, heart rate, QRS duration, Cornell voltage-duration product, and Sokolow-Lyon voltage left ventricular hypertrophy treated as time-varying covariates, new-onset AF remained associated with a >3-fold increased risk of SCD (hazard ratio, 3.13; 95% confidence interval, 1.87-5.24; P<0.001)., Conclusions: Development of new-onset AF identifies hypertensive patients at increased risk of SCD., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260.

Aims: To compare the value of serial electrocardiographic (ECG) changes by the two most widely used ECG classification systems-the Minnesota Code (MC) and Novacode (Nova) for the prediction of subsequent coronary heart disease (CHD) and total mortality., Methods and Results: We studied 12-lead ECGs from 12,477 participants (average age 54 years at baseline; 58% women; 76% non-Hispanic white) in the Atherosclerosis Risk in Communities (ARIC) Study, who were free of CHD at baseline in 1987, had both good-quality ECGs at baseline and at first study-scheduled follow-up visit, and had ECG QRS duration <120 ms. A total 2119 participants died (17%), including 280 CHD deaths during an average 17-year follow up. Cox regression models assessed outcome associated with significant serial ECG changes by MC and Nova separately. For CHD death the hazard ratio was 6.8 (95% CI 3.5-13.3) for incident Nova myocardial infarction (MI), and 5.7 (95% CI 2.7-11.9) for MC-MI in a multivariable model adjusted for clinical and demographic characteristics, and ECG left ventricular hypertrophy. The increased risk for total mortality doubled for both Nova and MC serial ECG MI. Major evolving ST-T wave abnormalities alone were associated with a ≥132% increased risk for CHD death and a 50% increased risk for total mortality by either Nova or MC., Conclusion: ECG serial change by both MC and Nova are equally valuable predictors for future fatal cardiac events and total mortality and hence equally useful prognostic indicators in clinical trials and epidemiological studies.

A United States national sample of 20,962 participants (57% women, 44% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study provided general population estimates for electrocardiographic (ECG) abnormalities among black and white men and women. The participants were recruited from 2003 to 2007 by random selection from a commercially available nationwide list, with oversampling of blacks and those from the stroke belt, with a cooperation rate of 49%. The measurement of risk factors and 12-lead electrocardiograms (centrally coded using Minnesota code criteria) showed 28% had ≥1 major ECG abnormality. The prevalence of abnormalities was greater (≥35%) for those ≥65 years old, with no differences between blacks and whites. However, among men <65 years, blacks had more major abnormalities than whites, most notably for atrial fibrillation, major Q waves, and left ventricular hypertrophy. Men generally had more ECG abnormalities than women. The most common ECG abnormalities were T-wave abnormalities. The average heart rate-corrected QT interval was longer in women than in men, similar in whites and blacks, and increased with age. However, the average heart rate was greater in women than in men and in blacks than in whites and decreased with age. The prevalence of ECG abnormalities was related to the presence of hypertension, diabetes, blood pressure, and age. In conclusion, black men and women in the United States have a significantly greater prevalence of ECG abnormalities than white men and women at age 45 to 64 years; however, these proportions, although larger, tended to equalize or reverse after age 65., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease., Methods and Results: The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several predefined baseline demographic or clinical factors as well as change in volume removal, blood pressure, or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1 g; 95% CI, 5.0-21.3 g; P=0.002), LVM index (6.9 g/m(2); 95% CI, 2.4-11.3 g/m(2); P=0.003), and percent change in geometric mean of LVM (7.0%; 95% CI, 1.0%-12.6; P=0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001) and were not significantly associated with changes in other parameters., Conclusions: Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00264758.

Heart failure is a common clinical feature of advanced cardiovascular disease that carries a high mortality risk. This review focuses on my journey seeking to understand the pathogenesis of heart failure and on how to translate experimental findings into the clinic.

Endothelin-1 (ET-1), a circulating vasoactive peptide with potent vasoconstricting and mitogenic properties, may contribute to target-organ damage in hypertension. We investigated whether plasma levels of C-terminal pro-endothelin-1 (CT-pro-ET-1) are associated with left ventricular (LV) mass and aortic root diameter in African-American adults with hypertension. Plasma CT-pro-ET-1 was measured by an immunoluminometric assay in 1041 African Americans (65±9 years, 72% women) with hypertension. LV mass and aortic root diameter were measured according to the American Society of Echocardiography guidelines, and LV mass was indexed by height to the power 2.7 (LVMi). Multivariable regression analyses were used to assess whether plasma CT-pro-ET-1 was associated with LVMi and aortic root diameter, independent of potential confounding variables. Plasma CT-pro-ET-1 was modestly correlated with LVMi (r=0.21, P<0.0001) and aortic root diameter (r=0.09, P=0.004). In separate multivariable regression models that adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, smoking history, diabetes, history of myocardial infarction or stroke, and blood pressure-lowering medication and statin use, log CT-pro-ET-1 was significantly associated with greater LVMi (P=0.001) and larger aortic root diameter (P=0.006). CT-pro-ET-1 is independently associated with LVMi and aortic root diameter and may be a marker of target-organ damage in African-Americans adults with hypertension.

Objective: The purpose of this study was to evaluate the relationship of left ventricular (LV) mass and geometry measured with cardiac magnetic resonance imaging (MRI) to incident cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) study., Background: MRI is highly accurate for evaluation of heart size and structure and has not previously been used in a large epidemiologic study to predict cardiovascular events., Methods: A total of 5,098 participants in the MESA study underwent cardiac MRI at the baseline examination and were followed up for a median of 4 years. Cox proportional hazard models were constructed to predict the end points of coronary heart disease (CHD), stroke, and heart failure (HF) after adjustment for cardiovascular risk factors., Results: A total of 216 incident events were observed during the follow-up period. In adjusted models, the end points of incident CHD and stroke were positively associated with increased LV mass-to-volume ratio (CHD, hazard ratio [HR]: 2.1 per g/ml, p = 0.02; stroke, HR: 4.2 per g/ml, p = 0.005). In contrast, LV mass showed the strongest association with incident HF events (HR: 1.4 per 10% increment, p < 0.0001). The HF events occurred primarily in participants with LV hypertrophy, that is, >or=95th percentile of LV mass (HR: 8.6, 95% confidence interval: 3.7 to 19.9, reference group <50th percentile of LV mass)., Conclusions: The LV size was related to incident HF, stroke, and CHD in this multiethnic cohort. Whereas body size-adjusted LV mass alone predicted incident HF, concentric ventricular remodeling predicted incident stroke and CHD.

Background and Methods: An international registry of left ventricular volume reduction (LVVR) procedures, including partial left ventriculectomy, has been expanded, updated, and refined to include 568 cases voluntarily reported from 52 hospitals in 12 countries., Results: Gender, age, ventricular dimension, ethnology, myocardial mass, presence or absence of mitral regurgitation, as well as transplant indication, had little effect on event-free survival, which was defined as either absence of death or ventricular failure requiring mechanical assist or transplantation. Poor preoperative patient condition such as New York Heart Association classification IV, depressed contractility and decompensation requiring an emergency procedure were associated with reduced event-free survival. Other risk factors included an early surgery date, lack of experience, dilated cardiomyopathy as the underlying pathology and extended myocardial resection. Performance of LVVR reached a peak by 1998, but was largely abandoned by 2001, except in Asia, where experienced institutes continue to perform it in patients in better condition with preserved myocardial contractility., Conclusion: Avoidance of risk factors appears to have contributed to the recent survival improvement and may help stratify patients for LVVR. While performance has been decreasing, the concept has been extended to other LVVR and less invasive procedures, which are now under clinical trials.

Although recent studies have suggested that blacks compared with whites have an increased prevalence of left ventricular hypertrophy, it remains uncertain whether this is true despite adjustment for body composition (fat mass and fat-free mass) and when assessed by cardiac MRI in the general population. The Dallas Heart Study is a population-based study of Dallas County in which 1335 black and 858 white participants 30 to 67 years of age underwent detailed assessment including dual-energy x-ray absorptiometry scan to measure body composition and cardiac MRI. Left ventricular hypertrophy, whether defined by indexation to body surface area (P<0.001), fat-free mass (P=0.002), or height2.7 (P<0.001) was 2- to 3-fold more common in black versus white women. Similar results were seen when comparing black and white men (P<0.001 when left ventricular hypertrophy was indexed to body surface area or height2.7 and P=0.05 when indexed to fat-free mass). Ethnic disparities in left ventricular mass persisted in multivariable models despite adjustment for fat mass, fat-free mass, systolic blood pressure, age, gender, and measures of socioeconomic status. We conclude that blacks compared with whites have increased left ventricular mass and a 2- to 3-fold higher prevalence of left ventricular hypertrophy in the general population, as assessed by cardiac MRI. The ethnic differences in left ventricular mass are independent of differences in body composition.

Background: Stratifiers of sudden and total mortality risk are needed to optimally target preventive therapies in patients with coronary artery disease and impaired ventricular function. We assessed the prognostic significance of ECG markers of conduction abnormalities and left ventricular hypertrophy in the Multicenter Unsustained Tachycardia Trial (MUSTT)., Methods and Results: We analyzed the ECGs of 1638 patients from MUSTT who did not receive antiarrhythmic therapy (antiarrhythmic medication or implantable cardioverter-defibrillator). After adjustment for other significant factors, left bundle-branch block and intraventricular conduction delay were associated with a 50% increase in the risk of both arrhythmic and total mortality. Right bundle-branch block was not associated with arrhythmic or total mortality. Left ventricular hypertrophy was the only ECG predictor of arrhythmic (hazard ratio, 1.35; 95% CI, 1.08 to 1.69) but not total mortality., Conclusions: In patients with coronary artery disease, depressed left ventricular function, and nonsustained ventricular tachycardia, QRS prolongation resulting from left bundle-branch block or intraventricular conduction delay but not right bundle-branch block provided prognostic information about the risk of arrhythmic and total mortality independently of electrophysiological evaluation and ejection fraction. Left ventricular hypertrophy was associated with increased arrhythmic but not total mortality.

Left ventricular hypertrophy (LVH) is a dominant characteristic of cardiovascular mortality. We investigated the interaction between physical activity and LVH on stroke mortality, based on a 40-year follow-up of the Corfu cohort from the Seven Countries Study. The population studied consisted of 529 rural men (40-59 years old) enrolled in the Study at 1961. LVH was electrographically confirmed according to Minnesota coding. Physical activity levels were assessed by self-reports of habitual, occupational and leisure-time activities. Cox proportional hazard models were used to evaluate exercise levels with respect to stroke mortality in people with and without LVH. During the follow-up, 461 (87%) died, and 74 (16%) of these deaths were due to stroke. LVH was present in 40 (7.5%) men. A total of 362 (68%) men were defined as physically active. Physical activity was associated with a lower risk of stroke (hazard ratio=0.65, P<0.05). On the other hand, LVH had 5.8-fold the risk of stroke (P<0.001) among sedentary and 4.5-fold the risk (P<0.001) among physically active men, after controlling for several potential confounders. However, moderate physical activity decreased the risk of stroke by 49% in men with LVH as compared to sedentary without LVH (hazard ratio=0.51, P<0.01), while hard exercise did not confer any significant reduction in stroke risk. We revealed the benefits from moderate physical activity on stroke mortality among men with LVH. Physicians and other health-care professionals should encourage patients with LVH to adopt a physically active lifestyle.

Left ventricular (LV) hypertrophy is very common, particularly among hypertensives. The presence of LV hypertrophy profoundly affects morbidity and mortality from cardiovascular diseases and stroke, and is now recognized as the most important predictor of chronic heart failure. Hypertension, obesity, and diabetes are important determinants of LV hypertrophy, but they fail to identify many individuals with the condition, suggesting that other factors, likely genetic in origin, play a role. Although much research has been undertaken to understand the causes of hypertrophy and the medical treatments that can lead to its regression, much remains unknown about its genetic basis. LV hypertrophy is considered a complex genetic disease, likely representing an interaction of several genes with the environment. The heritability of LV mass, measured as a quantitative trait, falls between 0.3 and 0.7 in different populations, suggesting it has a familial component. Genes encoding proteins involved in LV structure, as well as genes encoding cell signal transduction, hormones, growth factors, calcium homeostasis, substrate metabolism, and blood pressure are likely candidates for the development of common forms of LV hypertrophy. An overview of the pathophysiology of LV hypertrophy and dysfunction is provided, in addition to evidence of the genetic basis for LV hypertrophy in humans and animal models.

Objectives: We sought to compare systolic and diastolic function in American Indians with diabetes mellitus (DM) based on albuminuria status., Background: Albuminuria has been shown to predict cardiovascular disease (CVD) in populations with DM. However, the mechanism of the association of albuminuria and CVD is unclear., Methods: We compared echo-derived indices of left ventricular (LV) systolic and diastolic function in three groups of American Indians with DM based on albuminuria status: I = no albuminuria (<30 mg albumin/g creatinine); II = microalbuminuria (30 to 300 mg/g); and III = macroalbuminuria (>300 mg/g)., Results: Group II and III were slightly older than Group I with no significant gender difference between groups. Systolic blood pressure increased and body mass index decreased from Group I to Group III. Left ventricular systolic function was lower in the groups with albuminuria with step-wise decreases in ejection fraction and stress-corrected midwall shortening (MWS) from Group I to Group III. Similar findings were noted in diastolic LV filling with lower mitral E/A ratios and longer deceleration times in groups with albuminuria. The proportion of participants with abnormal MWS and abnormal LV diastolic relaxation showed step-wise increases from no albuminuria to macroalbuminuria. In multivariate analysis, albuminuria status remained independently associated with both systolic and diastolic dysfunction after adjusting for age, gender, body mass index, systolic blood pressure, duration of diabetes, coronary artery disease, and LV mass., Conclusions: Albuminuria is independently associated with LV systolic and diastolic dysfunction in type 2 DM; this may explain in part the relationship of albuminuria to increased cardiovascular (CV) events in the DM population. Screening for albuminuria identifies individuals with high CV risk and possible cardiac dysfunction.