Subclinical association of aortic stiffness with cardiac structure and function in African-Americans: The Jackson Heart Study.

Cardiovascular disease (CVD) morbidity and mortality are high among black adults. We aimed to study the granular subclinical relations of aortic stiffness and left ventricular (LV) function and remodeling in blacks, in whom limited data are available. In the Jackson Heart Study, 1050 U.S. community-dwelling black adults without CVD underwent 1.5 T cardiovascular magnetic resonance. We assessed regional and global aortic stiffness and LV structure and function, including LV mass indexed to body surface area (LVMI), end-diastolic volume (LVEDV), ejection fraction (EF), and global and regional circumferential strain (Ecc). Phase contrast images of the cross-sectional aorta at the pulmonary artery bifurcation and abdominal aorta bifurcation were acquired to measure pulse wave velocity of the aortic arch (AA-PWV) and thoracic aorta (T-PWV). Results of multivariable-adjusted analyses are presented as SD unit change in LV variables per SD change in PWV variables. Participants were 62% women with mean age of 59 ± 10 years. Higher AA-PWV and T-PWV were associated with greater LVMI: for T-PWV, ß = 0.10, 95% CI = 0.03-0.16, p = 0.002. Higher AA-PWV and T-PWV were associated with worse (more positive) Ecc at the LV base (for AA-PWV, ß = 0.13, 95% CI = 0.05-0.20, p = 0.0007), but not mid-LV or apex. AA-PWV and T-PWV were not associated with LV mass/LVEDV or EF. In this cross-sectional study of blacks without CVD in the U.S., aortic stiffness is associated with subclinical adverse LV function in basal segments. Future studies may elucidate the temporal relationships of aortic stiffness on the pattern and progression of LV remodeling, dysfunction, and associated prognosis in blacks.

Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy.

Importance: Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death. Objective: To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups. Design, Setting, and Participants: A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively. Exposures: The presence of DCM in a proband. Main Outcomes and Measures: Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative. Results: The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]). Conclusions and Relevance: In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives. Trial Registration: ClinicalTrials.gov Identifier: NCT03037632.

Investigation of association of genetic variant rs3918242 of matrix metalloproteinase-9 with hypertension, myocardial infarction and progression of ventricular dysfunction in Irish Caucasian patients with diabetes: a report from the STOP-HF follow-up programme.

BACKGROUND: Hypertension and/or myocardial infarction are common causes of heart failure in Type 2 diabetes. Progression to heart failure is usually preceded by ventricular dysfunction, linked to matrix metalloproteinase (MMP) mediated extracellular matrix changes. We hypothesise that the minor allele of genetic variant rs3918242 in the promoter region of the MMP-9 gene is associated with hypertension and/or myocardial infarction, with resultant progression of dysfunctional cardiac remodelling in patients with diabetes without symptomatic heart failure. METHODS: We genotyped 498 diabetes patients participating in the St Vincent's Screening TO Prevent Heart Failure (STOP-HF) follow-up programme for the rs3918242 single nucleotide polymorphism and investigated associations with the co-primary endpoints hypertension and/or myocardial infarction using a dominant model. We also evaluated resulting cardiometabolic phenotype and progression of ventricular dysfunction and cardiac structural abnormalities over a median follow-up period of 3.5 years. RESULTS: The CT/TT genotype comprised 28.1% of the cohort and was associated with a twofold higher risk of myocardial infarction (17.9% vs 8.4%), a reduction in ejection fraction and greater left ventricular systolic dysfunction progression [adjusted OR = 2.56 (1.09, 6.01), p = 0.026] over a median follow-up of 3.5 years [IQR 2.6, 4.9 years]. Conversely, rs3918242 was not associated with hypertension, blood pressure, pulse pressure or left ventricular mass index at baseline or over follow up. CONCLUSIONS: Diabetes patients with the minor T allele of rs3918242 in the STOP-HF follow up programme have greater risk of myocardial infarction, lower ejection fraction and greater progression of left ventricular systolic abnormalities, a precursor to heart failure. These data may support further work on MMP-9 as a biomarker of ventricular dysfunction and the investigation of MMP-9 inhibitors for heart failure prevention in diabetes, particularly in the post-infarction setting. ClinicalTrials.gov Identifier: NCT00921960.

Association Between Sleep Disordered Breathing and Left Ventricular Function: A Cross-Sectional Analysis of the ECHO-SOL Ancillary Study.

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/m2 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.

Cardiac MR manifestations in two cases of PRKAG2 mutations in a Chinese family.

PRKAG2 syndrome (PS) is a rare autosomal dominant syndrome that mainly presents with hypertrophic cardiomyopathy, ventricular preexcitation, and conduction abnormalities. Few reports have demonstrated the morphologic manifestation of patients with PRKAG2 gene defect. This case report demonstrates the cardiac magnetic resonance characteristics of the PS patients from a Chinese family.

Phenotyping diabetic cardiomyopathy in Europeans and South Asians.

BACKGROUND: The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans. METHODS: T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model. RESULTS: A total of 131 individuals were included (54 South Asians [50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [- 0.20 (- 0.36; - 0.03), P = 0.021] and Europeans [- 0.20 (- 0.36; - 0.04), P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30), P < 0.001] (P for interaction by ethnicity = 0.005) with a lower extracellular volume fraction [- 1.9% (- 3.4; - 0.4), P = 0.013] (P for interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content [+ 0.59% (0.35; 0.84), P = 0.001] (P for interaction = 0.002) than their control group. CONCLUSIONS: Diabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required.

Association of Arsenic Exposure With Cardiac Geometry and Left Ventricular Function in Young Adults.

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.

Racial differences in myocardial deformation in obese children: Significance of inflammatory state.

BACKGROUND AND AIMS: The association between racial differences in myocardial deformation and cardiometabolic risk factors is unknown in obese children. Our objective was to: 1) investigate for racial differences in myocardial deformation between white and black obese children and 2) identify biomarkers associated with these observed racial differences. We hypothesized that decreased myocardial deformation observed in black obese children could be accounted for by the differences in the markers of metabolic syndrome between the groups. METHODS AND RESULTS: Obese children were recruited prospectively. All clinical and laboratory tests for the metabolic syndrome were conducted during a single assessment using a standardized protocol. Speckle-tracking echocardiography was performed to obtain longitudinal and circumferential measures of deformation. 310 patients were included in the analysis; 158 (51%) white and 152 (49%) black. The median age was 11.3 years (IQR 5.9). Blacks demonstrated worse longitudinal strain (-14.7 ± 2.7% vs. -15.4 ± 2.9%, p = 0.04). There was no difference in circumferential strain between the groups. Multivariable linear regression showed a significant relationship between longitudinal strain and hsCRP (ß = 0.16, p = 0.03) and HOMA-IR (ß = 0.15, p = 0.04); there was no independent association between longitudinal strain and race. CONCLUSION: Black subjects demonstrated worse longitudinal strain than whites. Only hsCRP and HOMA-IR levels, not race, had an independent association with longitudinal strain, suggesting that the observed racial differences in longitudinal strain may be secondary to differences in inflammation and insulin resistance between the groups.

Transient left bundle branch block and left ventricular dysfunction in a patient with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome.

The NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome is a rare novel autoinflammatory disorder. Cardiac involvement has not been previously reported. We present a 12-year-old girl with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome who was diagnosed with severely impaired left ventricular function and complete left bundle branch block during an exacerbation of the disease. Cardiac dysfunction proved to be rapidly reversible after initiation of high-dose methylprednisolone.

Diabetes mellitus and insulin resistance associate with left ventricular shape and torsion by cardiovascular magnetic resonance imaging in asymptomatic individuals from the multi-ethnic study of atherosclerosis.

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 ).

Serum N1-methylnicotinamide is Associated with Left Ventricular Systolic Dysfunction in Chinese.

We previously reported that serum N1-methylnicotinamide (me-NAM), an indicator of nicotinamide N-methyltransferase (NNMT) activity, was associated with obesity, diabetes, and coronary artery disease in Chinese patients. However, whether NNMT might play a role in the development of heart failure remains to be elucidated. In this study, the associations between levels of serum me-NAM and left ventricular structure and function were investigated in Chinese patients. Serum me-NAM was measured by liquid chromatography-mass spectrometry in 265 subjects. M-mode, 2-dimensional and Doppler echocardiography were performed with the GE Vivid E9 system to assess left ventricular structure and function. Of note, the participants in the top tertile of me-NAM had the lowest left ventricular ejection fraction (LVEF), preload recruitable stroke work (PRSW), and highest prevalence of left ventricular systolic dysfunction (LVSD). Serum me-NAM was negatively correlated with LVEF and PRSW before and after adjusted for potential confounding variables (P ≤ 0.02). In multiple logistic regression analyses, the subjects in the top tertile of me-NAM had highest risks for LVSD (OR 6.80; 95% CI 1.26-36.72; P = 0.026), which was also observed in continuous analyses (OR 9.48; 95% CI 1.41-63.48; P = 0.02). In conclusion, serum me-NAM is negatively associated with LVEF and PRSW and accordingly positively associated with the prevalence of LVSD in Chinese patients.

Cardiac Structural Remodeling, Longitudinal Systolic Strain, and Torsional Mechanics in Lean and Nonlean Dysglycemic Chinese Adults.

BACKGROUND: Diabetes mellitus and pre-diabetes mellitus are associated with lower body mass indices and increased risk of cardiovascular events (including heart failure) at lower glucose thresholds in Chinese compared with Western cohorts. However, the extent of cardiac remodeling and regulation on cardiac mechanics in lean and nonlean dysglycemic Chinese adults is understudied. METHODS AND RESULTS: We studied 3950 asymptomatic Chinese (aged 49.7±10.7 years; 65% male; body mass index: 24.3±3.5 kg/m2) with comprehensive echocardiography including speckle tracking for left ventricular global longitudinal strain/torsion, with plasma sugar, glycosylated hemoglobin (HbA1c), and insulin resistance (homeostasis model assessment of insulin resistance) obtained. Participants were classified as (1) nondiabetic (fasting glucose <100 mg/mL; HbA1c <5.7%; n=1416), prediabetic (fasting glucose 100-126 mg/dL; HbA1c 5.7%-6.4%; n=2029), or diabetic (n=505) and (2) lean (body mass index <23 kg/m2; n=1445) or nonlean (n=2505). Higher sugar, HbA1c, and homeostasis model assessment of insulin resistance were independently associated with higher left ventricular mass, greater mass-to-volume ratio, more impaired diastolic indices, and worse global longitudinal strain even after adjusting for clinical covariates (adjusted coefficient value: 0.28/0.12 for global longitudinal strain per 1 U HbA1c/homeostasis model assessment of insulin resistance increment; both P<0.001), with a consistent trend toward greater torsion (all trend P<0.001). The optimal cutoffs in identifying subclinical systolic dysfunction (global longitudinal strain more impaired than -18%) for lean versus nonlean individuals were 97 versus 106 mg/dL for fasting sugar, 130 versus 135 mg/mL for postprandial sugar, 5.62% versus 6.28% for HbA1c, and 1.81 versus 2.40 for homeostasis model assessment of insulin resistance, respectively. CONCLUSIONS: These data demonstrate the presence of preclinical cardiac remodeling and systolic dysfunction in prediabetic and diabetic Chinese adults, occurring at lower thresholds of glycemic indices than defined by international standards, particularly in lean individuals.

"Malignant" Left Ventricular Hypertrophy Identifies Subjects at High Risk for Progression to Asymptomatic Left Ventricular Dysfunction, Heart Failure, and Death: MESA (Multi-Ethnic Study of Atherosclerosis).

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.

Diastolic wall strain is associated with incident heart failure in African Americans: Insights from the atherosclerosis risk in communities study.

BACKGROUND: Increased left ventricular (LV) myocardial stiffness may be associated with impaired LV hemodynamics and incident heart failure (HF). However, an indicator that estimates LV myocardial stiffness easily and non-invasively is lacking. The purpose of this study was to determine whether diastolic wall strain (DWS), an echocardiographic estimator of LV myocardial stiffness, is associated with incident HF in a middle-aged community-based cohort of African Americans. METHODS AND RESULTS: We investigated associations between DWS and incident HF among 1528 African Americans (mean age 58.5 years, 66% women) with preserved LV ejection fraction (EF ≥50%) and without a history of cardiovascular disease in the Atherosclerosis Risk in Communities Study. Participants with the smallest DWS quintile (more LV myocardial stiffness) had a higher LV mass index, higher relative wall thickness, and lower arterial compliance than those in the larger four DWS quintiles (p<0.01 for all). Over a mean follow-up of 15.6 years, there were 251 incident HF events (incidence rate: 10.9 per 1000 person-years). After adjustment for traditional risk factors and incident coronary artery disease, both continuous and categorical DWS were independently associated with incident HF (HR 1.21, 95%CI 1.04-1.41 for 0.1 decrease in continuous DWS, p=0.014, HR 1.40, 95%CI 1.05-1.87 for the smallest DWS quintile vs other combined quintiles, p=0.022). CONCLUSIONS: DWS was independently associated with an increased risk of incident HF in a community-based cohort of African Americans. DWS could be used as a qualitative estimator of LV myocardial stiffness.

Better Indigenous Risk stratification for Cardiac Health study (BIRCH) protocol: rationale and design of a cross-sectional and prospective cohort study to identify novel cardiovascular risk indicators in Aboriginal Australian and Torres Strait Islander adults.

BACKGROUND: Of the estimated 10-11 year life expectancy gap between Indigenous (Aboriginal and Torres Strait Islander people) and non-Indigenous Australians, approximately one quarter is attributable to cardiovascular disease (CVD). Risk prediction of CVD is imperfect, but particularly limited for Indigenous Australians. The BIRCH (Better Indigenous Risk stratification for Cardiac Health) project aims to identify and assess existing and novel markers of early disease and risk in Indigenous Australians to optimise health outcomes in this disadvantaged population. It further aims to determine whether these markers are relevant in non-Indigenous Australians. METHODS/DESIGN: BIRCH is a cross-sectional and prospective cohort study of Indigenous and non-Indigenous Australian adults (≥ 18 years) living in remote, regional and urban locations. Participants will be assessed for CVD risk factors, left ventricular mass and strain via echocardiography, sleep disordered breathing and quality via home-based polysomnography or actigraphy respectively, and plasma lipidomic profiles via mass spectrometry. Outcome data will comprise CVD events and death over a period of five years. DISCUSSION: Results of BIRCH may increase understanding regarding the factors underlying the increased burden of CVD in Indigenous Australians in this setting. Further, it may identify novel markers of early disease and risk to inform the development of more accurate prediction equations. Better identification of at-risk individuals will promote more effective primary and secondary preventive initiatives to reduce Indigenous Australian health disadvantage.

Pacemaker syndrome with sub-acute left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker: consequence of lead switch at the header.

In the daily practice of pacemaker insertion, the occurrence of atrial and ventricular lead switch at the pacemaker box header is a rare and unintentional phenomenon, with less than five cases reported in the literature. The lead switch may have dire consequences, depending on the indication for the pacemaker. One of these consequences is pacemaker syndrome, in which the normal sequence of atrial and ventricular activation is impaired, leading to sub-optimal ventricular filling and cardiac output. It is important for the attending physician to recognise any worsening of symptoms in a patient who has recently had a permanent pacemaker inserted. In the case of a dual-chamber pacemaker, switching of the atrial and ventricular leads at the pacemaker box header should be strongly suspected. We present an unusual case of pacemaker syndrome and right ventricular-only pacinginduced left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker.

Reference Ranges and Regional Patterns of Left Ventricular Strain and Strain Rate Using Two-Dimensional Speckle-Tracking Echocardiography in a Healthy Middle-Aged Black and White Population: The CARDIA Study.

BACKGROUND: Strain and strain rate are sensitive markers of left ventricular (LV) myocardial function. The aim of this study was to assess reference ranges and regional patterns of LV strain and strain rate using two-dimensional speckle-tracking echocardiography in a large population of black and white subjects. METHODS: This study involved a retrospective review of prospectively collected images in 557 participants in the Coronary Artery Risk Development in Young Adults study who remained healthy at the year 25 examination. LV deformation parameters were measured in apical four-chamber, apical two-chamber, and parasternal short-axis views in 509, 391, and 521 subjects, respectively. RESULTS: Patients' mean age was 49.6 ± 3.6 years, 61.6% were women, and 69.5% were white. White women showed the highest LV systolic and diastolic deformation values, reflected by a more negative reference range for apical four-chamber longitudinal strain (-16.4%; 95% prediction interval [PI], -20.8% to -12.0%) and a higher positive reference range for early diastolic strain rate (0.93 1/sec; 95% PI, 0.41 to 1.46 1/sec), respectively. The lowest LV systolic and diastolic deformation values were found in black men, with apical four-chamber longitudinal strain (14.7%; 95% PI, -19.1% to -10.3%) and early diastolic strain rate (0.79 1/sec; 95% PI, 0.42 to 1.16 1/sec). Absolute strain increased from the epicardium toward the endocardium. A base-to-apex gradient of longitudinal strain toward the apex was exhibited in inferior and inferoseptal regions and, in contrast, in the opposite direction in anterior and anterolateral walls. Sex had the strongest influence on LV deformation variability. CONCLUSIONS: Strain and strain rate reference values were sex and race related. White women showed the highest reference ranges for LV deformation, while the lowest values were found in black men. Significant layer- and level-specific patterns in regional LV deformation were identified.

Electrocardiographic Predictors of Heart Failure With Reduced Versus Preserved Ejection Fraction: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Several markers detected on the routine 12-lead ECG are associated with future heart failure events. We examined whether these markers are able to separate the risk of heart failure with reduced ejection fraction (HFrEF) from heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We analyzed data of 6664 participants (53% female; mean age 62±10 years) from MESA (Multi-Ethnic Study of Atherosclerosis) who were free of cardiovascular disease at baseline (2000-2002). A competing risks analysis was used to compare the association of several baseline ECG predictors with HFrEF and HFpEF detected during a median follow-up of 12.1 years. A total of 127 HFrEF and 117 HFpEF events were detected during follow-up. In a multivariable adjusted model, prolonged QRS duration, delayed intrinsicoid deflection, left-axis deviation, right-axis deviation, prolonged QT interval, abnormal QRS-T axis, left ventricular hypertrophy, ST/T-wave abnormalities, and left bundle-branch block were associated with HFrEF. In contrast, higher resting heart rate, abnormal P-wave axis, and abnormal QRS-T axis were associated with HFpEF. The risk of HFrEF versus HFpEF was significantly differently for delayed intrinsicoid deflection (hazard ratio: 4.90 [95% confidence interval (CI), 2.77-8.68] versus 0.94 [95% CI, 0.29-2.97]; comparison P=0.013), prolonged QT interval (hazard ratio: 2.39 [95% CI, 1.55-3.68] versus 0.52 [95% CI, 0.23-1.19]; comparison P<0.001), and ST/T-wave abnormalities (hazard ratio: 2.47 [95% CI, 1.69-3.62] versus 1.13 [95% CI, 0.72-1.77]; comparison P=0.0093). CONCLUSIONS: Markers of ventricular repolarization and delayed ventricular activation are able to distinguish between the future risk of HFrEF and HFpEF. These findings suggest a role for ECG markers in the personalized risk assessment of heart failure subtypes.

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study.

BACKGROUND: Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross-sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms. METHOD AND RESULTS: A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N-terminal pro-brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm3; P<0.0001) and hippocampal volumes (0.05±0.02 cm3, P=0.01). Reduced diastolic function was associated with poorer working memory (-0.21±0.07, P=0.004) and fluency scores (-0.18±0.08, P=0.02). Reduced global LV function was associated with smaller hippocampal volume (-0.10±0.03 cm3, P=0.004) and adverse visual memory (-0.076±0.03, P=0.02) and processing speed (0.063±0.02, P=0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory. CONCLUSIONS: In a community-based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways.

Association of Albuminuria With Cardiac Dysfunction in US Hispanics/Latinos.

Higher urine albumin-to-creatinine ratio (UACR) has been associated with cardiac dysfunction in the general population. We assessed the association of UACR with cardiac structure and function in the Echocardiographic Study of Latinos (Echo-SOL), an ancillary study of the Hispanic Community Health Study/Study of Latinos across 4 US sites. Echo-SOL participants underwent standard 2-dimensional echocardiography, including speckle-tracking strain analysis. UACR was categorized as normal and high-normal (based on the midpoint of values below microalbuminuria), microalbuminuria (≥17 mg/g for men; ≥25 mg/g for women), and macroalbuminuria (≥250 mg/g; ≥355 mg/g). Simultaneous assessments were made of left ventricular (LV) mass index and hypertrophy and measures of LV systolic and diastolic dysfunction. We assessed the association of UACR with subclinical cardiac measures, adjusting for sociodemographic and cardiometabolic factors. Among 1,815 participants (median age 54, women 65%), 42% had normal UACR, 43% high-normal UACR, 13% microalbuminuria, and 2% macroalbuminuria. Prevalence of LV hypertrophy was 13%, LV systolic dysfunction (ejection fraction <50%) 3%, and diastolic dysfunction 53%. After covariate adjustment, both micro- and macroalbuminuria were significantly associated with a twofold increase in LV hypertrophy. Microalbuminuria but not macroalbuminuria was associated with worse global longitudinal strain. Elevated UACR, even at high-normal levels, was significantly associated with greater diastolic dysfunction. In conclusion, elevated UACR was associated with LV hypertrophy and diastolic dysfunction in the largest known population sample of US Hispanic/Latinos. Screening and detection of even high-normal UACR could be of value to guide cardiovascular disease prevention efforts among Hispanic/Latino Americans.