Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European American (EA) ancestry group compared to those of Hispanic American (HA), African American (AA), and East Asian (EAS) ancestry. Further, we identified two genes ( CFHR1 and LRP6 ) that harbor multiple rare, putatively deleterious variants associated with mLOY susceptibility, show that subsets of human hematopoietic stem cells are enriched for activity of mLOY susceptibility variants, and that certain alleles on chromosome Y are more likely to be lost than others.

Proteomic Signature of HIV-Associated Subclinical Left Atrial Remodeling and Incident Heart Failure.

Background: People living with HIV (PLWH) are at higher risk of heart failure (HF) and preceding subclinical cardiac abnormalities, including left atrial dilation, compared to people without HIV (PWOH). Hypothesized mechanisms include premature aging linked to chronic immune activation. We leveraged plasma proteomics to identify potential novel contributors to HIV-associated differences in indexed left atrial volume (LAVi) among PLWH and PWOH and externally validated identified proteomic signatures with incident HF among a cohort of older PWOH. Methods: We performed proteomics (Olink Explore 3072) on plasma obtained concurrently with cardiac magnetic resonance imaging among PLWH and PWOH in the United States. Proteins were analyzed individually and as agnostically defined clusters. Cross-sectional associations with HIV and LAVi were estimated using multivariable regression with robust variance. Among an independent general population cohort, we estimated associations between identified signatures and LAVi using linear regression and incident HF using Cox regression. Results: Among 352 participants (age 55±6 years; 25% female), 61% were PLWH (88% on ART; 73% with undetectable HIV RNA) and mean LAVi was 29±9 mL/m 2 . Of 2594 analyzed proteins, 439 were associated with HIV serostatus, independent of demographics, hepatitis C virus infection, renal function, and substance use (FDR<0.05). We identified 73 of these proteins as candidate contributors to the independent association between positive HIV serostatus and higher LAVi, enriched in tumor necrosis factor (TNF) signaling and immune checkpoint proteins regulating T cell, B cell, and NK cell activation. We identified one protein cluster associated with LAVi and HIV regardless of HIV viral suppression status, which comprised 42 proteins enriched in TNF signaling, ephrin signaling, and extracellular matrix (ECM) organization. This protein cluster and 30 of 73 individual proteins were associated with incident HF among 2273 older PWOH (age 68±9 years; 52% female; 8.5±1.4 years of follow-up). Conclusion: Proteomic signatures that may contribute to HIV-associated LA remodeling were enriched in immune checkpoint proteins, cytokine signaling, and ECM organization. These signatures were also associated with incident HF among older PWOH, suggesting specific markers of chronic immune activation, systemic inflammation, and fibrosis may identify shared pathways in HIV and aging that contribute to risk of HF.

Joint effect of highly-sensitive cardiac troponin T and ankle-brachial index on incident cardiovascular events: The MESA and CHS.

Background: Elevated highly-sensitive cardiac troponin-T (hs-cTnT≥14 ng/L) and low ankle-brachial index (ABI<0.9) are risk factors for atherosclerotic cardiovascular diseases (ASCVD) but their joint effect on the risk of ASCVD events is unknown. Methods: We used data from the two population-based cohort studies, the Multi-Ethnic study of Atherosclerosis (MESA) and Cardiovascular Heart Study (CHS) among 10,897 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident ASCVD was defined as CHD (fatal/non-fatal MI or revascularization), transient ischemic attack, or stroke,. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During a median follow-up of 13.6 years (interquartile range, 7.5-14.7 years), there were 2590 incident ASCVD and 1542 incident CHD events. The hazard of CHD and ASCVD was higher in participants with both elevated hs-cTnT and low ABI [HR(95% CI): CHD: 2.04 (1.45, 2.88), ASCVD: 2.05 (1.58, 2.66)] than those with only elevated hs-cTnT [CHD: 1.65 (1.37, 1.99), ASCVD: 1.67 (1.44, 1.99)] or only low ABI [CHD: 1.87 (1.52, 2.31), ASCVD: 1.67 (1.42, 1.97)]. Antagonistic multiplicative interaction was observed for CHD (LR test p-value=0.042) but not for ASCVD (LR test p-value =0.08). No significant additive interaction was detected for CHD and ASCVD (RERI p-value ≥0.23). Conclusion: The observed joint effect of elevated cTnT and low ABI on ASCVD risk was smaller (i.e., antagonistic interaction) than that expected by the combined independent effects of each risk factor.

Association of HIV infection with clinical features and outcomes of patients with aortic aneurysms.

Data on the characteristics and outcomes of hospitalized patients with aortic aneurysms (AA) and HIV remain scarce. This is a cohort study of hospitalized adult patients with a diagnosis of AA from 2013 to 2019 using the US National Inpatient Readmission Database. Patients with a diagnosis of HIV were identified. Our outcomes included trends in hospitalizations and comparison of clinical characteristics, complications, and mortality in patients with AA and HIV compared to those without HIV. Among 1,905,837 hospitalized patients with AA, 4416 (0.23%) were living with HIV. There was an overall age-adjusted increase in the rate of HIV among patients hospitalized with AA over the years (14-29 per 10,000 person-years; age-adjusted p-trend < 0.001). Patients with AA and HIV were younger than those without HIV (median age: 60 vs 76 years, p < 0.001) and were less likely to have a history of smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity. Thoracic aortic aneurysms were more prevalent in those with HIV (37.5% vs 26.7%, p < 0.001). On multivariable logistic regression, HIV was not associated with increased risk of aortic rupture (OR: 0.79; 95% CI: 0.61-1.01, p = 0.06), acute aortic dissection (OR: 0.73; 95% CI: 0.51-1.06, p = 0.3), readmissions (OR: 1.04; 95% CI: 0.95-1.13, p = 0.4), or aortic repair (OR: 0.89; 95% CI: 0.79-1.00, p = 0.05). Hospitalized patients with AA and HIV had a lower crude mortality rate compared to those without HIV (OR: 0.75 (0.63-0.91), p = 0.003). Hospitalized patients with AA and HIV likely constitute a distinct group of patients with AA; they are younger, have fewer traditional cardiovascular risk factors, and a higher rate of thoracic aorta involvement. Differences in clinical features may account for the lower mortality rate observed in patients with AA and HIV compared to those without HIV.

Association of immune cell subsets with cardiac mechanics in the Multi-Ethnic Study of Atherosclerosis.

BackgroundImmunomodulatory therapy may help prevent heart failure (HF). Data on immune cells and myocardial remodeling in older adults with cardiovascular risk factors are limited.MethodsIn the Multi-Ethnic Study of Atherosclerosis cohort, 869 adults had 19 peripheral immune cell subsets measured and underwent cardiac MRI during the baseline exam, of which 321 had assessment of left ventricular global circumferential strain (LV-GCS). We used linear regression with adjustment for demographics, cardiovascular risk factors, and cytomegalovirus serostatus to evaluate the cross-sectional association of immune cell subsets with left ventricular mass index (LVMI) and LV-GCS.ResultsThe average age of the cohort was 61.6 ± 10.0 years and 53% were women. Higher proportions of γ/δ T cells were associated with lower absolute (worse) LV-GCS (-0.105% [95% CI -0.164%, -0.046%] per 1 SD higher proportion of γ/δ T cells, P = 0.0006). This association remained significant after Bonferroni's correction. Higher proportions of classical monocytes were associated with worse absolute LV-GCS (-0.04% [95% CI -0.07%, 0.00%] per 1 SD higher proportion of classical monocytes, P = 0.04). This did not meet significance after Bonferroni's correction. There were no other significant associations with LV-GCS or LVMI.ConclusionPathways associated with γ/δ T cells may be potential targets for immunomodulatory therapy targeted at HF prevention in populations at risk.FundingContracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and grant R01 HL98077 from the National Heart, Lung, and Blood Institute/NIH and grants KL2TR001424, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences/NIH.

Sex differences in vectorcardiogram of African-Americans with and without cardiovascular disease: a cross-sectional study in the Jackson Heart Study cohort.

OBJECTIVES: We hypothesised that (1) the prevalent cardiovascular disease (CVD) is associated with global electrical heterogeneity (GEH) after adjustment for demographic, anthropometric, socioeconomic and traditional cardiovascular risk factors, (2) there are sex differences in GEH and (3) sex modifies an association of prevalent CVD with GEH. DESIGN: Cross-sectional, cohort study. SETTING: Prospective African-American The Jackson Heart Study (JHS) with a nested family cohort in 2000-2004 enrolled residents of the Jackson, Mississippi metropolitan area. PARTICIPANTS: Participants from the JHS with analysable ECGs recorded in 2009-2013 (n=3679; 62±12 y; 36% men; 863 family units). QRS, T and spatial ventricular gradient (SVG) vectors' magnitude and direction, spatial QRS-T angle and sum absolute QRST integral (SAI QRST) were measured. OUTCOME: Prevalent CVD was defined as the history of (1) coronary heart disease defined as diagnosed/silent myocardial infarction, or (2) revascularisation procedure defined as prior coronary/peripheral arterial revascularisation, or (3) carotid angioplasty/carotid endarterectomy, or (4) stroke. RESULTS: In adjusted mixed linear models, women had a smaller spatial QRS-T angle (-12.2 (95% CI -19.4 to -5.1)°; p=0.001) and SAI QRST (-29.8 (-39.3 to -20.3) mV*ms; p<0.0001) than men, but larger SVG azimuth (+16.2(10.5-21.9)°; p<0.0001), with a significant random effect between families (+20.8 (8.2-33.5)°; p=0.001). SAI QRST was larger in women with CVD as compared with CVD-free women or men (+15.1 (3.8-26.4) mV*ms; p=0.009). Men with CVD had a smaller T area (by 5.1 (95% CI 1.2 to 9.0) mV*ms) and T peak magnitude (by 44 (95%CI 16 to 71) µV) than CVD-free men. T vectors pointed more posteriorly in women as compared with men (peak T azimuth + 17.2(8.9-25.6)°; p<0.0001), with larger sex differences in T azimuth in some families by +26.3(7.4-45.3)°; p=0.006. CONCLUSIONS: There are sex differences in the electrical signature of CVD in African-American men and women. There is a significant effect of unmeasured genetic and environmental factors on cardiac repolarisation.

Cardiovascular ultrashort echo time to map fibrosis-promises and challenges.

Increased collagen, or fibrosis, is an important marker of disease and may improve identification of patients at risk. In addition, fibrosis imaging may play an increasing role in guiding therapy and monitoring its effectiveness. MRI is the most frequently used modality to detect, visualize and quantify fibrosis non-invasively. However, standard MRI techniques used to phenotype cardiac fibrosis such as delayed enhancement and extracellular volume determination by T1 mapping, require the administration of gadolinium-based contrast and are particularly difficult to use in patients with cardiac devices such as pacemakers and automatic defibrillators. Therefore, such methods are limited in the serial evaluation of cardiovascular fibrosis as part of chronic disease monitoring. A method to directly measure collagen amount could be of great clinical benefit. In the current review we will discuss the potential of a novel MR technique, ultrashort echo time (UTE) MR, for fibrosis imaging. Although UTE imaging is successfully applied in other body areas such as musculoskeletal applications, there is very limited experience so far in the heart. We will review the established methods and currently available literature, discuss the technical considerations and challenges, show preliminary in vivo images and provide a future outlook on potential applications of cardiovascular UTE.

Factors of health in the protection against death and cardiovascular disease among adults with subclinical atherosclerosis.

BACKGROUND: Although cardiovascular disease (CVD) prevention traditionally emphasizes risk factor control, recent evidence also supports the promotion of "health factors" associated with cardiovascular wellness. However, whether such health factors exist among adults with advanced subclinical atherosclerosis is unknown. We aimed to study the association between health factors and events among persons with elevated coronary artery calcium (CAC). METHODS: Self-reported health-factors studied included nonsmoking, physical activity, Mediterranean-style diet, sleep quality, emotional support, low stress burden, and absence of depression. Measured health-factors included optimal weight, blood pressure, lipids, and glucose. Multivariable-adjusted Cox models examined the association between health factors and incident CVD or mortality, independent of risk factor treatment. Accelerated failure time models assessed whether health factors were associated with relative time delays in disease onset. RESULTS: Among 1,601 Multi-Ethnic Study of Atherosclerosis participants with CAC >100 without baseline clinical atherosclerotic CVD, mean age was 69 (±9) years, 64% were male, and median CAC score was 332 Agatston units. Over 12 years of follow-up, nonsmoking, high-density lipoprotein cholesterol levels >40 mg/dL for men and >50 mg/dL for women, and low stress burden were inversely associated with ASCVD (hazard ratios ranging from 0.58 to 0.71, all P<.05). Nonsmoking, glucose levels <100 mg/dL, regular physical activity, and low stress burden were inversely associated with mortality (hazard ratios ranging from 0.40 to 0.77, all P<.05). Each of these factors was also associated with delays in onset of clinical disease, as was absence of depression. CONCLUSIONS: Adults with elevated CAC appear to have healthy lifestyle options to lower risk and delay onset of CVD, over and above standard preventive therapies.

Three-Dimensional Volumetric Assessment of Diastolic Function by Cardiac Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND:: Cardiac Magnetic Resonance is in need of a simple and robust method for diastolic function assessment that can be done with routine protocol sequences. OBJECTIVE:: To develop and validate a three-dimensional (3D) model-based volumetric assessment of diastolic function using cardiac magnetic resonance (CMR) imaging and compare the results obtained with the model with those obtained by echocardiography. METHODS:: The study participants provided written informed consent and were included if having undergone both echocardiography and cine steady-state free precession (SSFP) CMR on the same day. Guide points at the septal and lateral mitral annulus were used to define the early longitudinal relaxation rate (E'), while a time-volume curve from the 3D model was used to assess diastolic filling parameters. We determined the correlation between 3D CMR and echocardiography and the accuracy of CMR in classifying the diastolic function grade. RESULTS:: The study included 102 subjects. The E/A ratio by CMR was positively associated with the E/A ratio by echocardiography (r = 0.71, p < 0.0001). The early diastolic relaxation velocity by tissue Doppler and longitudinal relaxation rate for the lateral mitral annulus displacement were positively associated (p = 0.007), as were the ratio between Doppler E/e' and CMR E/E' (p = 0.01). CMR-determined normalized peak E (NE) and deceleration time (DT) were able to predict diastolic dysfunction (areas under the curve [AUCs] = 0.70 and 0.72, respectively). In addition, the lateral E/E' ratio showed good utility in identifying diastolic dysfunction (AUC = 0.80). Overall, echocardiography and CMR interobserver and intraobserver agreements were excellent (intraclass correlation coefficient range 0.72 - 0.97). CONCLUSION:: 3D modeling of standard cine CMR images was able to identify study subjects with reduced diastolic function and showed good reproducibility, suggesting a potential for a routine diastolic function assessment by CMR. FUNDAMENTO:: A ressonância magnética cardíaca necessita de um método simples e robusto para a avaliação da função diastólica que pode ser feito com sequências protocolares de rotina. OBJETIVO:: Desenvolver e validar a avaliação volumétrica da função diastólica através de um modelo tridimensional (3D) com utilização de imagens de ressonância magnética cardíaca (RMC) e comparar os resultados obtidos com este modelo com os obtidos por ecocardiografia. MÉTODOS:: Os participantes do estudo assinaram um termo de consentimento e foram incluídos se tivessem sido submetidos no mesmo dia tanto à ecocardiografia quanto à cine RMC com precessão livre no estado estacionário (steady-state free precession, SSFP). Pontos-guia foram utilizados no anel mitral septal e lateral para definir a velocidade de estiramento no início da diástole (E'), enquanto curvas de volume-tempo do modelo 3D foram utilizadas para avaliar os parâmetros de enchimento diastólico. Foram determinadas a correlação entre a RMC 3D e a ecocardiografia, além da acurácia da RMC em classificar o grau de função diastólica. RESULTADOS:: Ao todo, 102 sujeitos foram incluídos no estudo. A razão E/A pela RMC esteve positivamente associada com a razão E/A obtida pela ecocardiografia (r = 0,71, p < 0,0001). Estiveram positivamente associadas a velocidade de relaxamento diastólico inicial ao Doppler tecidual e a velocidade de relaxamento longitudinal de deslocamento do anel mitral lateral (p = 0,007), bem como a razão entre E/e' por Doppler e E/E' pela RMC (p = 0,01). A velocidade normalizada de pico de enchimento (EM) determinada pela RMC e o tempo de desaceleração (TD) foram capazes de predizer a disfunção diastólica (áreas sob a curva [AUCs] = 0,70 e 0,72, respectivamente). Além disso, a razão E/E' lateral mostrou boa utilidade para a identificação da disfunção diastólica (AUC = 0,80). No geral, a ecocardiografia e a RMC apresentaram excelente concordância interobservador e intraobservador (coeficiente de correlação intraclasse 0,72 - 0,97). CONCLUSÃO:: Uma modelagem 3D de imagens padrões de cine RMC foi capaz de identificar os indivíduos do estudo com função diastólica reduzida e mostrou uma boa reprodutibilidade, sugerindo ter potencial na avaliação rotineira da função diastólica por RMC.

Three-Dimensional Volumetric Assessment of Diastolic Function by Cardiac Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA) / Avaliação Volumétrica Tridimensional da Função Diastólica Por Ressonância Magnética Cardíaca: Multi-Ethnic Study Of Atherosclerosis (MESA)

Abstract Background: Cardiac Magnetic Resonance is in need of a simple and robust method for diastolic function assessment that can be done with routine protocol sequences. Objective: To develop and validate a three-dimensional (3D) model-based volumetric assessment of diastolic function using cardiac magnetic resonance (CMR) imaging and compare the results obtained with the model with those obtained by echocardiography. Methods: The study participants provided written informed consent and were included if having undergone both echocardiography and cine steady-state free precession (SSFP) CMR on the same day. Guide points at the septal and lateral mitral annulus were used to define the early longitudinal relaxation rate (E'), while a time-volume curve from the 3D model was used to assess diastolic filling parameters. We determined the correlation between 3D CMR and echocardiography and the accuracy of CMR in classifying the diastolic function grade. Results: The study included 102 subjects. The E/A ratio by CMR was positively associated with the E/A ratio by echocardiography (r = 0.71, p < 0.0001). The early diastolic relaxation velocity by tissue Doppler and longitudinal relaxation rate for the lateral mitral annulus displacement were positively associated (p = 0.007), as were the ratio between Doppler E/e' and CMR E/E' (p = 0.01). CMR-determined normalized peak E (NE) and deceleration time (DT) were able to predict diastolic dysfunction (areas under the curve [AUCs] = 0.70 and 0.72, respectively). In addition, the lateral E/E' ratio showed good utility in identifying diastolic dysfunction (AUC = 0.80). Overall, echocardiography and CMR interobserver and intraobserver agreements were excellent (intraclass correlation coefficient range 0.72 - 0.97). Conclusion: 3D modeling of standard cine CMR images was able to identify study subjects with reduced diastolic function and showed good reproducibility, suggesting a potential for a routine diastolic function assessment by CMR.

Resumo Fundamento: A ressonância magnética cardíaca necessita de um método simples e robusto para a avaliação da função diastólica que pode ser feito com sequências protocolares de rotina. Objetivo: Desenvolver e validar a avaliação volumétrica da função diastólica através de um modelo tridimensional (3D) com utilização de imagens de ressonância magnética cardíaca (RMC) e comparar os resultados obtidos com este modelo com os obtidos por ecocardiografia. Métodos: Os participantes do estudo assinaram um termo de consentimento e foram incluídos se tivessem sido submetidos no mesmo dia tanto à ecocardiografia quanto à cine RMC com precessão livre no estado estacionário (steady-state free precession, SSFP). Pontos-guia foram utilizados no anel mitral septal e lateral para definir a velocidade de estiramento no início da diástole (E'), enquanto curvas de volume-tempo do modelo 3D foram utilizadas para avaliar os parâmetros de enchimento diastólico. Foram determinadas a correlação entre a RMC 3D e a ecocardiografia, além da acurácia da RMC em classificar o grau de função diastólica. Resultados: Ao todo, 102 sujeitos foram incluídos no estudo. A razão E/A pela RMC esteve positivamente associada com a razão E/A obtida pela ecocardiografia (r = 0,71, p < 0,0001). Estiveram positivamente associadas a velocidade de relaxamento diastólico inicial ao Doppler tecidual e a velocidade de relaxamento longitudinal de deslocamento do anel mitral lateral (p = 0,007), bem como a razão entre E/e' por Doppler e E/E' pela RMC (p = 0,01). A velocidade normalizada de pico de enchimento (EM) determinada pela RMC e o tempo de desaceleração (TD) foram capazes de predizer a disfunção diastólica (áreas sob a curva [AUCs] = 0,70 e 0,72, respectivamente). Além disso, a razão E/E' lateral mostrou boa utilidade para a identificação da disfunção diastólica (AUC = 0,80). No geral, a ecocardiografia e a RMC apresentaram excelente concordância interobservador e intraobservador (coeficiente de correlação intraclasse 0,72 - 0,97). Conclusão: Uma modelagem 3D de imagens padrões de cine RMC foi capaz de identificar os indivíduos do estudo com função diastólica reduzida e mostrou uma boa reprodutibilidade, sugerindo ter potencial na avaliação rotineira da função diastólica por RMC.

The Effect of Heart Rate on Exposure Window and Best Phase for Stress Perfusion Computed Tomography: Lessons From the CORE320 Study.

OBJECTIVES: The aim of this study is to evaluate the effect of heart rate on exposure window, best phase, and image quality for stress computed tomography perfusion (CTP) in the CORE320 study. METHODS: The CTP data sets were analyzed to determine the best phase for perfusion analysis. A predefined exposure window covering 75% to 95% of the R-R cycle was used. RESULTS: Of the 368 patients included in the analysis, 93% received oral ß blockade before the rest scan. The median heart rate during the stress acquisition was 69 bpm (interquartile range [IQR], 60-77). The median best phase was 81% (IQR, 76-90), and length of exposure window was 22% (IQR, 19-24). The best phase was significantly later in the cardiac cycle with higher heart rates (P < 0.001), and higher heart rates resulted in a small, but higher number of poor quality scans (6%, P < 0.001). The median effective dose of the stress scan was 5.3 mSv (IQR, 3.8-6.1). CONCLUSIONS: Stress myocardial CTP imaging can be performed using prospective electrocardiography triggering, an exposure window of 75% to 95%, and ß-blockade resulting in good or excellent image quality in the majority (80%) of patients while maintaining a low effective radiation dose.

Left ventricular shape predicts different types of cardiovascular events in the general population.

OBJECTIVE: To investigate whether sphericity volume index (SVI), an indicator of left ventricular (LV) remodelling, predicts incident cardiovascular events (coronary heart disease, CHD; all cardiovascular disease, CVD; heart failure, HF; atrial fibrillation, AF) over 10 years of follow-up in a multiethnic population (Multi-Ethnic Study of Atherosclerosis). METHODS: 5004 participants free of known CVD had magnetic resonance imaging (MRI) in 2000-2002. Cine images were analysed to compute, [Formula: see text] equivalent to LV volume/volume of sphere with length of LV as the diameter. The highest (greatest sphericity) and lowest (lowest sphericity) quintiles of SVI were compared against the reference group (2-4 quintiles combined). Risk-factor adjusted hazard's ratio (HR) from Cox regression assessed the predictive performance of SVI at end-diastole (ED) and end-systole (ES) to predict incident outcomes over 10 years in retrospective interpretation of prospective data. RESULTS: At baseline, participants were aged 61±10 years; 52% men and 39%/13%/26%/22% Cauc/Chinese/Afr-Amer/Hispanic. Low sphericity was associated with higher Framingham CVD risk, greater coronary calcium score and higher N-terminal pro-brain natriuretic peptide (NT-proBNP); while increased sphericity was associated with higher NT-proBNP and lower ejection fraction. Low sphericity predicted incident CHD (HR: 1.48, 1.55-2.59 at ED) and CVD (HR: 1.82, 1.47-2.27 at ED). However, both low (HR: 1.81, 1.20-2.73 at ES) and high (HR: 2.21, 1.41-3.46 at ES) sphericity predicted incident HF. High sphericity also predicted AF. CONCLUSIONS: In a multiethnic population free of CVD at baseline, lowest sphericity was a predictor of incident CHD, CVD and HF over a 10-year follow-up period. Extreme sphericity was a strong predictor of incident HF and AF. SVI improved risk prediction models beyond established risk factors only for HF, but not for all CVD or CHD.

Escore de cálcio e angiotomografia coronariana na estratificação do risco cardiovascular / Coronary artery calcium score and coronary computed tomographic angiography for cardiovascular risk stratification

A doença cardiovascular representa a principal causa de mortalidade no mundo. A capacidade de identificar, dentre os indivíduos assintomáticos, o subgrupo que apresenta maior risco de desenvolver eventos cardiovasculares no futuro representa uma etapa fundamental em qualquer estratégia voltada para a diminuição da taxas de eventos cardiovasculares. O primeiro passo na estratificação do risco cardiovascular é a utilização dos "escores de risco global", dentre os quais o mais frequentemente utilizado é o escore de Framingham. Entretanto, estudos prévios demonstraram que embora muito úteis, os escores clínicos, quando utilizados isoladamente, apresentam capacidade limitada de estratificação do risco cardiovascular em uma parcela significativa da população. É nesse contexto que o escore de cálcio (EC) coronariano e a angiotomografia das artérias coronárias podem desempenhar papel importante como ferramentas complementares na estratificação de risco dos pacientes assintomáticos. O EC coronariano proporciona importantes informações prognósticas que são incrementais aos escores clínicos baseados nos fatores de risco tradicionais e a outras modalidades diagnósticas, como a dosagem da proteína C reativa, por exemplo. Além disso, o EC também tem o potencial de alterar a conduta e auxiliar no manejo clínico dos pacientes. Já a angiotomografia coronariana proporciona avaliação detalhada da anatomia das artérias coronárias, permitindo visualizar não apenas o lúmen, mas também as paredes arteriais coronarianas. Comparada à coronariografia invasiva convencional, a angiotomografia apresenta excelente acurácia para identificar e, principalmente, excluir a presença de lesões obstrutivas significativas. Adicionalmente, demonstrou-se capaz de proporcionar informações prognósticas incrementais aos fatores de risco tradicionais e ao EC coronariano.

Cardiovascular disease is the leading mortality cause worldwide. The capacity to identify among the asymptomatic individuals the subgroup at greater risk for developing cardiovascular events is fundamental in any strategy aimed at reducing the rate of cardiovascular events. The first step in cardiovascular risk stratification is the use of global risk scores, the Framingham risk score being the most frequently used. However, previous studies have shown that, although very useful, clinical scores, when used alone, have a limited capacity for stratifying cardiovascular risk in a significant part of the population. In that context, coronary artery calcium score (CACS) and coronary computed tomographic angiography might play an important role as complementary tools for risk stratification of asymptomatic patients. The CACS provides important prognostic information that is incremental to clinical scores based on traditional risk factors and other diagnostic modalities, such as C-reactive protein measurement. In addition, CACS has the potential to change and help the patients' clinical management. On the other hand, coronary computed tomographic angiography provides a detailed assessment of the anatomy of the coronary arteries, allowing visualizing not only the lumen, but also the coronary arterial walls. Compared with conventional invasive coronary angiography, coronary computed tomographic angiography has excellent accuracy to identify and mainly exclude the presence of significant obstructive lesions. In addition, it proved to be able to provide incremental prognostic information to traditional risk factors and CACS.

Cardiac CT and MRI guide surgery in impending left ventricular rupture after acute myocardial infarction.

We report the case of a 67 year-old patient who presented with worsening chest pain and shortness of breath, four days post acute myocardial infarction. Contrast enhanced computed tomography of the chest ruled out a pulmonary embolus but revealed an unexpected small subepicardial aneurysm (SEA) in the lateral left ventricular wall which was confirmed on cardiac magnetic resonance imaging. Intraoperative palpation of the left lateral wall was guided by the cardiac MRI and CT findings and confirmed the presence of focally thinned and weakened myocardium, covered by epicardial fat. An aneurysmorrhaphy was subsequently performed in addition to coronary bypass surgery and a mitral valve repair. The patient was discharged home on post operative day eight in good condition and is feeling well 2 years after surgery.