RESUMO
BACKGROUND: Social unacceptability of food access is part of the lived experience of food insecurity but is not assessed as part of the United States Household Food Security Survey Module (HFSSM). OBJECTIVES: The objectives were as follows: 1) to determine the psychometric properties of 2 additional items on social unacceptability in relation to the HFSSM items and 2) to test whether these 2 items provided added predictive accuracy to that of the HFSSM items for mental health outcomes. METHODS: Cross-sectional data used were from the Intersection of Material-Need Insecurities and HIV and Cardiovascular Health substudy of the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study. Data on the 10-item HFSSM and 2 new items reflecting social unacceptability were collected between Fall 2020 and Fall 2021 from 1342 participants from 10 United States cities. The 2 social unacceptability items were examined psychometrically in relation to the HFSSM-10 items using models from item response theory. Linear and logistic regression was used to examine prediction of mental health measured by the 20-item Center for Epidemiologic Studies Depression scale and the 10-item Perceived Stress Scale. RESULTS: The social unacceptability items were affirmed throughout the range of severity of food insecurity but with increasing frequency at higher severity of food insecurity. From item response theory models, the subconstructs reflected in the HFSSM-10 and the subconstruct of social unacceptability were distinct, not falling into one dimension. Regression models confirmed that social unacceptability was distinct from the subconstructs reflected in the HFSSM-10. The social unacceptability items as a separate scale explained more (â¼1%) variation in mental health than when combined with the HFSSM-10 items in a single scale, and the social unacceptability subconstruct explained more (â¼1%) variation in mental health not explained by the HFSSM-10. CONCLUSIONS: Two social unacceptability items used as a separate scale along with the HFSSM-10 predicted mental health more accurately than did the HFSSM-10 alone.
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Abastecimento de Alimentos , Infecções por HIV , Testes Psicológicos , Autorrelato , Humanos , Feminino , Estados Unidos , Estudos de Coortes , Estudos Transversais , Segurança AlimentarRESUMO
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.
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Aneurisma Aórtico , Infecções por HIV , Humanos , Pessoa de Meia-Idade , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Estudos de Coortes , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/epidemiologia , Aneurisma Aórtico/terapiaRESUMO
BACKGROUND: Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH). METHODS: Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics. RESULTS: Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise. CONCLUSIONS: Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.
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Cardiomiopatias , Infecções por HIV , Biomarcadores , Feminino , Fator 15 de Diferenciação de Crescimento , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Átrios do Coração/diagnóstico por imagem , Humanos , Interleucina-6 , Receptores de Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico , Fragmentos de PeptídeosRESUMO
PURPOSE OF REVIEW: Because of effective combination antiretroviral therapy, people living with HIV (PLWH) are living longer but developing chronic age-related conditions including cardiovascular disease (CVD), the leading cause of death globally. This review aims to discuss the epidemiology, mechanisms, and clinical considerations of CVD in PLWH from a global perspective. RECENT FINDINGS: PLWH are at greater risk for CVD at chronologically younger ages than those without HIV. Potential underlying mechanisms for CVD in PLWH include systemic inflammation, comorbidities, immune-mediated, or treatment-related mechanisms. There is also risk factor variation based on geographical location, including non-traditional CVD risk factors. CVD is prevalent in PLWH and increasing on a global scale. Further understanding the unique epidemiology, risk factors, and treatment of CVD in this population will improve the care of PLWH.
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Doenças Cardiovasculares , Sistema Cardiovascular , Infecções por HIV , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Inflamação , Fatores de RiscoRESUMO
BACKGROUND: People living with human immunodeficiency virus (HIV+) have greater risk for sudden arrhythmic death than HIV-uninfected (HIV-) individuals. HIV-associated abnormal cardiac repolarization may contribute to this risk. We investigated whether HIV serostatus is associated with ventricular repolarization lability by using the QT variability index (QTVI), defined as a log measure of QT-interval variance indexed to heart rate variance. METHODS: We studied 1123 men (589 HIV+ and 534 HIV-) from MACS (Multicenter AIDS Cohort Study), using the ZioXT ambulatory electrocardiography patch. Beat-to-beat analysis of up to 4 full days of electrocardiographic data per participant was performed using an automated algorithm (median analyzed duration [quartile 1-quartile 3]: 78.3 [66.3-83.0] hours/person). QTVI was modeled using linear mixed-effects models adjusted for demographics, cardiac risk factors, and HIV-related and inflammatory biomarkers. RESULTS: Mean (SD) age was 60.1 (11.9) years among HIV- and 54.2 (11.2) years among HIV+ participants (P<0.001), 83% of whom had undetectable (<20 copies/mL) HIV-1 viral load (VL). In comparison with HIV- men, HIV+ men had higher QTVI (adjusted difference of +0.077 [95% CI, +0.032 to +0.123]). The magnitude of this association depended on the degree of viremia, such that in HIV+ men with undetectable VL, adjusted QTVI was +0.064 (95% CI, +0.017 to +0.111) higher than in HIV- men, whereas, in HIV+ men with detectable VL, adjusted QTVI was higher by +0.150 (95% CI, 0.072-0.228) than in HIV- referents. Analysis of QTVI subcomponents showed that HIV+ men had: (1) lower heart rate variability irrespective of VL status, and (2) higher QT variability if they had detectable, but not with undetectable, VL, in comparison with HIV- men. Higher levels of C-reactive protein, interleukin-6, intercellular adhesion molecule-1, soluble tumor necrosis factor receptor 2, and soluble cluster of differentiation-163 (borderline), were associated with higher QTVI and partially attenuated the association with HIV serostatus. CONCLUSIONS: HIV+ men have greater beat-to-beat variability in QT interval (QTVI) than HIV- men, especially in the setting of HIV viremia and heightened inflammation. Among HIV+ men, higher QTVI suggests ventricular repolarization lability, which can increase susceptibility to arrhythmias, whereas lower heart rate variability signals a component of autonomic dysfunction.
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Arritmias Cardíacas/fisiopatologia , Eletrocardiografia , Infecções por HIV/fisiopatologia , HIV-1 , Ventrículos do Coração/fisiopatologia , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Carga ViralRESUMO
BACKGROUND: Patients with cardiac sarcoidosis (CS) are at increased risk of life-threatening ventricular arrhythmias (VA). Current approaches to risk stratification have limited predictive value. OBJECTIVES: To assess the utility of spatial dispersion analysis of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), as a quantitative measure of myocardial tissue heterogeneity, in risk stratifying patients with CS for VA and death. METHODS: Sixty two patients with CS underwent LGE-CMR. LGE images were segmented and dispersion maps of the left and right ventricles were generated as follows. Based on signal intensity (SI), each pixel was categorized as abnormal (SI ≥3SD above the mean), intermediate (SI 1-3 SD above the mean) or normal (SI <1SD above the mean); and each pixel was then assigned a value of 0 to 8 based on the number of adjacent pixels of a different category. Average dispersion score was calculated for each patient. The primary endpoint was VA during follow up. The composite of VA or death was assessed as a secondary endpoint. RESULTS: During 4.7 ± 3.5 years of follow up, six patients had VA, and five without documented VA died. Average dispersion score was significantly higher in patients with VA versus those without (0.87 ± 0.08 vs. 0.71 ± 0.16; p = .002) and in patients with events versus those without (0.83 ± 0.08 vs. 0.70 ± 0.16; p = .003). Patients at higher tertiles of dispersion score had a higher incidence of VA (p = .03) and the composite of VA or death (p = .01). CONCLUSIONS: Increased substrate heterogeneity, quantified by spatial dispersion analysis of LGE-CMR, may be helpful in risk-stratifying patients with CS for adverse events, including life-threatening arrhythmias.
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Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/etiologia , Imageamento por Ressonância Magnética/métodos , Sarcoidose/complicações , Sarcoidose/diagnóstico por imagem , Meios de Contraste , Feminino , Gadolínio , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
BACKGROUND: The total QT interval comprises both ventricular depolarization and repolarization currents. Understanding how HIV serostatus and other risk factors influence specific QT interval subcomponents could improve our mechanistic understanding of arrhythmias. METHODS: Twelve-lead electrocardiograms (ECGs) were acquired in 774 HIV-infected (HIV+) and 652 HIV-uninfected (HIV-) men from the Multicenter AIDS Cohort Study. Individual QT subcomponent intervals were analyzed: R-onset to R-peak, R-peak to R-end, JT segment, T-onset to T-peak, and T-peak to T-end. Using multivariable linear regressions, we investigated associations between HIV serostatus and covariates, including serum concentrations of inflammatory biomarkers such as interleukin-6 (IL-6), and each QT subcomponent. RESULTS: After adjustment for demographics and risk factors, HIV+ versus HIV- men differed only in repolarization phase durations with longer T-onset to T-peak by 2.3 ms (95% CI 0-4.5, p < .05) and T-peak to T-end by 1.6 ms (95% CI 0.3-2.9, p < .05). Adjusting for inflammation attenuated the strength and significance of the relationship between HIV serostatus and repolarization. The highest tertile of IL-6 was associated with a 7.3 ms (95% CI 3.2-11.5, p < .01) longer T-onset to T-peak. Age, race, body mass index, alcohol use, and left ventricular hypertrophy were each associated with up to 2.2-12.5 ms longer T-wave subcomponents. CONCLUSIONS: HIV seropositivity, in combination with additional risk factors including increased systemic inflammation, is associated with longer T-wave subcomponents. These findings could suggest mechanisms by which the ventricular repolarization phase is lengthened and thereby contribute to increased arrhythmic risk in men living with HIV.
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Eletrocardiografia , Infecções por HIV , Inflamação , Síndrome do QT Longo/complicações , Síndrome do QT Longo/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Clinical research and medical practice can be advanced through the prediction of an individual's health state, trajectory, and responses to treatments. However, the majority of current clinical risk prediction models are based on regression approaches or machine learning algorithms that are static, rather than dynamic. To benefit from the increasing emergence of large, heterogeneous data sets, such as electronic health records (EHRs), novel tools to support improved clinical decision making through methods for individual-level risk prediction that can handle multiple variables, their interactions, and time-varying values are necessary. METHODS: We introduce a novel dynamic approach to clinical risk prediction for survival, longitudinal, and multivariate (SLAM) outcomes, called random forest for SLAM data analysis (RF-SLAM). RF-SLAM is a continuous-time, random forest method for survival analysis that combines the strengths of existing statistical and machine learning methods to produce individualized Bayes estimates of piecewise-constant hazard rates. We also present a method-agnostic approach for time-varying evaluation of model performance. RESULTS: We derive and illustrate the method by predicting sudden cardiac arrest (SCA) in the Left Ventricular Structural (LV) Predictors of Sudden Cardiac Death (SCD) Registry. We demonstrate superior performance relative to standard random forest methods for survival data. We illustrate the importance of the number of preceding heart failure hospitalizations as a time-dependent predictor in SCA risk assessment. CONCLUSIONS: RF-SLAM is a novel statistical and machine learning method that improves risk prediction by incorporating time-varying information and accommodating a large number of predictors, their interactions, and missing values. RF-SLAM is designed to easily extend to simultaneous predictions of multiple, possibly competing, events and/or repeated measurements of discrete or continuous variables over time. TRIAL REGISTRATION: LV Structural Predictors of SCD Registry (clinicaltrials.gov, NCT01076660), retrospectively registered 25 February 2010.
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Tomada de Decisão Clínica/métodos , Morte Súbita Cardíaca/epidemiologia , Previsões/métodos , Medição de Risco/métodos , Teorema de Bayes , Análise de Dados , Registros Eletrônicos de Saúde , Nível de Saúde , Ventrículos do Coração/patologia , Humanos , Aprendizado de Máquina , Análise Multivariada , Prognóstico , Risco , Análise de SobrevidaRESUMO
INTRODUCTION: Inappropriate implantable cardioverter-defibrillator (ICD) shocks, commonly caused by atrial fibrillation (AF), are associated with an increased mortality. Because impaired left atrial (LA) function predicts development of AF, we hypothesized that impaired LA function predicts inappropriate shocks beyond a history of AF. METHODS AND RESULTS: We prospectively analyzed the association between LA function and incident inappropriate shocks in primary prevention ICD candidates. In the Prospective Observational Study of ICD (PROSE-ICD), we assessed LA function using tissue-tracking cardiac magnetic resonance (CMR) prior to ICD implantation. A total of 162 patients (113 males, age 56 ± 15 years) were included. During the mean follow-up of 4.0 ± 2.9 years, 26 patients (16%) experienced inappropriate shocks due to AF (n = 19; 73%), supraventricular tachycardia (n = 5; 19%), and abnormal sensing (n = 2; 8%). In univariable analyses, inappropriate shocks were associated with AF history prior to ICD implantation, age below 70 years, QRS duration less than 120 milliseconds, larger LA minimum volume, lower LA stroke volume, lower LA emptying fraction, impaired LA maximum and preatrial contraction strains (Smax and SpreA ), and impaired LA strain rate during left ventricular systole and atrial contraction (SRs and SRa ). In multivariable analysis, impaired Smax (hazard ratio [HR]: 0.96, P = 0.044), SpreA (HR: 0.94, P = 0.030), and SRa (HR: 0.25, P < 0.001) were independently associated with inappropriate shocks. The receiver-operating characteristics curve showed that SRa improved the predictive value beyond the patient demographics including AF history (P = 0.033). CONCLUSION: Impaired LA function assessed by tissue-tracking CMR is an independent predictor of inappropriate shocks in primary prevention ICD candidates beyond AF history.
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Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo/fisiologia , Desfibriladores Implantáveis/efeitos adversos , Prevenção Primária/métodos , Adulto , Idoso , Fibrilação Atrial/prevenção & controle , Desfibriladores Implantáveis/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevenção Primária/tendências , Estudos ProspectivosRESUMO
BACKGROUND: Increased QRS score and wide spatial QRS-T angle are independent predictors of cardiovascular mortality in the general population. Our main objective was to assess whether a QRS score ≥ 5 and/or QRS-T angle ≥ 105° enable screening of patients for myocardial scar features. METHODS: Seventy-seven patients of age ≤ 70 years with QRS score ≥ 5 and/or spatial QRS-T angle ≥ 105° as well as left ventricular ejection fraction (LVEF) >35% were enrolled in the study. All participants underwent complete clinical examination, signal-averaged ECG (SAECG), 30-minute ambulatory ECG recording for T-wave alternans (TWA), and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Relationship between QRS score, QRS-T angle with scar presence and pattern, as well as gray zone, core, and total scar size by LGE-CMR were assessed. RESULTS: Myocardial scar was present in 41 (53%) patients, of whom 19 (46%) exhibited a typical ischemic pattern. QRS score but not QRS-T angle was related to total scar size and gray zone size (R(2) = 0.12, P = 0.002; R(2) = 0.17; P ≤ 0.0001, respectively). Patients with QRS scores ≥ 6 had significantly greater myocardial scar and gray zone size, increased QRS duration and QRS-T angle, a higher prevalence of late potentials (LPs) presence, increased LV end-diastolic volume and decreased LVEF. There was a significant independent and positive association between TWA value and total scar (P = 0.001) and gray zone size (P = 0.01). CONCLUSION: Patients with preserved LVEF and myocardial scar by CMR also have electrocardiographic features that could be involved in ventricular arrhythmogenesis.
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Cicatriz/diagnóstico , Eletrocardiografia , Isquemia Miocárdica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Volume Sistólico , Adulto JovemRESUMO
BACKGROUND: The antisynthetase (AS) syndrome is characterized by autoimmune myopathy, interstitial lung disease, cutaneous involvement, arthritis, fever, and antibody specificity. We describe 2 patients with AS syndrome who also developed myocarditis, depressed biventricular function, and congestive heart failure. METHODS AND RESULTS: Both patients were diagnosed with AS syndrome based on clinical manifestations, detection of serum AS antibodies, and myositis confirmation with the use of skeletal muscle magnetic resonance imaging and skeletal muscle biopsy. In addition, myocarditis resulting in heart failure was confirmed with the use of cardiac magnetic resonance imaging and from endomyocardial biopsy findings. After treatment for presumed AS syndrome-associated myocarditis, one patient recovered and the other patient died. CONCLUSIONS: AS syndrome is a rare entity with morbidity and mortality typically attributed to myositis and lung involvement. This is the first report of AS syndrome-associated myocarditis leading to congestive heart failure in 2 patients. Given the potentially fatal consequences, myocarditis should be considered in patients with AS syndrome presenting with heart failure.
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Insuficiência Cardíaca/diagnóstico , Miocardite/diagnóstico , Miosite/diagnóstico , Corticosteroides/administração & dosagem , Adulto , Biópsia por Agulha , Eletrocardiografia/métodos , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Imuno-Histoquímica , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Miocardite/complicações , Miocardite/tratamento farmacológico , Miocárdio/patologia , Miosite/complicações , Miosite/tratamento farmacológico , Doenças Raras , Medição de Risco , Estudos de Amostragem , Resultado do TratamentoRESUMO
BACKGROUND: Many advanced human tumors, including hepatocellular carcinomas (HCC) are auxotrophic for arginine due to down-regulation of argininosuccinate synthetase (ASS1), the rate-limiting enzyme in arginine synthesis. The arginine-lowering agent PEGylated arginine deiminase (ADI-PEG 20) has shown efficacy as a monotherapy in clinical trials for treating arginine-auxotrophic tumors and is currently being evaluated in combination with cisplatin in other cancer types. Epigenetic silencing via methylation of the ASS1 promoter has been previously demonstrated in other cancer types, and a reciprocal relationship between ASS1 expression and cisplatin resistance has also been observed in ovarian cancer. However, the mechanism of ASS1 down-regulation, as well as the correlation with cisplatin resistance has not been explored in HCC. The present study investigates ADI-PEG 20 and cisplatin sensitivities in relation to ASS1 expression in HCC. In addition, we show how this biomarker is regulated by cisplatin alone and in combination with ADI-PEG 20. METHODS: ASS1 protein expression in both untreated and drug treated human HCC cell lines was assessed by western blot. The correlation between ASS1 protein levels, ADI-PEG 20 sensitivity and cisplatin resistance in these cell lines was established using a luminescence-based cell viability assay. Epigenetic regulation of ASS1 was analyzed by bisulfite conversion and methylation-specific PCR. RESULTS: A good correlation between absence of ASS1 protein expression, ASS1 promoter methylation, sensitivity to ADI-PEG 20 and resistance to cisplatin in HCC cell lines was observed. In addition, cisplatin treatment down-regulated ASS1 protein expression in select HCC cell lines. While, at clinically relevant concentrations, the combination of ADI-PEG 20 and cisplatin restored ASS1 protein levels in most of the cell lines studied. CONCLUSION: ASS1 silencing in HCC cell lines is associated with simultaneous cisplatin resistance and ADI-PEG 20 sensitivity which suggests a promising combination therapeutic strategy for the management of HCC.
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Antineoplásicos/farmacologia , Argininossuccinato Sintase/metabolismo , Carcinoma Hepatocelular/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Hidrolases/farmacologia , Neoplasias Hepáticas/metabolismo , Polietilenoglicóis/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Argininossuccinato Sintase/genética , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Metilação de DNA , Sinergismo Farmacológico , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Purpose: As health studies increasingly monitor free-living heart performance via ECG patches with accelerometers, researchers will seek to investigate cardio-electrical responses to physical activity and sedentary behavior, increasing demand for fast, scalable methods to process accelerometer data. We extend a posture classification algorithm for accelerometers in ECG patches when researchers do not have ground-truth labels or other reference measurements (i.e., upright measurement). Methods: Men living with and without HIV in the Multicenter AIDS Cohort study wore the Zio XT® for up to two weeks (n = 1,250). Our novel extensions for posture classification include (1) estimation of an upright posture for each individual without a reference upright measurement; (2) correction of the upright estimate for device removal and re-positioning using novel spherical change-point detection; and (3) classification of upright and recumbent periods using a clustering and voting process rather than a simple inclination threshold used in other algorithms. As no posture labels exist in the free-living environment, we perform numerous sensitivity analyses and evaluate the algorithm against labelled data from the Towson Accelerometer Study, where participants wore accelerometers at the waist. Results: On average, 87.1% of participants were recumbent at 4am and 15.5% were recumbent at 1pm. Participants were recumbent 54 minutes longer on weekends compared to weekdays. Performance was good in comparison to labelled data in a separate, controlled setting (accuracy = 96.0%, sensitivity = 97.5%, specificity = 95.9%). Conclusions: Posture may be classified in the free-living environment from accelerometers in ECG patches even without measuring a standard upright position. Furthermore, algorithms that fail to account for individuals who rotate and re-attach the accelerometer may fail in the free-living environment.
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BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic heart disease associated with life-threatening ventricular arrhythmias. Diagnosis of ARVC is based on the 2010 Task Force Criteria (TFC), application of which often requires clinical expertise at specialized centers. OBJECTIVE: To develop and validate an electrocardiogram (ECG) deep-learning (DL) tool for ARVC diagnosis. METHODS: ECGs of patients referred for ARVC evaluation were used to develop (n=551, 80.1%) and test (n=137, 19.9%) an ECG-DL model for prediction of TFC-defined ARVC diagnosis. The ARVC ECG-DL model was externally validated in a cohort of patients with pathogenic or likely pathogenic (P/LP) ARVC gene variants identified through the Geisinger MyCode Community Health Initiative (N=167). RESULTS: Of 688 patients evaluated at JHH (57.3% male, mean age 40.2 years), 329 (47.8%) were diagnosed with ARVC. While ARVC diagnosis made by referring cardiologist ECG interpretation was unreliable (c-statistic 0.53 [CI: 0.52, 0.53]), ECG-DL discrimination in the hold-out testing cohort was excellent (0.87 [0.86, 0.89]) and compared favorably to that of ECG interpretation by an ARVC expert (0.85 [0.84, 0.86]). In the Geisinger cohort, prevalence of ARVC was lower (n=17, 10.2%), but ECG-DL based identification of ARVC phenotype remained reliable (0.80 [0.77, 0.83]). Discrimination was further increased when ECG-DL predictions were combined with non-ECG-derived TFC in the JHH testing (c-statistic 0.940 [95%CI: 0.933; 0.948]) and Geisinger validation (0.897 [95%CI: 0.883; 0.912]) cohorts. CONCLUSION: ECG-DL augments diagnosis of ARVC to the level of an ARVC expert and can differentiate true ARVC diagnosis from phenotype-mimics and at-risk family members/genotype-positive individuals.
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BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at risk of sudden death, and individuals with ≥1 major risk markers are considered for primary prevention implantable cardioverter-defibrillators. Guidelines recommend cardiac magnetic resonance (CMR) imaging to identify high-risk imaging features. However, CMR imaging is resource intensive and is not widely accessible worldwide. OBJECTIVE: The purpose of this study was to develop electrocardiogram (ECG) deep-learning (DL) models for the identification of patients with HCM and high-risk imaging features. METHODS: Patients with HCM evaluated at Tufts Medical Center (N = 1930; Boston, MA) were used to develop ECG-DL models for the prediction of high-risk imaging features: systolic dysfunction, massive hypertrophy (≥30 mm), apical aneurysm, and extensive late gadolinium enhancement. ECG-DL models were externally validated in a cohort of patients with HCM from the Amrita Hospital HCM Center (N = 233; Kochi, India). RESULTS: ECG-DL models reliably identified high-risk features (systolic dysfunction, massive hypertrophy, apical aneurysm, and extensive late gadolinium enhancement) during holdout testing (c-statistic 0.72, 0.83, 0.93, and 0.76) and external validation (c-statistic 0.71, 0.76, 0.91, and 0.68). A hypothetical screening strategy using echocardiography combined with ECG-DL-guided selective CMR use demonstrated a sensitivity of 97% for identifying patients with high-risk features while reducing the number of recommended CMRs by 61%. The negative predictive value with this screening strategy for the absence of high-risk features in patients without ECG-DL recommendation for CMR was 99.5%. CONCLUSION: In HCM, novel ECG-DL models reliably identified patients with high-risk imaging features while offering the potential to reduce CMR testing requirements in underresourced areas.
Assuntos
Cardiomiopatia Hipertrófica , Aprendizado Profundo , Eletrocardiografia , Imagem Cinética por Ressonância Magnética , Humanos , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Imagem Cinética por Ressonância Magnética/métodos , Medição de Risco/métodos , Estudos Retrospectivos , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy have increased symptomatic burden. Mavacamten was recently approved for treatment of obstructive hypertrophic cardiomyopathy based on 2 randomized controlled trials. However, its use under real-world conditions and in diverse populations is under-studied. METHODS AND RESULTS: This was a prospective observational cohort study of patients seen at the Johns Hopkins HCM center and prescribed mavacamten for obstructive hypertrophic cardiomyopathy between July 7, 2022 and January 6, 2024. Patients were followed longitudinally, with serial echocardiography and clinical evaluation as mandated by the risk evaluation and mitigation strategy program. Sixty-six patients received mavacamten (mean age 59 years, 47% male, 29% non-White [Black, Hispanic/Latino, Asian, Native Hawaiian or Pacific Islander], 47% obese). Before treatment, all patients had New York Heart Association class II (51.5%) or III (48.5%) heart failure symptoms. Initial maximum peak left ventricular outflow tract gradient was 107±46 mm Hg. Median treatment duration was 9 months. For patients on mavacamten after ≥6 months (n=43), symptoms improved by ≥1 New York Heart Association class in 72% of patients, and peak left ventricular outflow tract gradient decreased by 80±46 mm Hg, eliminating hemodynamically significant left ventricular outflow tract obstruction in 79.1% of patients. Mavacamten was temporarily discontinued in 3 patients due to left ventricular ejection fraction decrease <50%. There were no medication-related adverse events. Effectiveness and safety were similar between White and non-White patients, but symptomatic relief was attenuated in patients with body-mass index ≥35 kg/m2. CONCLUSIONS: Mavacamten was effective and safe when used under real-world conditions in a racially diverse population of symptomatic patients with obstructive hypertrophic cardiomyopathy. Patients with comorbid obesity were less likely to experience symptomatic improvement while on mavacamten.
Assuntos
Cardiomiopatia Hipertrófica , Humanos , Masculino , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/etnologia , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Resultado do Tratamento , Idoso , Benzilaminas/uso terapêutico , Uracila/análogos & derivados , Uracila/uso terapêutico , Uracila/efeitos adversos , Pirimidinonas/uso terapêutico , Pirimidinonas/efeitos adversos , Função Ventricular Esquerda/efeitos dos fármacos , Fatores de Tempo , EcocardiografiaRESUMO
BACKGROUND: People with HIV (PWH) are at greater risk for diastolic dysfunction compared with persons without HIV (PWOH). An increase in visceral adipose tissue is common among PWH and greater visceral adipose tissue is associated with diastolic dysfunction among PWOH. We investigated associations of visceral adipose tissue, subcutaneous adipose tissue, and other fat depots with subclinical diastolic dysfunction among men with and without HIV (MWH and MWOH). DESIGN: Cross-sectional analysis of MWH and MWOH in the Multicenter AIDS Cohort Study (MACS). METHODS: Participants underwent echocardiography for diastolic dysfunction assessment and CT scanning including subcutaneous, visceral, epicardial, and liver adiposity measurements. Diastolic dysfunction was defined by characterizing heart function on antiretroviral therapy0 criteria. Odds for diastolic dysfunction with each measure of adiposity were estimated using multivariable logistic regression. RESULTS: Among 403 participants (median age 57, 55% white, median BMI 26âkg/m 2 ), 25% met criteria for diastolic dysfunction and 59% MWH (82% undetectable plasma HIV RNA). Greater epicardial adipose tissue area was associated with higher odds of diastolic dysfunction [odds ratio:1.54 per SD; 95%confidence interval (CI) 1.15-2.05] when adjusted for demographics, HIV serostatus, and cardiovascular risk factors. This association did not differ by HIV serostatus and persisted when excluding MWH who were not virally suppressed. Less subcutaneous adipose tissue was associated with higher odds of diastolic dysfunction. Other adipose depots were not associated with diastolic dysfunction. CONCLUSION: Greater epicardial adipose tissue and less subcutaneous adipose tissue were associated with diastolic dysfunction, regardless of HIV serostatus and viral suppression. Greater epicardial adipose tissue and less subcutaneous adipose tissue observed among PWH may contribute to risk for heart failure with preserved ejection fraction in this population.
Assuntos
Infecções por HIV , Gordura Intra-Abdominal , Gordura Subcutânea , Humanos , Masculino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Transversais , Pessoa de Meia-Idade , Gordura Subcutânea/diagnóstico por imagem , Gordura Intra-Abdominal/diagnóstico por imagem , Pericárdio/diagnóstico por imagem , Ecocardiografia , Adulto , Tomografia Computadorizada por Raios X , IdosoRESUMO
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.
RESUMO
BACKGROUND: Left bundle-branch block (LBBB) is a marker of increased delay between septal and left ventricular (LV) lateral wall electrical activation and is a predictor of which patients will benefit from cardiac resynchronization therapy. Recent analysis has suggested that one-third of patients meeting the conventional electrocardiogram criteria for LBBB are misdiagnosed, and new strict LBBB criteria have been proposed. We tested the hypothesis that patients with strict LBBB have greater LV mechanical dyssynchrony than do patients meeting the nonstrict LBBB criteria, whereas there is no difference between patients with nonstrict LBBB and LV conduction delay with a QRS duration of 110 to 119 ms. METHODS: Sixty-four patients referred for primary prevention implantable cardioverter-defibrillators underwent 12-lead electrocardiogram and cardiac magnetic resonance myocardial tagging. The patients were classified as strict LBBB, nonstrict LBBB, or non-LBBB (nonspecific LV conduction delay with a QRS duration of 110-119 ms). The time delay between septal and lateral LV wall peak circumferential strain (septal-to-lateral wall delay) was measured by cardiac magnetic resonance. RESULTS: Patients with strict LBBB (n = 31) had a greater septal-to-lateral wall delay compared with patients with nonstrict LBBB (n = 19) (210 ± 137 ms vs 122 ± 102 ms, P = .045). There was no significant difference between nonstrict LBBB and non-LBBB (n = 14) septal-to-lateral wall delay (122 ± 102 ms vs 100 ± 86 ms, P = .51). CONCLUSIONS: Strict LBBB criteria identify patients with greater mechanical dyssynchrony compared with patients only meeting the nonstrict LBBB criteria, whereas there was no significant difference between patients with nonstrict LBBB and non-LBBB. The greater observed LV dyssynchrony may explain why patients with strict LBBB have a better response to cardiac resynchronization therapy.
Assuntos
Bloqueio de Ramo/diagnóstico , Terapia de Ressincronização Cardíaca/métodos , Eletrocardiografia , Ventrículos do Coração/patologia , Imagem Cinética por Ressonância Magnética/métodos , Contração Miocárdica/fisiologia , Disfunção Ventricular Esquerda/diagnóstico , Bloqueio de Ramo/fisiopatologia , Bloqueio de Ramo/terapia , Diagnóstico Diferencial , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
INTRODUCTION: Outcome of cardiac resynchronization therapy is severely worsened by myocardial scar at the left ventricular (LV) pacing site. We aimed to describe the diagnostic performance of electrocardiographic (ECG) criteria based on the Selvester QRS scoring system, first in localizing myocardial scar and second in screening for any non-septal scar in patients with strictly defined LBBB. METHODS AND RESULTS: In 39 cardiomyopathy patients with LBBB, 17 with scar, 22 without scar, late gadolinium-enhancement cardiac magnetic resonance images (CMR-LGE) and 12-lead ECGs were analyzed for scar presence in 5 LV wall segments. The ECG criteria with the best diagnostic performance in detecting scar in each segment and in the four non-septal segments together were identified. Criteria for detecting non-septal scar had 75% (95% CI: 51%-90%) sensitivity, 95% (78%-99%) specificity, 92% (67%-99%) positive predictive value and 84% (65%-94%) negative predictive value. For each individual wall segment, 40%-60% sensitivities and 77%-100% specificities were found. CONCLUSIONS: The 12-lead ECG can convey information about scar presence and location in this population of cardiomyopathy patients with LBBB. ECG screening criteria for scar in potential CRT LV pacing sites were identified. Further exploration is required to determine the clinical utility of the 12-lead ECG in combination with other imaging modalities to screen for scar in potential LV pacing sites in CRT candidates.