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1.
J Cardiovasc Electrophysiol ; 34(5): 1164-1174, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36934383

RESUMO

BACKGROUND: Structural changes in the left atrium (LA) modestly predict outcomes in patients undergoing catheter ablation for atrial fibrillation (AF). Machine learning (ML) is a promising approach to personalize AF management strategies and improve predictive risk models after catheter ablation by integrating atrial geometry from cardiac computed tomography (CT) scans and patient-specific clinical data. We hypothesized that ML approaches based on a patient's specific data can identify responders to AF ablation. METHODS: Consecutive patients undergoing AF ablation, who had preprocedural CT scans, demographics, and 1-year follow-up data, were included in the study for a retrospective analysis. The inputs of models were CT-derived morphological features from left atrial segmentation (including the shape, volume of the LA, LA appendage, and pulmonary vein ostia) along with deep features learned directly from raw CT images, and clinical data. These were merged intelligently in a framework to learn their individual importance and produce the optimal classification. RESULTS: Three hundred twenty-one patients (64.2 ± 10.6 years, 69% male, 40% paroxysmal AF) were analyzed. Post 10-fold nested cross-validation, the model trained to intelligently merge and learn appropriate weights for clinical, morphological, and imaging data (AUC 0.821) outperformed those trained solely on clinical data (AUC 0.626), morphological (AUC 0.659), or imaging data (AUC 0.764). CONCLUSION: Our ML approach provides an end-to-end automated technique to predict AF ablation outcomes using deep learning from CT images, derived structural properties of LA, augmented by incorporation of clinical data in a merged ML framework. This can help develop personalized strategies for patient selection in invasive management of AF.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Masculino , Feminino , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Tomografia Computadorizada por Raios X/métodos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Aprendizado de Máquina , Recidiva , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia
2.
Circ Res ; 128(2): 172-184, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33167779

RESUMO

RATIONALE: Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside. OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes. METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF. CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.


Assuntos
Cardiomiopatias/diagnóstico , Morte Súbita Cardíaca/etiologia , Diagnóstico por Computador , Técnicas Eletrofisiológicas Cardíacas , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , Máquina de Vetores de Suporte , Taquicardia Ventricular/diagnóstico , Fibrilação Ventricular/diagnóstico , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/etiologia , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/fisiopatologia
3.
Europace ; 25(3): 969-977, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36636951

RESUMO

AIMS: Remote monitoring (RM) for implantable cardioverter-defibrillators (ICDs) is advocated for the potential of early detection of disease progression and device dysfunction. While studies have examined the effect of RM on clinical outcomes in carefully selected populations of heart failure patients implanted with ICDs from a single vendor, there is a paucity of data in real-world patients. We aimed to assess the long-term effect of RM in a representative ICD population using real-world data. METHODS AND RESULTS: This is an observational retrospective longitudinal study of 1004 patients implanted with an ICD or cardiac resynchronization therapy device (CRT-D) from all device vendors between 2010 and 2021. Patients started on RM (N = 403) within 90 days following de novo device implantation and yearly in-office visits were compared with patients with only bi-yearly in-office follow-up (non-RM, N = 601). In a propensity score matched cohort of 430 patients (mean age 61.4 ± 14.3 years, 26.7% female), all-cause mortality at 4-year was 12.6% in the RM and 27.7% in the non-RM group [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.32-0.82; P = 0.005]. No difference in inappropriate ICD-therapy (HR 1.90, 95% CI 0.86-4.21; P = 0.122) was observed. The risk of appropriate ICD-therapy (HR 1.71, 95% CI 1.07-2.74; P = 0.026) was higher in the RM group. CONCLUSION: Remote monitoring was associated with a reduction in long-term all-cause and cardiac mortality compared with traditional office visits in a real-world ICD population.


Assuntos
Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Retrospectivos , Estudos Longitudinais , Dispositivos de Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Terapia de Ressincronização Cardíaca/efeitos adversos , Resultado do Tratamento
4.
Europace ; 25(5)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-36932716

RESUMO

AIMS: There is a clinical spectrum for atrial tachyarrhythmias wherein most patients with atrial tachycardia (AT) and some with atrial fibrillation (AF) respond to ablation, while others do not. It is undefined if this clinical spectrum has pathophysiological signatures. This study aims to test the hypothesis that the size of spatial regions showing repetitive synchronized electrogram (EGM) shapes over time reveals a spectrum from AT, to AF patients who respond acutely to ablation, to AF patients without acute response. METHODS AND RESULTS: We studied n = 160 patients (35% women, 65.0 ± 10.4 years) of whom (i) n = 75 had AF terminated by ablation propensity matched to (ii) n = 75 without AF termination and (iii) n = 10 with AT. All patients had mapping by 64-pole baskets to identify areas of repetitive activity (REACT) to correlate unipolar EGMs in shape over time. Synchronized regions (REACT) were largest in AT, smaller in AF termination, and smallest in non-termination cohorts (0.63 ± 0.15, 0.37 ± 0.22, and 0.22 ± 0.18, P < 0.001). Area under the curve for predicting AF termination in hold-out cohorts was 0.72 ± 0.03. Simulations showed that lower REACT represented greater variability in clinical EGM timing and shape. Unsupervised machine learning of REACT and extensive (50) clinical variables yielded four clusters of increasing risk for AF termination (P < 0.01, χ2), which were more predictive than clinical profiles alone (P < 0.001). CONCLUSION: The area of synchronized EGMs within the atrium reveals a spectrum of clinical response in atrial tachyarrhythmias. These fundamental EGM properties, which do not reflect any predetermined mechanism or mapping technology, predict outcome and offer a platform to compare mapping tools and mechanisms between AF patient groups.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Feminino , Masculino , Ablação por Cateter/métodos , Átrios do Coração , Fibrilação Atrial/cirurgia , Taquicardia
5.
Europace ; 25(9)2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37712675

RESUMO

AIMS: Left ventricular ejection fraction (LVEF) is suboptimal as a sole marker for predicting sudden cardiac death (SCD). Machine learning (ML) provides new opportunities for personalized predictions using complex, multimodal data. This study aimed to determine if risk stratification for implantable cardioverter-defibrillator (ICD) implantation can be improved by ML models that combine clinical variables with 12-lead electrocardiograms (ECG) time-series features. METHODS AND RESULTS: A multicentre study of 1010 patients (64.9 ± 10.8 years, 26.8% female) with ischaemic, dilated, or non-ischaemic cardiomyopathy, and LVEF ≤ 35% implanted with an ICD between 2007 and 2021 for primary prevention of SCD in two academic hospitals was performed. For each patient, a raw 12-lead, 10-s ECG was obtained within 90 days before ICD implantation, and clinical details were collected. Supervised ML models were trained and validated on a development cohort (n = 550) from Hospital A to predict ICD non-arrhythmic mortality at three-year follow-up (i.e. mortality without prior appropriate ICD-therapy). Model performance was evaluated on an external patient cohort from Hospital B (n = 460). At three-year follow-up, 16.0% of patients had died, with 72.8% meeting criteria for non-arrhythmic mortality. Extreme gradient boosting models identified patients with non-arrhythmic mortality with an area under the receiver operating characteristic curve (AUROC) of 0.90 [95% confidence intervals (CI) 0.80-1.00] during internal validation. In the external cohort, the AUROC was 0.79 (95% CI 0.75-0.84). CONCLUSIONS: ML models combining ECG time-series features and clinical variables were able to predict non-arrhythmic mortality within three years after device implantation in a primary prevention population, with robust performance in an independent cohort.


Assuntos
Desfibriladores Implantáveis , Humanos , Feminino , Masculino , Seleção de Pacientes , Volume Sistólico , Função Ventricular Esquerda , Aprendizado de Máquina , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Prevenção Primária
6.
Europace ; 22(6): 897-905, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243508

RESUMO

AIMS: Persistent atrial fibrillation (AF) has been explained by multiple mechanisms which, while they conflict, all agree that more disorganized AF is more difficult to treat than organized AF. We hypothesized that persistent AF consists of interacting organized areas which may enlarge, shrink or coalesce, and that patients whose AF areas enlarge by ablation are more likely to respond to therapy. METHODS AND RESULTS: We mapped vectorial propagation in persistent AF using wavefront fields (WFF), constructed from raw unipolar electrograms at 64-pole basket catheters, during ablation until termination (Group 1, N = 20 patients) or cardioversion (Group 2, N = 20 patients). Wavefront field mapping of patients (age 61.1 ± 13.2 years, left atrium 47.1 ± 6.9 mm) at baseline showed 4.6 ± 1.0 organized areas, each separated by disorganization. Ablation of sites that led to termination controlled larger organized area than competing sites (44.1 ± 11.1% vs. 22.4 ± 7.0%, P < 0.001). In Group 1, ablation progressively enlarged unablated areas (rising from 32.2 ± 15.7% to 44.1 ± 11.1% of mapped atrium, P < 0.0001). In Group 2, organized areas did not enlarge but contracted during ablation (23.6 ± 6.3% to 15.2 ± 5.6%, P < 0.0001). CONCLUSION: Mapping wavefront vectors in persistent AF revealed competing organized areas. Ablation that progressively enlarged remaining areas was acutely successful, and sites where ablation terminated AF were surrounded by large organized areas. Patients in whom large organized areas did not emerge during ablation did not exhibit AF termination. Further studies should define how fibrillatory activity is organized within such areas and whether this approach can guide ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Cardioversão Elétrica , Átrios do Coração/cirurgia , Humanos , Pessoa de Meia-Idade
7.
J Card Fail ; 25(8): 654-665, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128242

RESUMO

BACKGROUND: Worsening renal function (WRF) during acute heart failure (AHF) occurs frequently and has been associated with adverse outcomes, though this association has been questioned. WRF is now evaluated by function and injury. We evaluated whether urine neutrophil gelatinase-associated lipocalin (uNGAL) is superior to creatinine for prediction and prognosis of WRF in patients with AHF. METHODS AND RESULTS: We performed a multicenter, international, prospective cohort of patients with AHF requiring IV diuretics. The primary outcome was whether uNGAL predicted development of WRF, defined as a sustained increase in creatinine of 0.5 mg/dL or ≥50% above first value or initiation of renal replacement therapy, within the first 5 days. The main secondary outcome was a composite of in-hospital adverse events. We enrolled 927 patients (mean 68.5 years of age, 62% men). The primary outcome occurred in 72 patients (7.8%). The first, peak and the ratio of uNGAL to urine creatinine (area under curves (AUC) ≤ 0.613) did not have diagnostic utility over the first creatinine (AUC 0.662). There were 235 adverse events in 144 patients. uNGAL did not predict (AUCs ≤ 0.647) adverse clinical events better than creatinine (AUC 0.695). CONCLUSIONS: uNGAL was not superior to creatinine for predicting WRF or adverse in-hospital outcomes and cannot be recommended for WRF in AHF.


Assuntos
Injúria Renal Aguda/urina , Insuficiência Cardíaca/urina , Hospitalização/tendências , Internacionalidade , Rim/fisiologia , Lipocalina-2/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Testes de Função Renal/tendências , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Circulation ; 135(3): 251-263, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27831500

RESUMO

BACKGROUND: The relationship of LPA single nucleotide polymorphisms (SNPs), apolipoprotein(a) isoforms, and lipoprotein(a) [Lp(a)] levels with major adverse cardiovascular events (MACE) in different ethnic groups is not well known. METHODS: LPA SNPs, apolipoprotein(a) isoforms, Lp(a), and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) levels were measured in 1792 black, 1030 white, and 597 Hispanic subjects enrolled in the Dallas Heart Study. Their interdependent relationships and prospective association with MACE after median 9.5-year follow-up were determined. RESULTS: LPA SNP rs3798220 was most prevalent in Hispanics (42.38%), rs10455872 in whites (14.27%), and rs9457951 in blacks (32.92%). The correlation of each of these SNPs with the major apolipoprotein(a) isoform size was highly variable and in different directions among ethnic groups. In the entire cohort, Cox regression analysis with multivariable adjustment revealed that quartiles 4 of Lp(a) and OxPL-apoB were associated with hazard ratios (95% confidence interval) for time to MACE of 2.35 (1.50-3.69, P<0.001) and 1.89 (1.26-2.84, P=0.003), respectively, versus quartile 1. Addition of the major apolipoprotein(a) isoform and the 3 LPA SNPs to these models attenuated the risk, but significance was maintained for both Lp(a) and OxPL-apoB. Evaluating time to MACE in specific ethnic groups, Lp(a) was a positive predictor and the size of the major apolipoprotein(a) isoform was an inverse predictor in blacks, the size of the major apolipoprotein(a) isoform was an inverse predictor in whites, and OxPL-apoB was a positive predictor in Hispanics. CONCLUSIONS: The prevalence and association of LPA SNPs with size of apolipoprotein(a) isoforms, Lp(a), and OxPL-apoB levels are highly variable and ethnicity-specific. The relationship to MACE is best explained by elevated plasma Lp(a) or OxPL-apoB levels, despite significant ethnic differences in LPA genetic markers.


Assuntos
Doenças Cardiovasculares/sangue , Lipoproteína(a)/sangue , Polimorfismo de Nucleotídeo Único/genética , Adulto , Etnicidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
9.
J Card Fail ; 24(5): 303-309, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28918108

RESUMO

BACKGROUND: Recent studies have described the entity of heart failure with recovered ejection fraction (HFrecEF), but population-specific studies remain lacking. The aim of this study was to characterize patients enrolled in the African-American Heart Failure Trial (A-HeFT) who had significant improvement in their ejection fraction (EF) during the 1st 6 months of follow-up. METHODS AND RESULTS: Subjects with HFrecEF (improvement in EF from <35% to >40% in 6 months; n = 59) were compared with 259 subjects with heart failure and persistently reduced EF (HFrEF), defined as EF ≤40% at 6-month follow-up. The effects of improvement in EF on all-cause mortality and 1st and all hospitalizations were analyzed. Compared with HFrEF, subjects with HFrecEF had a nonsignificant trend toward lower mortality (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.02-1.15; P = .068), fewer 1st HF hospitalizations (HR 0.22, 95% CI 0.07-0.71; P = .011), fewer recurrent HF hospitalizations (HR 0.13, 95% CI 0.05-0.37; P <.001), similar 1st all-cause hospitalizations (HR 0.67, 95% CI 0.39-1.15; P = .150), and fewer recurrent all-cause hospitalizations (HR 0.41, 95% CI 0.24-0.68; P <.001). CONCLUSIONS: These data confirm that, as in other populations, a small subgroup of black patients receiving standard care improve their EF with favorable outcomes. Further studies are required to determine whether myocardial recovery is permanent and the best management strategies in such patients.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Negro ou Afro-Americano , Insuficiência Cardíaca/tratamento farmacológico , Hidralazina/uso terapêutico , Dinitrato de Isossorbida/uso terapêutico , Recuperação de Função Fisiológica , Volume Sistólico/fisiologia , Causas de Morte/tendências , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Vasodilatadores/uso terapêutico , Função Ventricular Esquerda/fisiologia
10.
Arterioscler Thromb Vasc Biol ; 37(6): 1213-1221, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28473443

RESUMO

OBJECTIVE: Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups. APPROACH AND RESULTS: IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100-immune complexes were measured in 3509 individuals (1814 blacks, 1031 whites, 589 Hispanics, and 85 no race identifier) from the Dallas Heart Study with median 10.5-year follow-up. Coronary artery calcium score, abdominal aortic plaque by magnetic resonance imaging, and MACE were quantified. IgG MDA-LDL and IgG and IgM apolipoprotein B-100-immune complexes were significantly different between groups, with blacks having the highest levels of IgG MDA-LDL and IgG apolipoprotein B-100-immune complexes and Hispanics having the highest levels of IgM apolipoprotein B-100-immune complexes (P<0.001 for all). IgGs tended to be higher and IgMs lower with age for all markers. In multivariable-adjusted binary logistic regression analysis, a doubling of IgG MDA-LDL levels was associated with prevalent coronary artery calcium score >10 Agatston units (odds ratio [95% confidence interval], 1.21 [1.07-1.36]; P=0.002). Multivariable-adjusted Cox regression analysis revealed that IgG MDA-LDL was independently associated with time to incident MACE in the entire group (hazard ratio [95% confidence interval], 1.76 [1.16-2.72]; P=0.009 for fourth versus first quartile). This effect was particularly prominent in black subjects (hazard ratio [95% confidence interval], 2.52 [1.39-4.57]; P=0.002). CONCLUSIONS: Autoantibodies to oxidized lipoproteins and immune complexes with apoB-100 lipoproteins vary significantly by sex, age, and ethnicity. Higher baseline IgG MDA-LDL titers independently associate with new MACE. These findings may contribute to the understanding of differences in ethnic-specific MACE events.


Assuntos
Doenças da Aorta/imunologia , Apolipoproteína B-100/imunologia , Aterosclerose/imunologia , Autoanticorpos/sangue , Autoimunidade , Doença da Artéria Coronariana/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lipoproteínas LDL/imunologia , Malondialdeído/análogos & derivados , Adolescente , Adulto , Negro ou Afro-Americano , Doenças da Aorta/sangue , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etnologia , Doenças Assintomáticas , Aterosclerose/sangue , Aterosclerose/diagnóstico por imagem , Aterosclerose/etnologia , Causas de Morte , Distribuição de Qui-Quadrado , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etnologia , Feminino , Disparidades nos Níveis de Saúde , Hispânico ou Latino , Humanos , Modelos Logísticos , Masculino , Malondialdeído/imunologia , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores Sexuais , Texas/epidemiologia , População Branca , Adulto Jovem
11.
Am J Emerg Med ; 35(2): 274-280, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27847253

RESUMO

BACKGROUND: Copeptin is a marker of endogenous stress including early myocardial infarction(MI) and has value in early rule out of MI when used with cardiac troponin I(cTnI). OBJECTIVES: The goal of this study was to demonstrate that patients with a normal electrocardiogram and cTnI<0.040µg/l and copeptin<14pmol/l at presentation and after 2 h may be candidates for early discharge with outpatient follow-up potentially including stress testing. METHODS: This study uses data from the CHOPIN trial which enrolled 2071 patients with acute chest pain. Of those, 475 patients with normal electrocardiogram and normal cTnI(<0.040µg/l) and copeptin<14pmol/l at presentation and after 2 h were considered "low risk" and selected for further analysis. RESULTS: None of the 475 "low risk" patients were diagnosed with MI during the 180day follow-up period (including presentation). The negative predictive value of this strategy was 100% (95% confidence interval(CI):99.2%-100.0%). Furthermore no one died during follow up. 287 (60.4%) patients in the low risk group were hospitalized. In the "low risk" group, the only difference in outcomes (MI, death, revascularization, cardiac rehospitalization) was those hospitalized underwent revascularization more often (6.3%[95%CI:3.8%-9.7%] versus 0.5%[95%CI:0.0%-2.9%], p=.002). The hospitalized patients were tested significantly more via stress testing or angiogram (68.6%[95%CI:62.9%-74.0%] vs 22.9%[95%CI:17.1%-29.6%], p<.001). Those tested had less cardiac rehospitalizations during follow-up (1.7% vs 5.1%, p=.040). CONCLUSIONS: In conclusion, patients with a normal electrocardiogram, troponin and copeptin at presentation and after 2 h are at low risk for MI and death over 180days. These low risk patients may be candidates for early outpatient testing and cardiology follow-up thereby reducing hospitalization.


Assuntos
Dor no Peito/diagnóstico , Glicopeptídeos/sangue , Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Biomarcadores/sangue , Dor no Peito/sangue , Dor no Peito/etiologia , Análise Custo-Benefício , Diagnóstico Precoce , Eletrocardiografia , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/normas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Infarto do Miocárdio/sangue , Admissão do Paciente/economia , Admissão do Paciente/normas , Admissão do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco/economia , Medição de Risco/métodos
12.
J Cardiovasc Electrophysiol ; 27(6): 661-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26918971

RESUMO

INTRODUCTION: Recurrent atrial fibrillation (AF) after ablation is associated with reconnection of initially isolated pulmonary vein (PV) trigger sites. Substrates are often targeted in addition to PVI, but it is unclear how substrates progress over time. We studied if substrates in recurrent AF are conserved or have developed de novo from pre-ablation AF. METHODS AND RESULTS: Of 137 patients undergoing Focal Impulse and Rotor Mapping (FIRM) at their index procedure for AF, 29 consecutive patients (60 ± 8 years, 79% persistent) recurred and were also mapped at repeat procedure (21 ± 20 months later) using carefully placed 64-pole baskets and RhythmView(TM) (Topera, Menlo Park, CA, USA) to identify AF sources and disorganized zones. Compared to index AF, recurrent AF had a longer cycle length (177 ± 21 vs. 167 ± 19 milliseconds, P = 0.01). All patients (100%) had 1 or more conserved AF rotors between procedures with surrounding disorganization. The number of sources was similar for recurrent AF post-PVI versus index AF (3.2 ± 1.4 vs. 3.1 ± 1.0, P = 0.79), but was lower for recurrent AF after FIRM+PVI versus index AF (4.4 ± 1.4 vs. 2.9 ± 1.7, P = 0.03). Overall, 81% (61/75) of AF sources lay in conserved regions, while 19% (14/75) were detected de novo. CONCLUSION: Electrical propagation patterns for recurrent AF after unsuccessful ablation are similar in individual patients to their index AF. These data support temporospatial stability of AF substrates over 1-2 years. Trials should determine the relative benefit of adding substrate mapping and ablation to PVI for recurrent AF.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Sistema de Condução Cardíaco/cirurgia , Veias Pulmonares/cirurgia , Potenciais de Ação , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/fisiopatologia , Recidiva , Falha de Tratamento
13.
J Card Fail ; 22(4): 283-93, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26433086

RESUMO

BACKGROUND: Heart failure is a common cause of hospitalization and can be divided into types with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). In this subanalysis of the HABIT (Heart Failure Assessment With BNP in the Home) trial, we examined the differences between home B-type natriuretic peptide (BNP) testing and weight monitoring in patients with HFpEF and with HFrEF before decompensation. METHODS AND RESULTS: This was a retrospective review of patients with HFpEF and HFrEF from the HABIT trial. The HFpEF patients compared with HFrEF patients were older and more obese and had lower baseline BNP values. Intra-individual BNP dispersion (spread of distribution over time) was greater in HFpEF than in HFrEF owing to rapid fluctuations (within 3 days). Slowly varying changes in BNP (estimated by a moving average) were equally predictive of ADHF risk in both HFpEF and HFrEF. However, in HFpEF, a rapid rise in BNP >200 pg/mL within 3 days was associated with an increased risk of acute decompensated heart failure (ADHF; hazard ratio 4.0), whereas a similar association was not observed in HFrEF. Weight gain ≥5 lb in 3 days had a high specificity but low sensitivity for ADHF in both HFpEF and HFrEF, whereas a lower threshold of ≥2 lb weight gain over 3 days in patients with HFpEF (but not HFrEF) was a moderately sensitive cutoff associated with decompensation (60% sensitivity). CONCLUSIONS: Patients with HFpEF and HFrEF have variations in their BNP and weight before decompensation. The rapid time scale behaves differently between the groups. In those with HFpEF, a 3-day period characterized by ≥2 lb weight gain and/or >200 pg/mL BNP rise was significantly associated with decompensation. Future prospective studies investigating different weight and BNP cutoffs for home monitoring of HFpEF and HFrEF patients should be performed to fully learn the value of BNP changes before clinical deompensation.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Serviços de Assistência Domiciliar , Peptídeo Natriurético Encefálico/sangue , Volume Sistólico/fisiologia , Aumento de Peso/fisiologia , Idoso , Biomarcadores/sangue , Peso Corporal/fisiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos
14.
Am Heart J ; 170(6): 1170-83, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26678639

RESUMO

BACKGROUND: N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (TnT) predict cardiovascular disease (CVD) risk in a variety of populations. Whether their predictive value varies by ethnicity is unknown. We sought to determine whether NT-proBNP and TnT improve prediction of incident coronary heart disease (CHD) and CVD, independent of CVD risk factors, in a multiethnic population; whether NT-proBNP improves prediction compared with the Framingham Risk Score or the Pooled Cohort Risk Equation; and whether a second NT-proBNP further improves prediction. METHODS: Both NT-proBNP and TnT were measured in 5,592 MESA white, black, Hispanic, and Chinese participants (60% nonwhite; mean age 62.3 ± 10.3 years) in 2000 to 2002 and 2004 to 2005. We evaluated adjusted risk of incident CHD and CVD based on baseline and change in biomarker concentration. RESULTS: Participants were followed up through 2011 and incurred 370 CVD events (232 CHD). Concentrations of NT-proBNP and TnT varied by ethnicity. Both NT-proBNP and TnT were associated with an increased risk of events (adjusted hazard ratio [HR] for CHD [95% CI] for fifth quintile vs other 4 quintiles of NT-proBNP, 2.03 [1.50-2.76]; HR for CHD for detectable vs undetectable TnT, 3.95 [2.29-6.81]). N-terminal-pro-B-type natriuretic peptide improved risk prediction and classification compared with the Framingham Risk Score and the Pooled Cohort Risk Equation. Change in NT-proBNP was independently associated with events (HR for CHD per unit increase in ΔlogNT-proBNP, 1.95 [1.16-3.26]). None of the observed associations varied by ethnicity. CONCLUSIONS: Both NT-proBNP and TnT are predictors of incident CHD, independent of established risk factors and ethnicity, in a multiethnic population without known CVD. Change in NT-proBNP may add additional prognostic information.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina T/sangue , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/etnologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco/métodos , Fatores de Risco , Estados Unidos/epidemiologia
15.
Hepatology ; 59(3): 1052-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24115225

RESUMO

UNLABELLED: The rationale for screening inflammatory serum biomarkers of the hepatic vein pressure gradient (HVPG) is based on the fact that portal hypertension is pathogenically related to liver injury and fibrosis, and that in turn these are associated with the activation of inflammatory pathways. This was a nested cohort study in the setting of a randomized, clinical trial to assess the development of gastroesophageal varices (GEV) (N Engl J Med 2005;353:2254). Patients had cirrhosis and portal hypertension but did not have GEV. A total of 90 patients who had baseline day-1 sera available were enrolled in the present study. The objective of this study was to determine whether inflammatory biomarkers in conjunction with clinical parameters could be used to develop a predictive paradigm for HVPG. The correlations between HVPG and interleukin (IL)-1ß (P=0.0052); IL-1R-α (P=0.0085); Fas-R (P=0.0354), and serum VCAM-1 (P=0.0007) were highly significant. By using multivariate logistic regression analysis and selected parameters (transforming growth factor beta [TGFß]; heat shock protein [HSP]-70; at-risk alcohol use; and Child class B) we could exclude HVPG ≥ 12 mmHg with 86% accuracy (95% confidence interval [CI]: 67.78 to 96.16%) and the sensitivity was 87.01% (95% CI: 69.68 to 96.34%). Therefore, the composite test could identify 86% of compensated cirrhosis patients with HVPG below 12 mmHg and prevent unnecessary esophagogastroduodenoscopy with its associated morbidity and costs in these patients. Our diagnostic test was not efficient in predicting HVPG ≥ 12 mmHg. CONCLUSION: A blood test for HVPG could be performed in cirrhosis patients to prevent unnecessary esophagogastroduodenoscopy.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Varizes Esofágicas e Gástricas/prevenção & controle , Hipertensão Portal/imunologia , Hipertensão Portal/metabolismo , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Varizes Esofágicas e Gástricas/imunologia , Varizes Esofágicas e Gástricas/metabolismo , Feminino , Veias Hepáticas/fisiopatologia , Hepatite Crônica/imunologia , Hepatite Crônica/metabolismo , Hepatite Crônica/fisiopatologia , Humanos , Hipertensão Portal/fisiopatologia , Cirrose Hepática/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta/fisiologia , Estudos Prospectivos , Sensibilidade e Especificidade
16.
J Cardiovasc Electrophysiol ; 26(10): 1117-26, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26179310

RESUMO

INTRODUCTION: Recent work has suggested a role for organized sources in sustaining ventricular fibrillation (VF). We assessed whether ablation of rotor substrate could modulate VF inducibility in canines, and used this proof-of-concept as a foundation to suppress antiarrhythmic drug-refractory clinical VF in a patient with structural heart disease. METHODS AND RESULTS: In 9 dogs, we introduced 64-electrode basket catheters into one or both ventricles, used rapid pacing at a recorded induction threshold to initiate VF, and then defibrillated after 18±8 seconds. Endocardial rotor sites were identified from basket recordings using phase mapping, and ablation was performed at nonrotor (sham) locations (7 ± 2 minutes) and then at rotor sites (8 ± 2 minutes, P = 0.10 vs. sham); the induction threshold was remeasured after each. Sham ablation did not alter canine VF induction threshold (preablation 150 ± 16 milliseconds, postablation 144 ± 16 milliseconds, P = 0.54). However, rotor site ablation rendered VF noninducible in 6/9 animals (P = 0.041), and increased VF induction threshold in the remaining 3. Clinical proof-of-concept was performed in a patient with repetitive ICD shocks due to VF refractory to antiarrhythmic drugs. Following biventricular basket insertion, VF was induced and then defibrillated. Mapping identified 4 rotors localized at borderzone tissue, and rotor site ablation (6.3 ± 1.5 minutes/site) rendered VF noninducible. The VF burden fell from 7 ICD shocks in 8 months preablation to zero ICD therapies at 1 year, without antiarrhythmic medications. CONCLUSIONS: Targeted rotor substrate ablation suppressed VF in an experimental model and a patient with refractory VF. Further studies are warranted on the efficacy of VF source modulation.


Assuntos
Mapeamento Potencial de Superfície Corporal/métodos , Sistema de Condução Cardíaco/cirurgia , Cirurgia Assistida por Computador/métodos , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/cirurgia , Animais , Cães , Estudos de Viabilidade , Projetos Piloto , Resultado do Tratamento
17.
Clin Chem Lab Med ; 53(3): 507-13, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25252752

RESUMO

BACKGROUND: Our aim was to determine if, in elderly heart failure (eHF) patients, serial B-type natriuretic peptide (BNP) assessments obtained during follow-up after hospital discharge could have prognostic utility for death and rehospitalizations. In eHF patients, BNP assessment at hospital discharge has been demonstrated to have a high prognostic value; however, its predictive role for future cardiovascular events in eHF patients, when assessed in the period after discharge, both for the correct timing and cut-off levels, has not been completely elucidated. METHODS: This study is a monocentric subanalysis of the Italian RED (Rapid Emergency Department) study. We studied 180 consecutive patients admitted for acute HF through serial BNP assessments: at hospital arrival; at discharge; and at 30, 90, and 180 days follow-up outpatient visit. RESULTS: Both a BNP >400 pg/mL at 30 days after discharge and the percentage variation of BNP from discharge to 30 days (Δ%BNP), compared with a BNP at discharge >400 pg/mL, showed a higher area under the curve (AUC) and odds ratio (OR) in predicting events [AUC=0.842, p<0.0001; OR 7.9 (3.3-19.0), p<0.001 for 30 days BNP and AUC=0.851, p<0.0001; OR 9.5 (4.065-22.572), p<0.0001 for Δ%BNP compared with AUC=0.638, p<0.002; OR 2.4 (1.1-5.3), p=0.032 for BNP at discharge]. CONCLUSIONS: In patients at a high risk for future events, BNP levels assessed 30 days after hospital discharge in the absence of signs and symptoms could be predictive of subsequent hospitalization and death. These patients should be considered for closer monitoring and treatment adjustment.


Assuntos
Serviço Hospitalar de Emergência , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Hospitalização/estatística & dados numéricos , Peptídeo Natriurético Encefálico/análise , Alta do Paciente , Idoso , Feminino , Humanos , Itália , Masculino , Valor Preditivo dos Testes , Curva ROC , Medição de Risco , Análise de Sobrevida , Fatores de Tempo
18.
Clin Nephrol ; 83(1): 29-35, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25512100

RESUMO

AIMS: Acute kidney injury (AKI) occurs in up to 40% of patients undergoing cardiac surgery. Proenkephalin A 119-159 (pro-ENK) is a novel, stable surrogate biomarker for enkephalins, endogenous opioids involved in various physiological processes, including neurohormonal stress. MATERIAL AND METHODS: 92 patients undergoing cardiac surgery at the Veterans Affairs San Diego Healthcare System had a post-hoc analysis performed to determine the ability of pro-ENK to predict AKI as well as to compare it against other risk factors for development of AKI. RESULTS: Of 92 patients, 20 patients developed AKI post-operatively. Pro-ENK levels were significantly elevated in patients who develop AKI. Log pro-ENK value pre-operatively has an odds ratio of 23.8 (p = 0.011, 95% CI = 2 - 270) in its association with AKI. Pro-ENK performs similarly to baseline creatinine in its ability to predict post-operative AKI. Importantly, pro-ENK has a strong positive correlation with creatinine (r = 0.806). Additionally, changes in pro-ENK level, from pre-operatively to 12 hours post-operatively have greatest area under curve by ROC analysis for AKI after post-operative day 1. CONCLUSION: Pro-ENK is associated with prediction of AKI in patients undergoing cardiac surgery. Pro-ENK likely has decreased clearance in the setting of AKI. However, future studies analyzing this novel biomarker should be considered to further elucidate its clinical utility and to better understand mechanisms of renal injury.


Assuntos
Injúria Renal Aguda/sangue , Procedimentos Cirúrgicos Cardíacos/métodos , Encefalinas/sangue , Precursores de Proteínas/sangue , Injúria Renal Aguda/diagnóstico , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de Risco
19.
Gastroenterology ; 145(3): 574-82.e1, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23727264

RESUMO

BACKGROUND & AIMS: Obeticholic acid (OCA; INT-747, 6α-ethyl-chenodeoxycholic acid) is a semisynthetic derivative of the primary human bile acid chenodeoxycholic acid, the natural agonist of the farnesoid X receptor, which is a nuclear hormone receptor that regulates glucose and lipid metabolism. In animal models, OCA decreases insulin resistance and hepatic steatosis. METHODS: We performed a double-blind, placebo-controlled, proof-of-concept study to evaluate the effects of OCA on insulin sensitivity in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus. Patients were randomly assigned to groups given placebo (n = 23), 25 mg OCA (n = 20), or 50 mg OCA (n = 21) once daily for 6 weeks. A 2-stage hyperinsulinemic-euglycemic insulin clamp was used to measure insulin sensitivity before and after the 6-week treatment period. We also measured levels of liver enzymes, lipid analytes, fibroblast growth factor 19, 7α-hydroxy-4-cholesten-3-one (a BA precursor), endogenous bile acids, and markers of liver fibrosis. RESULTS: When patients were given a low-dose insulin infusion, insulin sensitivity increased by 28.0% from baseline in the group treated with 25 mg OCA (P = .019) and 20.1% from baseline in the group treated with 50 mg OCA (P = .060). Insulin sensitivity increased by 24.5% (P = .011) in combined OCA groups, whereas it decreased by 5.5% in the placebo group. A similar pattern was observed in patients given a high-dose insulin infusion. The OCA groups had significant reductions in levels of γ-glutamyltransferase and alanine aminotransferase and dose-related weight loss. They also had increased serum levels of low-density lipoprotein cholesterol and fibroblast growth factor 19, associated with decreased levels of 7α-hydroxy-4-cholesten-3-one and endogenous bile acids, indicating activation of farnesoid X receptor. Markers of liver fibrosis decreased significantly in the group treated with 25 mg OCA. Adverse experiences were similar among groups. CONCLUSIONS: In this phase 2 trial, administration of 25 or 50 mg OCA for 6 weeks was well tolerated, increased insulin sensitivity, and reduced markers of liver inflammation and fibrosis in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Longer and larger studies are warranted. ClinicalTrials.gov, Number: NCT00501592.


Assuntos
Ácido Quenodesoxicólico/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Receptores Citoplasmáticos e Nucleares/agonistas , Adulto , Idoso , Biomarcadores/sangue , Ácido Quenodesoxicólico/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Resultado do Tratamento
20.
Am Heart J ; 167(5): 674-82.e1, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24766977

RESUMO

BACKGROUND: Galectin-3 is a marker of myocardial fibrosis that has been implicated in the pathophysiologic pathway of fibrosis; its association with all-cause and cardiovascular disease (CVD) mortality in a community-based cohort free of baseline CVD has not been reported. Our aim was to determine the association between galectin-3 levels and all-cause and CVD mortality in community-dwelling older adults without known CVD. METHODS: We measured plasma galectin-3 levels in 1,393 Rancho Bernardo Study participants without CVD with a mean age of 70 years. Participants were followed up for a mean of 11 years for coronary heart disease, CVD mortality, and all-cause mortality. RESULTS: During follow-up, 436 participants died (169 from CVD). In models adjusted for traditional CVD risk factors and renal function, galectin-3 was a significant predictor of CVD mortality (hazard ratio [HR] per SD log increase 1.30, 95% CI 1.10-1.53) and all-cause mortality (HR 1.12, 1.01-1.24), but not coronary heart disease (HR 1.09, 0.92-1.30). After further adjusting for N-terminal pro B-type natriuretic peptide, galectin-3 remained an independent predictor (HR 1.24, 1.05-1.47) of CVD mortality. Galectin-3 improved the c statistic (0.847-0.851, P = .003) for prediction of CVD death. Net reclassification improvement (>0) with the addition of galectin-3 was 35% (P < .0001); the integrated discrimination index was also significant (P = .03). Participants with both galectin-3 and N-terminal pro B-type natriuretic peptide above the median had increased risk of CVD death vs those with higher levels of only 1 of these markers (HR 1.74, 1.24-2.43). CONCLUSION: Higher levels of galectin-3 are independently associated with all-cause and CVD mortality among community-dwelling older adults with no known CVD at baseline.


Assuntos
Doenças Cardiovasculares/mortalidade , Galectina 3/sangue , Consentimento Livre e Esclarecido , Medição de Risco/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , California/epidemiologia , Doenças Cardiovasculares/sangue , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo
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