RESUMEN
BACKGROUND: Identification of a subclinical cardiomyopathy in pediatric patients with Friedreich's ataxia (FA) has not been well-described. METHODS: We performed echocardiography (Echo), cardiac magnetic resonance imaging (cMRI), and neurologic assessment in a cross-sectional analysis of 48 genetically confirmed FA subjects aged 9-17 years with moderate neurologic impairment but without a cardiovascular history. Echo- and cMRI-determined left ventricular mass were indexed (LVMI) to height in grams/m2.7. LV remodeling was categorized as concentric remodeling (CR), concentric hypertrophy (CH), or eccentric hypertrophy based upon Echo- determined relative LV wall thickness. RESULTS: Echo LVMI exceeded age-based normal values in 85% of subjects, and cMRI-determined LVMI correlated with depression of both diastolic and systolic tissue Doppler velocity (E': r = -0.65, P < .001, S': r = -0.46, P < .001) as well as increased early diastolic Doppler flow velocity/tissue velocity ratio (r= 0.55, P < .001), a marker of elevated LV filling pressure. Similar associations were found with echo-determined LV mass. Evidence of depressed LV relaxation and increased LV stiffness were observed in 88% and 71%, of subjects, respectively, despite a normal LV ejection fraction in almost all cases (mean = 60% + 7%). CR and CH were present in 40% and 44% of the study group, respectively, although significant depressions of E' and S' were observed only in subjects with CH (P < .005). CONCLUSIONS: A subclinical hypertrophic cardiomyopathy is common in pediatric FA patients and CH is associated with both diastolic and systolic dysfunction.
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Cardiomiopatía Hipertrófica/etiología , Ecocardiografía Doppler/métodos , Ataxia de Friedreich/complicaciones , Ventrículos Cardíacos/diagnóstico por imagen , Imagen por Resonancia Cinemagnética/métodos , Función Ventricular Izquierda/fisiología , Adolescente , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , Niño , Estudios Transversales , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Remodelación VentricularAsunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Selección de Paciente , Fenotipo , Volumen Sistólico/fisiología , Fármacos Cardiovasculares/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Ensayos Clínicos como Asunto/normas , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , Factores de RiesgoRESUMEN
BACKGROUND AND PURPOSE: Chronic effects of hypertension may be observed in multiple end organs. Previous reports suggest that cardiovascular morphological features can mirror cerebral infarction. In this cross-sectional analysis of elderly subjects, we investigated the relationship of a comprehensive set of echocardiographic measures with cerebral infarction detected by MRI. METHODS: We compared echocardiographically determined left ventricular (LV) mass, left atrial volume, aortic root diameter, mitral annular calcification, and measures of diastolic function with cerebral infarction determined by MRI using logistic regression in a random sample drawn from the Age Gene/Environment Susceptibility-Reykjavik Study cohort. The model was first adjusted for age and gender, and then for age, gender, and vascular risk factors. RESULTS: Among 692 subjects aged 75 (standard deviation, 6) years, 28% had at least 1 cerebral infarct. When adjusted for age and gender, the presence of cerebral infarction was modestly related to LV mass (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and left atrial volume (OR, 1.03; 95% CI, 1.01-1.05), as well as the lowest quartile of early-to-late pulsed Doppler velocity ratio (early-to-late pulsed Doppler velocity ratio <0.75; OR, 1.87; 95% CI, 1.22-2.87). The latter relation remained significant after adjustment for vascular risk factors and LV ejection fraction (OR, 1.82; 95% CI, 1.16-2.86). CONCLUSIONS: Of all echocardiographic parameters, LV filling abnormality as indicated by low early-to-late pulsed Doppler velocity ratio displayed the strongest association with cerebral infarction and this relationship was independent of vascular risk factors. This simple marker of cerebral infarction may be useful when evaluating older patients.
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Infarto Cerebral/diagnóstico por imagen , Ecocardiografía , Atrios Cardíacos/diagnóstico por imagen , Hipertensión/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Oportunidad Relativa , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the exercise capacity of children and adolescents with Friedreich's Ataxia (FA) and to evaluate the effects of 6 months of idebenone treatment on exercise capacity. DESIGN: Exploratory endpoint in a randomized double-blind, placebo-controlled, phase II clinical trial designed to investigate the effects of idebenone on a biomarker of oxidative stress. SETTING: Exercise physiology laboratory in a single clinical research center. PARTICIPANTS: Ambulatory subjects (N=48; age range, 9-17 y) with genetically confirmed FA. INTERVENTION: Idebenone administered orally 3 times a day for a total daily dose of approximately 5, 15, and 45 mg/kg or matching placebo for 6 months. MAIN OUTCOME MEASURES: Peak oxygen consumption per unit time (peak VO(2)) and peak work rate (WR) were measured during incremental exercise testing at baseline and after treatment. Echocardiography and neurologic assessments were also completed before and after treatment. RESULTS: Baseline mean peak VO(2) +/- SD was 746+/-246 mL/min (16.2+/-5.8 mL/kg/min), and WR was 40+/-23 W for all subjects. Peak VO(2) and WR were correlated with short guanine-adenine-adenine allele length and neurologic function. Relative left ventricular wall thickness was increased but left ventricular ejection fraction was normal in most subjects; there was no relationship between any exercise and echocardiographic measures. There were no significant changes in mean peak VO(2) or WR after idebenone treatment at any dose level relative to placebo. CONCLUSIONS: Exercise capacity in children and adolescents with FA was significantly impaired. The basis for the impairment appears to be multifactorial and correlated to the degree of neurologic impairment. Although idebenone has previously been shown potentially to improve features of FA, idebenone treatment did not increase exercise capacity relative to placebo.
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Antioxidantes/uso terapéutico , Prueba de Esfuerzo , Ataxia de Friedreich/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Ubiquinona/análogos & derivados , 8-Hidroxi-2'-Desoxicoguanosina , Adolescente , Antioxidantes/administración & dosificación , Niño , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Ataxia de Friedreich/metabolismo , Ataxia de Friedreich/fisiopatología , Humanos , Masculino , Consumo de Oxígeno/efectos de los fármacos , Ubiquinona/administración & dosificación , Ubiquinona/uso terapéuticoRESUMEN
UNLABELLED: The purpose of this study was to prospectively assess the effects of two adaptive postprocessing techniques on the evaluation of myocardial function with displacement-encoded magnetic resonance (MR) imaging, including sensitivity for abnormal wall motion, with two-dimensional echocardiography as the reference standard. Sixteen patients (11 men, five women; age range, 26-74 years) and 12 volunteers (six men, six women; age range, 29-53 years) underwent breath-hold MR imaging. Institutional review board approval and informed consent were obtained. Adaptive phase-unwrapping and spatial filtering techniques were compared with conventional phase-unwrapping and spatial filtering techniques. Use of the adaptive techniques led to a reduced rate of failure with the phase-unwrapping technique from 18.9% to 0.6% (P < .001), resulted in lower variability of segmental strain measurements among healthy volunteers (P < .001 to P = .02), and increased the sensitivity of quantitative detection of abnormal segments in patients from 82.5% to 87.7% (P = .034). The adaptive techniques improved the semiautomated postprocessing of displacement-encoded cardiac images and increased the sensitivity of detection of abnormal wall motion in patients. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/246/1/229/DC1.
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Corazón/fisiopatología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Exaggerated systolic blood pressure (BP) augmentation with exercise has been associated with impaired endothelial function and cardiovascular risk. However, previous studies were largely restricted to men, did not evaluate diastolic BP, and focused on peak exercise measures, which are influenced by effort and fitness level. The aim of this study was to determine the association of exercise BP responses with risk of incident cardiovascular disease (CVD). BP was assessed during stage 2 of the Bruce protocol and during recovery in 3,045 Framingham Study subjects (mean age 43 years; 53% women). The association between exercise BP and CVD events during 20 years of follow-up was examined using Cox proportional hazards models. In age- and sex-adjusted analyses, exercise systolic and diastolic BP were associated with incident CVD (adjusted hazard ratios [HRs] for top quintile 1.55, 95% confidence interval [CI] 1.18 to 2.04; and 1.77, 95% CI 1.35 to 2.31, respectively, relative to the lower 4 quintiles; p <0.005). After adjustment for BP at rest and conventional risk factors, exercise diastolic BP (HR 1.41, 95% CI 1.01 to 1.95, p = 0.04), but not exercise systolic BP (HR 0.97, 95% CI 0.68 to 1.38, p = 0.86), remained a significant predictor of CVD. Similarly, in recovery responses after exercise, only diastolic BP (HR 1.53, 95% CI 1.08 to 2.18, p = 0.02) predicted incident CVD in multivariable models. In conclusion, in middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD. Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group.
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Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/epidemiología , Ejercicio Físico/fisiología , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Intervalos de Confianza , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: In patients with systolic heart failure, the ability of cardiopulmonary exercise testing (CPX) variables to reflect pathophysiology is well established. The relationship between CPX and pathophysiology has, however, not been thoroughly investigated in patients with nonobstructive hypertrophic cardiomyopathy (NHCM). The objective of this study was to assess the ability of CPX variables to reflect resting hemodynamics in patients with nonobstructive hypertrophic cardiomyopathy NHCM. METHODS: We performed CPX and right heart catheterization on 83 subjects with NHCM (51 male/32 female, mean age = 38 +/- 10 yr, NYHA I-III mean = 1.7). Peak oxygen consumption ( O2) and minute ventilation/carbon dioxide ratio (V E/VCO2) at peak exercise were compared to resting hemodynamics including pulmonary artery systolic, diastolic and mean pressures (PASP, PADP and MPAP), and pulmonary capillary wedge pressure (PCWP). RESULTS: Elevations in PCWP (> or = 15 mm Hg), PASP (> or =30 and > or = 40 mm Hg), PADP (> 15 mm Hg) and MPAP (> or = 20 mm Hg) were detected in 22, 33, 10, and 23% of subjects, respectively. Peak V E/VCO2 (positive correlation) and peak VO2 (negative correlation) correlated modestly with all pressure measurements (r = 0.33-0.51, P < 0.01 for all measurements). By receiver operating curve analysis, a V E/VCO2 >35.5 exhibited the best diagnostic accuracy with a curve areas of 0.81 for PAP > or = 30 mm Hg (sensitivity/specificity = 86%/67%), 0.87 for PAP > or = 40 mm Hg (77%/100%), 0.86 for MPAP > 20 mm Hg (83%/79%), and 0.84 for PCWP > or = 15 mm Hg (80%/76%). CONCLUSIONS: CPX can accurately identify abnormal resting hemodynamics in patients with NHCM. Further testing of this modality in other forms of diastolic dysfunction may be warranted.
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Cardiomiopatía Hipertrófica/fisiopatología , Hemodinámica , Ventilación Pulmonar , Adulto , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Distribución de Chi-Cuadrado , Ecocardiografía , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Consumo de Oxígeno , Curva ROC , DescansoRESUMEN
BACKGROUND: The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown. METHODS: We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 195 consecutive patients (82 men and 113 women; mean [+/-SD] age, 36+/-12 years). Pulmonary hypertension was prospectively defined as a tricuspid regurgitant jet velocity of at least 2.5 m per second. Patients were followed for a mean of 18 months, and data were censored at the time of death or loss to follow-up. RESULTS: Doppler-defined pulmonary hypertension occurred in 32 percent of patients. Multiple logistic-regression analysis, with the use of the dichotomous variable of a tricuspid regurgitant jet velocity of less than 2.5 m per second or 2.5 m per second or more, identified a self-reported history of cardiovascular or renal complications, increased systolic blood pressure, high lactate dehydrogenase levels (a marker of hemolysis), high levels of alkaline phosphatase, and low transferrin levels as significant independent correlates of pulmonary hypertension. The fetal hemoglobin level, white-cell count, and platelet count and the use of hydroxyurea therapy were unrelated to pulmonary hypertension. A tricuspid regurgitant jet velocity of at least 2.5 m per second, as compared with a velocity of less than 2.5 m per second, was strongly associated with an increased risk of death (rate ratio, 10.1; 95 percent confidence interval, 2.2 to 47.0; P<0.001) and remained so after adjustment for other possible risk factors in a proportional-hazards regression model. CONCLUSIONS: Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Therapeutic trials targeting this population of patients are indicated.
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Anemia de Células Falciformes/complicaciones , Causas de Muerte , Hipertensión Pulmonar/etiología , Adulto , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/mortalidad , Antidrepanocíticos/uso terapéutico , Presión Sanguínea , Resistencia a Medicamentos , Ecocardiografía Doppler , Femenino , Hemólisis , Humanos , Hidroxiurea/uso terapéutico , Hipertensión Pulmonar/clasificación , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Modelos Logísticos , Masculino , Prevalencia , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Factores de Riesgo , Tasa de Supervivencia , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/fisiopatología , Función VentricularRESUMEN
OBJECTIVES: The aim of this study was to determine echocardiographic predictors of outcome in patients with advanced heart failure (HF) due to severe left ventricular (LV) systolic dysfunction in the Beta-blocker Evaluation of Survival Trial (BEST). BACKGROUND: Previous studies indicate that echocardiographic measurements of LV size and function, mitral deceleration time, and mitral regurgitation (MR) predict adverse outcomes in HF. However, complete quantitative echocardiograms evaluating all of these parameters have not been reported in a prospective randomized clinical trial in the era of modern HF therapy. METHODS: Complete echocardiograms were performed in 336 patients at 26 sites and analyzed by a core laboratory. A Cox proportional-hazards regression model was used to determine which echocardiographic variables predicted the primary end point of death or the secondary end point of death, HF hospitalization, or transplant. Significant variables were then entered into a multivariable model adjusted for clinical and demographic covariates. RESULTS: On multivariable analysis adjusted for clinical covariates, only LV end-diastolic volume index predicted death (events = 75), with a cut point of 120 ml/m(2). Three echocardiographic variables predicted the combined end point of death (events = 75), HF hospitalization (events = 97), and transplant (events = 9): LV end-diastolic volume index, mitral deceleration time, and the vena contracta width of MR. Optimal cut points for these variables were 120 ml/m(2), 150 ms, and 0.4 cm, respectively. CONCLUSIONS: Echocardiographic predictors of outcome in advanced HF include LV end-diastolic volume index, mitral deceleration time, and vena contracta width. These variables indicate that LV remodeling, increased LV stiffness, and MR are independent predictors of outcome in patients with advanced HF.
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Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/mortalidad , Ecocardiografía Doppler/métodos , Femenino , Insuficiencia Cardíaca/patología , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Estados Unidos/epidemiología , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
BACKGROUND: The left atrium is afterload sensitive, responding to immediate changes in left ventricular (LV) diastolic pressure, and left atrial volumetric remodeling has been reported in conditions associated with abnormal diastolic function. We examined the relationship between left atrial volumetric remodeling and objective measures of exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (HCM). METHODS: We compared LA volume indices, other 2-dimensional and Doppler echocardiographic parameters, invasive hemodynamic measures, and magnetic resonance imaging (MRI)-derived LV mass with exercise duration, maximal oxygen uptake (MV* O2), anaerobic threshold (AT), and ventilatory efficiency (VE/V* CO2 slope) in 43 patients with nonobstructive HCM. Patients underwent cardiac catheterization within 48 hours and metabolic stress testing within 1 week of their echocardiogram and MRI examinations. RESULTS: Left atrial volume at end-ventricular systole (LA max) and end-atrial emptying (LA min) correlated with MV* O2 (r = -0.39, P < .01 for both), AT (r = -0.42, r = -0.39, respectively, P < .01 for both), and VE/V* CO2 slope (r = 0.45, P = .003; r = 0.41, P = .008). Patients with an LA max > or =33 mL/m2 had significantly lower MV* O2 (P = .025) and AT levels (P = .017) and higher VE/V* CO2 slope levels (P = .004) as compared with patients with a smaller LA size. In multivariate analysis, MRI-determined LV mass, which was not a univariate correlate of exercise tolerance, provided additional effect when combined with LA volume index. CONCLUSIONS: Left atrial volumetric remodeling predicts exercise capacity in nonobstructive HCM and may reflect chronic LV diastolic burden. This simple noninvasive measure of LA size may provide a long-term indication of the effects of chronically elevated filling pressures in patients with HCM and further studies testing its prognostic value are necessary.
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Tolerancia al Ejercicio/fisiología , Atrios Cardíacos/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Derecha/fisiopatología , Adulto , Aerobiosis , Cateterismo Cardíaco , Adaptabilidad , Ecocardiografía Doppler , Prueba de Esfuerzo , Femenino , Tabiques Cardíacos/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Insuficiencia de la Válvula Mitral/complicaciones , Tamaño de los Órganos , Consumo de Oxígeno , Presión , Estudios RetrospectivosRESUMEN
We sought to identify the clinical characteristics and outcomes of patients who had advanced heart failure and nonfatal myocardial infarction (MI) in the beta-Blocker Evaluation of Survival Trial (BEST) and to investigate whether bucindolol alters the risk of developing nonfatal MI. Of the 2,708 patients enrolled in the study, 142 had suspected MI and 69 had confirmed MI; there were 860 deaths overall. The rate of nonfatal MI in the BEST was low over the 4.1 years of follow-up (4.8% had suspected events and 2.4% had adjudicated events) and was similar to that in high-risk populations. Cox's proportional hazard model with 23 prespecified candidate variables associated advanced age, heart failure symptoms, male gender, ischemic etiology, diabetes, and hypertension with nonfatal MI or cardiovascular death. The 2-year mortality rate was 56% for the cohort that had suspected nonfatal MI versus 30% for the cohort that did not (p = 0.01). Likewise, the risk of hospitalization for congestive heart failure was twofold greater. Beta-blocker therapy with bucindolol resulted in a 52% decrease in suspected nonfatal MI (2.9% vs 5.5%, p = 0.001). In conclusion, nonfatal MI occurs at low rates but increases the risks for mortality and hospitalization in patients who have advanced heart failure. Beta-blocker therapy with bucindolol appears to attenuate the risk of nonfatal MI in this population.
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Antagonistas Adrenérgicos beta/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Propanolaminas/uso terapéutico , Anciano , Causas de Muerte , Método Doble Ciego , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Modelos de Riesgos Proporcionales , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The mechanisms underlying reduced exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (NHCM) could include perturbations of ventricular relaxation, diastolic compliance, or compensatory atrial systolic function. We hypothesized that a loss of atrial contractility in NHCM patients leads to reduced functional capacity. To test this hypothesis, we compared resting noninvasive left atrial ejection phase indices in 49 consecutive patients with NHCM (ages 36+/-10 years; 41% female) and normal left ventricular ejection fraction (mean, 68%+/-8%) with objective metabolic exercise parameters. Left atrial active emptying fraction, ejection force, and kinetic energy failed to predict exercise capacity. Only left atrial total and active emptying volumes correlated weakly with minute volume/CO2 production slope (r=0.31 and r=0.33; p<0.05 for both). Furthermore, when subjects were stratified by New York Heart Association symptomatology, exercise parameters--but not atrial contractility--differed between groups. These data, obtained at rest, fail to suggest that NHCM-related heart failure symptoms are due to an atrial myopathy.
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Función del Atrio Izquierdo , Cardiomiopatía Hipertrófica/fisiopatología , Tolerancia al Ejercicio , Contracción Miocárdica , Adulto , Ecocardiografía , Femenino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Mitral annular calcification (MAC) has been associated with adverse cardiovascular disease outcomes and stroke in longitudinal and community-based cohorts. Prospective data are limited on its association with atrial fibrillation (AF). METHODS: We examined the association between MAC and the long-term risk of AF over 16 years of follow-up in participants in the original cohort of the Framingham Heart Study who attended a routine examination between 1979 and 1981. MAC was assessed by M-mode echocardiography. cox proportional-hazards models were used to estimate hazard ratios (hr) for incident af. RESULTS: Of 1126 subjects who had adequate echocardiographic assessment and were AF-free at baseline, 149 (13%) had MAC. There were 217 cases of incident AF (42 in subjects with MAC). The age- and sex-adjusted incidence rate was 362 per 10,000 person-years in subjects with MAC compared with 185 per 10,000 person-years in those without MAC. In multivariable-adjusted analyses, MAC was associated with an increased risk of AF (HR 1.6, 95% CI 1.1-2.2). This association was attenuated upon further adjustment for left atrial size (HR 1.4, 95% CI 0.9-2.0). CONCLUSIONS: The association between MAC and incident AF may be mediated partially through left atrial enlargement. These data suggest the importance of better understanding the mechanisms involved in cardiac valvular calcification.
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Fibrilación Atrial/epidemiología , Calcinosis/epidemiología , Estenosis de la Válvula Mitral/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/diagnóstico , Calcinosis/diagnóstico , Estudios de Cohortes , Comorbilidad , Ecocardiografía Doppler , Electrocardiografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/diagnóstico , Probabilidad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por SexoRESUMEN
Acute massive pulmonary embolus (PE) when undiagnosed may lead to hemodynamic compromise and death. Echocardiography offers several clues to the diagnosis of PE. We describe how transesophageal echo was used in the diagnosis and management of two patients with this disorder.
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Disfunción Ventricular/epidemiología , Función Ventricular/fisiología , Adulto , Angina de Pecho/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Ecocardiografía , Humanos , Incidencia , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/epidemiología , Infarto del Miocardio/mortalidad , Prevalencia , Estados Unidos/epidemiología , Disfunción Ventricular/diagnóstico por imagenRESUMEN
AIMS: There is little evidence of beta-blocker treatment benefit in patients with heart failure and reduced left ventricular ejection fraction (HFREF) and atrial fibrillation (AF). We investigated the effects of bucindolol in HFREF patients with AF enrolled in the Beta-blocker Evaluation of Survival Trial (BEST). METHODS AND RESULTS: A post-hoc analysis of patients in BEST with and without AF was performed to estimate the effect of bucindolol on mortality and hospitalization. Patients were also evaluated for treatment effects on heart rate and the influence of beta1-adrenergic receptor position 389 (ß(1)389) arginine (Arg) vs. glycine (Gly) genotypes. In the 303/2708 patients in AF, patients receiving bucindolol were more likely to achieve a resting heart rate ≤ 80 b.p.m. at 3 months (P < 0.005) in the absence of treatment-limiting bradycardia. In AF patients and sinus rhythm (SR) patients who achieved a resting heart rate ≤ 80 b.p.m., there were beneficial treatment effects on cardiovascular mortality/cardiovascular hospitalization [hazard ratio (HR) 0.61, P = 0.025, and 0.79, P = 0.002]. Without achieving a resting heart rate ≤ 80 b.p.m., there were no treatment effects on events in either group. ß(1)389-Arg/Arg AF patients had nominally significant reductions in all-cause mortality/HF hospitalization and cardiovascular mortality/hospitalization with bucindolol (HR 0.23, P = 0.037 and 0.28, P = 0.039), whereas Gly carriers did not. There was no evidence of diminished heart rate response in ß(1)389-Arg homozygotes. CONCLUSION: In HFREF patients with AF, bucindolol was associated with reductions in composite HF endpoints in those who achieved a resting heart rate ≤ 80 b.p.m. and nominally in those with the ß(1)389-Arg homozygous genotype.
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Antagonistas Adrenérgicos beta/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Propanolaminas/uso terapéutico , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/mortalidad , Estudios de Casos y Controles , Resistencia a Medicamentos/genética , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Frecuencia Cardíaca/efectos de los fármacos , Hospitalización/estadística & datos numéricos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Receptores Adrenérgicos beta 1/genética , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Pharmacogenetics involves complex interactions of gene products affecting pharmacodynamics and pharmacokinetics, but there is little information on the interaction of multiple genetic modifiers of drug response. Bucindolol is a ß-blocker/sympatholytic agent whose efficacy is modulated by polymorphisms in the primary target (ß(1) adrenergic receptor [AR] Arg389 Gly on cardiac myocytes) and a secondary target modifier (α(2C) AR Ins [wild-type (Wt)] 322-325 deletion [Del] on cardiac adrenergic neurons). The major allele homozygotes and minor allele carriers of each polymorphism are respectively associated with efficacy enhancement and loss, creating the possibility for genotype combination interactions that can be measured by clinical trial methodology. METHODOLOGY: In a 1,040 patient substudy of a bucindolol vs. placebo heart failure clinical trial, we tested the hypothesis that combinations of ß(1)389 and α(2C)322-325 polymorphisms are additive for both efficacy enhancement and loss. Additionally, norepinephrine (NE) affinity for ß(1)389 AR variants was measured in human explanted left ventricles. PRINCIPAL FINDINGS: The combination of ß(1)389 Arg+α(2C)322-325 Wt major allele homozygotes (47% of the trial population) was non-additive for efficacy enhancement across six clinical endpoints, with an average efficacy increase of 1.70-fold vs. 2.32-fold in ß(1)389 Arg homozygotes+α(2C)322-325 Del minor allele carriers. In contrast, the minor allele carrier combination (13% subset) exhibited additive efficacy loss. These disparate effects are likely due to the higher proportion (42% vs. 8.7%, Pâ=â0.009) of high-affinity NE binding sites in ß(1)389 Arg vs. Gly ARs, which converts α(2C)Del minor allele-associated NE lowering from a therapeutic liability to a benefit. CONCLUSIONS: On combination, the two sets of AR polymorphisms 1) influenced bucindolol efficacy seemingly unpredictably but consistent with their pharmacologic interactions, and 2) identified subpopulations with enhanced (ß(1)389 Arg homozygotes), intermediate (ß(1)389 Gly carriers+α(2C)322-325 Wt homozygotes), and no (ß(1)389 Gly carriers+α(2C)322-325 Del carriers) efficacy.