RESUMEN
In the outpatient setting, ambulatory electrocardiography is the most frequently used diagnostic modality for the evaluation of patients in whom cardiac arrhythmias or conduction abnormalities are suspected. Proper selection of the device type and monitoring duration is critical for optimizing diagnostic yield and cost-effective resource utilization. However, despite guidance from major professional societies, the lack of systematic guidance for proper test selection in many institutions results in the need for repeat testing, which leads to not only increased resource utilization and cost of care, but also suboptimal patient care. To address this unmet need at our own institution, we formed a multidisciplinary panel to develop a concise, yet comprehensive algorithm, incorporating the most common indications for ambulatory electrocardiography, to efficiently guide clinicians to the most appropriate test option for a given clinical scenario, with the goal of maximizing diagnostic yield and optimizing resource utilization. The algorithm was designed as a single-page, color-coded flowchart to be utilized both as a rapid reference guide in printed form, and a decision support tool embedded within the electronic medical records system at the point of order entry. We believe that systematic adoption of this algorithm will optimize diagnostic efficiency, resource utilization, and importantly, patient care and satisfaction.
Asunto(s)
Electrocardiografía Ambulatoria , Sistemas de Atención de Punto , Algoritmos , Análisis Costo-Beneficio , Electrocardiografía , Humanos , Pacientes AmbulatoriosRESUMEN
BACKGROUND: Vascular endothelial fibrinolytic function is impaired in adults with prehypertension and hypertension and plays a mechanistic role in the development of atherothrombotic events. The influence of ß-blockers on endothelial fibrinolysis is unknown. This study compared the effects of chronic nebivolol and metoprolol treatment on endothelial tissue-type plasminogen activator (t-PA) release in adults with elevated blood pressure (BP). METHODS AND RESULTS: Forty-four middle-aged adults (36% women) with elevated BP completed a 3-month, double-blind, randomized, placebo-controlled trial comparing nebivolol (5 mg/d), metoprolol succinate (100 mg/d), and placebo. Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside before and after each intervention. In a subset, the dose-response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C. At baseline, resting BP and endothelial t-PA release were comparable between the 3 groups. BP decreased to a similar extent (≈10 mm Hg) in the nebivolol- and metoprolol-treated groups. There was a substantial increase (≈30%; P<0.05) in the capacity of the endothelium to release t-PA following chronic treatment with nebivolol but not metoprolol or placebo. Mitigating oxidant stress with vitamin C coinfusion potentiated t-PA release (90%; P<0.05) at baseline in all groups. However, after the intervention, t-PA release was unchanged by vitamin C coinfusion in the nebivolol group only. CONCLUSIONS: Nebivolol but not metoprolol improves endothelial t-PA release in adults with elevated BP. This may be an important vascular benefit of nebivolol. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01595516.
Asunto(s)
Presión Sanguínea/fisiología , Endotelio Vascular/efectos de los fármacos , Fibrinólisis/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Metoprolol/administración & dosificación , Nebivolol/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Endotelio Vascular/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vasodilatadores/administración & dosificaciónRESUMEN
OBJECTIVE: To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure. STUDY DESIGN: Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression. RESULTS: Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right ventricular function (38%). CONCLUSIONS: Fibrosis is not a primary contributor to right ventricular failure in infants and young children with single ventricular heart disease. Additional studies are required to understand whether antifibrotic therapies are beneficial in this population.
Asunto(s)
Regulación hacia Abajo , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/patología , Ventrículos Cardíacos/anomalías , Ventrículos Cardíacos/patología , Miocardio/patología , Niño , Preescolar , Femenino , Fibrosis , Marcadores Genéticos , Insuficiencia Cardíaca/congénito , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Humanos , Síndrome del Corazón Izquierdo Hipoplásico/genética , Síndrome del Corazón Izquierdo Hipoplásico/patología , Lactante , Recién Nacido , Masculino , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVE: To determine whether left ventricular assist device (LVAD) treatment in children with heart failure would result in the modification of molecular pathways involved in heart failure pathophysiology. STUDY DESIGN: Forty-seven explanted hearts from children were studied (16 nonfailing control, 20 failing, and 11 failing post-LVAD implantation [F-LVAD]). Protein expression and phosphorylation states were determined by receptor binding assays and Western blots. mRNA expression was measured with real-time quantitative polymerase chain reaction. To evaluate for interactions and identify correlations, 2-way ANOVA and regression analysis were performed. RESULTS: Treatment with LVAD resulted in recovery of total ß-adrenergic receptor expression and ß1-adrenergic receptor (ß1-AR) in failing hearts to normal levels (ß-adrenergic receptor expression : 67.2 ± 11.5 fmol/mg failing vs 99.5 ± 27.7 fmol/mg nonfailing, 104 ± 38.7 fmol/mg F-LVAD, P ≤ .01; ß1-AR: 52.2 ± 10.3 fmol/mg failing vs 83.0 ± 23 fmol/mg non-failing, 76.5 ± 32.1 fmol/mg F-LVAD P ≤ .03). The high levels of G protein-coupled receptor kinase-2 were returned to nonfailing levels after LVAD treatment (5.6 ± 9.0 failing vs 1.0 ± 0.493 nonfailing, 1.0 ± 1.3 F-LVAD). Interestingly, ß2-adrenergic receptor expression was significantly greater in F-LVAD (27.5 ± 12; P < .005) hearts compared with nonfailing (16.4 ± 6.1) and failing (15.1 ± 4.2) hearts. Phospholamban phosphorylation at serine 16 was significantly greater in F-LVAD (7.7 ± 11.7) hearts compared with nonfailing (1.0 ± 1.2, P = .02) and failing (0.8 ± 1.0, P = .01) hearts. Also, atrial natriuretic factor (0.6 ± 0.8) and brain natriuretic peptide (0.1 ± 0.1) expression in F-LVAD was significantly lower compared with failing hearts (2.8 ± 3.6, P = .01 and 0.6 ± 0.7, P = .02). CONCLUSION: LVAD treatment in children with heart failure results in reversal of several pathologic myocellular processes, and G protein-coupled receptor kinase-2 may regulate ß1-AR but not ß2-adrenergic receptor expression in children with heart failure.