RESUMEN
BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes. RESULTS: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001). CONCLUSIONS: Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Metilprednisolona , Humanos , Metilprednisolona/efectos adversos , Estudios Prospectivos , InsulinaRESUMEN
Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease and death, yet little data exist regarding the comparative efficacy of coronary revascularization procedures in CKD patients with multivessel disease. We created a cohort of 4,687 adults who underwent cardiac catheterization, had a serum creatinine value measured within 30 days, and had more than one vessel with ≥50% stenosis. We used Cox proportional hazard regression modeling weighted by the inverse probability of treatment to examine the association between 4 treatment strategies (medical management, percutaneous coronary intervention [PCI] with bare metal stent, PCI with drug-eluting stent, and coronary artery bypass grafting [CABG]) and mortality among patients across categories of estimated glomerular filtration rate; secondary outcome was a composite of mortality, myocardial infarction, or revascularization. Compared with medical management, CABG was associated with a reduced risk of death for patients of any nondialysis CKD severity (hazard ratio [HR] range 0.43 to 0.59). There were no significant mortality differences between CABG and PCI, except a decreased death risk in CABG-treated CKD patients (HR range 0.54 to 0.55). Compared with medical management and PCI, CABG was associated with a lower risk of death, myocardial infarction, or revascularization in nondialysis CKD patients (HR range 0.41 to 0.64). There were similar associations between decreased estimated glomerular filtration rate and increased mortality across all multivessel coronary artery disease patient treatment groups. When accounting for treatment propensity, surgical revascularization was associated with improved outcomes in patients of all CKD severities. A prospective randomized trial in CKD patients is required to confirm our findings.
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Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos , Fallo Renal Crónico/terapia , Intervención Coronaria Percutánea/métodos , Sistema de Registros , Anciano , Tratamiento Conservador , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Mortalidad , Infarto del Miocardio/epidemiología , Revascularización Miocárdica/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/complicaciones , Stents , Resultado del TratamientoRESUMEN
Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function.
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Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares , Diabetes Mellitus , Hipertensión , Fosfato de Sitagliptina , Anciano , Presión Sanguínea/efectos de los fármacos , Determinación de la Presión Sanguínea/métodos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Comorbilidad , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Monitoreo de Drogas/métodos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Modelos de Riesgos Proporcionales , Medición de Riesgo/métodos , Factores de Riesgo , Fosfato de Sitagliptina/administración & dosificación , Fosfato de Sitagliptina/efectos adversosRESUMEN
BACKGROUND: Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. METHODS AND RESULTS: In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD. CONCLUSIONS: HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.
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Diástole/efectos de los fármacos , Tolerancia al Ejercicio/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Arteria Pulmonar/efectos de los fármacos , Circulación Pulmonar/efectos de los fármacos , Citrato de Sildenafil/uso terapéutico , Volumen Sistólico/efectos de los fármacos , Disfunción Ventricular Derecha/tratamiento farmacológico , Función Ventricular Derecha/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/enzimología , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/efectos de los fármacos , Inhibidores de Fosfodiesterasa 5/efectos adversos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Ventilación Pulmonar/efectos de los fármacos , Recuperación de la Función , Índice de Severidad de la Enfermedad , Citrato de Sildenafil/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía , Disfunción Ventricular Derecha/diagnóstico , Disfunción Ventricular Derecha/enzimología , Disfunción Ventricular Derecha/fisiopatología , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
OBJECTIVES: The Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial was an investigator-initiated study to evaluate if predischarge carvedilol initiation in stabilized patients hospitalized for heart failure (HF) increased the number of patients treated with beta-blockade at 60 days after randomization without increasing side effects or length of hospital stay. BACKGROUND: Beta-blockers are underused in HF. Predischarge initiation may improve the use of evidence-based beta-blockade. METHODS: The IMPACT-HF was a prospective, randomized open-label trial conducted in 363 patients hospitalized for HF. Patients were randomized to carvedilol initiation pre-hospital discharge or to postdischarge initiation (>2 weeks) of beta-blockade at the physicians' discretion. The primary end point of the study was the number of patients treated with beta-blockade at 60 days after randomization. Secondary end points included the number of patients discontinuing beta-blockade, median dose achieved, and a composite of death, rehospitalization, unscheduled visit for HF, or > or =50% increase in oral diuretic, new oral diuretic, or any intravenous therapy with diuretics, inotropes, or other vasoactive agents. RESULTS: At 60 days 165 patients (91.2%) randomized to predischarge carvedilol initiation were treated with a beta-blocker, compared with 130 patients (73.4%) randomized to initiation postdischarge (p < 0.0001). Predischarge initiation was not associated with an increased risk of serious adverse events. The median length of stay was five days in both groups. CONCLUSIONS: Predischarge initiation of carvedilol in stabilized patients hospitalized for HF improved the use of beta-blockade at 60 days without increasing side effects or length of stay. Predischarge initiation may be one approach to improve beta-blocker use in this population.
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Antagonistas Adrenérgicos beta/uso terapéutico , Carbazoles/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización , Propanolaminas/uso terapéutico , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antiarrítmicos/uso terapéutico , Carvedilol , Digoxina/uso terapéutico , Diuréticos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Alta del Paciente , Estudios Prospectivos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Myocardial ischemic injury complicating acute myocardial infarction (AMI) and coronary revascularization procedures remains an unresolved clinical dilemma. In preclinical studies, treatment with pyridoxal-5'-phosphate monohydrate (MC-1), a vitamin B6 metabolite, has demonstrated cardioprotective effects. Sixty patients scheduled for elective percutaneous coronary intervention (PCI) who had clinically high-risk characteristics for ischemic complications were randomized to treatment with MC-1 or placebo in a 2:1 double-blinded fashion. The primary end point was defined as infarct size as measured by area under the curve creatine kinase MB (CK-MB) enzymes. Secondary end points included periprocedural ischemia as assessed by continuous electrocardiographic monitoring, 30-day major adverse cardiac events, and net clinical safety, which included liver function testing. The primary end point, median periprocedural CK-MB area under the curve, was reduced from 32.9 ng/ml in the placebo group to 18.6 ng/ml with MC-1 treatment (p = 0.038), reflecting a shift in the distribution of CK-MB. By categorical classification, the occurrence of 30-day nonfatal AMI did not differ between groups. There were no deaths, and 30-day composite adverse event rates were similar (17.9% MC-1 vs 15.0% placebo, p = 1.0). There were no significant differences in ischemia parameters per continuous electrocardiographic monitoring, and no safety issues were identified. In this phase II pilot study, treatment of high-risk patients who underwent PCI with MC-1 was associated with a decrease in the total amount of CK-MB released after PCI. These results support the evaluation of MC-1 in pivotal trials of patients at risk for developing myocardial ischemia, infarction, or reperfusion injury.
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Angioplastia Coronaria con Balón/efectos adversos , Cardiotónicos/uso terapéutico , Enfermedad Coronaria/terapia , Isquemia Miocárdica/etiología , Isquemia Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/prevención & control , Fosfato de Piridoxal/uso terapéutico , Anciano , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Método Doble Ciego , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico por imagen , Daño por Reperfusión Miocárdica/diagnóstico por imagen , NecrosisRESUMEN
BACKGROUND: Hospitalizations for decompensated heart failure are frequent. The Initiation Management Pre-discharge Assessment of Carvedilol Heart Failure (IMPACT-HF) registry collected observational data in patients hospitalized for worsening heart failure to characterize an unselected group of patients and to confirm the generalizability of the IMPACT-HF main trial population. METHODS AND RESULTS: The IMPACT-HF registry was conducted concurrently with the IMPACT-HF study, a randomized trial of in-hospital initiation of carvedilol compared with the standard practice of postdischarge beta-blocker initiation. Patients were eligible for registry enrollment if they were hospitalized for heart failure regardless of ejection fraction. There were no exclusions to participation. Patients were followed for 60 days. The IMPACT-HF Registry enrolled 567 patients. The mean age was 71 years, 52% of the patients were men and 82% were Caucasian. At discharge, 71% received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 41% received digoxin, and 62% received beta-blockers. The 60-day rate of rehospitalization or death was 31%. CONCLUSION: The IMPACT-HF registry enrolled elderly patients admitted for worsening heart failure primarily resulting from progressive volume overload. The 60-day rate of death or rehospitalization was high despite the use of evidence-based therapies. New treatments for this population are needed to decrease the morbidity and mortality associated with decompensated heart failure.