RESUMEN
Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen.
Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Cardiomiopatías/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Prednisona/administración & dosificación , Sarcoidosis/tratamiento farmacológico , Arritmias Cardíacas/fisiopatología , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/fisiopatología , Deprescripciones , Quimioterapia Combinada , Electrocardiografía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Recurrencia , Estudios Retrospectivos , Sarcoidosis/diagnóstico por imagen , Sarcoidosis/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: A long-term trial showed that the oral prostacyclin (PGl2) receptor (IP) agonist, selexipag, delayed disease progression in patients with pulmonary arterial hypertension (PAH). Transition to selexipag in patients treated with more burdensome inhaled therapies that target the prostacyclin pathway may be considered by patients and physicians. The Phase 3b, prospective, open-label TRANSIT-1 (Tolerability and Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension) study evaluated the safety and tolerability of transition from inhaled treprostinil to oral selexipag. METHODS: Patients receiving non-prostanoid oral PAH therapy and inhaled treprostinil at stable doses, in World Health Organization Functional Class II/III, with 6-minute walk distance ≥ 300 meters were enrolled. The 16-week main treatment period included downtitration of inhaled treprostinil over 8 weeks and parallel uptitration of selexipag over 12 weeks. Sustained treatment transition at Week 16 was defined as (1) receiving selexipag at Week 16; (2) no selexipag interruption(s) totaling ≥ 8 days; and (3) no inhaled treprostinil or other prostanoids after Week 8. Clinical parameters and patient-reported treatment satisfaction outcomes were assessed at Week 16. RESULTS: All 34 enrolled patients completed the study. At Week 16, 32 patients (94.1%) had stopped inhaled treprostinil and were receiving selexipag. Twenty-eight patients (82.4%) met all criteria for sustained treatment transition. During the study, 3 patients discontinued selexipag due to adverse events. Overall, most adverse events were typical of prostanoid therapies and started during the uptitration phase. In general, patients remained clinically stable throughout treatment and reported improved convenience. CONCLUSIONS: Transition to oral selexipag from inhaled treprostinil in PAH patients was successful and well tolerated in most patients, and associated with greater convenience. CLINICAL TRIAL NUMBER: NCT02471183.
Asunto(s)
Acetamidas/administración & dosificación , Tolerancia a Medicamentos , Epoprostenol/análogos & derivados , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Pirazinas/administración & dosificación , Administración por Inhalación , Administración Oral , Antihipertensivos/administración & dosificación , Relación Dosis-Respuesta a Droga , Sustitución de Medicamentos , Epoprostenol/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Profármacos , Estudios Prospectivos , Hipertensión Arterial Pulmonar/fisiopatología , Presión Esfenoidal Pulmonar/fisiología , Resultado del TratamientoRESUMEN
PURPOSE: Safe transition of patients with pulmonary arterial hypertension (PAH) from parenteral treprostinil to oral selexipag therapy in both inpatient and outpatient settings is described. SUMMARY: There is a paucity of published data on how to safely transition patients to oral therapy in the event of complications and problems during parenteral administration of prostacyclins, which can include bloodstream infections, injection-site pain (with use of subcutaneous treprostinil), infusion pump malfunction, and dosing errors due to incorrect dose preparation. This case series describes the transition of 4 patients with World Health Organization (WHO) group I PAH (WHO functional classes II-IV) from i.v. (n = 3) and subcutaneous (n = 1) treprostinil infusion therapy to oral selexipag use. The transition process was completed through the use of 2 cross-titration methods (rapid and slow). A rapid approach was used in 2 cases involving inpatients, with parenteral-to-oral transition completed over 8-13 days; a slow transition method was used in 2 cases, in which outpatients completed the transition over 19-25 weeks. Adverse events during the transitions were headache, nausea, vomiting, diarrhea, and jaw pain. CONCLUSION: Four patients with WHO group I PAH who were not candidates for continued parenteral treprostinil therapy were safely transitioned to oral selexipag in both inpatient and outpatient settings.
Asunto(s)
Acetamidas/uso terapéutico , Antihipertensivos/uso terapéutico , Epoprostenol/análogos & derivados , Hipertensión Pulmonar/tratamiento farmacológico , Pirazinas/uso terapéutico , Acetamidas/administración & dosificación , Acetamidas/efectos adversos , Administración Intravenosa , Administración Oral , Adulto , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Sustitución de Medicamentos/efectos adversos , Sustitución de Medicamentos/métodos , Epoprostenol/administración & dosificación , Epoprostenol/efectos adversos , Epoprostenol/uso terapéutico , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Pirazinas/administración & dosificación , Pirazinas/efectos adversosRESUMEN
BACKGROUND: Pulmonary hypertension carries significant maternal and fetal risk during pregnancy and the postpartum period. As maternal mortality is high, specific targeted therapy for pulmonary hypertension may be required during pregnancy. CASES: We describe 2 pregnant patients who presented with severe secondary pulmonary arterial hypertension during their last trimester. They were electively treated in the late antepartum and early postpartum periods with sildenafil and intravenous epoprostenol and successfully delivered healthy infants via cesarean section without postpartum complications. CONCLUSION: Although pulmonary hypertension is associated with a risk of maternal mortality and most women are advised against pregnancy, new therapies may improve the outcome of pregnancy in patients with pulmonary hypertension.
Asunto(s)
Epoprostenol/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Piperazinas/uso terapéutico , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Sulfonas/uso terapéutico , Vasodilatadores/uso terapéutico , Adulto , Cesárea , Quimioterapia Combinada , Epoprostenol/efectos adversos , Femenino , Humanos , Recién Nacido , Piperazinas/efectos adversos , Embarazo , Tercer Trimestre del Embarazo , Presión Esfenoidal Pulmonar/efectos de los fármacos , Purinas/efectos adversos , Purinas/uso terapéutico , Citrato de Sildenafil , Esterilización Tubaria , Sulfonas/efectos adversos , Resistencia Vascular/efectos de los fármacos , Vasodilatadores/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Clinical profile and predictors of major adverse events (MAE) associated with peripartum cardiomyopathy (PPCM) have not been characterized. METHODS AND RESULTS: A retrospective review and analysis of clinical data of 182 patients with PPCM. Forty-six patients had >or=1 MAE, including death (13), heart transplantation (11), temporary circulatory support (4), cardiopulmonary arrest (6), fulminant pulmonary edema (17), thromboembolic complications (4), and defibrillator or pacemaker implantation (10). Diagnosis of PPCM was delayed >or=1 week in 48% of patients with MAE that preceded the diagnosis in 50% of these patients. Seven (32%) of the surviving patients who had MAE and did not undergo heart transplantation had residual brain damage. Significant predictors of MAE were: left ventricular ejection fraction Asunto(s)
Cardiomiopatías/complicaciones
, Cardiomiopatías/mortalidad
, Complicaciones Cardiovasculares del Embarazo/mortalidad
, Adulto
, Cardiomiopatías/fisiopatología
, Femenino
, Estudios de Seguimiento
, Humanos
, Valor Predictivo de las Pruebas
, Embarazo
, Complicaciones Cardiovasculares del Embarazo/fisiopatología
, Estudios Retrospectivos
, Tasa de Supervivencia/tendencias
, Disfunción Ventricular Izquierda/complicaciones
, Disfunción Ventricular Izquierda/mortalidad
, Disfunción Ventricular Izquierda/fisiopatología
, Adulto Joven
RESUMEN
BACKGROUND: We assessed the effect of increases in serum creatinine on mortality in nesiritide-treated versus control subjects with acute decompensated heart failure (ADHF). HYPOTHESIS: Mortality effect of nesiritide-related increases in serum creatinine differs from that of standard therapies. METHODS: Scios Inc., granted unrestricted access to data from all 5 randomized, controlled nesiritide infusion trials completed to date in patients hospitalized with ADHF. We used 2 different definitions of acute serum creatinine increase: >0.3 mg/dL and > 0.5mg/dL within 30 days of study enrollment and determined 30-day mortality risk for nesiritide-treated versus control subjects utilizing each definition. RESULTS: A total of 1,270 subjects participated in the 5 trials. A >0.3 mg/dL increase in serum creatinine was associated with a significant increase in mortality risk in control subjects, (hazard ratio [HR]: 3.47, 95% confidence interval [CI]: 1.49-8.09) but not in nesiritide-treated subjects (HR: 1.65, 95% CI: 0.90-3.05). Results were similar for a >0.5 mg/dL increase (control HR: 5.12, 95% CI: 2.09-12.57 and nesiritide HR: 1.77, 95% CI: 0.90-3.51). In subjects with >0.3 mg/dL and >0.5 mg/dL increases in serum creatinine, respectively, the 30-day mortality odds ratios for nesiritide relative to control were 0.73 (95% CI: 0.29-1.93) and 0.52 (95% CI: 0.17-1.63) using a stratified Mantel-Haenszel analysis. CONCLUSIONS: The impact of increased serum creatinine on mortality was attenuated in nesiritide-treated patients compared to control, suggesting that the mechanism and clinical significance of increases in serum creatinine associated with nesiritide treatment may differ from those associated with standard therapies. Further investigation is warranted.
Asunto(s)
Creatinina/sangre , Insuficiencia Cardíaca/mortalidad , Natriuréticos/efectos adversos , Péptido Natriurético Encefálico/efectos adversos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Natriuréticos/uso terapéutico , Péptido Natriurético Encefálico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal/sangre , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/etiología , Análisis de SupervivenciaRESUMEN
Recent guidelines by the Heart Failure Society of America have recommended consideration for use of nitroprusside, nitroglycerin, or nesiritide in addition to diuretics to achieve hemodynamic and symptomatic improvement. This article reviews the results of previous studies evaluating the pharmacologic and clinical effects and safety profiles of these drugs in patients with heart failure.
Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/uso terapéutico , Nitratos/uso terapéutico , Nitroprusiato/uso terapéutico , Vasodilatadores/uso terapéutico , Enfermedad Aguda , Circulación Coronaria/efectos de los fármacos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/efectos de los fármacos , Humanos , Infusiones Intravenosas , Riñón/efectos de los fármacos , Insuficiencia de la Válvula Mitral/tratamiento farmacológico , Péptido Natriurético Encefálico/efectos adversos , Péptido Natriurético Encefálico/farmacología , Nitratos/farmacología , Nitroprusiato/farmacología , Vasodilatadores/efectos adversos , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: A "renal dose" of dopamine is often used to increase renal blood flow; however, data on the magnitude of effect and site of action in patients with heart failure are scarce. METHODS AND RESULTS: Renal effects of intravenous dopamine (1, 2, 3, 5, and 10 mug . kg(-1) . min(-1)) were evaluated in 13 patients with chronic heart failure. Renal blood flow was calculated from renal artery cross-sectional area measured with intravascular ultrasound and renal blood flow velocity-time integral measured by the intravascular Doppler technique. Cross-sectional area increased and was significantly higher than baseline (0.30+/-0.04 cm(2)) at 5 mug . kg(-1) . min(-1) (0.36+/-0.05 cm(2)) and 10 mug . kg(-1) . min(-1) (0.38+/-0.06 cm(2)). The velocity-time integral was significantly higher than baseline (22+/-3 cm) at doses of 3 and 5 mug . kg(-1) . min(-1) (both 31+/-4 cm). Renal blood flow increased, whereas renal vascular resistance decreased, reaching statistical significance at 2 mug . kg(-1) . min(-1) through 10 mug . kg(-1) . min(-1). Cardiac output gradually increased, reaching statistical significance at doses of 5 and 10 mug . kg(-1) . min(-1) (5.5+/-0.5 and 6.1+/-0.7 versus 4.5+/-5.2 L/min at baseline), but the increase in renal blood flow appeared proportionately larger than corresponding increases in cardiac output. CONCLUSIONS: Dopamine is associated with an increase in renal blood flow in patients with heart failure. This effect is due to dilation of both the large conductance and small resistance renal blood vessels. Further evaluation of the efficacy and safety of dopamine for improvement of renal function in hospitalized patients with heart failure is warranted.
RESUMEN
UNLABELLED: Attenuation of endothelial-dependent coronary vasodilation has been reported in idiopathic dilated cardiomyopathy and anatomically normal coronaries; however, data are insufficient for understanding the incidence and extent of this finding. The response of conductance and resistance coronary arteries to endothelial stimulation with acetylcholine was examined in 25 patients. Coronary blood flow had a variable response to acetylcholine and suggested coronary endothelial dysfunction in approximately half of the patients. Abnormal endothelial dysfunction involved the large conductance epicardial coronary arteries and the small resistance vessels. Abnormal endothelial response of coronary blood flow to acetylcholine could not be predicted by demographic and hemodynamic data. CONCLUSIONS: Coronary artery endothelial function is heterogeneous in patients with idiopathic dilated cardiomyopathy. Endothelial dysfunction is present in approximately half of the cases and involves both resistance as well as conductance coronary blood vessels. Furthermore, coronary endothelial function cannot be predicted by demographic and hemo-dynamic parameters or left ventricular ejection fraction.