RESUMEN
Peripartum cardiomyopathy is a rare and life-threatening disease of unknown etiology. This diagnosis should be limited to previously healthy women who present with congestive heart failure (CHF) and decreased left ventricular systolic function in the last month of pregnancy or within 5 months after delivery. The diagnosis is not made in the presence of other causes of cardiac dysfunction. Patients who fail to demonstrate improvement within 2 weeks after the onset of symptoms should be evaluated for myocarditis. The type and duration of heart failure treatment is determined by the patient's heart performance at rest and with exertion. Those with normal left ventricular function at rest and with exercise or dobutamine have a good prognosis, and their medical therapy can be tapered off or discontinued over a period of 6-12 months. Patients with normal ventricular function at rest, but abnormal response to exercise should be treated for long periods of time with angiotensin converting enzyme (ACE) inhibitors or beta-blockers. Patients who continue to have depressed LV function have a poor prognosis and require treatment with appropriate medications for the rest of their lives. Pharmacological treatment includes ACE inhibitors, beta-blocking agents, diuretics, digoxin, and anticoagulation. Angiotensin converting enzyme inhibitors are used only after delivery because of their teratogenic effects. Patients who fail to recover may require inotropic therapy, intra-aortic balloon pump and left ventricular assist device as needed. Cardiac transplantation should be considered for patients who fail therapy.
Asunto(s)
Cardiomiopatías/terapia , Complicaciones Cardiovasculares del Embarazo/terapia , Adulto , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/etiología , Cardiomiopatías/fisiopatología , Fármacos Cardiovasculares/uso terapéutico , Femenino , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo/fisiopatología , PronósticoRESUMEN
BACKGROUND: Acute cellular rejection in cardiac allografts is a major cause of graft loss, and is associated with activation of the coagulation system. We investigated whether plasma markers of coagulation predict the presence of allograft rejection. METHODS: A total of 132 blood specimens and endomyocardial biopsies were collected from 35 patients, between February of 1997 and May of 1998. We measured plasma prothrombin fragment 1.2 (PF1.2) and p-selectin, fibrinogen, thrombomodulin, and d-dimer. Biopsies were graded according to the International Society of Heart and Lung Transplantation system, with a range of 0 to 4. Grades 0 and 1A were grouped as "no rejection," and the higher grades as "rejection." Linear and logistic regression, accounting for longitudinal data, were the principal analytic tools. RESULTS: p-Selectin level increased progressively with increasing rejection grade (P<0.001). With multivariate analysis, both p-selectin and prothrombin fragment levels significantly predicted rejection. p-Selectin levels were predictive of prothrombin fragment levels (P<0.0001) but not of d-dimer, fibrinogen, or thrombomodulin levels. This model allowed correct prediction of rejection, based on p-selectin and prothrombin fragment values, up to 85% of the time. Dichotomizing patients by a p-selectin level of 65 ng/ml resulted in an odds of rejection of 21.4 [95% C.I. 7.1-64.7] for the patients in the high- compared with the lower risk group. CONCLUSIONS: In heart transplant recipients, p-selectin levels and PF 1.2 levels are highly predictive of organ rejection. The elevation of PF 1.2 suggests that there is systemic generation of thrombin generation. These markers may be useful for noninvasively monitoring patients for organ rejection or for after response to treatment.
Asunto(s)
Coagulación Sanguínea , Rechazo de Injerto/epidemiología , Trasplante de Corazón/fisiología , Selectina-P/sangre , Fragmentos de Péptidos/análisis , Protrombina/análisis , Biomarcadores/sangre , Rechazo de Injerto/sangre , Trasplante de Corazón/inmunología , Humanos , Valor Predictivo de las Pruebas , Probabilidad , Pronóstico , Análisis de Regresión , Trombomodulina/análisis , Factores de TiempoRESUMEN
BACKGROUND: The reported mortality rate of peripartum cardiomyopathy (PPCM) is high, although the potential for spontaneous recovery of ventricular function is well established. The prevalence of myocarditis in PPCM has varied widely between studies. The purposes of this study were to define the long-term prognosis in a referral population of patients with PPCM, to determine the prevalence of myocarditis on endomyocardial biopsy in this population, and to identify clinical variables associated with poor outcome. METHODS: We analyzed clinical, echocardiographic, hemodynamic, and histologic features of 42 women with PPCM evaluated at our institution over a 15-year period. Each patient underwent an extensive evaluation, including echocardiography, endomyocardial biopsy, and right heart catheterization. Data were analyzed to identify features at initial examination associated with the combined end point of death or cardiac transplantation by the use of Kaplan-Meier survival curves and a Cox proportional hazards model. RESULTS: Three (7%) patients died and 3 (7%) patients underwent heart transplantation during a median follow-up of 8.6 years. Endomyocardial biopsy demonstrated a high prevalence of myocarditis (62%), but the presence or absence of myocarditis was not associated with survival. Of the prespecified variables assessed, only decreased left ventricular stroke work index was associated with worsened outcome. CONCLUSIONS: In patients with PPCM, (1) long-term survival is better than has been historically reported, (2) the prevalence of myocarditis is high, and (3) decreased left ventricular stroke work index is associated with worse clinical outcomes.
Asunto(s)
Cardiomiopatías/mortalidad , Miocarditis/mortalidad , Trastornos Puerperales/mortalidad , Adulto , Biopsia , Cateterismo Cardíaco , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/patología , Cardiomiopatías/fisiopatología , Factores de Confusión Epidemiológicos , Ecocardiografía , Femenino , Hemodinámica , Humanos , Maryland/epidemiología , Miocarditis/diagnóstico por imagen , Miocarditis/patología , Miocarditis/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Trastornos Puerperales/diagnóstico por imagen , Trastornos Puerperales/patología , Trastornos Puerperales/fisiopatología , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVES: We sought to use echocardiography to assess the presentation and potential for recovery of left ventricular (LV) function of patients with fulminant myocarditis compared with those with acute myocarditis. BACKGROUND: The clinical course of patients with myocarditis remains poorly defined. We have previously proposed a classification that provides prognostic information in myocarditis patients. Fulminant myocarditis causes a distinct onset of illness and severe hemodynamic compromise, whereas acute myocarditis has an indistinct presentation, less severe hemodynamic compromise and a greater likelihood of progression to dilated cardiomyopathy. METHODS: Echocardiography was performed at presentation and at six months to test the hypothesis that fulminant (n = 11) or acute (n = 43) myocarditis could be distinguished morphologically. RESULTS: Patients with both fulminant (fractional shortening 19 +/- 4%) and acute myocarditis (17 +/- 7%) had LV systolic dysfunction. Patients with fulminant myocarditis had near normal LV diastolic dimensions (5.3 +/- 0.9 cm) but increased septal thickness (1.2 +/- 0.2 cm) at presentation, while those with acute myocarditis had increased diastolic dimensions (6.1 +/- 0.8 cm, p < 0.01 vs. fulminant) but normal septal thickness (1.0 +/- 0.1 cm, p = 0.01 vs. fulminant). At six months, patients with fulminant myocarditis had dramatic improvement in fractional shortening (30 +/- 8%) compared with no improvement in patients with acute myocarditis (19 +/- 7%, p < 0.01 for interaction between time and type of myocarditis). CONCLUSIONS: Fulminant myocarditis is distinguishable from acute myocarditis by echocardiography. Patients with fulminant myocarditis exhibit a substantial improvement in ventricular function at six months compared with those with acute myocarditis. Echocardiography has value in classifying patients with myocarditis and may provide prognostic information.
Asunto(s)
Ecocardiografía , Miocarditis/diagnóstico por imagen , Enfermedad Aguda , Biopsia , Progresión de la Enfermedad , Frecuencia Cardíaca , Humanos , Contracción Miocárdica , Miocarditis/patología , Miocarditis/fisiopatología , Pronóstico , Presión Esfenoidal Pulmonar , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Previous studies of the prognosis of patients with heart failure due to cardiomyopathy categorized patients according to whether they had ischemic or nonischemic disease. The prognostic value of identifying more specific underlying causes of cardiomyopathy is unknown. METHODS: We evaluated the outcomes of 1230 patients with cardiomyopathy. The patients were grouped into the following categories according to underlying cause: idiopathic cardiomyopathy (616 patients), peripartum cardiomyopathy (51); and cardiomyopathy due to myocarditis (111), ischemic heart disease (91), infiltrative myocardial disease (59), hypertension (49), human immunodeficiency virus (HIV) infection (45), connective-tissue disease (39), substance abuse (37), therapy with doxorubicin (15), and other causes (117). Cox proportional-hazards analysis was used to assess the association between the underlying cause of cardiomyopathy and survival. RESULTS: During a mean follow-up of 4.4 years, 417 patients died and 57 underwent cardiac transplantation. As compared with the patients with idiopathic cardiomyopathy, the patients with peripartum cardiomyopathy had better survival (adjusted hazard ratio for death, 0.31; 95 percent confidence interval, 0.09 to 0.98), and survival was significantly worse among the patients with cardiomyopathy due to infiltrative myocardial disease (adjusted hazard ratio, 4.40; 95 percent confidence interval, 3.04 to 6.39), HIV infection (adjusted hazard ratio, 5.86; 95 percent confidence interval, 3.92 to 8.77), therapy with doxorubicin (adjusted hazard ratio, 3.46; 95 percent confidence interval, 1.67 to 7.18), and ischemic heart disease (adjusted hazard ratio, 1.52; 95 percent confidence interval, 1.07 to 2.17). CONCLUSIONS: The underlying cause of heart failure has prognostic value in patients with unexplained cardiomyopathy. Patients with peripartum cardiomyopathy appear to have a better prognosis than those with other forms of cardiomyopathy. Patients with cardiomyopathy due to infiltrative myocardial diseases, HIV infection, or doxorubicin therapy have an especially poor prognosis.
Asunto(s)
Cardiomiopatías/etiología , Cardiomiopatías/mortalidad , Adulto , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Isquemia Miocárdica/complicaciones , Embarazo , Complicaciones del Embarazo , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Lymphocytic myocarditis causes left ventricular dysfunction that may be persistent or reversible. There are no clinical criteria that predict which patients will recover ventricular function and which cases will progress to dilated cardiomyopathy. We hypothesized that patients with fulminant myocarditis may have a better long-term prognosis than those with acute (nonfulminant) myocarditis. METHODS: We identified 147 patients considered to have myocarditis according to the findings on endomyocardial biopsy and the Dallas histopathological criteria. Fulminant myocarditis was diagnosed on the basis of clinical features at presentation, including the presence of severe hemodynamic compromise, rapid onset of symptoms, and fever. Patients with acute myocarditis did not have these features. The incidence of the end point of this study, death or heart transplantation, was ascertained by contact with the patient or the patient's family or by a search of the National Death Index. The average period of follow-up was 5.6 years. RESULTS: A total of 15 patients met the criteria for fulminant myocarditis, and 132 met the criteria for acute myocarditis. Among the patients with fulminant myocarditis, 93 percent were alive without having received a heart transplant 11 years after biopsy (95 percent confidence interval, 59 to 99 percent), as compared with only 45 percent of those with acute myocarditis (95 percent confidence interval, 30 to 58 percent; P=0.05 by the log-rank test). Fulminant myocarditis was an independent predictor of survival after adjustments were made for age, histopathological findings, and hemodynamic variables. The rate of transplantation-free survival did not differ significantly between the patients considered to have borderline myocarditis and those considered to have active myocarditis according to the Dallas histopathological criteria. CONCLUSIONS: Fulminant myocarditis is a distinct clinical entity with an excellent long-term prognosis. Aggressive hemodynamic support is warranted for patients with this condition.
Asunto(s)
Trasplante de Corazón , Miocarditis/clasificación , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Biopsia , Femenino , Estudios de Seguimiento , Humanos , Linfocitos , Masculino , Miocarditis/complicaciones , Miocarditis/mortalidad , Miocarditis/terapia , Miocardio/inmunología , Miocardio/patología , Pronóstico , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Disfunción Ventricular Izquierda/etiologíaRESUMEN
OBJECTIVE: To determine the short-term safety and tolerability of the addition of ecadotril to conventional therapy in patients with mild to moderate heart failure. METHODS: Fifty ambulatory patients, 18 to 75 years of age, with mild to moderate heart failure, left ventricular ejection fraction
Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Profármacos/uso terapéutico , Tiorfan/análogos & derivados , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Índice de Severidad de la Enfermedad , Tiorfan/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Prolonged warm or cold ischemia is associated with poor survival of cardiac transplants, and ischemic changes in early posttransplantation endomyocardial biopsies correlate with the later development of chronic rejection. In animal models, tissue ischemia has been shown to activate complement. METHODS: To determine whether ischemic changes in endomyocardial biopsies were associated with complement deposition, biopsies obtained 1-3 weeks after transplantation from 33 patients were evaluated immunohistologically for C4d and C3d deposition as well as for IgM, IgG, and IgA. The histological changes associated with ischemic injury were scored independently, using previously reported criteria without knowledge of the immunohistochemical results. RESULTS: Diffuse capillary and pericapillary deposition of C4d or C3d were detected in endomyocardial biopsies of 14 of the 33 patients. The majority of biopsies (79%) with C4d or C3d deposits had histological evidence of ischemic injury, including eight of the nine biopsies containing both C4d and C3d deposition. In contrast, only 8 of 18 (45%) of the biopsies without C4d or C3d deposition had ischemic injury. Only trace amounts of IgM and no IgG or IgA were demonstrable in the biopsies. Only 2 of the 14 biopsies with C4d or C3d deposition had evidence of moderate acute rejection, whereas 5 of the 18 biopsies without C4d or C3d deposition had moderate acute rejection. However, C4d and C3d deposition did correlate with repeated acute rejection episodes on subsequent biopsies. CONCLUSIONS: Thus, ischemic changes are associated with the activation of complement. Complement activation may in turn promote tissue injury and provide a potential target for future treatment.
Asunto(s)
Complemento C4b , Proteínas del Sistema Complemento/metabolismo , Trasplante de Corazón/inmunología , Trasplante de Corazón/patología , Daño por Reperfusión/metabolismo , Adulto , Especificidad de Anticuerpos/inmunología , Reacciones Antígeno-Anticuerpo , Biopsia , Puente Cardiopulmonar , Complemento C3d/metabolismo , Complemento C4/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente Directa , Rechazo de Injerto/metabolismo , Humanos , Inmunoglobulinas/metabolismo , Masculino , Persona de Mediana Edad , Miocardio/patología , Adhesión en Parafina , Fragmentos de Péptidos/metabolismo , Factores de TiempoRESUMEN
This report describes the evaluation of 1,278 patients referred to The Johns Hopkins Hospital with dilated cardiomyopathy. After a careful history and physical examination, selected laboratory tests, and endomyocardial biopsy, a specific diagnosis was made in 49% of cases. In 16% of cases the biopsy demonstrated a specific histologic diagnosis. Myocarditis and coronary artery disease were the most frequent specific diagnoses; 51% of patients were classified as idiopathic. Thus a rigorous and systematic search can demonstrate an underlying cause for approximately one-half of patients with unexplained cardiomyopathy. Endomyocardial biopsy plays a crucial role in this evaluation. Six cases are presented which demonstrate the utility of endomyocardial biopsy in specific clinical situations. In addition to its routine use in monitoring rejection in heart transplant recipients, endomyocardial biopsy is indicated in the evaluation of possible infiltrative cardiomyopathy, in differentiating restrictive cardiomyopathy from constrictive pericarditis, and in diagnosing and monitoring doxorubicin cardiotoxicity. The importance of diagnosing myocarditis remains controversial, and disagreement persists about the utility of immunosuppressive therapy in these patients. A combination of clinical and histologic features can divide patients with myocarditis into 4 subgroups--acute, fulminant, chronic active, and chronic persistent. This classification provides prognostic information and may identify those patients who may respond to immunosuppression, as well as those likely to have adverse outcomes from such treatment. The continued development of novel molecular techniques may allow endomyocardial biopsy to provide greater prognostic and therapeutic information in the future.
Asunto(s)
Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/diagnóstico , Amiloidosis/tratamiento farmacológico , Antineoplásicos/envenenamiento , Cardiomiopatía Dilatada/tratamiento farmacológico , Diagnóstico Diferencial , Doxorrubicina/envenenamiento , Femenino , Cardiopatías/diagnóstico , Cardiopatías/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Miocarditis/complicaciones , Miocarditis/tratamiento farmacológico , Miocarditis/patología , Miocardio/patología , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Sarcoidosis/diagnóstico , Sarcoidosis/tratamiento farmacológicoRESUMEN
Successful strategies for avoiding obesity and hypercholesterolemia are difficult to validate because of imprecise problem identification. The purpose of this study was to describe the incidence, severity, and onset of obesity and hypercholesterolemia among heart transplant recipients and identify relationships between demographic variables and weight or cholesterol levels during the first year following transplantation. Data were collected from retrospective chart review. Forty-two patients were randomly selected from 224 patients who were undergoing heart transplantation at the Johns Hopkins Hospital between July 1983 and December 1995. Significant differences were found in weight and cholesterol level during the first 12 months. Patients with ideal body weight less than 110%, compared with greater than 110%, survived longer. Relationships were identified between prednisone dose and weight, cumulative prednisone dose and weight, and weight change and change in total cholesterol level 1 year following transplantation. Multivariate analysis showed cumulative prednisone as an independent predictor of weight. Obesity and hypercholesterolemia were significant problems within 3 months of transplantation. Although prednisone dosage should be adjusted to the lowest possible dose, dietary and lifestyle changes remain the foundation of effective management of these posttransplant complications.
Asunto(s)
Trasplante de Corazón/efectos adversos , Hipercolesterolemia/etiología , Obesidad/etiología , Adulto , Femenino , Cardiopatías/cirugía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Primary amyloidosis, systemic senile amyloidosis, isolated atrial amyloidosis, and transthyretin isoleucine 122 amyloidosis frequently involve the heart. Amyloid fibrils infiltrate the myocardium, impairing ventricular contraction and relaxation. The clinical manifestations of cardiac infiltration in these disorders are protean, though congestive heart failure and arrhythmias are most common. Treatment of cardiac amyloidosis is directed at the underlying cause and at relief of symptoms. Heart transplantation is not a viable treatment option for patients with primary amyloidosis; its role in the other amyloidoses has not been established. The prognosis of patients with cardiac amyloidosis varies and is largely determined by the underlying disorder responsible for amyloid infiltration.
Asunto(s)
Amiloidosis , Cardiomiopatías , Anciano , Amiloide/análisis , Humanos , Miocardio/patologíaRESUMEN
Quilty lesions, as first described by Billingham in 1981, or 'Quilty Effect' (QE) are distinct endomyocardial mononuclear cell infiltrates that have been observed in human heart transplant recipients, as well as in experimental models of heart transplantation. In the present investigations, the pattern and extent of apoptosis (programmed cell death) and myocyte necrosis, as well as specific lymphocyte subsets in Quilty lesions was assessed. Endomyocardial biopsies obtained from 13 patients at 10-3362 days post-transplant were examined. Apoptosis, as identified by DNA nick end-labeling, was found in myocytes at the periphery of Quilty lesions in 11 of 13 cases (85%), and 'early' stages of myocyte necrosis, as demonstrated by specific staining with alpha light chain myosin monoclonal antibodies (mAb), was observed at the same sites in 10 of 13 cases (77%) of both Quilty type A and type B lesions. Apoptosis was not identified in the lymphocyte infiltrates of any of the lesions examined. Lymphocyte subsets were characterized using mAb for T cell receptor (CD3), for helper/inducer T cells (CD4), for cytotoxic/suppressor T cells (CD8) and for mature B cells (CD20). Immunostaining revealed separate clusters of T lymphocytes with less prevalent B cells within the Quilty lesions. CD4+ cells were found in larger numbers than CD8+ cells in all cases. Non-B, non-T large lymphocytes were occasionally present. Except for the extent of the cellular infiltrate, no major cytochemical lymphocyte distribution differences were found between Quilty type A and B lesions. Myocyte apoptosis and early necrosis at the periphery of Quilty lesions suggest that early myocyte injury occurring in B lesions may represent initial or 'abortive stages' of cardiac allograft rejection. Why these lesions do not progress to overt rejection indeed warrant further detailed studies.
Asunto(s)
Apoptosis , Endocardio/patología , Trasplante de Corazón , Miocardio/patología , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/patología , Adolescente , Adulto , Anciano , Biopsia , Endocardio/inmunología , Femenino , Humanos , Inmunohistoquímica , Subgrupos Linfocitarios/citología , Masculino , Persona de Mediana Edad , Miocardio/inmunología , Miocardio/metabolismo , Cadenas Ligeras de Miosina/metabolismo , NecrosisRESUMEN
BACKGROUND: Dilated cardiomyopathy (DCM) is associated with a high incidence of malignant ventricular arrhythmias and sudden death. Abnormalities in repolarization of ventricular myocardium have been implicated in the development of these arrhythmias. Spatial heterogeneity in repolarization has been studied in DCM, but temporal fluctuations in repolarization in this setting have been largely ignored. We sought to test the hypothesis that beat-to-beat QT interval variability is increased in DCM patients compared with control subjects. METHODS AND RESULTS: Eighty-three patients with ischemic and nonischemic DCM and 60 control subjects served as the study population. Beat-to-beat QT interval variability was measured by automated analysis on the basis of 256-second records of the surface ECG. A QT variability index (QTVI) was calculated for each subject as the logarithm of the ratio of normalized QT variance to heart rate variance. The coherence between heart rate and QT interval fluctuations was determined by spectral analysis. In patients, ejection fractions were assessed by echocardiography or ventriculography, and spatial QT dispersion was determined from the standard 12-lead ECG. DCM patients had greater QT variance than control subjects (60.4+/-63.1 versus 25.7+/-24.8 ms2, P<.0001) despite reduced heart rate variance (6.7+/-7.8 versus 10.5+/-10.4 bpm2, P=.01). The QTVI was higher in DCM patients than in control subjects, with a high degree of significance (-0.43+/-0.71 versus -1.29+/-0.51, P<10[-12]). QTVI did not correlate with ejection fraction or spatial QT dispersion but did depend on New York Heart Association functional class. QTVI did not differ between DCM patients with ischemic and those with nonischemic origin. Coherence between heart rate and QT interval fluctuations at physiological frequencies was lower in DCM patients compared with control subjects (0.28+/-0.14 versus 0.39+/-0.18, P<.0001). CONCLUSIONS: DCM is associated with beat-to-beat fluctuations in QT interval that are larger than normal and uncoupled from variations in heart rate. QT interval variability increases with worsening functional class but is independent of ejection fraction. These data indicate that DCM leads to temporal lability in ventricular repolarization.
Asunto(s)
Cardiomiopatía Dilatada/fisiopatología , Electroencefalografía , Isquemia Miocárdica/fisiopatología , Adulto , Cardiomiopatía Dilatada/complicaciones , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Valores de Referencia , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Vesnarinone is a novel oral agent that improves survival and symptoms of patients with dilated cardiomyopathy. Although it is thought to have positive inotropic effects, clinical data supporting this mechanism in patients with severe heart failure remain scant. The present study tested whether 3 months of oral vesnarinone therapy increases the inotropic state and whether this response is dose dependent. Twenty-one patients with dilated cardiomyopathy (New York Heart Association class III to IV) were randomized to 30 mg/day (n = 11) or to 60 mg/day (n = 10) of vesnarinone. Cardiac function was assessed before and after therapy by radionuclide ventriculography to measure left ventricular volume and flow and by noninvasive measurement of the central aortic pressure wave. The inotropic effect of vesnarinone was assessed by a recently validated index equal to the ratio of left ventricular maximal ventricular power divided by the square of end-diastolic volume (PWRmax/ EDV2). This ratio is sensitive to inotropic change but is minimally altered by chamber loading. After 3 months of 60 mg/day therapy, PWRmax/EDV2 increased by 28 +/- 32%. Ejection fraction and cardiac output also increased by 21 +/- 14% and 14 +/- 14%, respectively, and arterial load decreased by 10.5 +/- 12.4% (all p < 0.005). End-systolic volume also declined by 7 +/- 10%, suggesting reverse remodeling. These changes were smaller and none achieved statistical significance at the 30 mg/day dose (e.g., 14.2 +/- 35.4% for PWRmax/ EDV2). Heart rate was unchanged with either dose. Thus, chronic vesnarinone treatment dose modestly raises the inotropic state and lowers afterload in patients with dilated cardiomyopathy in a dose-dependent fashion.
Asunto(s)
Cardiomiopatías/complicaciones , Cardiomiopatías/fisiopatología , Cardiotónicos/administración & dosificación , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/efectos de los fármacos , Quinolinas/administración & dosificación , Función Ventricular/efectos de los fármacos , Administración Oral , Cardiotónicos/farmacología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Pirazinas , Quinolinas/farmacología , Análisis de RegresiónRESUMEN
It has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids have been observed in the coronary arteries of allografted hearts, suggesting a possible role for the interaction of CMV with p53 in the development of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 19 transplanted hearts were immunostained for the p53 gene product using Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the anti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arteries were also available from six of the 19 hearts, and these fresh-frozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and weak staining for p53 was observed in smooth muscle and endothelial cells in two of 19 vessels, whereas the remaining 17 did not stain. CMV nucleic acids were previously shown in six of 13 of these hearts by in situ hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels did stain intensely for WAF1. These results suggest three possibilities: (1) CMV-p53 interactions are not important in the development of accelerated graft arteriosclerosis; or (2) there is an interaction, but it is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-E6. The expression of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels.
Asunto(s)
Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios/metabolismo , Ciclinas/fisiología , Infecciones por Citomegalovirus/complicaciones , Trasplante de Corazón/fisiología , Proteína p53 Supresora de Tumor/biosíntesis , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Citomegalovirus/aislamiento & purificación , Regulación de la Expresión Génica , Genes Inmediatos-Precoces/genética , Trasplante de Corazón/efectos adversos , Humanos , Hibridación in SituRESUMEN
INTRODUCTION: Bundle branch reentry and interfascicular reentry are potential mechanisms of ventricular tachycardia in the setting of a dilated cardiomyopathy. We report a patient with myotonic dystrophy who presented with near syncope, in whom both of these mechanisms were present, leading to two different wide complex tachycardias. METHODS AND RESULTS: Electrophysiologic study demonstrated infra-Hisian conduction system disease and inducible bundle branch reentrant ventricular tachycardia. Catheter ablation of the right bundle eliminated bundle branch reentry. However, following this, the patient had inducible interfascicular reentry, which subsequently occurred spontaneously while still hospitalized. Catheter ablation of the left posterior fascicle successfully eliminated this second tachycardia, and the patient has had no further arrhythmias. CONCLUSIONS: This report is of an unusual patient with coexistent bundle branch reentry and interfascicular reentry producing two different forms of sustained ventricular tachycardia. This is the first report of catheter ablation of the left posterior fascicle for elimination of conduction system reentry.
Asunto(s)
Bloqueo de Rama/cirugía , Ablación por Catéter , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Adulto , Bloqueo de Rama/complicaciones , Bloqueo de Rama/fisiopatología , Estimulación Cardíaca Artificial , Electrocardiografía , Femenino , Humanos , Distrofias Musculares/complicaciones , Taquicardia por Reentrada en el Nodo Atrioventricular/complicaciones , Taquicardia por Reentrada en el Nodo Atrioventricular/fisiopatologíaRESUMEN
BACKGROUND: Eosinophilic myocarditis is an inflammatory condition of the heart in which the infiltrate is composed predominately of eosinophils. DESIGN: We identified three cases of eosinophilic myocarditis in which the infiltrating eosinophils showed a remarkable intimate association with bundles of collagen. Two of the hearts examined were explants from heart transplant recipients with hypersensitivity myocarditis at the time of transplant and the third was from an autopsied patient with Churg-Strauss syndrome. These hearts were examined using light and electron microscopy. The cellular infiltrate in all three cases was characterized using immunoperoxidase stains with a panel including antibodies against myeloperoxidase, common leukocyte antigen (CD45), B lymphocytes (CD20), T lymphocytes (CD3), active-memory T lymphocytes (CD45RO), inactive T lymphocytes (CD45RA), and macrophages (CD68). RESULTS: Ultrastructural examination in all three cases confirmed the apposition of eosinophils to both large bundles of collagen and smaller aggregates of collagen fibrils. The eosinophils and the bundles of collagen stained strongly for myeloperoxidase, suggesting at least partial degranulation of the eosinophils. A KP-1 stain (CD68) revealed macrophages admixed with the eosinophils adjacent to the collagen bundles, and stains for CD45RA (naive lymphocytes) and CD45RO (memory T cells) showed an interstitial infiltrate of predominantly CD45RO-positive cells. Clinically, the cardiac decompensation of one of the transplant patients was most likely due to ranitidine-induced hypersensitivity myocarditis. CONCLUSIONS: These results suggest that some cases of eosinophilic myocarditis may be caused by the expression of novel antigens bound to collagen bundles. In one of the patients awaiting cardiac transplant, cardiac decompensation was temporally associated with ranitidine therapy, an agent not previously implicated as a cause of hypersensitivity myocarditis.