RESUMEN
BACKGROUND: Calcium antagonists have proved disappointing in long-term congestive heart failure (CHF) studies. Mibefradil, a new calcium antagonist that selectively blocks T-type calcium channels, has been shown to be an effective antihypertensive, antianginal, and anti-ischemic agent, and because of its different mechanism of action, it may be beneficial as adjunct therapy in CHF patients. METHODS AND RESULTS: This multicenter, randomized, double-blind study compared mibefradil with placebo as adjunct to usual therapy in 2590 CHF patients (NYHA class II to IV; left ventricular fraction <35%). The initial 50-mg daily dose of mibefradil was uptitrated to 100 mg after 1 month and continued up to 3 years. Patients were monitored at 1 week; 1, 2, and 3 months; and every 3 months thereafter. All-cause mortality, cardiovascular mortality, and cardiovascular morbidity/mortality were analyzed by use of the log-rank test (alpha=0.05). Substudies included exercise tolerance, plasma hormone and cytokines, echocardiography, and quality of life. Total mortality was similar between mibefradil- and placebo-treated patients (P=0.151). The 14% increased risk of mortality with mibefradil in the first 3 months was not statistically significant (P=0.093). Treatment groups had similar cardiovascular mortality (P=0.246), cardiovascular morbidity/mortality (P=0.783), and reasons for death or hospitalization. Patients comedicated with mibefradil and antiarrhythmics (class I or III), including amiodarone, had a significantly increased risk of death. Substudies demonstrated no significant differences between treatments. CONCLUSIONS: When used as adjunct therapy, mibefradil did not affect the usual outcome of CHF. The potential interaction with antiarrhythmic drugs, especially amiodarone, and drugs associated with torsade de pointes may have contributed to poor outcomes early in the study.
Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Mibefradil/uso terapéutico , Anciano , Bloqueadores de los Canales de Calcio/efectos adversos , Canales de Calcio Tipo T/efectos de los fármacos , Método Doble Ciego , Prueba de Esfuerzo , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Mibefradil/efectos adversos , Persona de Mediana Edad , Morbilidad , Mortalidad , Resistencia Física/efectos de los fármacosRESUMEN
BACKGROUND: There is increasing evidence of a link between conduit vessel stiffness and cardiovascular events, although the association has never been tested in a large post-myocardial infarction patient population. METHODS AND RESULTS: We evaluated the relationship between baseline pulse pressure, measured by sphygmomanometry 3 to 16 days after myocardial infarction, and subsequent adverse clinical events in the 2231 patients enrolled in the SAVE Trial. Increased pulse pressure was associated with increased age, left ventricular ejection fraction, female sex, history of prior infarction, diabetes, and hypertension and use of digoxin and calcium channel blockers. Over a 42-month period, there were 503 deaths, 422 cardiovascular deaths, and 303 myocardial infarctions. Pulse pressure was significantly related to each of these end points as a univariate predictor. In a multivariate analysis, pulse pressure remained a significant predictor of total mortality (relative risk, 1.08 per 10 mm Hg increment in pulse pressure; 95% CI, 1.00 to 1.17; P<.05) and recurrent myocardial infarction (relative risk, 1.12; 95% CI, 1.01 to 1.23; P<.05) after control for age; left ventricular ejection fraction; mean arterial pressure; sex; treatment arm (captopril or placebo); smoking history; history of prior myocardial infarction, diabetes, or hypertension; and treatment with beta-blockers, calcium channel blockers, digoxin, aspirin, or thrombolytic therapy. CONCLUSIONS: These data provide strong evidence for a link between pulse pressure, which is related to conduit vessel stiffness, and subsequent cardiovascular events after myocardial infarction in patients with left ventricular dysfunction.
Asunto(s)
Presión Sanguínea , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Disfunción Ventricular Izquierda/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Método Doble Ciego , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , EsfigmomanometrosRESUMEN
In patients with chronic coronary artery disease, preservation of myocardial oxidative metabolism measured by positron emission tomography (PET) with 11C-acetate is a more accurate predictor of subsequent myocardial functional recovery than is maintenance of glucose metabolism estimated with 18F-fluorodeoxyglucose. However, whether measurements of myocardial oxidative metabolism are more accurate than measurements of glucose metabolism in predicting functional recovery in patients with recent myocardial infarction is unknown. Myocardial oxidative metabolism was measured within 10 days of infarction in 19 patients by analysis of the rate of myocardial clearance of 11C-acetate. Metabolism of glucose was assessed by analysis of the uptake of 18F-fluorodeoxyglucose. Criteria for prediction of the recovery of function based on measurements of oxidative metabolism and glucose metabolism were compared. Threshold criteria with 11C-acetate exhibited superior positive and negative predictive values (89% and 73%, respectively) compared with the criteria of 18F-fluorodeoxyglucose (65% and 57%, respectively) (p <0.025). In addition, the magnitude of functional recovery after revascularization correlated with the severity of the metabolic abnormality present initially. In patients with recent myocardial infarction, the extent of functional recovery can be predicted accurately by measurement of regional oxidative metabolism by PET with 11C-acetate, and these measurements are superior to those of 18-fluorodeoxyglucose.
Asunto(s)
Acetatos/farmacocinética , Desoxiglucosa/análogos & derivados , Radioisótopos de Flúor/farmacocinética , Infarto del Miocardio/diagnóstico por imagen , Miocardio/metabolismo , Adulto , Anciano , Radioisótopos de Carbono , Enfermedad Crónica , Desoxiglucosa/farmacocinética , Femenino , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Consumo de Oxígeno , Valor Predictivo de las Pruebas , Sístole/fisiología , Tomografía Computarizada de Emisión , Función Ventricular Izquierda/fisiologíaRESUMEN
Criteria for the retrospective diagnosis of acute myocardial infarction rely heavily on increases in lactate dehydrogenase (LD) isoenzymes. However, increases of LD isoenzyme activities are not specific for myocardial injury. Recently, increased concentrations of cardiac troponin I (cTnI) have been shown to be highly specific for myocardial damage and to have sensitivity comparable with that of creatine kinase MB isoenzyme for detecting cardiac injury. Furthermore, increases of cTnI persist in plasma for at least several days. The present study was designed to determine the relative sensitivities of cTnI and LD isoenzymes over time for the diagnosis of infarction. The results indicate that cTnI values are at least as sensitive as LD isoenzymes: 90% of patients with myocardial infarction had above-normal concentrations of cTnI on the 4th day after admission to the coronary care unit. Criteria based on cTnI should improve the accuracy of retrospective diagnoses of acute myocardial infarction.
Asunto(s)
Creatina Quinasa/sangre , L-Lactato Deshidrogenasa/sangre , Infarto del Miocardio/diagnóstico , Troponina I/sangre , Animales , Perros , Electrocardiografía , Semivida , Humanos , Isoenzimas , Tasa de Depuración Metabólica , Infarto del Miocardio/sangre , Valores de Referencia , Análisis de Regresión , Sensibilidad y EspecificidadRESUMEN
Transthoracic two-dimensional (2D) Doppler echocardiography may provide new or additional information in patients, but it is often not known whether the results alter the treatment plan. We investigated whether results of clinically indicated 2D echocardiography were different from the physician's clinical examination or led to changes in management in 200 consecutive outpatients seen in a university-based clinic. A questionnaire was completed by the physician regarding physical findings and treatment plan before 2D echocardiography was performed. After results were known, the physician was asked to report any differences compared with clinical examination or changes in patient management. Most patients (83%) were studied to evaluate left ventricular (LV) or valvular function. 2D echocardiography confirmed clinical assessment in 182 patients (one inadequate 2D echocardiogram) and disclosed a new diagnosis in 17. 2D echocardiography provided additional information, not expected from clinical assessment or history, in 94 patients. Clinical assessment, compared with 2D echocardiography, was concordant in 154 (77%) of 199 patients with regard to LV systolic function but in only 22 (50%) of 44 with valve disease. Alterations in management based on results of 2D echocardiography were instituted in 73 patients (36%), most often manifested by changes in pharmacologic therapy (n = 45; 62%). Results of 2D echocardiography obviated the need for further cardiac evaluation, surgery, or procedures in 30 patients, avoiding additional patient charges of $125,754.00. In contrast, results of 2D echocardiography led to the need for further evaluation, surgery, or procedures in 32 patients, resulting in additional patient charges of $70,860.00. In conclusion, 2D echocardiography provides new or additional information that results in changes in management strategy in one third of patients, and 2D echocardiography offers relative cost savings by avoiding additional procedures.
Asunto(s)
Ecocardiografía Doppler , Cardiopatías/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Competencia Clínica , Costos y Análisis de Costo , Toma de Decisiones , Femenino , Cardiopatías/economía , Cardiopatías/terapia , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Examen Físico , Función Ventricular IzquierdaRESUMEN
With positron emission tomography, the resting flow abnormalities underlying reversible left ventricular dysfunction in 17 patients with chronic coronary artery disease were delineated. The level of flow in reversible dysfuncTional segments (i.e., those demonstrating improvement after revascularization) was markedly variable, ranging from 0.32 to 1.25 ml/gm/min. In 20 of these segments, flow was preserved, whereas in 12 segments, flow was reduced, when compared with that in, age-matched controls. Preservation of flow was associated with preservation of myocardial oxygen consumption and no alterations in myocardial substrate use. In contrast, a reduction in flow resulted in a decrease myocardial oxygen consumption and an increase in myocardial glucose use. Thus resting reversible left ventricular dysfunction in patients with chronic coronary artery disease can reflect a diversity of resting flow abnormalities. Moreover, myocardial perfusion at rest is frequently within normal limits, suggesting that the reversible mechanical dysfunction in these patients is attributable to intermittent myocardial stunning and not hibernation.
Asunto(s)
Enfermedad Coronaria/diagnóstico por imagen , Aturdimiento Miocárdico/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Adulto , Anciano , Enfermedad Crónica , Enfermedad Coronaria/etiología , Enfermedad Coronaria/fisiopatología , Enfermedad Coronaria/terapia , Femenino , Glucosa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Reperfusión Miocárdica , Aturdimiento Miocárdico/etiología , Aturdimiento Miocárdico/fisiopatología , Aturdimiento Miocárdico/terapia , Miocardio/metabolismo , Cintigrafía , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/terapiaRESUMEN
The Survival and Ventricular Enlargement (SAVE) Study demonstrated that long-term administration of the angiotensin-converting enzyme inhibitor captopril to recent survivors of myocardial infarction with left ventricular dysfunction resulted in a reduction in cardiovascular mortality and morbidity. Analysis of multiple subgroups demonstrated that baseline demographics (older age) and clinical characteristics (such as prior MI, history of diabetes or hypertension), that have previously been associated with a higher risk of cardiovascular events, were associated with greater end point event rates in SAVE regardless of therapy assignment at the time of randomization. The effectiveness of captopril therapy in reducing cardiovascular mortality and morbidity was examined in multiple subgroups. Although not all subgroups provided adequate statistical power, the benefits of captopril therapy were relatively uniform in the SAVE study. This indicates that the benefits were not confined to one particular subgroup and conversely that targeting of captopril therapy should be to the broadest group, as defined by SAVE entry criteria, to result in a reduction in cardiovascular mortality and morbidity.
Asunto(s)
Captopril/uso terapéutico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Estudios de Cohortes , Interpretación Estadística de Datos , Método Doble Ciego , Femenino , Humanos , Hipertrofia Ventricular Izquierda/mortalidad , Tablas de Vida , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Factores de RiesgoRESUMEN
A quality of life ancillary study was incorporated into the Survival and Ventricular Enlargement (SAVE) trial of captopril versus placebo among patients who survived an acute myocardial infarction with compromised ventricular functioning, but no overt heart failure. Assessments included patient symptoms, health perceptions, emotional, cognitive, social and sexual levels of functioning, as well as potential covariates, such as life events and social support. The purpose of this study was to evaluate the psychometric properties of the quality of life measures in the SAVE at baseline, and provide a pre-randomization profile of the SAVE patients. One hundred and eighty-four patients participated in this aspect of the trial. Reliability alpha coefficients were adequate or better for all questionnaires, except for life events and sexual activities. Consistent with prior studies, the quality of life parameters were uncorrelated with ventricular ejection fraction. Despite experiencing a recent myocardial infarction with compromised ventricular functioning, patients at baseline generally neither appeared depressed nor focused on symptoms. The baseline findings support the inclusion of the quality of life ancillary study in the overall SAVE trial because of the independent contribution likely to be achieved in terms of evaluating both disease progression and treatment efficacy.
Asunto(s)
Infarto del Miocardio/mortalidad , Calidad de Vida , Adulto , Anciano , Captopril/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/fisiopatología , Placebos , Sobrevivientes , Función Ventricular IzquierdaRESUMEN
The myocardium has the capacity to utilize a variety of metabolic substrates, including long-chain fatty acids, ketone bodies, glucose, lactate, and amino acids. Under most conditions long-chain fatty acids constitute the major myocardial energy source. Imaging of long-chain fatty acids can be accomplished with carbon 11-labeled palmitate (1-11C-palmitate) and positron emission tomography. Imaging can be performed in either static or dynamic modes. In normal subjects accumulation of the tracer is homogeneous throughout the heart. In patients with myocardial infarction, distinct defects in accumulation are seen. In dilated cardiomyopathy, uptake is spatially heterogeneous. Clearance of 1-11C-palmitate in normal myocardium is biexponential and homogeneous throughout the heart. Administration of glucose, or feeding, decreases uptake of the tracer into the early rapid turnover pool and decreases clearance of the tracer from that pool. In normal myocardium atrial pacing increases the rate of clearance; in ischemic myocardium the degree of increased clearance is attenuated. In patients with cardiomyopathy caused by long-chain fatty acid coenzyme A dehydrogenase deficiency, 1-11C-palmitate clearance is diminished compared with total myocardial oxygen consumption traced with carbon 11-labeled acetate. Thus positron emission tomography with 1-11C-palmitate permits assessment of patients with ischemic heart disease and cardiomyopathy of diverse causes, providing insights into both pathophysiologic mechanisms and the effectiveness of various therapeutic interventions.
Asunto(s)
Radioisótopos de Carbono , Miocardio/metabolismo , Ácido Palmítico/metabolismo , Cardiomiopatía Dilatada/metabolismo , Humanos , Tomografía Computarizada de EmisiónRESUMEN
OBJECTIVES: This study was designed to determine in patients with advanced coronary disease whether prediction of recovery of mechanical function after coronary revascularization could be accomplished more effectively by positron emission tomography (PET) with carbon-11 (11C)-acetate than by PET with fluorine-18 (18F)-fluorodeoxyglucose. BACKGROUND: Results of previous studies have demonstrated that preservation of myocardial oxidative metabolism (measured by PET with 11C-acetate) is necessary for recovery of systolic function after coronary revascularization. METHODS: Myocardial oxidative metabolism was quantified before revascularization in 34 patients by the analysis of the rate of myocardial clearance of 11C-acetate. Metabolism of glucose was assessed by analysis of uptake of 18F-fluorodeoxyglucose. Receiver operating characteristic curves for predicting functional recovery were derived for the measurements of oxidative metabolism and glucose metabolism. In addition, criteria for prediction of recovery of function based on measurements of oxidative metabolism and glucose metabolism were developed and compared. RESULTS: Analysis of receiver operating characteristic curves indicated that estimates of oxidative metabolism were more robust in predicting functional recovery than were estimates of glucose metabolism (p < 0.02). Moreover, threshold criteria with 11C-acetate exhibited superior positive and negative predictive values (67% and 89%, respectively) than did the criteria with 18F-fluorodeoxyglucose (52% and 81%, respectively), p < 0.01. In segments with initially severe dysfunction, estimates of oxidative metabolism tended to be more robust than estimates of glucose metabolism in predicting functional recovery. Moreover, in such segments, the threshold criteria with 11C-acetate tended to exhibit superior positive and negative predictive values (85% and 87%, respectively) than did the criteria with 18F-fluorodeoxyglucose (72% and 82%, respectively), although statistical significance was not achieved. CONCLUSIONS: In patients with advanced coronary artery disease, the extent to which functional recovery can be anticipated after coronary revascularization can be delineated accurately by quantification of regional oxidative metabolism by PET with 11C-acetate.
Asunto(s)
Radioisótopos de Carbono , Enfermedad Coronaria/diagnóstico por imagen , Desoxiglucosa/análogos & derivados , Radioisótopos de Flúor , Tomografía Computarizada de Emisión/métodos , Acetatos , Ácido Acético , Adulto , Anciano , Circulación Coronaria/fisiología , Enfermedad Coronaria/metabolismo , Enfermedad Coronaria/terapia , Desoxiglucosa/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica , Oxidación-Reducción , Valor Predictivo de las Pruebas , Sístole/fisiologíaRESUMEN
OBJECTIVES: This study was conducted to assess the utility of dobutamine stress echocardiography for determining the presence of significant coronary artery disease and for predicting surgical outcome and long-term prognosis in patients scheduled to undergo peripheral vascular or aortic aneurysm surgery. BACKGROUND: Assessment of coronary artery disease in patients scheduled to undergo peripheral vascular surgery can avoid perioperative complications. METHODS: Dobutamine stress echocardiography was performed in 98 consecutive patients scheduled to undergo aortic or peripheral vascular surgery. Intravenous dobutamine was infused in a graded fashion, with two-dimensional digital echocardiographic monitoring of ventricular function and segmental wall motion. Group 1 (n = 70) consisted of patients who exhibited a normal response to dobutamine infusion (negative dobutamine study); group 2 (n = 23) comprised those patients with an abnormal response to dobutamine, characterized by the development of new or worsening wall motion abnormalities at rest, indicating the presence of myocardial ischemia (positive dobutamine study). Five patients with an inconclusive dobutamine study (because of inadequate heart rate) were excluded from analysis. RESULTS: No major adverse effects occurred with testing in any patient. Sixty-eight of 70 patients with a negative study had peripheral vascular or aortic surgery performed without perioperative cardiac events (2 patients refused surgery). Nineteen of 23 patients with a positive study underwent coronary angiography and all had > 50% lumen narrowing in one or more major coronary artery distributions; 13 underwent coronary artery bypass grafting or angioplasty before peripheral vascular or aortic surgery and all had an uneventful perioperative period. Four of the 10 patients from group 2 who did not undergo coronary revascularization had a perioperative cardiac event (myocardial infarction in 2, an ischemic episode requiring urgent coronary bypass grafting in 1 and congestive heart failure in 1). CONCLUSIONS: Positive and negative dobutamine study results are significant predictors of the presence or absence of perioperative events (20% vs. 0%, p = 0.003). A positive test warrants coronary angiography and further medical or surgical intervention, or both, but a negative test indicates a low likelihood of perioperative cardiac complications of aortic or peripheral vascular surgery. During the long-term follow-up period in this study (group 1 mean, 24 months; group 2 mean, 15 months), two patients (3%) from group 1 and three (15%) from group 2 developed cardiac complications (p = 0.038). Thus, dobutamine stress echocardiography is safe and can predict surgical outcome in patients undergoing aortic aneurysm repair or surgery for occlusive disease of the peripheral arteries. In addition, a negative test result is a strong predictor of decreased perioperative and long-term cardiac morbidity and mortality.
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Aneurisma de la Aorta/cirugía , Enfermedad Coronaria/diagnóstico por imagen , Dobutamina , Ecocardiografía , Prueba de Esfuerzo/métodos , Enfermedades Vasculares Periféricas/cirugía , Anciano , Aneurisma de la Aorta/complicaciones , Cineangiografía , Angiografía Coronaria , Enfermedad Coronaria/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/epidemiología , Enfermedades Vasculares Periféricas/complicaciones , Cuidados Preoperatorios , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: There are major differences in the organization of the health care systems in Canada and the United States. We hypothesized that these differences may be accompanied by differences in patient care. METHODS: To test our hypothesis, we compared the treatment patterns for patients with acute myocardial infarction in 19 Canadian and 93 United States hospitals participating in the Survival and Ventricular Enlargement (SAVE) study, which tested the effectiveness of captopril in this population of patients after a myocardial infarction. RESULTS: In Canada, 51 percent of the patients admitted to a participating coronary care unit had acute myocardial infarctions, as compared with only 35 percent in the United States (P < 0.001). Despite the similar clinical characteristics of the 1573 U.S. patients and 658 Canadian patients participating in the study, coronary arteriography was more commonly performed in the United States than in Canada (in 68 percent vs. 35 percent, P < 0.001), as were revascularization procedures before randomization (31 percent vs. 12 percent, P < 0.001). During an average follow-up of 42 months, these procedures were also performed more commonly in the United States than in Canada. These differences were not associated with any apparent difference in mortality (22 percent in Canada and 23 percent in the United States) or rate of reinfarction (14 percent in Canada and 13 percent in the United States), but there was a higher incidence of activity-limiting angina in Canada than in the United States (33 percent vs. 27 percent, P < 0.007). CONCLUSIONS: The threshold for the admission of patients to a coronary care unit or for the use of invasive diagnostic and therapeutic interventions in the early and late periods after an infarction is higher in Canada than in the United States. This is not associated with any apparent difference in the rate of reinfarction or survival, but is associated with a higher frequency of activity-limiting angina.
Asunto(s)
Unidades de Cuidados Coronarios/estadística & datos numéricos , Infarto del Miocardio/terapia , Pautas de la Práctica en Medicina/estadística & datos numéricos , Angina de Pecho/epidemiología , Canadá , Captopril/uso terapéutico , Angiografía Coronaria/estadística & datos numéricos , Estudios de Seguimiento , Humanos , Infarto del Miocardio/mortalidad , Revascularización Miocárdica/estadística & datos numéricos , Calidad de la Atención de Salud , Distribución Aleatoria , Recurrencia , Resultado del Tratamiento , Estados UnidosRESUMEN
Accelerated graft atherosclerosis is a major cause of death after cardiac transplantation. Although its detection currently requires surveillance angiography, loss of vasodilator responsivity may precede obstructive lesions and be detectable by noninvasive assessment of myocardial perfusion. Thirty-five allograft recipients were studied an average of 31 +/- 19 (mean +/- SD) months after transplantation. All were free from angiographically definable macrovascular obstructive coronary artery lesions. Nutritive myocardial perfusion at rest, estimated in absolute terms by positron emission tomography with oxygen-15 water averaged 1.63 +/- 0.51 ml/g/min in patients and was greater than that in 26 healthy volunteers (1.17 +/- 0.33 ml/g/min, p < 0.001). The increase correlated with increased cardiac work at rest in transplant recipients with arterial hypertension and tachycardia. Peak myocardial perfusion induced by intravenous administration of dipyridamole was normal in the transplant recipients (3.49 +/- 1.70 ml/g/min compared with 3.60 +/- 1.41 ml/g/min in volunteers). Because of the high flow at rest, myocardial perfusion reserve (the ratio of hyperemic flow to flow at rest) was diminished (2.3 +/- 1.2 compared with 3.3 +/- 1.5 in volunteers, p < 0.005). These results indicate that the responsivity to vasodilator stimulation is well preserved in transplant recipients devoid of macroscopic coronary arterial lesions obviating detection of early vascular dysfunction in individual subjects. Positron emission tomography may be useful, however, in quantifying the magnitude of the increase in flow at rest secondary to increased cardiac work--a potentially remedial cause of accelerated coronary vascular disease induced by high shear force activation of platelets in the coronary bed, and in detecting impaired perfusion once macrovascular vascular disease is extant.
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Vasos Coronarios/fisiopatología , Trasplante de Corazón/fisiología , Vasodilatación , Adulto , Anciano , Radioisótopos de Carbono , Circulación Coronaria/efectos de los fármacos , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/fisiopatología , Enfermedad Coronaria/cirugía , Vasos Coronarios/diagnóstico por imagen , Dipiridamol , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Radioisótopos de Oxígeno , Periodo Posoperatorio , Tomografía Computarizada de Emisión/instrumentación , Tomografía Computarizada de Emisión/métodos , Trasplante Homólogo , Vasodilatación/efectos de los fármacosRESUMEN
Left ventricular dilation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, long-term therapy with captopril, an angiotension-converting enzyme inhibitor, decreased ventricular dilation and rearrangement. This study was undertaken to examine whether captopril may reduce morbidity and mortality in patients with left ventricular dysfunction following myocardial infarction. On days 3 to 16 after myocardial infarction, 2231 patients with <40% ejection fraction, but without signs of obvious heart failure ot symptoms of myocardial ischemia were studied in a double-blind study, of them 1116 took placebo and 1115 had captopril. The follow-up averaged 42 months. The mortabity due to any causes was significantly lower in the captopril group (228 deaths or 20% than in the placebo group (275 deaths or 25%). The decrease in the risk was 19 percent (95 percent confidence interval, 3 to 32 percent; p = 0.019). The incidence of fatal and grave nonfatal cardiovascular events significantly decreased in captopril-treated patients. The risk decrease was 21 percent (95 percent confidence interval, 5 to 35 percent; p = 0.014) for cardiovascular mortality; 37 percent (95 percent confidence interval, 20 to 50 percent; p < 0.001) for the development of severe heart failure; 22 percent (95 percent confidence, 4 to 37 percent, p = 0.019) for congestive heart failure requiring hospitalization; 25 percent (95 percent confidence interval, 5 to 40 percent; p = 0.015) for recurrent myocardial infarction. Thus, long-term captopril use in patients with asymptomatic left ventricular dysfunction following prior myocardial infarction resulted in survival improvement and decreased morbidity and mortality due to severe cardiovascular events. There were positive results both in patients treated with thrombolytics, aspirin or <$Ebeta>-blockers and in those untreated with the above drugs. This suggests that the use of captopril additionally improved the therapeutic outcomes in patients with prior myocardial infection.
Asunto(s)
Captopril/uso terapéutico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Infarto del Miocardio/complicaciones , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Gasto Cardíaco Bajo/tratamiento farmacológico , Gasto Cardíaco Bajo/epidemiología , Gasto Cardíaco Bajo/etiología , Gasto Cardíaco Bajo/fisiopatología , Intervalos de Confianza , Método Doble Ciego , Quimioterapia Combinada , Femenino , Fibrinolíticos/uso terapéutico , Estudios de Seguimiento , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Humanos , Hipertrofia Ventricular Izquierda/mortalidad , Masculino , Persona de Mediana Edad , Morbilidad , Infarto del Miocardio/fisiopatología , Pronóstico , Recurrencia , Factores de Riesgo , Volumen Sistólico , Tasa de Supervivencia , Factores de Tiempo , Función Ventricular IzquierdaRESUMEN
OBJECTIVES: This study was performed to define the importance of maintenance of oxidative metabolism as a descriptor and determinant of functional recovery after revascularization in patients with left ventricular dysfunction attributable to chronic coronary artery disease. BACKGROUND: Although myocardial accumulation of 18F-fluorodeoxyglucose indicates the presence of tissue that is metabolically active, it may not identify those metabolic processes required for restoration of myocardial contractility. Experimental studies suggest that, under conditions of ischemia and reperfusion, maintenance of myocardial oxidative metabolism is an important metabolic determinant of the capacity for functional recovery. METHODS: In 16 patients positron emission tomography was performed to characterize myocardial perfusion (with H(2)15O), oxidative metabolism (with 11C-acetate) and utilization of glucose (with 18F-fluorodeoxyglucose). Dysfunctional but viable myocardium was differentiated from nonviable myocardium on the basis of assessments of regional function before and after coronary revascularization. To define the importance of coronary revascularization on myocardial perfusion and metabolism, tomography was repeated in 11 patients after revascularization. RESULTS: Before revascularization, perfusion in 24 dysfunctional but viable myocardial segments and 29 nonviable segments averaged 79% and 74%, respectively, of that in 42 normal myocardial segments (both p less than 0.01). Dysfunctional but viable myocardium exhibited oxidative metabolism comparable to that in normal myocardium. In contrast, in nonviable myocardium, oxidative metabolism was only 66% of that in normal (p less than 0.01) and 69% of that in reversibly dysfunctional myocardium (p less than 0.003). Regional utilization of glucose normalized to regional perfusion in dysfunctional but viable myocardium was greater than that in normal myocardium (p less than 0.01). However, in both reversibly and persistently dysfunctional myocardium, utilization of glucose normalized to relative perfusion was markedly variable. CONCLUSIONS: The results indicate that preservation of oxidative metabolism is a necessary condition for recovery of function after coronary recanalization in patients with chronic coronary artery disease. Consequently, approaches that measure myocardial oxygen consumption, such as dynamic positron emission tomography with 11C-acetate, should facilitate the identification of those patients most likely to benefit from coronary revascularization.
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Enfermedad Coronaria/metabolismo , Miocardio/metabolismo , Adulto , Anciano , Enfermedad Crónica , Circulación Coronaria/fisiología , Enfermedad Coronaria/terapia , Femenino , Glucosa/metabolismo , Corazón/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica , Oxidación-Reducción , Tomografía Computarizada de Emisión , Resultado del Tratamiento , Función VentricularRESUMEN
BACKGROUND: Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. METHODS: Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. RESULTS: Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. CONCLUSIONS: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.
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Captopril/uso terapéutico , Cardiomegalia/tratamiento farmacológico , Infarto del Miocardio/complicaciones , Función Ventricular Izquierda , Adulto , Captopril/administración & dosificación , Captopril/efectos adversos , Cardiomegalia/mortalidad , Cardiomegalia/fisiopatología , Enfermedades Cardiovasculares/mortalidad , Método Doble Ciego , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Cooperación del Paciente , Volumen Sistólico , Tasa de SupervivenciaRESUMEN
This study was performed to define the importance of maintenance of oxidative metabolism as a descriptor and determinant of the potential for functional recovery after revascularization in patients with recent myocardial infarction. In 11 patients (mean interval after infarction 6 days; 5 patients given thrombolytic therapy), positron emission tomography (PET) was performed to characterize myocardial perfusion (with oxygen-15-labeled water), glucose utilization (with fluorine-18-fluorodeoxyglucose) and oxidative metabolism (with carbon-11-acetate). Dysfunctional but viable myocardium was differentiated from nonviable myocardium by assessments of regional function before and after coronary revascularization. The impact of coronary revascularization on regional myocardial perfusion and metabolism was assessed in nine patients in whom tomography was repeated after revascularization. Before revascularization, dysfunctional but viable myocardium (19 segments) and nonviable myocardium (10 segments) exhibited relative perfusion equivalent to 74% and 63% of that of normal myocardium (33 segments), respectively (p less than 0.02). Dysfunctional but viable myocardium exhibited oxidative metabolism equivalent to 74% of that of normal myocardium (p less than 0.02). In contrast, in nonviable myocardium, oxidative metabolism was only 45% of that seen in normal (p less than 0.02) and 60% of that in reversibly dysfunctional myocardium (p less than 0.003). Regional glucose utilization (normalized to regional perfusion) in dysfunctional but viable myocardium was higher than that in normal myocardium (p less than 0.02). Nonviable myocardium exhibited lower levels of glucose utilization than did normal tissue (p less than 0.02). However, in both reversibly and persistently dysfunctional myocardium utilization of glucose normalized to relative perfusion was markedly variable.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Contracción Miocárdica/fisiología , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Oxígeno/metabolismo , Adulto , Anciano , Angioplastia Coronaria con Balón , Puente de Arteria Coronaria , Circulación Coronaria , Femenino , Glucosa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Terapia Trombolítica , Tomografía Computarizada de Emisión , Resultado del Tratamiento , Función VentricularRESUMEN
Aging is accompanied by a decline in many aspects of cardiovascular function but little is known regarding its influence on myocardial perfusion. Eleven young adults (mean age 25 +/- 4 (s.d.) yr) and 15 older adults (mean age 55 +/- 9 yr) without history or symptoms of cardiovascular disease were studied using H2 15O and positron emission tomography under resting conditions and following administration of intravenous dipyridamole. Myocardial perfusion at rest was similar in the older and younger subjects, averaging 1.17 +/- 0.35 and 1.16 +/- 0.32 ml/g/min, respectively (p = ns). Following dipyridamole, peak myocardial perfusion was blunted in the older subjects, averaging 3.12 +/- 1.09 ml/g/min compared with 4.25 +/- 1.54 ml/g/min in the young adults (p = 0.044). Accordingly, present standards for normal perfusion responses to intravenous dipyridamole may require adjustment for age.
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Envejecimiento/fisiología , Corazón/diagnóstico por imagen , Hemodinámica/fisiología , Tomografía Computarizada de Emisión , Adulto , Anciano , Dipiridamol , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioisótopos de Oxígeno , Valores de Referencia , AguaRESUMEN
The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies.
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Cardiomiopatías/diagnóstico por imagen , Corazón/diagnóstico por imagen , Miocardio/metabolismo , Tomografía Computarizada de Emisión , Radioisótopos de Carbono , Cardiomiopatías/metabolismo , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/metabolismo , Humanos , Distrofias Musculares/diagnóstico por imagen , Distrofias Musculares/metabolismo , Ácido Palmítico , Ácidos Palmíticos/metabolismo , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Despite the fact that coronary artery disease is the leading cause of death among women, previous studies have suggested that physicians are less likely to pursue an aggressive approach to coronary artery disease in women than in men. To define this issue further, we compared the care previously received by men and women who were enrolled in a large postinfarction intervention trial. METHODS: We assessed the nature and severity of anginal symptoms and the use of antianginal and antiischemic interventions before enrollment in the 1842 men and 389 women with left ventricular ejection fractions less than or equal to 40 percent after an acute myocardial infarction who were randomized in the Survival and Ventricular Enlargement trial. RESULTS: Before their index infarction, women were as likely as men to have had angina and to have been treated with antianginal drugs. However, despite reports by women of symptoms consistent with greater functional disability from angina, fewer women had undergone cardiac catheterization (15.4 percent of women vs. 27.3 percent of men, P less than 0.001) or coronary bypass surgery (5.9 percent of women vs. 12.7 percent of men, P less than 0.001). When these differences were adjusted for important covariates, men were still twice as likely to undergo an invasive cardiac procedure as women, but bypass surgery was performed with equal frequency among the men and women who did undergo cardiac catheterization. CONCLUSIONS: Physicians pursue a less aggressive management approach to coronary disease in women than in men, despite greater cardiac disability in women.