RESUMO
BACKGROUND: Long-term results from randomized, controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited. METHODS: We assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 to 43 were randomly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary outcome was a glycated hemoglobin level of 6.0% or less with or without the use of diabetes medications. RESULTS: Of the 150 patients who underwent randomization, 1 patient died during the 5-year follow-up period; 134 of the remaining 149 patients (90%) completed 5 years of follow-up. At baseline, the mean (±SD) age of the 134 patients was 49±8 years, 66% were women, the mean glycated hemoglobin level was 9.2±1.5%, and the mean BMI was 37±3.5. At 5 years, the criterion for the primary end point was met by 2 of 38 patients (5%) who received medical therapy alone, as compared with 14 of 49 patients (29%) who underwent gastric bypass (unadjusted P=0.01, adjusted P=0.03, P=0.08 in the intention-to-treat analysis) and 11 of 47 patients (23%) who underwent sleeve gastrectomy (unadjusted P=0.03, adjusted P=0.07, P=0.17 in the intention-to-treat analysis). Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone (2.1% vs. 0.3%, P=0.003). At 5 years, changes from baseline observed in the gastric-bypass and sleeve-gastrectomy groups were superior to the changes seen in the medical-therapy group with respect to body weight (-23%, -19%, and -5% in the gastric-bypass, sleeve-gastrectomy, and medical-therapy groups, respectively), triglyceride level (-40%, -29%, and -8%), high-density lipoprotein cholesterol level (32%, 30%, and 7%), use of insulin (-35%, -34%, and -13%), and quality-of-life measures (general health score increases of 17, 16, and 0.3; scores on the RAND 36-Item Health Survey ranged from 0 to 100, with higher scores indicating better health) (P<0.05 for all comparisons). No major late surgical complications were reported except for one reoperation. CONCLUSIONS: Five-year outcome data showed that, among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing, or in some cases resolving, hyperglycemia. (Funded by Ethicon Endo-Surgery and others; STAMPEDE ClinicalTrials.gov number, NCT00432809 .).
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Derivação Gástrica , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Obesidade/complicações , Adulto , Glicemia/análise , Índice de Massa Corporal , HDL-Colesterol/sangue , Terapia Combinada , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
OBJECTIVE: This study investigated the effect of type 2 diabetes duration on glucose regulation 24 months post-bariatric surgery. METHODS: Twenty-seven adults with short- (<5 years) and long-duration (≥10 years) type 2 diabetes received a mixed-meal tolerance test at baseline and 24 months postsurgery. Body weight, insulin sensitivity, first- and second-phase meal-stimulated insulin secretion, disposition index (i.e., DI or pancreatic ß-cell function), and incretin responses were examined. RESULTS: Adults with short-duration type 2 diabetes had better HbA(1c), greater insulin secretory capacity, and greater DI compared with adults with long-duration type 2 diabetes, despite similar weight loss and incretin responses. Diabetes duration correlated with smaller improvements in HbA(1c) and DI but not weight loss. CONCLUSIONS: Enhanced ß-cell function characterizes the effect of bariatric surgery in adults with diabetes for <5 years, independent of weight loss or incretins. Additional therapy postsurgery may be required to improve glycemia for people with long-standing type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Adulto , Cirurgia Bariátrica , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Índice Glicêmico , Humanos , Incretinas/metabolismo , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos ProspectivosRESUMO
BACKGROUND: In short-term randomized trials (duration, 1 to 2 years), bariatric surgery has been associated with improvement in type 2 diabetes mellitus. METHODS: We assessed outcomes 3 years after the randomization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary end point was a glycated hemoglobin level of 6.0% or less. RESULTS: The mean (±SD) age of the patients at baseline was 48±8 years, 68% were women, the mean baseline glycated hemoglobin level was 9.3±1.5%, and the mean baseline body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.0±3.5. A total of 91% of the patients completed 36 months of follow-up. At 3 years, the criterion for the primary end point was met by 5% of the patients in the medical-therapy group, as compared with 38% of those in the gastric-bypass group (P<0.001) and 24% of those in the sleeve-gastrectomy group (P=0.01). The use of glucose-lowering medications, including insulin, was lower in the surgical groups than in the medical-therapy group. Patients in the surgical groups had greater mean percentage reductions in weight from baseline, with reductions of 24.5±9.1% in the gastric-bypass group and 21.1±8.9% in the sleeve-gastrectomy group, as compared with a reduction of 4.2±8.3% in the medical-therapy group (P<0.001 for both comparisons). Quality-of-life measures were significantly better in the two surgical groups than in the medical-therapy group. There were no major late surgical complications. CONCLUSIONS: Among obese patients with uncontrolled type 2 diabetes, 3 years of intensive medical therapy plus bariatric surgery resulted in glycemic control in significantly more patients than did medical therapy alone. Analyses of secondary end points, including body weight, use of glucose-lowering medications, and quality of life, also showed favorable results at 3 years in the surgical groups, as compared with the group receiving medical therapy alone. (Funded by Ethicon and others; STAMPEDE ClinicalTrials.gov number, NCT00432809.).
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Derivação Gástrica , Hipoglicemiantes/uso terapêutico , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , LDL-Colesterol/sangue , Terapia Combinada , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Complicações Pós-Operatórias , Qualidade de Vida , Triglicerídeos/sangue , Redução de PesoRESUMO
OBJECTIVE: To evaluate the effects of two bariatric procedures versus intensive medical therapy (IMT) on ß-cell function and body composition. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, controlled trial of 60 subjects with uncontrolled type 2 diabetes (HbA1c 9.7 ± 1%) and moderate obesity (BMI 36 ± 2 kg/m(2)) randomized to IMT alone, IMT plus Roux-en-Y gastric bypass, or IMT plus sleeve gastrectomy. Assessment of ß-cell function (mixed-meal tolerance testing) and body composition was performed at baseline and 12 and 24 months. RESULTS: Glycemic control improved in all three groups at 24 months (N = 54), with a mean HbA1c of 6.7 ± 1.2% for gastric bypass, 7.1 ± 0.8% for sleeve gastrectomy, and 8.4 ± 2.3% for IMT (P < 0.05 for each surgical group versus IMT). Reduction in body fat was similar for both surgery groups, with greater absolute reduction in truncal fat in gastric bypass versus sleeve gastrectomy (-16 vs. -10%; P = 0.04). Insulin sensitivity increased significantly from baseline in gastric bypass (2.7-fold; P = 0.004) and did not change in sleeve gastrectomy or IMT. ß-Cell function (oral disposition index) increased 5.8-fold in gastric bypass from baseline, was markedly greater than IMT (P = 0.001), and was not different between sleeve gastrectomy versus IMT (P = 0.30). At 24 months, ß-cell function inversely correlated with truncal fat and prandial free fatty acid levels. CONCLUSIONS: Bariatric surgery provides durable glycemic control compared with intensive medical therapy at 2 years. Despite similar weight loss as sleeve gastrectomy, gastric bypass uniquely restores pancreatic ß-cell function and reduces truncal fat, thus reversing the core defects in diabetes.
Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/terapia , Células Secretoras de Insulina/fisiologia , Obesidade/cirurgia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Derivação Gástrica , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Obesidade/metabolismo , Redução de Peso/fisiologiaRESUMO
BACKGROUND: Observational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery. METHODS: In this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49±8 years, and 66% were women. The average glycated hemoglobin level was 9.2±1.5%. The primary end point was the proportion of patients with a glycated hemoglobin level of 6.0% or less 12 months after treatment. RESULTS: Of the 150 patients, 93% completed 12 months of follow-up. The proportion of patients with the primary end point was 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group (P=0.002) and 37% (18 of 49 patients) in the sleeve-gastrectomy group (P=0.008). Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5±1.8% in the medical-therapy group, 6.4±0.9% in the gastric-bypass group (P<0.001), and 6.6±1.0% in the sleeve-gastrectomy group (P=0.003). Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (-29.4±9.0 kg and -25.1±8.5 kg, respectively) than in the medical-therapy group (-5.4±8.0 kg) (P<0.001 for both comparisons). The use of drugs to lower glucose, lipid, and blood-pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. The index for homeostasis model assessment of insulin resistance (HOMA-IR) improved significantly after bariatric surgery. Four patients underwent reoperation. There were no deaths or life-threatening complications. CONCLUSIONS: In obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results. (Funded by Ethicon Endo-Surgery and others; ClinicalTrials.gov number, NCT00432809.).
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Derivação Gástrica , Hipoglicemiantes/uso terapêutico , Obesidade/cirurgia , Adulto , Índice de Massa Corporal , Colesterol/sangue , Terapia Combinada , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Síndrome Metabólica/terapia , Pessoa de Meia-Idade , Obesidade/complicações , Complicações Pós-Operatórias , Redução de PesoRESUMO
BACKGROUND: The exercise treadmill test is recommended for risk stratification among patients with intermediate to high pretest probability of coronary artery disease. Posttest risk stratification is based on the Duke treadmill score, which includes only functional capacity and measures of ischemia. OBJECTIVE: To develop and externally validate a post-treadmill test, multivariable mortality prediction rule for adults with suspected coronary artery disease and normal electrocardiograms. DESIGN: Prospective cohort study conducted from September 1990 to May 2004. SETTING: Exercise treadmill laboratories in a major medical center (derivation set) and a separate HMO (validation set). PATIENTS: 33,268 patients in the derivation set and 5821 in the validation set. All patients had normal electrocardiograms and were referred for evaluation of suspected coronary artery disease. MEASUREMENTS: The derivation set patients were followed for a median of 6.2 years. A nomogram-illustrated model was derived on the basis of variables easily obtained in the stress laboratory, including age; sex; history of smoking, hypertension, diabetes, or typical angina; and exercise findings of functional capacity, ST-segment changes, symptoms, heart rate recovery, and frequent ventricular ectopy in recovery. RESULTS: The derivation data set included 1619 deaths. Although both the Duke treadmill score and our nomogram-illustrated model were significantly associated with death (P < 0.001), the nomogram was better at discrimination (concordance index for right-censored data, 0.83 vs. 0.73) and calibration. We reclassified many patients with intermediate- to high-risk Duke treadmill scores as low risk on the basis of the nomogram. The model also predicted 3-year mortality rates well in the validation set: Based on an optimal cut-point for a negative predictive value of 0.97, derivation and validation rates were, respectively, 1.7% and 2.5% below the cut-point and 25% and 29% above the cut-point. LIMITATIONS: Blood test-based measures or left ventricular ejection fraction were not included. The nomogram can be applied only to patients with a normal electrocardiogram. Clinical utility remains to be tested. CONCLUSION: A simple nomogram based on easily obtained pretest and exercise test variables predicted all-cause mortality in adults with suspected coronary artery disease and normal electrocardiograms.
Assuntos
Causas de Morte , Doença da Artéria Coronariana/diagnóstico , Eletrocardiografia , Teste de Esforço , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de RiscoRESUMO
Although peak oxygen consumption (VO(2)) during exercise is frequently used to help predict optimal timing for heart transplantation, its long-term prognostic value in women is not known. We followed 2,105 adult patients with heart failure (HF) and with impaired left ventricular (LV) systolic function for 5 years, including 525 women (25%) who underwent metabolic stress testing between January 1995 and December 2002. Multivariable proportional hazards modeling related VO(2) to survival with adjustments for >30 confounders and with transplantation considered as a time-dependent covariate. During follow-up, 129 women (26%) died, as did 572 men (36%). There were 175 transplants, including 34 women. Women and men were similar in age (54 vs 55 years), but women were less likely to have coronary artery disease (28% vs 58%). Peak VO(2) was strongly predictive of time to death in women (adjusted hazard ratio [HR] for peak VO(2) decreasing from 15 to 14 ml/kg/min, 1.11, 95% confidence interval [CI] 1.05 to 1.18, p <0.0001) and in men (adjusted HR 1.12, 95% CI 1.08 to 1.16, p <0.0001). There was no gender interaction with peak VO(2) (p = 0.80), but for any given peak VO(2) women were at lower risk (adjusted HR for men compared with women 2.22, 95% CI 1.58 to 3.10, p <0.0001). A significant interaction was found between gender and presence of coronary artery disease (p for interaction 0.02); in women, those with ischemic cardiomyopathy had a worse survival for any given peak VO(2). In conclusion, in this large cohort, peak VO(2) predicted survival in women and men whether or not coronary artery disease was present, but an interaction was noted between coronary artery, gender, and survival.
Assuntos
Insuficiência Cardíaca/mortalidade , Consumo de Oxigênio/fisiologia , Disfunção Ventricular Esquerda/mortalidade , Estudos de Coortes , Feminino , Insuficiência Cardíaca/terapia , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores Sexuais , Disfunção Ventricular Esquerda/terapiaRESUMO
OBJECTIVES: Exercise-induced QT/RR hysteresis exists when, for a given R-R interval, the QT interval duration is shorter during recovery after exercise than during exercise. We sought to assess the association between QT/RR hysteresis and imaging evidence of myocardial ischemia. BACKGROUND: Because ischemia induces cellular disturbances known to decrease membrane action potential duration, we hypothesized a correlation between QT/RR and myocardial ischemia. METHODS: We digitally analyzed 4-second samples of QT duration and R-R-interval duration in 260 patients referred for treadmill exercise stress and rest single photon emission computed tomography myocardial perfusion imaging; a cool-down period was used after exercise. None of the patients were in atrial fibrillation or used digoxin, and none had marked baseline electrocardiographic abnormalities. Stress and rest myocardial perfusion images were analyzed visually and quantitatively to define the extent and severity of stress-induced ischemia. QT/RR hysteresis was calculated using a computerized algorithm. RESULTS: There were 82 patients (32%) who manifested myocardial ischemia by single photon emission computed tomography myocardial perfusion imaging. The likelihood of ischemia increased with increasing QT/RR hysteresis, with prevalence according to quartiles of 20%, 30%, 26%, and 49% (P = .003 for trend). In analyses adjusting for ST-segment changes, exercise capacity, heart rate recovery, and other confounders, QT/RR hysteresis was independently predictive of presence of myocardial ischemia (adjusted odds ratio for 100-point increase of QT/RR hysteresis, 1.61; 95% confidence interval, 1.22-2.12; P = .0008). QT/RR hysteresis was also predictive of severe ischemia. CONCLUSION: Exercise-induced QT/RR hysteresis is a strong and independent predictor of myocardial ischemia and provides additional information beyond that afforded by standard ST-segment measures.
Assuntos
Eletrocardiografia/métodos , Eletrocardiografia/estatística & dados numéricos , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Medição de Risco/métodos , Idoso , Feminino , Humanos , Masculino , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
CONTEXT: Lower socioeconomic status (SES) confers heightened cardiovascular risk and mortality, although the mediating pathways are unclear. OBJECTIVE: To evaluate the extent to which exercise physiologic characteristics account for the association between lower SES and mortality. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 30 043 consecutive patients living in 7 counties in northeast Ohio referred between 1990 and 2002 for symptom-limited stress testing for evaluation of known or suspected coronary artery disease. Follow-up for mortality continued through February 2004. MAIN OUTCOME MEASURES: Estimated functional capacity in metabolic equivalents and heart rate recovery, physiologic characteristics that are determined directly from exercise; testing and all-cause mortality during a median follow-up of 6.5 years. RESULTS: Multivariable models adjusting for demographics, insurance status, smoking status, and clinical confounders demonstrated a strong association between a composite SES score based on census block data and functional capacity (adjusted odds ratio comparing 25th with 75th percentile values, 1.72; 95% confidence interval [CI], 1.56-1.89; P<.001) as well as heart rate recovery (adjusted odds ratio comparing 25th with 75th percentile values, 1.18; 95% CI, 1.07-1.30; P<.001). There were 2174 deaths, with mortality risk increasing from 5% to 10% as SES decreased by quartile (P<.001). Cox proportional hazards models that included all confounding variables except exercise physiologic characteristics demonstrated increased mortality as SES decreased (adjusted hazard ratio comparing 25th with 75th percentile values, 1.32; 95% CI, 1.22-1.42; P<.001). After further adding functional capacity and heart rate recovery, the magnitude of this relationship was reduced (comparing 25th with 75th percentile values; adjusted hazard ratio, 1.17; 95% CI, 1.08-1.26; P<.001), with these variables explaining 47% of the association. CONCLUSIONS: Impaired functional capacity and abnormal heart rate recovery were strongly associated with lower SES and accounted for a major proportion of the correlation between SES and mortality. Efforts to modify these clinical features among patients with low SES may narrow disparities in mortality.
Assuntos
Doenças Cardiovasculares/epidemiologia , Fenômenos Fisiológicos Cardiovasculares , Mortalidade , Fatores Socioeconômicos , Adulto , Idoso , Estudos de Coortes , Teste de Esforço , Feminino , Frequência Cardíaca , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , OhioRESUMO
BACKGROUND: The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomography (PET) with fluorodeoxyglucose (FDG) imaging may identify patients for whom revascularization may lead to improved survival. We performed a propensity analysis to determine whether there might be a survival advantage from revascularization. METHODS AND RESULTS: We analyzed the survival of 765 consecutive patients (age 64+/-11 years, 80% men) with advanced left ventricular systolic dysfunction (ejection fraction < or =35%) and without significant valvular heart disease who underwent PET/FDG study at the Cleveland Clinic between 1997 and 2002. Early intervention was defined as any cardiac intervention (surgical or percutaneous) within the first 6 months of the PET/FDG study. In the entire cohort, 230 patients (30%) underwent early intervention (188 [25%] had open heart surgery, most commonly coronary artery bypass grafting, and 42 [5%] had percutaneous revascularization); 535 (70%) were treated medically. Using 39 demographic, clinical and PET/FDG variables, we were able to propensity-match 153 of the 230 patients with 153 patients who did not undergo early intervention. Among the propensity-matched group, there were 84 deaths during a median of 3 years follow-up. Early intervention was associated with a markedly lower risk of death (3-year mortality rate of 15% versus 35%, propensity adjusted hazard ratio 0.52, 95% CI 0.33 to 0.81, P=0.0004). CONCLUSIONS: Among systolic heart failure patients referred for PET/FDG, early intervention may be associated with improved survival irrespective of the degree of viability.
Assuntos
Revascularização Miocárdica/mortalidade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica , Tomografia por Emissão de Pósitrons , Análise de Sobrevida , Sístole , Sobrevivência de Tecidos , Disfunção Ventricular Esquerda/mortalidadeRESUMO
Chronotropic incompetence, or an inability to increase heart rate during exercise, independently predicts death in patients not taking beta blockers. Whether it predicts death in patients taking beta blockers is not known. Consecutive patients (n = 3,736; mean age 58 +/- 11 years; 68% men), who were taking either metoprolol tartrate or atenolol and were referred for symptom-limited exercise testing from 1990 to 2002 at a major academic medical center, formed the prospective study cohort. None had heart failure, pacemakers, atrial fibrillation, or any electrocardiographic abnormalities. Patients were followed for a median of 4.5 years for all-cause mortality. Chronotropic response was defined as the percentage of heart rate reserve used. A value of < or =62%, which was noted in 813 patients (22%), was considered abnormal, meaning that chronotropic incompetence was present. There were 173 deaths. After adjusting for age, gender, heart rate at rest, standard risk factors, other medications, Duke treadmill score, and heart rate recovery, chronotropic incompetence predicted death (adjusted hazard ratio 1.94, 95% confidence interval 1.43 to 2.64, p <0.0001). The association of chronotropic incompetence with death was present, irrespective of which drug was taken or the number of half-lives that had elapsed since the last dose. In conclusion, in patients taking beta blockers, chronotropic incompetence is independently predictive of death.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Atenolol/uso terapêutico , Eletrocardiografia , Frequência Cardíaca/fisiologia , Metoprolol/uso terapêutico , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Causas de Morte , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: The aim of the study was to derive and externally validate a mortality prediction rule for patients undergoing exercise testing. BACKGROUND: The prognostic value of exercise testing is increasingly appreciated. However, global prognosis estimates ideally should account for numerous routinely obtained variables, including demographics, risk factors, resting electrocardiogram, and multiple exercise test measures. METHODS: A prediction rule was derived by parametric hazards modeling on a derivation set of 46047 Cleveland Clinic patients (age 55 +/- 11 years, 67% male) who had no history of heart failure, valve disease, or atrial fibrillation. Twenty-two variables covering demographics, risk factors, exercise hemodynamics, and electrocardiogram findings at rest and during exercise were considered. The resulting model included 16 variables and was tested on 4981 patients (age 50 +/- 12 years, 55% male) who underwent exercise testing at West Virginia University. RESULTS: In the derivation cohort there were 3173 deaths during a mean of 7 years of follow-up, whereas in the validation cohort there were 180 deaths during a mean of 5 years of follow-up. Comparisons of predicted and observed death rates showed very good agreement among all patients across all spectrums of risk, as well as among prespecified high-risk subgroups. Model discrimination was also good, with c statistic of c = 0.79 in the derivation group and c = 0.81 in the validation cohort. CONCLUSIONS: We have externally validated a mortality prediction rule for patients undergoing exercise testing and confirmed its accuracy among a wide spectrum of patients.
Assuntos
Teste de Esforço , Mortalidade , Prognóstico , Adulto , Idoso , Calibragem , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Eletrocardiografia , Exercício Físico/fisiologia , Feminino , Seguimentos , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Descanso/fisiologia , Fatores de RiscoRESUMO
BACKGROUND: Peak oxygen uptake (peak VO2) is a strong predictor of mortality and is commonly used in the evaluation of patients for cardiac transplantation. Beta-blockers reduce mortality in patients with heart failure, without influencing peak VO2, raising the possibility that peak VO2 is no longer suitable as an indicator of prognosis in these patients. METHODS AND RESULTS: We analyzed prospectively gathered data on 2105 patients referred for cardiopulmonary testing for all-cause mortality and for occurrence of death or transplantation. Patients receiving beta-blockers were younger, more likely to have coronary disease, and had a greater mean ejection fraction but had a similar peak VO2. There were 555 deaths (26%) and 194 (9%) transplants during a median follow-up of 3.5 years. Peak VO2 was a predictor of mortality irrespective of beta-blocker use; a decrease of 1 mL x kg(-1) x min(-1) resulted in an adjusted hazard ratio (HR) of 1.13 (95% CI 1.09 to 1.17, P<0.0001) in patients not receiving beta-blockers and 1.27 (95% CI 1.18 to 1.36, P<0.0001) in patients receiving beta-blockers. Similar findings were noted when considering death or transplantation as an end point. Beta-blocker use was associated with better outcomes until peak VO2 values became very low (approximately 10 mL x kg(-1) x min(-1)), at which level survival rates were equally poor. CONCLUSION: Peak VO2 is a determinant of survival in patients in heart failure even in the setting of beta-blockade. Because of improved survival in patients treated with beta-blockers, the cut point value of 14 mg x kg(-1) x min(-1) for referral for cardiac transplantation in these patients requires reevaluation, and a lower cut point may be more appropriate.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca/mortalidade , Consumo de Oxigênio , Valor Preditivo dos Testes , Adulto , Idoso , Morte , Teste de Esforço , Insuficiência Cardíaca/tratamento farmacológico , Transplante de Coração/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Volume SistólicoRESUMO
Although it is well established that a blunted chronotropic response to exercise is associated with a higher risk of death, recent data suggest a similar association between mortality risk and blunted heart rate response to vasodilatory stress. We investigated the heart rate response to dipyridamole-induced stress as a predictor of death in the setting of normal myocardial perfusion and a normal electrocardiogram. We followed 1,087 patients for 8 years (range 5.7 to 11.8) who underwent dipyridamole vasodilator stress and had normal perfusion scans and electrocardiograms. None had heart failure, known left ventricular systolic dysfunction, pacemaker implantation, or valve disease. Heart rate response was assessed as the ratio of heart rate at peak stress to heart rate at rest. The primary end point was all-cause mortality. Quartile values for the peak-to-rest heart rate ratio were <1.19, 1.19 to 1.30, 1.31 to 1.44, and >1.44. There were 246 deaths. Death rates according to quartiles of heart rate ratio were 103 of 271 (38%), 64 of 272 (24%), 52 of 272 (19%), and 27 of 272 (10%). After adjusting for age, gender, heart rate at rest, blood pressure response, standard cardiovascular risk factors, and other confounders, a blunted heart rate response remained predictive of death (adjusted hazard ratio for lowest vs highest quartile 3.3, 95% confidence interval 2.1 to 5.1, p <0.0001). When considered as a continuous variable, the logarithm of the heart rate ratio was the strongest predictor of death, aside from age. Thus, among patients who have normal myocardial perfusion and normal electrocardiograms, a blunted heart rate response to vasodilator stress is predictive of a marked increase in risk of death.
Assuntos
Dipiridamol , Teste de Esforço/métodos , Frequência Cardíaca , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Vasodilatadores , Idoso , Circulação Coronária , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Ohio , Valor Preditivo dos Testes , Análise de SobrevidaRESUMO
BACKGROUND: Although practice guidelines do not recommend routine exercise testing of patients after coronary stenting, several small studies have suggested that stress myocardial perfusion imaging can provide prognostic information about future adverse cardiac events. We sought to determine if exercise nuclear testing provides independent prognostic information in patients after coronary stenting. METHODS: We analyzed the outcomes of 370 patients who underwent dual isotope exercise nuclear scintigraphy at least 1 month after coronary stenting and had testing between April 1996 and May 2002. Patients were classified according to presence or absence of any ischemia. The primary endpoint was all-cause mortality or myocardial infarction (MI) during a median of 30 months (range 6-59) of follow-up. RESULTS: There were 86 patients (23%) who had ischemia. Major events--death or MI--occurred in 62 patients including 22 deaths. Among patients with no ischemia, the 30-month event rate was 9.1%, whereas among patients with ischemia, the event rate was 17.0% (P = .001). After adjusting for age, sex, standard cardiac risk factors, cardiac history, left ventricular ejection fraction, angiographic findings, procedural variables, exercise capacity, and heart-rate dynamics, the presence of scintigraphic evidence of ischemia predicted death or MI (adjusted hazard ratio 2.08, 95% CI 1.21-3.56, P = .008). The presence of ischemia similarly predicted events in asymptomatic patients (adjusted hazard ratio 2.19, 95% CI 1.17-4.11, P = .015). CONCLUSIONS: In patients with recent coronary stent placement, reversible nuclear perfusion defects independently predicted risk of death or MI.
Assuntos
Doença das Coronárias/terapia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Stents/estatística & dados numéricos , Tomografia Computadorizada de Emissão de Fóton Único , Angioplastia Coronária com Balão/estatística & dados numéricos , Comorbidade , Doença das Coronárias/epidemiologia , Intervalo Livre de Doença , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Isquemia Miocárdica/epidemiologia , Valor Preditivo dos Testes , Distribuição Aleatória , Medição de Risco/métodos , Distribuição por SexoRESUMO
BACKGROUND: Although heart rate recovery (HRR) predicts mortality after exercise testing, its ability to identify patients likely to benefit after revascularization is unknown. We sought to determine whether HRR can identify patients likely to have improved survival after revascularization. METHODS AND RESULTS: A total of 8861 patients undergoing treadmill nuclear or echocardiographic testing were divided into early revascularization (percutaneous coronary intervention or bypass surgery within 3 months) and non-early revascularization groups. Prespecified subgroup analysis was performed based on the presence or absence of ischemia, normal or impaired functional capacity, and normal or abnormal HRR. The primary end point was all-cause mortality. Early revascularization occurred in 552 patients. We propensity-matched 508 early revascularization patients to 508 non-early revascularization patients on the basis of 48 possible confounders. This constituted the present study cohort. During 8-year follow-up, 232 patients died. Overall, revascularization was associated with a slight but not significant decrease in mortality (hazard ratio [HR] 0.80, 95% CI 0.62 to 1.03). A significant decrease in mortality after revascularization was present in patients with imaging evidence of stress-induced ischemia (HR 0.62, 95% CI 0.44 to 0.87). Ischemic patients with normal HRR had significantly lower mortality with revascularization (HR 0.55, 95% CI 0.34 to 0.90), whereas ischemic patients with abnormal HRR did not (HR 0.78, 95% CI 0.47 to 1.29); however, the test for interaction between these 2 groups was not significant (P=0.34). CONCLUSIONS: In patients with imaging evidence of myocardial ischemia, an abnormal HRR is associated with a nonsignificant trend toward blunting the survival improvement associated with early revascularization. HRR does not appear to identify patients likely to have a survival benefit.
Assuntos
Ecocardiografia sob Estresse , Teste de Esforço , Frequência Cardíaca/fisiologia , Isquemia Miocárdica/fisiopatologia , Revascularização Miocárdica , Idoso , Causas de Morte , Estudos de Coortes , Fatores de Confusão Epidemiológicos , Feminino , Seguimentos , Humanos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Mortalidade , Isquemia Miocárdica/cirurgia , Isquemia Miocárdica/terapia , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do TratamentoRESUMO
CONTEXT: The usefulness of exercise stress test results and global cardiovascular risk systems for predicting all-cause mortality in asymptomatic individuals seen in clinical settings is unclear. OBJECTIVES: To determine the validity for prediction of all-cause mortality of the Framingham Risk Score and of a recently described European global scoring system Systematic Coronary Risk Evaluation (SCORE) for cardiovascular mortality among asymptomatic individuals evaluated in a clinical setting and to determine the potential prognostic value of exercise stress testing once these baseline risks are known. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 3554 asymptomatic adults between the ages of 50 and 75 years who underwent exercise stress testing as part of an executive health program between October 1990 and December 2002; participants were followed up for a mean of 8 years. MAIN OUTCOME MEASURES: Global risk based on the Framingham Risk Score and the European SCORE. Prospectively recorded exercise stress test result abnormalities included impaired physical fitness, abnormal heart rate recovery, ventricular ectopy, and ST-segment abnormalities. The primary end point was all-cause mortality. RESULTS: There were 114 deaths. The c-index, which corresponds to receiver operating characteristic curve values, and the Akaike Information Criteria found that the European SCORE was superior to the Framingham Risk Score in estimating global mortality risk. In a multivariable model, independent predictors of death were a higher SCORE (for 1% predicted increase in absolute risk, relative risk [RR], 1.07; 95% confidence interval [CI], 1.04-1.09; P<.001), impaired functional capacity (RR, 2.95; 95% CI, 1.98-4.39; P<.001), and an abnormal heart rate recovery (RR, 1.59; 95%, 1.04-2.41; P =.03). ST-segment depression did not predict mortality. Among patients in the highest tertile from the SCORE, an abnormal exercise stress test result, defined as either impaired functional capacity or an abnormal heart rate recovery, identified a mortality risk of more than 1% per year. CONCLUSION: Exercise stress testing when combined with the European global risk SCORE may be useful for stratifying risk in asymptomatic individuals in a comprehensive executive health screening program.
Assuntos
Teste de Esforço , Mortalidade , Medição de Risco , Idoso , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medicina Preventiva , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de SobrevidaRESUMO
PURPOSE: Chest symptoms, along with standard cardiovascular risk factors, are commonly factored into pretest risk stratification of patients who are referred for stress testing. We sought to determine the independent prognostic value of chest symptoms. METHODS: We studied the outcomes of 10,870 patients referred for symptom-limited exercise testing who had no history of myocardial revascularization, heart failure, or arrhythmias. Chest symptoms were prospectively characterized according to prespecified definitions. Propensity analysis was used to account for differences in baseline and exercise characteristics. RESULTS: Typical angina was present in 635 patients (6%), atypical angina in 3408 (33%), nonanginal chest pain in 1805 (17%), and dyspnea in 841 (8%). The remaining 4181 patients (38%) were asymptomatic. During a mean follow-up of 4.3 years, there were 381 deaths. After propensity matching patients who had typical angina with asymptomatic patients, symptoms were not predictive of mortality (adjusted hazard ratio [HR] = 0.8; 95% confidence interval [CI]: 0.6 to 1.3; P = 0.4). Among patients who had chest pain, typical angina was associated with a highly significant risk of mortality as compared with nonanginal chest pain (HR = 2.7; 95% CI: 1.4 to 5.1; P = 0.002), but not compared with atypical angina (HR = 1.3; 95% CI: 0.9 to 2.1; P = 0.21). CONCLUSION: After accounting for baseline and exercise characteristics, the presence of symptoms was not independently associated with increased mortality among patients undergoing testing for known or suspected coronary disease. Among patients who actually had chest pain, typical angina carried a higher mortality risk.
Assuntos
Doença das Coronárias/diagnóstico , Teste de Esforço , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/etiologia , Angina Pectoris/mortalidade , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Dor no Peito/mortalidade , Doença das Coronárias/classificação , Doença das Coronárias/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ohio/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores Sexuais , Análise de SobrevidaRESUMO
OBJECTIVES: The study was done to determine the prognostic importance of frequent ventricular ectopy in recovery after exercise among patients with systolic heart failure (HF). BACKGROUND: Although ventricular ectopy during recovery after exercise predicts death in patients without HF, its prognostic importance in patients with significant ventricular dysfunction is unknown. METHODS: Systematic electrocardiographic data during rest, exercise, and recovery were gathered on 2,123 consecutive patients with left ventricular systolic ejection fraction Assuntos
Teste de Esforço
, Insuficiência Cardíaca/mortalidade
, Insuficiência Cardíaca/fisiopatologia
, Complexos Ventriculares Prematuros/mortalidade
, Complexos Ventriculares Prematuros/fisiopatologia
, Estudos de Coortes
, Eletrocardiografia
, Feminino
, Humanos
, Masculino
, Prontuários Médicos
, Pessoa de Meia-Idade
, Ohio/epidemiologia
, Valor Preditivo dos Testes
, Prognóstico
, Estudos Retrospectivos
, Índice de Gravidade de Doença
, Análise de Sobrevida
RESUMO
Donor cause of death has been suggested to have a significant impact on cardiac transplant morbidity and mortality. Our objective was to evaluate the impact of donor spontaneous intracranial bleeding on clinical outcome after heart transplantation. A group of 160 recipients underwent cardiac transplantation from donors with spontaneous intracranial bleeding (ICB group). These were compared with 197 recipients who were transplanted from trauma donors (Trauma group). A higher 4-year mortality rate was noted in the ICB group (24% vs. 14%, p=0.015). ICB as a cause of donor death was an independent predictor of recipient mortality (adjusted hazard ratio 2.02, 95% CI 1.27-3.40, p<0.0001). Compared with the Trauma group, the ICB group had an increased incidence of post-transplant graft dysfunction during the first week of transplant (10% vs. 3%, p=0.007), and higher incidence of interstitial myocardial fibrosis on their endomyocardial biopsies within 4 weeks of transplant (21% vs. 9%, p=0.0012). There was a trend towards an increased rate of allograft vasculopathy in the ICB group (competing risks adjusted hazard ratio 1.39, 95% CI 0.90-2.13, p = 0.14).