Sirolimus Adverse Event Profile in a Non-Clinical Trial Cohort of Heart Transplantation Patients.

BACKGROUND Sirolimus has been used increasingly in heart transplantation for its ability to reduce acute rejection, prevent the progression of cardiac allograft vasculopathy (CAV), and preserve renal function. We sought to assess the adverse reactions associated with the use of sirolimus compared to mycophenolate mofetil (MMF). MATERIAL AND METHODS We retrospectively reviewed the charts of 221 adult heart transplant patients who received either sirolimus or MMF as part of their immunosuppression from June 1, 2001 to April 1, 2005. Patients were assigned to 2 groups based upon immunosuppression use. The prevalence and types of complications were recorded in each group. RESULTS Sirolimus was received by 109 patients and 112 patients received MMF during the study period. Seventy-seven patients (71%) in the sirolimus group experienced adverse reactions compared to 45 patients (40%) in the MMF group (P<0.01). Compared to MMF, the use of sirolimus was associated with a higher prevalence of elevated triglyceride levels, lower-extremity edema, and oral ulcerations. Sirolimus was discontinued due to adverse reactions in 22% of patients, whereas no patients in the MMF group experienced adverse effects requiring drug discontinuation. CONCLUSIONS Compared to MMF, sirolimus use is associated with a higher prevalence of adverse reactions requiring drug discontinuation, but most patients were able to stay on therapy despite adverse effects.

Association between cardiorespiratory fitness, obesity, and incidence of atrial fibrillation.

BACKGROUND: The interaction between cardiorespiratory fitness (CRF) and incidence of atrial fibrillation (AF) and the interaction between obesity and incidence of AF have been explored separately. Therefore, we evaluated the association between CRF, body mass index (BMI), and risk of developing AF in a cohort of middle-aged and older US Veterans. METHODS: Symptom limited exercise tests (ETT) were conducted among 16,397 Veterans (97% male) from January 9,1987 to December 31,2017. No history of AF was evident at the time of the ETTs. CRF was expressed as quartiles of peak metabolic equivalents (METs) achieved within each age decile. Weight status was classified as normal (BMI < 25 kg/m2), overweight (BMI 25-30 kg/m2), obese (BMI 30-35 kg/m2), or severely obese (BMI > 35 kg/m2). Multivariable Cox proportional hazards regression models were used to compare the association between BMI, CRF categories, and incidence of AF. RESULTS: Over a median follow-up of 10.7 years, 2,155 (13.1%) developed AF. Obese and severely obese subjects had 13% and 32% higher risks for incidence of AF, respectively, vs. normal weight subjects. Overweight and obese subjects in the most fit quartile had 50% decline in AF risk compared to the least-fit subjects. Severely obese subjects had marked increases in AF risk (~50-60%) regardless of fitness level. Risk of developing AF increases with higher BMI and lower CRF. CONCLUSION: Improving CRF should be advocated when assessing those at risk for developing AF.

Improved reclassification of mortality risk by assessment of physical activity in patients referred for exercise testing.

BACKGROUND: Inability to meet minimal guidelines on physical activity is associated with poor health outcomes, but quantifying activity can be complex. We studied whether a simple question regarding participation in regular activity improves risk classification for all-cause mortality. METHODS: Maximal exercise testing was performed in 6962 patients (mean age, 58.9 ± 11 years) for clinical reasons. Subjects also were assessed for participation in regular activity using a simple yes/no response to meeting minimal recommendations on activity. The incremental value of adding a simple physical activity assessment to clinical, demographic, and exercise test information to predict mortality was determined using Cox proportional hazards models, net reclassification improvement, and integrated discrimination index during a mean follow-up of 9.7 ± 4 years. RESULTS: Subjects who did not meet the minimal guidelines on activity had a lower exercise capacity (7.4 ± 4.3 vs 9.1 ± 3.6 metabolic equivalents, P < .0001) and a higher annual mortality rate (2.42% vs 1.71%, P < .001). Not meeting activity guidelines was associated with an age-adjusted 36% higher risk of mortality (hazard ratio, 1.36; 95% confidence interval, 1.22-1.51, P < .0001). Among clinical and exercise test variables, fitness had the highest C-index for predicting mortality (0.72, P < .001). The addition of physical activity classification to a model including traditional risk factors resulted in a net reclassification improvement of 22.8% (P < .001); adding fitness to the traditional risk factor model resulted in a net reclassification improvement of 43.5% (P < .001). CONCLUSIONS: The addition of a simple assessment of physical activity status significantly improves reclassification of risk for all-cause mortality among patients who are referred for exercise testing.

Cardiopulmonary and noninvasive hemodynamic responses to exercise predict outcomes in heart failure.

BACKGROUND: An impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which noninvasive estimates of cardiac hemodynamics during exercise in combination with cardiopulmonary exercise test (CPX) responses improved the estimation of risk for adverse events in patients with HF. METHODS AND RESULTS: CPX and impedance cardiography were performed in 639 consecutive patients (mean age 48 ± 14 years), evaluated for HF. Clinical, hemodynamic, and CPX variables were acquired at baseline and subjects were followed for a mean of 460 ± 332 days. Patients were followed for the composite outcome of cardiac-related death, hospitalization for worsening HF, cardiac transplantation, and left ventricular assist device implantation. Cox proportional hazards analyses including clinical, noninvasive hemodynamic, and CPX variables were performed to determine their association with the composite endpoint. There were 113 events. Among CPX variables, peak oxygen uptake (VO(2)) and the minute ventilation (VE)/carbon dioxide production (VCO(2)) slope were significant predictors of risk for adverse events (age-adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.05-1.11 for both; P < .001). Among hemodynamic variables, peak cardiac index was the strongest predictor of risk (HR 1.08, 95% CI 1.0-1.16; P = .01). In a multivariate analysis including CPX and noninvasively determined hemodynamic variables, the most powerful predictive model included the combination of peak VO(2), peak cardiac index, and the VE/VCO(2) slope, with each contributing significantly and independently to predicting risk; an abnormal response for all 3 yielded an HR of 5.1 (P < .001). CONCLUSIONS: These findings suggest that noninvasive indices of cardiac hemodynamics complement established CPX measures in quantifying risk in patients with HF.

Bloqueio completo do ramo esquerdo esforço-induzido: prevalência e prognóstico / Exercise-induced left bundle branch block: prevalence and prognosis / Bloqueo completo de la rama izquierda esfuerzo-inducido prevalencia y pronóstico

FUNDAMENTO: O bloqueio completo do ramo esquerdo esforço-induzido (BCRE E-I) é um achado infrequente ao teste de exercício e sua prevalência e significado prognóstico não são claros. OBJETIVO: Avaliar de forma longitudinal a prevalência e o significado prognóstico do BCRE E-I em homens americanos veteranos de guerra. MÉTODOS: Avaliamos 9.623 pacientes que realizaram ergometria em esteira (TE) entre 1987 e 2007. Os desfechos foram comparados entre aqueles com TE NL, os com BCRE E-I e os que apresentaram Dep ST anormal. A mortalidade e a causa das mortes foram identificadas de forma cega para os resultados do TE. RESULTADOS: Nesta coorte prospectiva, 6922 indivíduos apresentaram TE NL (57,2 ± 11,4 anos), 1.739 apresentaram Dep ST anormal (62,7 ± 9,8 anos) e 38 casos de BCRE E-I foram identificados (65,2 ± 11,9 anos). A prevalência do BCRE E-I foi 0,38 por cento. Após 8,8 anos, ocorreram 1.699 mortes por todas as causas e 610 mortes cardiovasculares (CV). Doença arterial coronária e insuficiência cardíaca foram mais prevalentes nos pacientes com BCRE E-I. Pacientes com BCRE E-I tiveram razão de azar de 2,37 (p = 0,002) para mortalidade por todas as causas, mas a mesma não foi significativa quando ajustada para idade ou quando a mortalidade cardiovascular foi o desfecho avaliado. CONCLUSÃO: BCRE E-I é um achado raro. Indivíduos com BCRE E-I apresentam maior mortalidade por todas as causas quando comparados aqueles com TE NL. No entanto, tal fato é explicado por esses pacientes serem significativamente mais velhos e por apresentarem mais enfermidades cardiovasculares associadas.

BACKGROUND: Exercise-induced left bundle branch block (EI-LBBB) is an infrequent finding. Its prevalence and prognostic significance are not clear. OBJECTIVE: To evaluate, in a longitudinal study, the prevalence and prognostic significance of EI-LBBB in American war veterans. METHODS: We evaluated 9,623 patients submitted to an exercise test (ET) in treadmill between 1987 and 2007. The outcomes were compared between those with normal TE, the ones with EI-LBBB and the ones with down-sloping ST-segment. Mortality and causes of death were identified while blinded to the ET results. RESULTS: In this prospective cohort, 6,922 individuals had normal ET results (57.2 ± 11.4 years), 1,739 had abnormal ST-segment depression (62.7 ± 9.8 years), and 38 had EI-LBBB (65.2 ± 11.9 years). The prevalence of EI-LBBB was 0.38 percent. After 8.8 years, there were 1,699 deaths due to all-cause mortality and 610 cardiovascular (CV) deaths; coronary artery disease and heart failure were more prevalent in patients with EI-LBBB. Patients with EI-BCRE had a hazard ratio of 2.37 (p = 0.002) for all-cause mortality, but it was not significant when adjusted for age or when the CV death was the assessed outcome. CONCLUSION: EI-LBBB is a rare clinical finding. Individuals with BCRE-EI have higher all-cause mortality when compared to those with normal ET results. However, this fact is explained by the fact that these patients are significantly older and have more associated cardiovascular diseases.

FUNDAMENTO: El bloqueo completo de rama izquierda esfuerzo-inducido (BCRI E-I) es un hallazgo infrecuente en el test de ejercicio y su prevalencia y significado pronóstico no son claros. OBJETIVO: Evaluar de forma longitudinal la prevalencia y el significado pronóstico del BCRI E-I en los hombres norteamericanos veteranos de guerra. MÉTODOS: Evaluamos 9.623 pacientes que realizaron ergometría en cinta (TE) entre 1987 y 2007. Los resultados fueron comparados entre aquellos con TE normal (TE NL), los con BCRI E-I y los que presentaron infradesnivel del segmento ST (Dep ST) anormal. La mortalidad y la causa de las muertes fueron identificadas de forma ciega para los resultados del TE. RESULTADOS: En esta cohorte prospectiva y después de las exclusiones, 6.922 individuos presentaron EC NL (57,2 ± 11,4 años), 1739 tuvieron Dep ST anormal (62,7 ± 9,8 años), y 32 casos de BCRI E-I fueron identificados (65,2 ± 11,9 años). La prevalencia del BCRI E-I fue del 0,38 por ciento. Después de 8,8 años, ocurrieron 1699 muertes por todas las causas y 610 muertes cardiovasculares (CV). La enfermedad arterial coronaria y la insuficiencia cardíaca fueron las más prevalentes en los pacientes con BCRI E-I. Los pacientes con BCRI E-I presentaron azar de 2,37 (p = 0,002) para la mortalidad por todas las causas, pero ella no fue significativa cuando se ajustó para la edad o cuando la mortalidad cardiovascular fue el desenlace evaluado. CONCLUSIÓN: BCRI E-I es un hallazgo raro. Los individuos con BCRI E-I presentan una mayor mortalidad por todas las causas cuando se les compara con los de EC NL. Sin embargo, ese hecho se explica porque esos pacientes son significativamente más viejos y por presentar más enfermedades cardiovasculares asociadas.

Exercise-induced left bundle branch block: prevalence and prognosis.

BACKGROUND: Exercise-induced left bundle branch block (EI-LBBB) is an infrequent finding. Its prevalence and prognostic significance are not clear. OBJECTIVE: To evaluate, in a longitudinal study, the prevalence and prognostic significance of EI-LBBB in American war veterans. METHODS: We evaluated 9,623 patients submitted to an exercise test (ET) in treadmill between 1987 and 2007. The outcomes were compared between those with normal TE, the ones with EI-LBBB and the ones with down-sloping ST-segment. Mortality and causes of death were identified while blinded to the ET results. RESULTS: In this prospective cohort, 6,922 individuals had normal ET results (57.2 ± 11.4 years), 1,739 had abnormal ST-segment depression (62.7 ± 9.8 years), and 38 had EI-LBBB (65.2 ± 11.9 years). The prevalence of EI-LBBB was 0.38%. After 8.8 years, there were 1,699 deaths due to all-cause mortality and 610 cardiovascular (CV) deaths; coronary artery disease and heart failure were more prevalent in patients with EI-LBBB. Patients with EI-BCRE had a hazard ratio of 2.37 (p = 0.002) for all-cause mortality, but it was not significant when adjusted for age or when the CV death was the assessed outcome. CONCLUSION: EI-LBBB is a rare clinical finding. Individuals with BCRE-EI have higher all-cause mortality when compared to those with normal ET results. However, this fact is explained by the fact that these patients are significantly older and have more associated cardiovascular diseases.

Cardiopulmonary exercise testing is equally prognostic in young, middle-aged and older individuals diagnosed with heart failure.

BACKGROUND: Previous research has demonstrated the prognostic value of cardiopulmonary exercise testing (CPX) in elderly patients with heart failure (HF). Investigations that have comprehensively examined the value of CPX across different age groups are lacking. The purpose of the present investigation was to evaluate the prognostic value of CPX in young, middle-aged and older patients with HF. METHODS: A total of 1605 subjects (age: 59.2 ± 13.7 years, 78% male) underwent CPX and were subsequently tracked for major cardiac events. Ventilatory efficiency (VE/VCO(2) slope) and peak oxygen consumption (VO(2)), both absolute and percent-predicted, were determined. The prognostic value of these CPX variables was assessed in ≤ 45, 46-65 and ≥ 66 year subgroups. RESULTS: The three year event rates for major cardiac events in the ≤ 45, 46-65 and ≥ 66 year subgroups were 8.8%, 6.0% and 5.7%, respectively. The VE/VCO(2) slope (Hazard ratio ≥ 1.07, p<0.001), peak VO(2) (Hazard ratio ≤ 0.87, p<0.001) and percent-predicted peak VO(2) (Hazard ratio 0 ≤ 0.98, p<0.001) were all significant prognostic markers in each age subgroup. While the VE/VCO(2) slope carried the greatest prognostic strength, peak VO(2) and percent-predicted peak VO(2) were retained in multivariate analyses (Residual Chi-Square ≥ 5.2, p<0.05). With respect to peak VO(2), the actual value was the more robust prognostic marker in the ≤ 45 and ≥ 66 year subgroups while the percent-predicted expression provided better predictive resolution in subjects who were 46-65 years old. CONCLUSIONS: These results indicate that, irrespective of a patient's age at presentation, CPX provides valuable prognostic information in the HF population.

Defining the optimal prognostic window for cardiopulmonary exercise testing in patients with heart failure.

BACKGROUND: Ventilatory efficiency (VE/VCO(2) slope) and peak oxygen consumption (VO) provide robust prognostic information in patients with heart failure undergoing cardiopulmonary exercise testing (CPX). The purpose of this study is to assess the change in prognostic characteristics of CPX at different time intervals. METHODS AND RESULTS: Seven hundred ninety-one subjects (74% male, mean age: 60.7+/-12.9 years, ejection fraction: 34.6+/-15.0%, ischemic etiology: 51%) underwent CPX and were tracked for major cardiac events over a 4-year period. All event-free subjects were tracked for at least 3 years. Mean VE/VCO(2) slope and peak VO(2) were 35.0+/-10.0 and 16.0+/-6.4 mL O(2) . kg(-1) . min(-1), respectively. There were a total of 263 major cardiac events (199 deaths, 45 transplants, and 19 left ventricular assist device implantations). Both continuous and dichotomous expressions of the VE/VCO(2) slope and peak VO(2) were prognostically significant up to 18 months post-CPX. Continuous and dichotomous expressions of the VE/VCO(2) slope remained prognostically significant up to 36 months post-CPX, whereas peak VO(2) was not predictive during the third and fourth year of follow-up. In a multivariate analysis, the VE/VCO(2) slope was consistently the superior prognostic marker, whereas peak VO(2) added predictive value and was retained in the regression up to 18 months post-CPX. CONCLUSIONS: These results indicate that commonly assessed CPX variables retain prognostic value for at least 2 years. The VE/VCO(2) slope is the superior predictor of adverse events throughout follow-up, although peak VO(2) provides additive prognostic information during the first 2 years of follow-up.

Prevalence and prognostic significance of exercise-induced right bundle branch block.

Exercise-induced (EI) right bundle branch block (RBBB) is an infrequent electrocardiographic phenomenon, and controversy exists regarding its association with cardiovascular disease. We compared the prevalence and prognostic significance of RBBB, abnormal ST depression, and normal electrocardiographic findings in response to exercise testing in 9,623 consecutive veterans who underwent exercise testing from 1987 to 2007. EI RBBB, EI ST depression, and a normal exercise electrocardiographic response occurred in 0.24%, 15.2%, and 71.9% veterans, respectively. After appropriate exclusions, of the 8,047 patients analyzed, 6 patients in the EI RBBB subgroup died. Of these 6 deaths, 3 were cardiovascular deaths during the 9 years of follow-up. The annual death rate was 7.3% (1.4% cardiac deaths), 2.6% (1.2% cardiac deaths), and 1.8% (0.6% cardiac death) among those with EI RBBB, EI ST depression, and a normal ST response, respectively (p <0.0001). The patients with EI RBBB were significantly older, more overweight, and had a greater prevalence of coronary artery disease, heart failure, and hypertension compared to the 2 other subgroups. Patients with EI RBBB had an age-adjusted Cox proportional hazard ratio of 1.13 (p = 0.75, 95% confidence interval 0.51 to 2.5) for all-cause mortality and 1.57 (p = 0.43, 95% confidence interval 0.51 to 4.8) for cardiovascular mortality, respectively. In conclusion, EI RBBB is a rare occurrence during routine clinical exercise testing that appears to be benign.

Prognostic characteristics of heart rate recovery according to sex in patients with heart failure.

We hypothesized that heart rate recovery (HRR) will provide superior prognostic resolution in female compared to male heart failure (HF) patients. A total of 745 patients with HF underwent exercise testing to determine HRR. While receiver operating characteristic curve analysis revealed HRR prognostic classification schemes were significant for both males (area: 0.72, 95% CI: 0.67-0.78, p<0.001) and females (area: 0.82, 95% CI: 0.75-0.89, p<0.001), it was stronger in the latter group. The prognostic strength of HRR may be superior in female HF patients. This discrepancy may be driven by the ability of HRR to better reflect autonomic function in females.

Characterizing differences in mortality at the low end of the fitness spectrum in individuals with cardiovascular disease.

BACKGROUND: A graded but nonlinear relationship exists between fitness and mortality, with the greatest mortality differences occurring between the least-fit (first, Q1) and the next-least-fit (second, Q2) quintiles of fitness. The purpose of this study was to compare clinical characteristics, exercise test responses, and physical activity (PA) patterns in Q1 versus Q2 in patients with cardiovascular disease (CVD). DESIGN: Observational retrospective study. METHODS: A total of 5101 patients with a history of CVD underwent clinical treadmill testing and were followed up for 9.1+/-5.5 years. Patients were classified into quintiles of exercise capacity measured in metabolic equivalents. Clinical characteristics, treadmill test results, and recreational PA patterns were compared between Q1 (n = 923) and Q2 (n = 929). RESULTS: Q1 had a nearly two-fold increase in age-adjusted relative risk of cardiovascular mortality compared with Q2 (hazard ratio: 3.79 vs. 2.04, P<0.05; reference: fittest quintile). Q1 patients were older, had more extensive use of medications, and were more likely to have a history of typical angina (35 vs. 28%), myocardial infarction (30 vs. 24%), chronic heart failure (25 vs. 14%), claudication (15 vs. 9%) and stroke (9 vs. 6%) compared with Q2 (all comparisons: P<0.05). Recent and lifetime recreational PA was not different between the two groups. CONCLUSION: Greater severity of disease in the least-fit versus the next-least-fit quintile likely contributes to but cannot fully explain marked differences in mortality rates in CVD patients. To achieve potential survival benefits, our results suggest that unfit CVD patients should engage in exercise programs of sufficient volume and intensity to improve fitness.

The prognostic value of the heart rate response during exercise and recovery in patients with heart failure: influence of beta-blockade.

BACKGROUND: The heart rate increase during exercise (DeltaHR) and heart rate recovery (HRR) have demonstrated prognostic value in several investigations, but its application in the heart failure (HF) population is limited, particularly in a beta-blocked (BB) cohort. METHODS: Five-hundred and twenty subjects with HF underwent cardiopulmonary exercise testing to determine peak oxygen consumption (VO(2)), the minute ventilation/carbon dioxide production (VE/VCO(2)) slope, DeltaHR and HRR at 1 min (HRR(1)). RESULTS: There were 79 cardiac-related deaths during the tracking period. A HRR(1) threshold of or=16 beats/min was a significant prognostic marker in the overall group (hazard ratio: 4.6, 95% CI: 2.8-7.5, p<0.001) as well as no-BB (hazard ratio: 9.1, 95% CI: 4.1-20.2, p<0.001) and BB (hazard ratio: 2.9, 95% CI: 1.6-5.4, p<0.001) subgroups. The DeltaHR was a significant univariate predictor in the overall group and no-BB subgroup only. Multivariate Cox regression analysis revealed HRR(1) was the strongest prognostic marker (chi-square: 39.9, p<0.001). The VE/VCO(2) slope (residual chi-square: 21.8, p<0.001) and LVEF (residual chi-square: 9.6, p=0.002) were also retained in the regression. CONCLUSIONS: These results indicate that HRR maintains prognostic value in HF irrespective of BB use. The routine inclusion of HRR in the prognostic assessment of patients with HF may be warranted.

Influence of etiology of heart failure on the obesity paradox.

Several investigations have demonstrated that higher body weight, as assessed by the body mass index, is associated with improved prognosis in patients with heart failure (HF). The purpose of the present investigation was to assess the influence of HF etiology on the prognostic ability of the body mass index in a cohort undergoing cardiopulmonary exercise testing. A total of 1,160 subjects were included in the analysis. All subjects underwent cardiopulmonary exercise testing, at which the minute ventilation/carbon dioxide production slope and peak oxygen consumption were determined. In the overall group, 193 cardiac deaths occurred during a mean follow-up of 30.7 +/- 25.6 months (annual event rate 6.0%). The subjects classified as obese consistently had improved survival compared to those classified as normal weight (overall survival rate 88.0% vs or=43.4, p <0.001) for both etiologies, and the body mass index added prognostic value (residual chi-square >or=4.7, p <0.05). In conclusion, these results further support the notion that obesity confers improved prognosis in patients with HF, irrespective of the HF etiology. Moreover, the body mass index appears to add predictive value during the cardiopulmonary exercise testing assessment. However, survival appears to differ according to HF etiology in subjects classified as overweight.

Determining the preferred percent-predicted equation for peak oxygen consumption in patients with heart failure.

BACKGROUND: Peak oxygen consumption (Vo(2)) is routinely assessed in patients with heart failure undergoing cardiopulmonary exercise testing. The purpose of the present investigation was to determine the prognostic ability of several established peak Vo(2) prediction equations in a large heart failure cohort. METHODS AND RESULTS: One thousand one hundred sixty-five subjects (70% males; age, 57.0+/-13.8 years; ischemic etiology, 43%) diagnosed with heart failure underwent cardiopulmonary exercise testing. Percent-predicted peak Vo(2) was calculated according to normative values proposed by Wasserman and Hansen (equation), Jones et al (equation), the Cooper Clinic (below low fitness threshold), a Veteran's Administration male referral data set (4 equations), and the St James Take Heart Project for women (equation). The prognostic significance of percent-predicted Vo(2) values derived from the 2 latter, sex-specific equations were assessed collectively. There were 179 major cardiac events (117 deaths, 44 heart transplantations, and 18 left ventricular assist device implantations) during the 2-year tracking period (annual event rate, 10%). Measured peak Vo(2) and all percent-predicted peak Vo(2) calculations were significant univariate predictors of adverse events (chi(2)> or =31.9, P<0.001) and added prognostic value to ventilatory efficiency (VE/Vco(2) slope), the strongest cardiopulmonary exercise testing predictor of adverse events (chi(2)=150.7, P<0.001), in a multivariate regression. The Wasserman/Hansen prediction equation provided optimal prognostic information. CONCLUSIONS: Actual peak Vo(2) and the percent-predicted models included in this analysis all were significant predictors of adverse events. It seems that the percent-predicted peak Vo(2) value derived from the Wasserman/Hansen equations may outperform other expressions of this cardiopulmonary exercise testing variable.

Does peak oxygen pulse complement peak oxygen uptake in risk stratifying patients with heart failure?

There is scarce information regarding the prognostic utility of peak exercise oxygen pulse (peak O(2) pulse), a surrogate for stroke volume, in patients with heart failure (HF). From May 1994 to November 2007, 998 patients with HF underwent cardiopulmonary exercise testing. The ability of peak oxygen uptake (VO(2)) and peak O(2) pulse to predict cardiac events was examined. Peak O(2) pulse was calculated by dividing peak VO(2) by heart rate at the time peak VO(2) was achieved and was expressed in both milliliters per beat and as a percentage achieved of the age-predicted value. There were 212 cardiac events (176 deaths, 26 transplantations, and 10 left ventricular assist device implantations) over a mean of 28 +/- 26 months of follow-up. Peak VO(2) and age-predicted peak O(2) pulse were demonstrated by univariate and multivariate Cox regression analyses to be independent predictors of mortality (p <0.001). The optimal cut points for peak VO(2) and age-predicted peak O(2) pulse (<14.3 and > or =14.3 [mL/kg(-1)/min(-1)] and <85% and > or =85%, respectively) were established by areas under the receiver-operating characteristic curves. Patients exhibiting abnormalities for both responses had 4.8-fold (95% confidence interval 2.7 to 8.5) and 6.7-fold (95% confidence interval 4.1 to 11.1) higher risks for mortality and cardiac events, respectively, than those whose responses were normal. Age-predicted peak O(2) pulse also predicted mortality in patients in the intermediate range of peak VO(2) (10 to 14 (mL/kg(-1)/min(-1))). The 3-year mortality rate for patients in this range who had age-predicted peak O(2) pulse values <85% was even slightly higher than those with peak VO(2) <10.1 (mL/kg(-1)/min(-1)). In conclusion, age-predicted peak O(2) pulse was a strong and independent predictor of cardiac mortality and complemented peak VO(2) in predicting risk in patients with HF.

Characterizing differences in mortality at the low end of the fitness spectrum.

PURPOSE: A graded nonlinear relationship exists between fitness and mortality with the most remarkable difference in mortality rates observed between the least-fit (first, Q1) and the next-least-fit (second, Q2) quintile of fitness. The purpose of this study was to compare clinical characteristics, exercise test responses, and physical activity patterns in Q1 versus Q2 in apparently healthy individuals. METHODS: A total of 4384 subjects referred for clinical treadmill testing from 1986 to 2006 were followed for a mean +/- SD period of 8.7 +/- 5.3 yr. All subjects had normal exercise ECG responses and no history of cardiovascular disease. Subjects were classified into quintiles of exercise capacity measured in METs. Clinical characteristics, physical activity patterns, and treadmill test results were compared between the first two quintiles (Q1: METs <5.9 (n = 693); Q2: METs 6.0-7.9 (n = 842)). RESULTS: Small differences in age (64 +/- 11 vs 60 +/- 10 yr, P < 0.001), use of antihypertensive medications, prevalence of diabetes (21% vs 16%, P = 0.02), and dyslipidemia (43% vs 49%, P = 0.04) were observed between Q1 and Q2. When the Cox proportional hazards model was adjusted for age and other clinical characteristics, the relative risk of mortality remained almost two times greater in Q1 versus Q2 (cardiovascular mortality: HR: 4.01 vs 2.01, P < 0.001; reference group: fittest subjects (Q5)). In a subset of 802 subjects, recent recreational physical activity was significantly lower in Q1 versus Q2. CONCLUSIONS: Reduced physical activity patterns rather than differences in clinical characteristics contribute to the striking difference in mortality rates between the least-fit and the next-least-fit quintile of fitness in healthy individuals.

Maximal exercise oxygen pulse as a predictor of mortality among male veterans referred for exercise testing.

BACKGROUND: Maximal oxygen pulse (O(2) pulse) mirrors the stroke volume response to exercise, and should therefore be a strong predictor of mortality. Limited and conflicting data are, however, available on this issue. METHODS: Nine hundred forty-eight participants, classified as those with cardiopulmonary disease (CPD) and those without (non-CPD), underwent cardiopulmonary exercise testing (CPX) for clinical reasons between 1993 and 2003. The ability of maximal O(2) pulse and maximal oxygen uptake (peak VO(2)) to predict mortality was investigated using proportional hazards and Akaike information criterion analyses. All-cause mortality was the endpoint. RESULTS: Over a mean follow-up of 6.3+/-3.2 years, there were 126 deaths. Maximal O(2) pulse, expressed in either absolute or relative to age-predicted terms, and peak VO(2) were significant and independent predictors of mortality in those with and without CPD (P<0.04). Akaike information criterion analysis revealed that the model including both maximal O(2) pulse and peak VO(2) had the highest accuracy for predicting mortality. The optimal cut-points for O(2) pulse and peak VO(2) (<12; > or =12 ml/beat and <16; > or =16 ml/(kg.min) respectively) were established by the area under the receiver-operating-characteristic curve. The relative risks of mortality were 3.4 and 2.2 (CPD and non-CPD, respectively) among participants with both maximal O(2) pulse and peak VO(2) responses below these cut-points compared with participants with both responses above these cut-points. CONCLUSION: These results indicate that maximal O(2) pulse is a significant predictor of mortality in patients with and without CPD. The addition of absolute and relative O(2) pulse data provides complementary information for risk-stratifying heterogeneous participants referred for CPX and should be routinely included in the CPX report.

Fitness and fatness as mortality predictors in healthy older men: the veterans exercise testing study.

BACKGROUND: Low body mass index (BMI) and low cardiorespiratory fitness (CRF) are independently associated with increased mortality in the elderly. However, interactions among BMI, CRF, and mortality in older persons have not been adequately explored. METHODS: Hazard ratios (HRs) were calculated for predetermined strata of BMI and CRF. Independent and joint associations of CRF, BMI, and all-cause mortality were assessed by Cox proportional hazards analyses in a prospective cohort of 981 healthy men aged at least 65 years (mean age [+/-SD], 71 [+/-5] years; range, 65-88 years) referred for exercise testing during 1987-2003. RESULTS: During a mean follow-up of 6.9 +/- 4.4 years, a total of 208 patients died. Multivariate relative risks (95% confidence interval [CI]) of mortality across BMI groups of <20.0, 20.0-25.0, 25.0-29.9, 30.0-34.9, and > or =35.0 were 2.51 (1.26-4.98), 1.0 (reference), 0.66 (0.48-0.90), 0.50 (0.31-0.78), and 0.44 (0.20-0.97), respectively, and across CRF groups of <5.0, 5.0-8.0, and >8.0 metabolic equivalents were 1.0 (reference), 0.56 (0.40-0.78), and 0.39 (0.26-0.58), respectively. In a separate analysis of within-strata CRF according to BMI grouping, the lowest mortality risk was observed in obese men with high fitness (HR [95% CI] 0.26 [0.10-0.69]; p = .007). CONCLUSIONS: In this cohort of elderly male veterans, we observed independent and joint inverse relations of BMI and CRF to mortality. This warrants further investigation of fitness, fatness, and mortality interactions in older persons.

Exercise capacity and all-cause mortality in African American and Caucasian men with type 2 diabetes.

OBJECTIVE: The purpose of this study was to assess the association between exercise capacity and mortality in African Americans and Caucasians with type 2 diabetes and to explore racial differences regarding this relationship. RESEARCH DESIGN AND METHODS: African American (n = 1,703; aged 60 +/- 10 years) and Caucasian (n = 1,445; aged 62 +/- 10 years) men with type 2 diabetes completed a maximal exercise test between 1986 and 2007 at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Three fitness categories were established (low-, moderate-, and high-fit) based on peak METs achieved. Subjects were followed for all-cause mortality for 7.3 +/- 4.7 years. RESULTS: The adjusted mortality risk was 23% higher in African Americans than in Caucasians (hazard ratio 1.23 [95% CI 1.1-1.4]). A graded reduction in mortality risk was noted with increased exercise capacity for both races. There was a significant interaction between race and METs (P < 0.001) and among race and fitness categories (P < 0.001). The association was stronger for Caucasians. Each 1-MET increase in exercise capacity yielded a 19% lower risk for Caucasians and 14% for African Americans (P < 0.001). Similarly, the risk was 43% lower (0.57 [0.44-0.73]) for moderate-fit and 67% lower (0.33 [0.22-0.48]) for high-fit Caucasians. The comparable reductions in African Americans were 34% (0.66 [0.55-0.80]) and 46% (0.54 [0.39-0.73]), respectively. CONCLUSIONS: Exercise capacity is a strong predictor of all-cause mortality in African American and Caucasian men with type 2 diabetes. The exercise capacity-related reduction in mortality appears to be stronger and more graded for Caucasians than for African Americans.