Jonathan K. Ehrman

Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease Six-Month Outcomes From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Study

Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P <0.001 for the comparison of SE versus OMC, P =0.02 for ST versus OMC, and P =0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: . Unique identifier: [NCT00132743][1]. # Clinical Perspective {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00132743&atom=%2Fcirculationaha%2F125%2F1%2F130.atomBackground Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise or stent revascularization.Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P<0.001 for the comparison of SE versus OMC, P=0.02 for ST versus OMC, and P=0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1. Unique identifier: NCT00132743.

Peak aerobic capacity predicts prognosis in patients with coronary heart disease

BACKGROUND It is unknown if contemporary preventive treatments such as statins or primary percutaneous coronary intervention in patients with coronary heart disease (CHD) have rendered obsolete the use of measured exercise capacity for assessment of future risk and prognosis. Using a sample of patients from 2 clinical sites, most of whom were taking beta-blockade, antiplatelet, and statin therapy, we hypothesized that peak oxygen consumption (Vo(2)) would remain a strong and independent predictor of all-cause and cardiovascular-specific mortality in men and women with CHD. METHODS We studied 2,812 patients with CHD between 1996 and 2004. All-cause and cardiovascular disease-specific mortality served as end points. RESULTS In all men and women and in a subgroup of patients following evidence-based care, peak Vo(2) remained a strong predictor of all-cause death, with every 1 mL x kg(-1) x min(-1) increase in peak Vo(2) associated with an approximate 15% decrease in risk of death. Among men, a peak Vo(2) (mL x kg(-1) x min(-1)) below approximately 15 was associated with the highest risk, whereas a peak Vo(2) above approximately 19 was associated with a low rate and risk for annual all-cause mortality. Among women, a peak Vo(2) below approximately 12 was associated with the highest risk, whereas a peak Vo(2) above approximately 16.5 was associated with the lowest rate and risk for annual all-cause mortality. CONCLUSIONS In men and women with CHD, peak Vo(2) remains an independent predictor of all-cause and cardiovascular-specific mortality.

The relationship of heart rate reserve to VO2 reserve in patients with heart disease

UNLABELLED Recent reports indicate that among healthy adults, % heart rate reserve (HRR) is more closely related to %VO2 reserve (VO2R) than it is to %VO2max. This finding, in addition to the disparity between %HRR and %VO2max which is greater at low intensities and among low fit individuals, led the American College of Sports Medicine to adopt the use of %VO2R in place of %VO2max when prescribing exercise intensity among healthy adults and persons with heart disease. However, the relationship of %HRR to %VO2R among persons with heart disease has not been described. PURPOSE Among patients with a myocardial infarction (MI) and patients with chronic heart failure (HF), test the hypothesis that %VO2R is equivalent to %HRR, while %VO2peak is not. METHODS Using a clinical cardiology outcomes database, symptom-limited treadmill tests from 65 patients with MI and 72 patients with HF were identified. Heart rate and VO2 data were measured continuously and averaged every 15 s. For each subject, linear regression was used to calculate the slope and y-intercept of %HRR versus %VO2R (assuming rest VO2 = 3.5 mL x kg(-1) x min(-1)) and %HRR versus %VO2peak. Mean slope and y-intercept were calculated for each group and compared with the line of identity (slope = 1, y-intercept = 0). RESULTS For the MI and HF groups, the slope of %HRR versus %VO2R was 0.96 +/- 0.02 (+/-SE; P = NS, slope vs 1) and 0.97 +/- 0.02 (P = NS), respectively. And the y-intercept was -1.9 +/- 2.1% (P = NS, y-intercept vs 0) and -5.9 +/- 2.1% (P < 0.05) for MI and HF, respectively. For both patient groups, the regression of %HRR versus %VO2peak resulted in a line that differed (P < 0.001) in both slope and y-intercept from the line of identity. CONCLUSIONS In patients with heart disease, %HRR is a better estimate of %VO2R than %VO2peak. This finding does not affect the current recommended use of %HRR. However, when prescribing exercise based on VO2, relative intensity should be expressed as %VO2R.

An Early Appointment to Outpatient Cardiac Rehabilitation at Hospital Discharge Improves Attendance at Orientation A Randomized, Single-Blind, Controlled Trial

Background— Outpatient cardiac rehabilitation (CR) decreases mortality rates but is underutilized. Current median time from hospital discharge to enrollment is 35 days. We hypothesized that an appointment within 10 days would improve attendance at CR orientation. Methods and Results— At hospital discharge, 148 patients with a nonsurgical qualifying diagnosis for CR were randomized to receive a CR orientation appointment either within 10 days (early) or at 35 days (standard). The primary end point was attendance at CR orientation. Secondary outcome measures were attendance at ≥1 exercise session, the total number of exercise sessions attended, completion of CR, and change in exercise training workload while in CR. Average age was 60±12 years; 56% of participants were male and 49% were black, with balanced baseline characteristics between groups. Median time (95% confidence interval) to orientation was 8.5 (7–13) versus 42 (35 to NA [not applicable]) days for the early and standard appointment groups, respectively (P<0.001). Attendance rates at the orientation session were 77% (57/74) versus 59% (44/74) in the early and standard appointment groups, respectively, which demonstrates a significant 18% absolute and 56% relative improvement (relative risk, 1.56; 95% confidence interval, 1.03–2.37; P=0.022). The number needed to treat was 5.7. There was no difference (P>0.05) in any of the secondary outcome measures, but statistical power for these end points was low. Safety analysis demonstrated no difference between groups in CR-related adverse events. Conclusions— Early appointments for CR significantly improve attendance at orientation. This simple technique could potentially increase initial CR participation nationwide. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01596036.

Greater improvement in cardiorespiratory fitness using higher-intensity interval training in the standard cardiac rehabilitation setting.

PURPOSE: We tested the hypothesis that higher-intensity interval training (HIIT) could be deployed into a standard cardiac rehabilitation (CR) setting and would result in a greater increase in cardiorespiratory fitness (ie, peak oxygen uptake, ) versus moderate-intensity continuous training (MCT). METHODS: Thirty-nine patients participating in a standard phase 2 CR program were randomized to HIIT or MCT; 15 patients and 13 patients in the HIIT and MCT groups, respectively, completed CR and baseline and followup cardiopulmonary exercise testing. RESULTS: No patients in either study group experienced an event that required hospitalization during or within 3 hours after exercise. The changes in resting heart rate and blood pressure at followup testing were similar for both HIIT and MCT. at ventilatory-derived anaerobic threshold increased more (P < .05) with HIIT (3.0 ± 2.8 mL·kg·−1min−1) versus MCT (0.7 ± 2.2 mL·kg·−1min−1). During followup testing, submaximal heart rate at the end of stage 2 of the exercise test was significantly lower within both the HIIT and MCT groups, with no difference noted between groups. Peak V˙o2 improved more after CR in patients in HIIT versus MCT (3.6 ± 3.1 mL·kg.−1·min−1 vs 1.7 ± 1.7 mL·kg.−1·min−1; P < .05). CONCLUSIONS: Among patients with stable coronary heart disease on evidence-based therapy, HIIT was successfully integrated into a standard CR setting and, when compared to MCT, resulted in greater improvement in peak exercise capacity and submaximal endurance.

The Ventilatory Anaerobic Threshold in Heart Failure: A Multicenter Evaluation of Reliability

BACKGROUND The ventilatory threshold (VT) is usually determined by visual assessment of the point where the rate of elimination of carbon dioxide (VCO(2)) increases nonlinearly with respect to oxygen uptake (VO(2)) (the V-Slope method). We quantified the reliability of VT determination using data from a multicenter study in patients with heart failure. METHODS AND RESULTS The Fix-Heart Failure-5 study of cardiac contractility modulation enrolled 428 patients from 50 centers in the United States. Cardiopulmonary exercise tests were performed at baseline and 12, 24, and 50 weeks after randomization, which provided 1679 tests. The VT was determined from each test in a core laboratory by 2 independent readers. VT could not be determined for 276 tests (16.4% indeterminate). Inter-observer variability (quantified by the 95% limits of agreement, LoA, expressed as a percent of the mean value) was 20.2% between the 2 readers, with a coefficient of variation (CV) of 7.3%. Intra-observer variability was assessed by resubmitting (blinded) 179 tests to the same readers; the LoA was 24.7% for reader 1 and 16.9% for reader 2, with CVs of 6.1 and 8.9%, respectively. Ninety-one tests were submitted to 2 additional readers at a second core lab. Inter-observer variability in the second lab was 26.7% with a CV of 9.6%. Inter-laboratory variability was 21.4%, with a CV of 7.7%. CONCLUSIONS Inter-observer, intra-observer, and inter-site variation in determining the VT should be considered when using the VT as an end point in clinical trials of heart failure.

Cardiorespiratory Fitness and Incident Diabetes: The FIT (Henry Ford Exercise Testing) Project

OBJECTIVE Prior evidence has linked higher cardiorespiratory fitness with a lower risk of diabetes in ambulatory populations. Using a demographically diverse study sample, we examined the association of fitness with incident diabetes in 46,979 patients from The Henry Ford ExercIse Testing (FIT) Project without diabetes at baseline. RESEARCH DESIGN AND METHODS Fitness was measured during a clinician-referred treadmill stress test performed between 1991 and 2009. Incident diabetes was defined as a new diagnosis of diabetes on three separate consecutive encounters derived from electronic medical records or administrative claims files. Analyses were performed with Cox proportional hazards models and were adjusted for diabetes risk factors. RESULTS The mean age was 53 years with 48% women and 27% black patients. Mean metabolic equivalents (METs) achieved was 9.5 (SD 3.0). During a median follow-up period of 5.2 years (interquartile range 2.6–8.3 years), there were 6,851 new diabetes cases (14.6%). After adjustment, patients achieving ≥12 METs had a 54% lower risk of incident diabetes compared with patients achieving <6 METs (hazard ratio 0.46 [95% CI 0.41, 0.51]; P-trend < 0.001). This relationship was preserved across strata of age, sex, race, obesity, hypertension, and hyperlipidemia. CONCLUSIONS These data demonstrate that higher fitness is associated with a lower risk of incident diabetes regardless of demographic characteristics and baseline risk factors. Future studies should examine the association between change in fitness over time and incident diabetes.

Left ventricular response to submaximal exercise in endurance-trained athletes and sedentary adults

This investigation examines the hypothesis that athletes increase stroke volume with submaximal exercise through an augmentation of left ventricular (LV) end-diastolic volume and a reduction of LV end-systolic volume, whereas sedentary adults only increase stroke volume modestly, because LV end-diastolic volume does not increase. Upright bicycle exercise was performed by 17 endurance-trained male athletes and 15 sedentary men. M-mode echocardiograms were obtained during submaximal exercise at predetermined heart rates. Athletes, at a heart rate of 130 beats/min, increased their stroke volume 67% from 72 +/- 18 ml to 120 +/- 26 ml (p less than 0.001). This resulted from an increase of LV end-diastolic volume from 119 +/- 23 to 152 +/- 28 ml (p less than 0.001) and a reduction in LV end-systolic volume from 46 +/- 14 to 31 +/- 9 ml (p less than 0.001). Sedentary men at the same heart rate increased stroke volume 22% from 63 +/- 15 to 77 +/- 21 ml (p less than 0.05). LV end-diastolic volume did not change (96 +/- 20 vs 97 +/- 28 ml) (p = not significant), but LV end-systolic volume decreased (33 +/- 11 vs 20 +/- 9 ml) (p less than 0.001). In conclusion, athletes increased cardiac output through a more prominent augmentation of stroke volume than sedentary subjects at submaximal exercise. This was accomplished through an augmentation of LV end-diastolic volume. This may have a conserving effect on myocardial oxygen consumption at these levels of exercise.

Leisure time physical activity of patients in maintenance cardiac rehabilitation

PURPOSE Increasing caloric expenditure through physical activity is associated with reduced mortality. On the basis of observational studies, previous authors have suggested that at least 1000 kcal per week and possibly 1500 kcal per week of physical activity is necessary for health benefits. The authors have previously reported that patients in maintenance cardiac rehabilitation accumulate approximately 230 kcal per exercise session, suggesting that additional activity outside of cardiac rehabilitation is needed to achieve the goal of 1500 kcal per week. The authors estimated the amount of energy expenditure performed each week by patients in cardiac rehabilitation during both program participation and leisure time. METHODS For this study, 104 patients enrolled in a supervised maintenance cardiac rehabilitation program at both tertiary care and community settings for at least 6 months completed a self-administered physical activity questionnaire. Energy expenditure in cardiac rehabilitation and leisure time activity was measured in kilocalories. Total caloric expenditure was determined by adding up the number of kilocalories expended by the patients each week climbing stairs, walking, participating in cardiac rehabilitation, and engaging in sports. RESULTS Patients in cardiac rehabilitation expended weekly, on the average, 1504 +/- 830 kcal in physical activity, 830 +/- 428 kcal in cardiac rehabilitation, and 675 +/- 659 kcal in leisure time activity. There was a significant difference in caloric expenditure between men and women, between those with a body mass index (BMI) less than 30 and those with a BMI of 30 or more, and between those younger than 70 years and those 70 years or older. There was no difference between races. Whereas 43% of the patients accumulated 1500 kcal, 57% did not. CONCLUSIONS The findings showed that 72% of the patients in cardiac rehabilitation accumulated at least 1000 kcal of energy expenditure per week and met public health guidelines. Also, 43% of the patients in cardiac rehabilitation accumulated more than 1500 kcal of energy expenditure per week, a level identified as necessary to reduce all-cause mortality. Women of either race, patients with a BMI of 30 or more, and patients age 70 years or older are the groups least likely to achieve 1500 kcal of energy expenditure per week. The authors recommend incorporating weekly kilocalories of energy expenditure in the exercise prescription of patients to ensure achievement of maximum health benefits.

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project

BACKGROUND Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. METHODS This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. RESULTS We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and β-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. CONCLUSION These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients.