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 ß-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.

Relationship Between Exercise Workload During Cardiac Rehabilitation and Outcomes in Patients With Coronary Heart Disease.

The purpose of this retrospective, observational study was to describe the relation between exercise workload during cardiac rehabilitation (CR), expressed as metabolic equivalents of task (METs), and prognosis among patients with coronary heart disease. We included patients with coronary heart disease who participated in CR between January 1998 and June 2007. METs were calculated from treadmill workload. Cox regression analysis was used to describe the relationship between METs and time to a composite outcome of all-cause mortality, nonfatal myocardial infarction, or heart failure hospitalization. Among 1,726 patients (36% women; median age 59 years [interquartile range, 52 to 66]), there were 467 events (27%) during a median follow-up of 5.8 years (interquartile range, 2.6 to 8.7). In analyses adjusted for age, sex, Charlson co-morbidity index, hypertension, diabetes, and CR referral diagnosis, METs were independently related to the composite outcome at CR start (Wald chi-square 43, hazard ratio 0.59 [95% confidence interval 0.51 to 0.70]) and CR end (Wald chi-square 47, hazard ratio 0.68 [95% confidence interval 0.61 to 0.76]). Patients exercising below 3.5 METs on exit from CR represent a high-risk group with 1- and 3-year event rates ≥7% and ≥18%, respectively. In conclusion, METs during CR is available at no additional cost and can be used to identify patients at increased risk for an event who may benefit from closer follow-up, extended length of stay in CR, and/or participation in other strategies aimed at maximizing adherence to secondary preventive behaviors and improving exercise capacity.

Comprehensive analysis of cardiopulmonary exercise testing and mortality in patients with systolic heart failure: the Henry Ford Hospital cardiopulmonary exercise testing (FIT-CPX) project.

BACKGROUND: Many studies have shown a strong association between numerous variables from a cardiopulmonary exercise (CPX) test and prognosis in patients with heart failure with reduced ejection fraction (HFrEF). However, few studies have compared the prognostic value of a majority of these variables simultaneously, so controversy remains regarding optimal interpretation. METHODS AND RESULTS: This was a retrospective analysis of patients with HFrEF (n = 1,201; age = 55 ± 13 y; 33% female) and a CPX test from 1997 to 2010. Thirty variables from a CPX test were considered in separate adjusted Cox regression analyses to describe the strength of the relation of each to a composite end point of all-cause mortality, left ventricular assist device implantation, or heart transplantation. During a median follow-up of 3.8 years, there were 577 (48.0%) events. The majority of variables were highly significant (P < .001). Among these, percentage of predicted maximum V˙O2 (ppMV˙O2; Wald = 203; P < .001; C-index = 0.73) was similar to VE-VCO2 slope (Wald = 201; P < .001; C = 0.72) and peak V˙O2 (Wald = 161; P < .001; C = 0.72). In addition, there was no significant interaction observed for peak respiratory exchange ratio <1 vs ≥1. CONCLUSIONS: Consistent with prior studies, many CPX test variables were strongly associated with prognosis in patients with HFrEF. The choice of which variable to use is up to the clinician. Renewed attention should be given to ppMV˙O2, which appears to be highly predictive of survival in these patients.

Prognostic value of exercise capacity in patients with coronary artery disease: the FIT (Henry Ford ExercIse Testing) project.

OBJECTIVE: To examine the prognostic value of exercise capacity in patients with nonrevascularized and revascularized coronary artery disease (CAD) seen in routine clinical practice. PATIENTS AND METHODS: We analyzed 9852 adults with known CAD (mean ± SD age, 61±12 years; 69% men [n=6836], 31% black race [n=3005]) from The Henry Ford ExercIse Testing (FIT) Project, a retrospective cohort study of patients who underwent physician-referred stress testing at a single health care system between January 1, 1991, and May 31, 2009. Patients were categorized by revascularization status (nonrevascularized, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) and by metabolic equivalents (METs) achieved on stress testing. Using Cox regression models, hazard ratios for mortality, myocardial infarction (MI), and downstream revascularizations were calculated after adjusting for potential confounders, including cardiac risk factors, pertinent medications, and stress testing indication. RESULTS: There were 3824 all-cause deaths during median follow-up of 11.5 years. In addition, 1880 MIs, and 1930 revascularizations were ascertained. Each 1-MET increment in exercise capacity was associated with a hazard ratio (95% CI) of 0.87 (0.85-0.89), 0.87 (0.85-0.90), and 0.86 (0.84-0.89) for mortality; 0.98 (0.96-1.01), 0.88 (0.84-0.92), and 0.93 (0.90-0.97) for MI; and 0.94 (0.92-0.96), 0.91 (0.88-0.95), and 0.96 (0.92-0.99) for downstream revascularizations in the nonrevascularized, PCI, and CABG groups, respectively. In each MET category, the nonrevascularized group had similar mortality risk as and higher MI and downstream revascularization risk than the PCI and CABG surgery groups (P<.05). CONCLUSION: Exercise capacity was a strong predictor of mortality, MI, and downstream revascularizations in this cohort. Furthermore, patients with similar exercise capacities had an equivalent mortality risk, irrespective of baseline revascularization status.

Cardiac rehabilitation improves functional capacity and patient-reported health status in patients with continuous-flow left ventricular assist devices: the Rehab-VAD randomized controlled trial.

OBJECTIVES: This study examined the effects of a cardiac rehabilitation (CR) program on functional capacity and health status (HS) in patients with newly implanted left ventricular assist devices (LVADs). BACKGROUND: Reduced functional capacity and HS are independent predictors of mortality in patients with heart failure. CR improves both, and is related to improved outcomes in patients with heart failure; however, there is a paucity of data that describe the effects of CR in patients with LVADs. METHODS: Enrolled subjects (n = 26; 7 women; age 55 ± 13 years; ejection fraction 21 ± 8%) completed a symptom-limited cardiopulmonary exercise test, the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 6-min walk test (6MW), and single-leg isokinetic strength test before 2:1 randomization to CR versus usual care. Subjects in the CR group underwent 18 visits of aerobic exercise at 60% to 80% of heart rate reserve. Within-group changes from baseline to follow-up were analyzed with a paired t-test, whereas an independent t-test was used to determine differences in the change between groups. RESULTS: Within-group improvements were observed in the CR group for peak oxygen uptake (10%), treadmill time (3.1 min), KCCQ score (14.4 points), 6MW distance (52.3 m), and leg strength (17%). Significant differences among groups were observed for KCCQ, leg strength, and total treadmill time. CONCLUSIONS: Indicators of functional capacity and HS are improved in patients with continuous-flow LVADs who attend CR. Future trials should examine the mechanisms responsible for these improvements, and if such improvements translate into improved clinical outcomes. (Cardiac Rehabilitation in Patients With Continuous Flow Left Ventricular Assist Devices:Rehab VAD Trial [RehabVAD]; NCT01584895).

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, (·)VO2) 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. (·)VO2 at ventilatory-derived anaerobic threshold increased more (P < .05) with HIIT (3.0 ± 2.8 mL·kg⁻¹·min⁻¹) versus MCT (0.7 ± 2.2 mL·kg⁻¹·min⁻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 (·)VO2 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.

Muscular strength and cardiorespiratory fitness are associated with health status in patients with recently implanted continuous-flow LVADs.

INTRODUCTION: Patient health status (PHS) and peak oxygen uptake (V.O2) are important predictors of clinical outcomes in individuals with heart failure. Preliminary studies of individuals with left ventricular assist devices (LVADs) show improvements in both PHS and peak V.O2. However, the relationship between peak V.O2 and PHS in this population is not well described. Likewise, data regarding muscular strength are also lacking in this population. We sought to describe the association between peak V.O2, muscular strength, and PHS in patients with continuous-flow LVADs. METHODS: Subjects (n = 26; 7 women) completed a symptom-limited graded exercise test within an average of 82 days (range, 33-167 days) of LVAD implant. In addition, subjects underwent a 6-Minute Walk Test and an isokinetic knee extension strength test and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). Spearman correlation coefficients were performed, adjusting for body weight and gender, to examine relationships between variables. RESULTS: Muscular strength, as measured by peak torque, and peak V.O2 were both moderately associated with the KCCQ (r = 0.58, P = .006; r = 0.51, P = .019). A subanalysis revealed that muscular strength and peak V.O2 were related to different domains within the KCCQ. CONCLUSIONS: Leg muscle strength and peak V.O2 appear to be important factors related to PHS in patients with continuous-flow LVADs. This is likely partially a result of deconditioning due to recent hospitalization, as well as persistent heart failure-related peripheral maladaptations in skeletal muscle. Incorporating both a cardiovascular as well as strength training program before and after LVAD implant surgery may be beneficial.

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.

A systematic approach to evaluation of pericardial effusion and cardiac tamponade.

Pericardial disease leading to pericardial effusion (PEF) is a common condition encountered by the clinician in day-to-day practice. If the PEF becomes large enough, it can cause hemodynamic compromise, resulting in a cardiogenic shock state known as cardiac tamponade. There are many clinical and echocardiographic signs that a clinician can use to assess whether a large PEF is hemodynamically significant. However, these signs can be either conflicting or even absent. The purpose of this review is to first, describe the physiology of the pericardium in health and how it changes with disease; second, outline the pathophysiology of pericardial tamponade and discuss how it is responsible for the physical and echocardiographic findings of cardiac tamponade; and third, suggest an approach to applying these findings in a systematic order to ensure a correct diagnosis.

Quality assurance and cardiopulmonary exercise testing in clinical trials.

BACKGROUND: Peak oxygen uptake (VO2) measured during cardiopulmonary exercise testing (CPX) is often used as an outcome measure in clinical trials. The purposes of this study are (a) to report the outcomes of a quality assurance (QA) procedure instituted in multisite clinical trials by a CPX data core laboratory and (b) to report a normative VO2 reference dataset for future use. METHODS: The CPX laboratory at each site participating in a multisite clinical trial in which Henry Ford Hospital served as the CPX data core laboratory was required to pass a standardized QA procedure before site activation and regularly thereafter. Data were compared with a VO2 reference dataset (pilot data) and assessed for test-retest reproducibility. VO2 data that represented a normal physiologic response were used to develop a final normative VO2 reference dataset. RESULTS: Between 2003 and 2006, 81 laboratories submitted 144 baseline QA tests. Of these, 34% did not initially meet the passing criteria, largely because of poor test-retest reproducibility. Among all QA tests submitted to the core laboratory, 159 unique volunteers had exercise data that met the criteria to be entered into the final normative VO2 reference dataset. Within this dataset, the mean coefficient of variation for VO2 between the test and retest was 5.1%. CONCLUSION: A standardized QA procedure can be used to identify aberrant data and minimize the variability of VO2 measured in a clinical trial or the routine evaluation of patients.

Predicting maximum heart rate among patients with coronary heart disease receiving beta-adrenergic blockade therapy.

BACKGROUND: The use of beta-adrenergic blockade (BB) therapy is common among patients with coronary heart disease (CHD), and as a result, these patients often undergo exercise testing while taking these medications. However, evaluation of maximal voluntary effort during exercise testing is often in question because current equations to predict maximum heart rate (HR(max); eg, 220 - age) are based on subjects without heart disease or BB therapy. The purpose of this study was to develop and validate an age-specific equation to predict HR(max) in patients with CHD who are receiving BB therapy. METHODS: We queried the Henry Ford Preventive Cardiology Outcomes database for patients with a history of myocardial infarction or revascularization procedure; preserved left ventricular function; age, 40 to 80 years; sinus rhythm; and a graded treadmill test with a respiratory exchange ratio > or =1.10. Data were split, based on date, such that tests performed between November 1996 and April 2001 were used as the BB prediction equation development group (n = 334; 73% men) and those performed between May 2001 and April 2002 were used as the BB cross-validation group (n = 94; 84% men). Linear regression was used to develop the equation to predict HR(max), based on age, and to calculate the correlation coefficient of the prediction equation among the cross-validation group. RESULTS: The resultant prediction equation was HR(max) = 164 - 0.7 x age (r2 = 0.13), with a standard error of the estimate of 18 per minute. Among the cross-validation group, mean predicted HR(max) was not significantly different from mean measured HR(max) (P = .7). The mean error of prediction was -0.4 +/- 2.0 per minute (mean +/- SEM), and the correlation was r = 0.38. CONCLUSIONS: This new equation provides a better estimate of HR(max) for patients with CHD receiving BB therapy than previously reported equations. Additional variables may improve the equation but may not be as convenient to use.

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.