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Exercise capacity (EC) is inversely related to the risk of cardiovascular disease and incident heart failure (HF) in healthy subjects. However, there are no present studies that exclusively evaluate EC and the risk of incident HF in patients with known coronary heart disease (CHD). We aimed to determine the relation between EC and incident HF in patients with an established clinical diagnosis of CHD. We retrospectively identified 8,387 patients (age 61 ± 12 years; 30% women; 33% non-White) with a history of myocardial infarction (MI) or coronary revascularization procedure and no history of HF at the time of a clinically indicated exercise stress test completed between 1991 and 2009. EC was quantified in metabolic equivalents of task (METs) estimated from treadmill testing. Incident HF was identified through June 2010 from administrative databases based on ≥3 encounters with International Classification of Diseases, Ninth Revision 428.x. Cox regression analysis was used to evaluate the risk of incident HF associated with METs. Covariates included age; gender; race; hypertension, diabetes, hyperlipidemia, smoking, and MI; medications for CHD and lung diseases; and clinical indication for treadmill testing. During a median follow-up of 8.2 years (interquartile range 4.7 to 12.4 years) after the exercise test, 23% of the cohort experienced a new HF diagnosis. Lower EC categories were associated with higher HF incidence compared with METs ≥12, with nearly fourfold greater adjusted risk among patients with METslt;6. Per unit increase in METs of EC was associated with a 12% lower adjusted risk for HF. There was no significant interaction based on race (p = 0.06), gender (p = 0.88), age ≤61 years (p = 0.60), history of MI (p = 0.31), or diabetes (p = 0.38). This study reveals that among men and women with CHD and no history of HF, EC is independently and inversely related to the risk of future HF.

The purpose of this study was to test the hypothesis that an individualized exercise training target heart rate (HR) based on a maximal graded exercise test (GXT) is associated with greater improvements in exercise tolerance during cardiac rehabilitation (CR) compared with no GXT. In this retrospective study, we identified patients who completed 9 to 36 visits of CR between 2001 and 2016, with a length of stay ≤18 weeks and a visit frequency of 1 to 3 days per week. Patients were grouped based on whether their exercise was guided by a target HR determined from a GXT. To assess the relation between GXT and change in exercise training metabolic equivalents of task (METs), we used generalized linear models adjusted for age, gender, race, referral reason, CR visits, CR frequency, METs at start, CR location, and year of participation. Out of 4,455 patients (37% female, 48% White, median age = 62 years), 53% were prescribed a target HR based on a GXT. Compared with no GXT, a GXT was associated with a significantly greater increase in covariate-adjusted METs during CR and percentage change from start (+0.44 METs [95% confidence interval [CI] 0.38 to 0.51] and +17% [95% CI 14% to 19%], respectively). In a sensitivity analysis limited to patients with 24 to 36 visits at ≥2 days per week (n = 1,319), a GXT was associated with a significantly greater increase in covariate-adjusted exercise training METs (+0.51 [95% CI 0.36 to 0.66]; +19% [95% CI 13% to 24%]). In conclusion, to maximize the potential increase in exercise capacity during CR, patients should undergo a GXT to determine an individualized exercise training target HR.

Cardiorespiratory fitness (CRF) is inversely associated with atherosclerotic cardiovascular disease (ASCVD) risk. It is unclear whether the prognostic value of CRF differs by baseline estimated ASCVD risk. We studied a retrospective cohort of patients without known heart failure or myocardial infarction (MI) who underwent treadmill stress testing. CRF was measured by metabolic equivalents of task (METs) and ASCVD risk was calculated using the Pooled Cohorts Equations. Multivariable-adjusted Cox regressions analyses examined the association between METs and incident all-cause mortality and MI outcomes stratified by baseline ASCVD risk. The C-index evaluated risk discrimination while net reclassification improvement evaluated reclassification with CRF added to the ASCVD risk score. Our study population consisted of 57,999 patients of mean age 53 (13) years, 49% women, 64% white, 29% black. Over a median follow-up 11 years (interquartile range 8 to 14 years) there were 6,670 (11%) deaths, while there were 1,757 (3.0%) MIs over a median follow-up of 6 years (interquartile range 3 to 8 years). Among patients with ASCVD risk ≥20%, those with METs ≥12 had a 77% lower risk of all-cause mortality (Hazard ratio 0.23 95% confidence interval = 0.20, 0.27) and 67% lower risk of MI (Hazard ratio 0.33 95% confidence interval = 0.24, 0.46) compared to METs6. Similar results were obtained for those with ASCVD risk5%. Addition of METs to ASCVD risk score improved the C-statistic from 0.778 to 0.798 for all-cause mortality and 0.726 to 0.733 for MI (both p0.001). Addition of METs to ASCVD risk score significantly reclassified risk of all-cause mortality (p0.001) but not MI (p = 0.052). In conclusion, CRF is inversely associated with risk of all-cause mortality and MI at all levels of ASCVD risk, and provides incremental risk discrimination and reclassification beyond the ASCVD risk score.

Isolated low high-density lipoprotein cholesterol (HDL-C) is associated with lower fitness and increased mortality. Whether the association between isolated low HDL-C and mortality differs by fitness is uncertain. Patients in the Henry Ford ExercIse Testing Project (FIT Project) completed a physician-referred treadmill stress test and those prescribed lipid-lowering medications or with known cardiovascular disease were excluded. Isolated low HDL-C was defined as HDL-C40 mg/dl for men and50 mg/dl for women with low-density lipoprotein cholesterol (LDL-C) and triglycerides100 mg/dl (n = 688). An optimal lipid panel was defined as HDL-C ≥40 mg/dl for men and ≥50 mg/dl for women with LDL-C and triglycerides100 mg/dl (n = 2,923). Mortality was ascertained through Social Security Death Index linkage. Patients with isolated low HDL-C had a mean age of 48.9 ± 12.9 years and 62.9% were women. Over a mean follow-up of 10.3 ± 5 years, 12.8% of patients with isolated low HDL-C and 8.7% with optimal lipids died. Compared to individuals with optimal lipids, those with isolated low HDL-C who achieved6 METs had a lower survival (p = 0.02), whereas there was no mortality difference for those who achieved 6 to 10 METs (p = 0.13) or ≥10 METs (p = 0.66). In adjusted Cox models, the mortality hazard for those with isolated low HDL-C compared with optimal lipids was 1.73 (95% confidence interval [CI] 1.18 to 2.54), 1.90 (95% CI 1.19 to 3.04), and 0.97 (95% CI 0.53 to 1.78) for the METS categories of6, 6 to 10, and ≥10. In conclusion, individuals with isolated low HDL-C fitness significantly improved risk stratification and only those with lower fitness had an increased totality mortality risk.

Previous studies have demonstrated that cardiorespiratory fitness is a strong marker of cardiovascular health. Machine learning (ML) can enhance the prediction of outcomes through classification techniques that classify the data into predetermined categories. The aim of the analysis is to compare the prediction of 10 years of all-cause mortality (ACM) using statistical logistic regression (LR) and ML approaches in a cohort of patients who underwent exercise stress testing. We included 34,212 patients (55% males, mean age 54 ± 13 years) free of coronary artery disease or heart failure who underwent exercise treadmill stress testing between 1991 and 2009 and had complete 10-year follow-up. The primary outcome of this analysis was ACM at 10 years. The probability of 10-years ACM was calculated using statistical LR and ML, and the accuracy of these methods was calculated and compared. A total of 3,921 patients died at 10 years. Using statistical LR, the sensitivity to predict ACM was 44.9% (95% confidence interval [CI] 43.3% to 46.5%), whereas the specificity was 93.4% (95% CI 93.1% to 93.7%). The sensitivity of ML to predict ACM was 87.4% (95% CI 86.3% to 88.4%), whereas the specificity was 97.2% (95% CI 97.0% to 97.4%). The ML approach was associated with improved model discrimination (area under the curve for ML [0.923 (95% CI 0.917 to 0.928)]) compared with statistical LR (0.836 [95% CI 0.829 to 0.846], p 0.0001). In conclusion, our analysis demonstrates that ML provides better accuracy and discrimination of the prediction of ACM among patients undergoing stress testing.

Whether lower heart rate thresholds (defined as the percentage of age-predicted maximal heart rate achieved, or ppMHR) should be used to determine chronotropic incompetence in patients on beta-blocker therapy (BBT) remains unclear. In this retrospective cohort study, we analyzed 64,549 adults without congestive heart failure or atrial fibrillation (54 ± 13 years old, 46% women, 29% black) who underwent clinician-referred exercise stress testing at a single health care system in Detroit, Michigan from 1991 to 2009, with median follow-up of 10.6 years for all-cause mortality (interquartile range 7.7 to 14.7 years). Using Cox regression models, we assessed the effect of BBT, ppMHR, and estimated exercise capacity on mortality, with adjustment for demographic data, medical history, pertinent medications, and propensity to be on BBT. There were 9,259 deaths during follow-up. BBT was associated with an 8% lower adjusted achieved ppMHR (91% in no BBT vs 83% in BBT). ppMHR was inversely associated with all-cause mortality but with significant attenuation by BBT (per 10% ppMHR HR: no BBT: 0.80 [0.78 to 0.82] vs BBT: 0.89 [0.87 to 0.92]). Patients on BBT who achieved 65% ppMHR had a similar adjusted mortality rate as those not on BBT who achieved 85% ppMHR (p >0.05). Estimated exercise capacity further attenuated the prognostic value of ppMHR (per-10%-ppMHR HR: no BBT: 0.88 [0.86 to 0.90] vs BBT: 0.95 [0.93 to 0.98]). In conclusion, the prognostic value of ppMHR was significantly attenuated by BBT. For patients on BBT, a lower threshold of 65% ppMHR may be considered for determining worsened prognosis. Estimated exercise capacity further diminished the prognostic value of ppMHR particularly in patients on BBT.

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.

Decreases in systolic blood pressure during exercise may predispose to arrhythmias such as atrial fibrillation (AF) because of underlying abnormal autonomic tone. We examined the association between systolic blood pressure response and incident AF in 57,442 (mean age 54 ± 13 years, 47% women, and 29% black) patients free of baseline AF who underwent exercise treadmill stress testing from the Henry Ford ExercIse Testing project. Exercise systolic blood pressure response was examined as a categorical variable across clinically relevant categories (>20 mm Hg: referent; 1 to 20 mm Hg, and ≤0 mm Hg) and per 1-SD decrease. Cox regression, adjusting for demographics, cardiovascular risk factors, medications, history of coronary heart disease, history of heart failure, and metabolic equivalent of task achieved, was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between systolic blood pressure response and incident AF. Over a median follow-up of 5.0 years, a total of 3,381 cases (5.9%) of AF were identified. An increased risk of AF was observed with decreasing systolic blood pressure response (>20 mm Hg: HR 1.0, referent; 1 to 20 mm Hg: HR 1.09, 95% CI 0.99, 1.20; ≤0 mm Hg: HR 1.22, 95% CI 1.06 to 1.40). Similar results were obtained per 1-SD decrease in systolic blood pressure response (HR 1.08, 95% CI 1.04 to 1.12). The results were consistent when stratified by age, sex, race, hypertension, and coronary heart disease. In conclusion, our results suggest that a decreased systolic blood pressure response during exercise may identify subjects who are at risk for developing AF.

High exercise capacity (EC) has been associated with a lower risk of incident diabetes, whereas statin therapy has been associated with a higher risk. We sought to investigate whether the association between EC and diabetes risk is modified by statin therapy. This retrospective cohort study included 47,337 patients without diabetes or coronary artery disease at baseline (age 53 ± 13 years, 48% women, 66% white) who underwent clinical treadmill stress testing within the Henry Ford Health System from January 1, 1991, to May 31, 2009. The patients were stratified by baseline statin use and estimated peak METs achieved during exercise testing. Hazard ratios for incident diabetes were calculated using Cox proportional hazards models adjusted for demographic characteristics, co-morbidities, pertinent medications, and stress test indication. We observed 6,921 new diabetes cases (14.6%) over a median follow-up period of 5.1 years (interquartile interval of 2.6 to 8.2 years). Compared with the statin group, the no-statin group achieved higher mean METs (8.9 ± 2.7 vs 9.6 ± 3.0, respectively; p 0.001). After adjustment for covariates, a higher EC was associated with a lower risk of incident diabetes, irrespective of statin use (p-interaction = 0.15). Each 1-MET increment was associated with an 8%, 8%, and 6% relative risk reduction in the total cohort, the no-statin, and the statin groups, respectively (95% confidence interval, 0.91 to 0.93, 0.91 to 0.93, and 0.91 to 0.96, respectively; p 0.001 for all). We conclude that a higher EC is associated with a lower risk of incident diabetes regardless of statin use.

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.

The incidence of coronary artery disease in allografts after heart transplant is approximately 20% at 2 years and up to 50 to 60% at 5 years. 1,2 A noninvasive assessment of myocardial ischemia in these patients would be useful. Only 1 report has addressed the usefulness of graded exercise tests for the detection of ischemia in patients with heart transplants, and these investigators showed a low sensitivity and predictive value. 3 The purpose of this investigation was to further evaluate the concept that graded exercise testing may not be a useful diagnostic method in such patients.