The effect of mild to moderate COVID-19 infection on the cardiorespiratory fitness of firefighters.

Introduction: An adequate level of cardiorespiratory fitness (CRF) is critical for firefighters to perform the strenuous and physiologically demanding work of firefighting safely and effectively. The coronavirus disease 2019 (COVID-19) has been shown to negatively impact CRF in both the acute phase and longer-term following infection. This study aimed to determine changes to the CRF of firefighters pre- to post-mild to moderate COVID-19 infection and to investigate the impact of days past COVID-19 infection on change in CRF. Methods: CRF measures from cardiopulmonary exercise testing (CPET) at annual occupational health exams that occurred pre-COVID-19 infection in 2019 were obtained for firefighters from seven Arizona fire departments. Measures were compared to CPET evaluations from annual health exams the following year in a cohort of firefighters who self-reported mild to moderate illness following COVID-19 infection between exams. Results: Among a cohort of 103 firefighters, mean age 40 ± 9 years, CRF [as measured by peak oxygen consumption (VO2)] declined by an average of 2.55 ml·kg-1·min-1 or 7.3% (d = -0.38, p < 0.001) following COVID-19 infection (mean time from COVID-19 infection to CPET was 110 ± 78 days). The number of days past COVID-19 infection showed a small, yet significant, relationship to peak VO2 (r = 0.250, p = 0.011). Estimated marginal effects indicated that when biological sex, age, and BMI are controlled for, predicted peak VO2 returned to pre-COVID-19 values ~300 days after COVID-19 infection. Conclusion: Peak VO2 (ml·kg-1·min-1) declined 7.3% among firefighters an average of 110 days past reporting mild to moderate COVID-19 infection. This decrease has implications for the operational readiness and safety of firefighters.

The evolving role of cardiopulmonary exercise testing in ischemic heart disease - state of the art review.

PURPOSE OF REVIEW: Cardiopulmonary exercise testing (CPET) is the gold standard for directly assessing cardiorespiratory fitness (CRF) and has a relatively new and evolving role in evaluating atherosclerotic heart disease, particularly in detecting cardiac dysfunction caused by ischemic heart disease. The purpose of this review is to assess the current literature on the link between cardiovascular (CV) risk factors, cardiac dysfunction and CRF assessed by CPET. RECENT FINDINGS: We summarize the basics of exercise physiology and the key determinants of CRF. Prognostically, several studies have been published relating directly measured CRF by CPET and outcomes allowing for more precise risk assessment. Diagnostically, this review describes in detail what is considered healthy and abnormal cardiac function assessed by CPET. New studies demonstrate that cardiac dysfunction on CPET is a common finding in asymptomatic individuals and is associated with CV risk factors and lower CRF. This review covers how key CPET parameters change as individuals transition from the asymptomatic to the symptomatic stage with progressively decreasing CRF. Finally, a supplement with case studies with long-term longitudinal data demonstrating how CPET can be used in daily clinical decision making is presented. SUMMARY: In summary, CPET is a powerful tool to provide individualized CV risk assessment, monitor the effectiveness of therapeutic interventions, and provide meaningful feedback to help patients guide their path to improve CRF when routinely used in the outpatient setting.

Subclinical Cardiac Dysfunction is Associated with Reduced Cardiorespiratory Fitness and Cardiometabolic Risk Factors in Firefighters.

BACKGROUND: Past studies have documented the ability of cardiopulmonary exercise testing to detect cardiac dysfunction in symptomatic patients with coronary artery disease. Firefighters are at high risk for work-related cardiac events. This observational study investigated the association of subclinical cardiac dysfunction detected by cardiopulmonary exercise testing with modifiable cardiometabolic risk factors in asymptomatic firefighters. METHODS: As part of mandatory firefighter medical evaluations, study subjects were assessed at 2 occupational health clinics serving 21 different fire departments. Mixed effects logistic regression analyses were used to estimate odds ratios (ORs) and account for clustering by fire department. RESULTS: Of the 967 male firefighters (ages 20-60 years; 84% non-Hispanic white; 14% on cardiovascular medications), nearly two-thirds (63%) had cardiac dysfunction despite having normal predicted cardiorespiratory fitness (median peak VO2 = 102%). In unadjusted analyses, cardiac dysfunction was significantly associated with advanced age, obesity, diastolic hypertension, high triglycerides, low high-density lipoprotein (HDL) cholesterol, and reduced cardiorespiratory fitness (all P values < .05). After adjusting for age and ethnicity, the odds of having cardiac dysfunction were approximately one-third higher among firefighters with obesity and diastolic hypertension (OR = 1.39, 95% confidence interval [CI] = 1.03-1.87 and OR = 1.36, 95% CI = 1.03-1.80) and more than 5 times higher among firefighters with reduced cardiorespiratory fitness (OR = 5.41, 95% CI = 3.29-8.90). CONCLUSION: Subclinical cardiac dysfunction detected by cardiopulmonary exercise testing is a common finding in career firefighters and is associated with substantially reduced cardiorespiratory fitness and cardiometabolic risk factors. These individuals should be targeted for aggressive risk factor modification to increase cardiorespiratory fitness as part of an outpatient prevention strategy to improve health and safety.

Peak oxygen pulse and mortality risk in healthy women and men: The Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST).

Peak oxygen pulse (O2 pulsepeak) may have predictive utility for health outcomes yet, presently, has only been examined in men and only using a single baseline measure. PURPOSE: The primary aim of this investigation was to evaluate the relationship between O2 pulsepeak and all-cause mortality in apparently healthy women and men. A secondary aim was to explore the relationship between longitudinal changes to O2 pulsepeak and mortality. METHODS: The sample included 3877 participants (43% women) for the primary aim and 759 participants (32% women) who performed two cardiopulmonary exercise tests ≥1 year apart for the secondary aim. Cox proportional hazard models were performed to determine the relationship between O2 pulsepeak and mortality. Prognostic peak oxygen consumption (VO2peak) and O2 pulsepeak models were compared using the concordance index and Akaike information criterion (AIC). RESULTS: In the assessment from baseline, there were 730 deaths over a 24.7 ± 11.8 year follow-up period. For men, a single measure of O2 pulsepeak was inversely associated with risk for mortality (P < 0.05). However, the concordance index and AIC indicated lower discrimination compared to VO2peak models and O2 pulsepeak did not provide complementary benefit to VO2peak models. For women, O2 pulsepeak was not associated with mortality risk. In the longitudinal analysis, there were 168 deaths over a follow-up of 20.1 ± 11.4 years. Changes to O2 pulsepeak were not significantly related to mortality in either sex. CONCLUSIONS: Within an apparently healthy cohort, a single assessment of O2 pulsepeak is related to all-cause mortality in men but not women. Further, longitudinal changes to O2 pulsepeak are not predictive of mortality in either sex. These findings suggest O2 pulsepeak may have limited prognostic utility in healthy individuals, particularly within healthy women.

Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial.

BACKGROUND: Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease. METHODS: In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed. RESULTS: No significant differences in ΔSAQ angina frequency scores (P=0.53) or Duke Activity Status Index (P=0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores (P=0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO2 max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 (P=0.02). CONCLUSIONS: Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.

Empagliflozin improves cardiorespiratory fitness in type 2 diabetes: translational implications.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to prevent heart failure and reduce cardiovascular death in patients with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Whether or not SGLT2 inhibitors improve indices of cardiorespiratory fitness (CRF), an independent predictor of mortality in patients with CVD, remains unknown. We evaluated the effects of empagliflozin on indices of CRF in patients with T2DM. Twenty patients with T2DM received either empagliflozin 10 mg or usual care. Baseline and 3- to 6-month post-treatment measurements of CRF were evaluated using cardiopulmonary exercise testing on a cycle ergometer. Treatment with empagliflozin led to an increased peak oxygen consumption (VO2), reduction in VE/VCO2 slope, and improvement in heart rate recovery. Our results suggest that SGLT2 inhibitors may improve markers of CRF in patients with T2DM. This may help provide important clues into the mechanism of benefit of SGLT2 inhibitors in clinical trials and provide a translational framework for the ongoing large studies of SGLT2 inhibitors in the treatment of heart failure.

Improvements in Key Cardiopulmonary Exercise Testing Variables Following Cardiac Rehabilitation in Patients With Coronary Artery Disease.

PURPOSE: Improvements in cardiorespiratory fitness ((Equation is included in full-text article.)O2peak) post-cardiac rehabilitation (post-CR) are used to gauge therapeutic efficacy. The aim of the present study was to assess the effect of supervised CR on other cardiopulmonary exercise testing (CPX) variables, specifically those that reflect ventilatory efficiency and (Equation is included in full-text article.)O2 changes in relation to changes in work rate (WR). METHODS: Patients (n = 142; mean age 63 ± 9 y; 23% female) with coronary artery disease (CAD) participated in supervised CR for 3 to 6 mo completing 60 ± 17 sessions (range: 32-96 sessions), with intensity derived from the baseline CPX. CPX was completed at baseline and post-CR on a cycle ergometer. The minimum heart rate (HR) during cycling was set 5 to 10 beats/min above the HR at ventilatory anaerobic threshold (VAT) while the maximum HR remained below the ischemic threshold observed during CPX, and this intensity was maintained for 25 min. (Equation is included in full-text article.)O2peak, peak O2 pulse, the minute ventilation/carbon dioxide production ((Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2) slope, the oxygen uptake efficiency slope (OUES), and the Δ(Equation is included in full-text article.)O2/ΔWR slope were determined at baseline and post-CR. RESULTS: Following CR, there were significant improvements (all P < .001) in (Equation is included in full-text article.)O2peak (17.7 ± 4.7 mL/kg/min vs 20.9 ± 5.4 mL/kg/min), peak O2 pulse (11.6 ± 3.2 mL/beat vs 13.4 ± 3.6 mL/beat), (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slope (28.4 ± 5.3 vs 27.5 ± 4.7), OUES (1.8 ± 0.5 vs 2.0 ± 0.6), and Δ(Equation is included in full-text article.)O2/ΔWR slope (9.1 ± 1.2 mL/min/W vs 9.6 ± 1.1 mL/min/W). CONCLUSION: Key markers of ventilatory efficiency and (Equation is included in full-text article.)O2 kinetics during CPX significantly improve following CR. Expanding the list of variables assessed via CPX may provide better resolution in validation of CR therapeutic efficacy in patients with CAD.

A practical clinical approach to utilize cardiopulmonary exercise testing in the evaluation and management of coronary artery disease: a primer for cardiologists.

PURPOSE OF REVIEW: There is growing clinical interest for the use of cardiopulmonary exercise testing (CPET) to evaluate patients with or suspected coronary artery disease (CAD). With mounting evidence, this concise review with relevant teaching cases helps to illustrate how to integrate CPET data into real world patient care. RECENT FINDINGS: CPET provides a novel and purely physiological basis to identify cardiac dysfunction in symptomatic patients with both obstructive-CAD and nonobstructive-CAD (NO-CAD). In many cases, abnormal cardiac response on CPET may be the only objective evidence of potentially undertreated ischemic heart disease. When symptomatic patients have NO-CAD on coronary angiogram, they are still at increased risk for cardiovascular events. This problem appears to be more common in women than men and may warrant more aggressive risk factor modification. As the main intervention is lifestyle (diet, smoking cessation, exercise) and medical therapy (statins, angiotensin-converting enzyme inhibitors, beta-blockers), serial CPET testing enables close surveillance of cardiovascular function and is responsive to clinical status. SUMMARY: CPET can enhance outpatient evaluation and management of CAD. Diagnostically, it can help to identify physiologically significant obstructive-CAD and NO-CAD in patients with normal routine cardiac testing. CPET may be of particular value in symptomatic women with NO-CAD. Prognostically, precise quantification of improvements in exercise capacity may help to improve long-term lifestyle and medication adherence for this chronic condition.

Abnormal heart-rate response during cardiopulmonary exercise testing identifies cardiac dysfunction in symptomatic patients with non-obstructive coronary artery disease.

BACKGROUND: Symptomatic non-obstructive coronary artery disease is a growing clinical dilemma for which contemporary testing is proving to be of limited clinical utility. New methods are needed to identify cardiac dysfunction. METHODS AND RESULTS: This is a prospective observational cohort study conducted from December 2013 to August 2015 in two outpatient cardiology clinics (symptomatic cohort) and 24 outpatient practices throughout the US (healthy cohort) with centralized methodology and monitoring to compare heart-rate responses during cardiopulmonary exercise testing (CPET). Participants were 208 consecutive patients (median age, 61; range, 32-86years) with exercise intolerance and without prior heart or lung disease in whom coronary anatomy was defined and 116 healthy subjects (median age, 45; range, 26-66years). Compared to stress ECG, the novel change in heart-rate as a function of work-rate parameter (ΔHR-WR Slope) demonstrated significantly higher sensitivity to detect under-treated atherosclerosis with similar specificity. In men, area under the ROC curve increased from 60% to 94% for non-obstructive CAD and from 64% to 80% for obstructive CAD. In women, AUC increased from 64% to 85% for non-obstructive CAD and from 66% to 90% for obstructive CAD. ΔHR-WR Slope correctly reclassified abnormal studies in the non-obstructive CAD group from 22% to 81%; in the obstructive CAD group from 18% to 84% and in the revascularization group from 35% to 78%. CONCLUSION: Abnormal heart-rate response during CPET is more effective than stress ECG for identifying under-treated atherosclerosis and may be of utility to identify cardiac dysfunction in symptomatic patients with normal routine cardiac testing.

The utility of cardiopulmonary exercise testing in the assessment of suspected microvascular ischemia.

Evidence demonstrating the potential value of cardiopulmonary exercise testing (CPET) to accurately detect myocardial ischemia secondary to macro-vascular disease is beginning to emerge. Despite distinct mechanisms mediating ischemia in micro-vascular and macrovascular coronary artery disease (CAD), the net physiologic effect of exercise-induced left ventricular (LV) dysfunction is common to both. The abnormal physiologic response to CPET may, therefore, be similar in patients with macro- and micro-vascular ischemia. The following case report describes the CPET abnormalities in a patient with suspected microvascular CAD and the subsequent improvement in LV function following three weeks of medical therapy with the anti-ischemic drug ranolazine.

The utility of cardiopulmonary exercise testing to detect and track early-stage ischemic heart disease.

Evidence demonstrating the potential value of noninvasive cardiopulmonary exercise testing (CPET) to accurately detect exercise-induced myocardial ischemia is emerging. This case-based concept report describes CPET abnormalities in an asymptomatic at-risk man with suspected early-stage ischemic heart disease. When CPET was repeated 1 year after baseline assessment, his cardiovascular function had worsened, and an anti-atherosclerotic regimen was initiated. When the patient was retested after 3.3 years, the diminished left ventricular function had reversed with pharmacotherapy directed at decreasing cardiovascular events in patients with coronary artery disease. Thus, in addition to identifying appropriate patients in need of escalating therapy for atherosclerosis, CPET was useful in monitoring progression and reversal of abnormalities of the coronary circulation in a safe and cost-effective manner without the use of radiation. Serial CPET parameters may be useful to track changes marking the progression and/or regression of the underlying global ischemic burden.

Exercise-induced myocardial ischemia detected by cardiopulmonary exercise testing.

Cardiopulmonary exercise testing (CPET) is a well-accepted physiologic evaluation technique in patients diagnosed with heart failure and in patients presenting with unexplained dyspnea on exertion. Several variables obtained during CPET, including oxygen consumption relative to heart rate and work rate provide consistent, quantitative patterns of abnormal physiologic responses to graded exercise when left ventricular dysfunction is caused by myocardial ischemia. This concept report describes both the methodology and clinical application of CPET associated with myocardial ischemia. Initial evidence indicates left ventricular dysfunction induced by myocardial ischemia may be accurately detected by an abnormal CPET response. CPET testing may complement current noninvasive testing modalities that elicit inducible ischemia. It provides a physiologic quantification of the work rate, heart rate, and O(2) uptake at which myocardial ischemia develops. In conclusion, adding CPET with gas exchange measurements is likely to be of value in diagnosing and quantifying both overt and occult myocardial ischemia and its reversibility with treatment.