Cardiopulmonary Exercise Stress Testing Research Articles

The Identification and Impact of Abnormal Spirometry Patterns on Exercise Capacity in Pediatric Patients with Fontan Palliation.

Reduced exercise capacity and restrictive lung physiology are common in patients after Fontan palliation (FP). However, there is paucity of data regarding the association between specific spirometry patterns and key exercise parameters in this population. This is a single-center, cross-sectional, study correlating pulmonary function and exercise parameters in children with FP. Patients who were ≤ 18years of age and underwent a comprehensive cardiopulmonary treadmill exercise stress test (CPT) and spirometry at the same time, were included. Patients were categorized as (i) normal or (ii) abnormal based on the results of spirometry. The abnormal group was subdivided into (a) restrictive, (b) obstructive, and (c) mixed patterns. Demographic and key exercise parameters were compared between groups. Our study included 82 patients who underwent CPT at 13.6 (IQR, 11.3-15.4) years of age. A reduced exercise capacity (%VO2 ≤ 85%) was noted in the majority (n = 50, 61%). Spirometry was abnormal in 47 (57%) patients [restrictive (n = 25, 30%), obstructive (n = 12, 15%), and mixed (n = 10, 12%)]. The abnormal spirometry group had significant lower %VO2 (77% vs. 92%, p = 0.01) and METS (8.4 vs. 9.6, p = 0.02). Subgroup analysis revealed that obstructive (p = 0.04) and mixed (p = 0.02) patterns were associated with a significant decrease in % VO2. Majority of the children demonstrated an abnormal spirometry pattern post-FP. Abnormal pulmonary function was associated with the reduced exercise capacity. Identification and treatment of the abnormal lung function may improve the exercise capacity in these patients and improve the morbidity.

The effect of age and gender on heart rate variability in healthy individuals

Abstract Funding Acknowledgements Type of funding sources: None. Objective Cardiovascular autonomic function, represented by heart rate variability (HRV) is a simple, non-invasive measure used to determine alteration of sympathetic and parasympathetic control. The aim of the present study was firstly to evaluate the effect of age and gender on HRV measures, and secondly to determine the relationship between measures of HRV and functional capacity in healthy individuals Methods This was a retrospective, single centre, cross-sectional, observational study. Data were collected between January 2018 and July 2019. Sixty-eight healthy participants (age range: 19-78 years) were stratified according to age into the younger age group (<40 years of age, N = 43, males, N = 26; females, N = 17) or the older age group (>55 years of age, N = 25, males, N = 14; females, N = 11). Frequency domain HRV measures (i.e. absolute and normalised low frequency power (LF), high frequency power HF and their ration i.e. LF/HF ratio) were derived from RR interval and recorded at rest (supine position) for 30 minutes. Simultaneous non-invasive gas-exchange and central haemodynamic measurements (bioimpedance) were collected at rest and during maximal graded cardiopulmonary exercise stress test using semi-recumbent cycle ergometer. Results The mean age of the younger group was 26 ± 6 years and older 64 ± 6 years. Cardiorespiratory fitness (i.e. peak oxygen consumption) was significantly reduced in older compared to younger age group (1.60 ± 0.57 vs. 2.38 ± 0.74 L/min, p < 0.01). The mean absolute values of HF power declined with age in males by 32% (younger, 1156 ± 806 ms2 vs. older, 835 ± 488 ms2, p = 0.18), but not in females 3% difference (younger, 1182 ± 958 ms2 vs older, 1150 ± 843 ms2, p= 0.92). There was no significant difference in HF power between males and females in the younger age group (young male, 1156 ± 806 ms2 vs. young female, 1182 ± 958ms2, p = 0.92), but older males demonstrated 32% lower HF power than older females (835 ± 488 ms2 vs. 1150 ± 843 ms2, p= 0.25). Further analyses revealed no significant relationship between measures of heart rate variability and functional capacity i.e. the HF power was not significantly related to peak oxygen consumption in males (r= - 0.15, p= 0.36) or females (r= 0.05, p = 0.80). Conclusions High frequency power of the heart rate variability declines with age more in men but not women. Gender difference in high frequency power is apparent in older but not younger age, with older women showing nearly one third higher HF than older men. Measures of heart rate variability do not predict cardiorespiratory fitness

The effect of age on mechanisms of exercise tolerance: Reduced arteriovenous oxygen difference causes lower oxygen consumption in older people.

To assess the effect of age on mechanisms of exercise tolerance. Prospective observational study recruited 71 healthy individuals divided into two groups according to their age i.e. younger (≤40years of age, N=43); and older (≥55years of age, N=28). All participants underwent maximal graded cardiopulmonary exercise stress testing using cycle ergometer with simultaneous non-invasive gas-exchange and central haemodynamic measurements. Using the Fick equation, arteriovenous O2 difference was calculated as the ratio between measured O2 consumption and cardiac output. The mean age of younger and older participants was 26.0±5.7years, and 65.1±6.6years respectively. Peak O2 consumption was significantly lower in older compared to the younger age group (18.8±5.2 vs 34.4±9.8mL/kg/min, p<0.01). Peak exercise cardiac output and cardiac index were not significantly different between the younger and older age groups (22.7±5.0 vs 22.1±3.9L/min, p=0.59; and 12.4±2.9 vs 11.8±1.9L/min/m2, p=0.29). Despite demonstrating significantly lower peak heart rate by 33 beats/min (129±18.3 vs 162±19.9, p<0.01), older participants demonstrated significantly higher stroke volume and stroke volume index compared to the younger age group (173±41.5 vs 142±34.9mL/min, p<0.01; and 92.1±18.1 vs 78.3±19.5mL/m2, p<0.01). Arteriovenous O2 difference was significantly lower in older compared to younger age group participants (9.01±3.0 vs 15.8±4.3 mlO2/100mL blood, p<0.01). Ability of skeletal muscles to extract delivered oxygen represented by reduced arteriovenous O2 difference at peak exercise appears to be the key determinant of exercise tolerance in healthy older individuals.

The Physiological Burden of the 6-Minute Walk Test Compared With Cardiopulmonary Exercise Stress Test in Patients With Severe Aortic Stenosis

BackgroundManagement of aortic stenosis (AS) relies on symptoms. Exercise testing is recommended for asymptomatic patients with significant AS but is often experienced as forbidding and/or technically unrealistic for patients who are often frail, deconditioned, and intimidated by the exercise test. We compared the physiological burden assessed with gas exchange assessments to gauge and respiratory exchange ratio (RER) of a 6-minute walk test (6MWT) to a cardiopulmonary exercise stress test (CPET) in patients with severe AS. peak oxygen utilization MethodsAdults with equivocal symptoms and severe AS (1-aortic valve area [AVA] ≤ 1.0 cm2 or AVA index ≤ 0.6 cm2/m2, 2-peak aortic jet velocity ≥ 4.0 m/sec, 3-mean transvalvular pressure gradient ≥ 40 mm Hg by rest or dobutamine stress echocardiography, or 4-aortic valve calcification ≥ 1200 in women or ≥ 2000 AU in men) were studied. All participants completed both a 6MWT and symptom-limited progressive bicycle exercise testing. Breath-by-breath gas analysis and 12-lead electrocardiography were completed during 6MWT and CPET. Results: Eleven patients were studied. Patients walked on average 330 ± 75 m during the 6MWT and achieved a maximal workload of 48 ± 14 watts during the CPET. During the 6MWT, peak maximal oxygen uptake (V˙O2peak) was 12.8 ± 2.5 vs 10.8 ± 4.2 mL/kg/min during the CPET. Respiratory exchange ratio exceeded 1.1 in both the 6MWT and CPET indicating similarly high exertion. Compared with the CPET, a larger proportion of the 6MWT was performed at a high intensity level (78% ± 28% vs 33% ± 24% at > 85% V̇O2peak; P = 0.004). ConclusionsThe 6MWT with breath-by-breath gas analysis was well tolerated and able to achieve a physiological intense RER and V˙O2peak that are similar to symptom-limited CPET in patients with severe AS.

Cardiopulmonary Response to Exercise at High Altitude in Adolescents with Congenital Heart Disease

Objective: To extend our knowledge on tolerance of acute high-altitude exposure and hemodynamic response to exercise in adolescents with congenital heart disease (AscCHD) without meaningful clinical or functional restriction. Methods: A symptom limited cardiopulmonary exercise stress test and a non-invasive cardiac output measurement during steady state exercise were performed at 540 m and at 3454 m a.s.l. Symptoms of acute mountain sickness were noted. Results: We recruited 21 healthy controls and 16 AscCHD (59% male, mean age 14.7 ± 1.1 years). Three subjects (2 controls, 1 AscCHD) presented light symptoms of acute mountain sickness (dizziness and headache). During the symptom limited exercise test at lowland, control subjects showed a significantly higher power to weight index (3.5 ± 0.6 W/kg vs. 3.0 ± 0.7 W/kg, p < 0.001), heart rate (188.8 ± 10.4 1/min vs. 179.4 ± 13.1 1/min, p < 0.050) and ventilation (92.8 ± 22.9 l/min vs. 75.4 ± 18.6 l/min,

Comparative study of cardiorespiratory adaptations in elite basketball players of different age groups.

Systematic training of basketball causes morphological cardiac and cardiorespiratory adaptations. Previous studies have mainly focused either on only cardiac or respiratory changes. However, the extent of these cardiac adaptations and their relationship with aerobic capacity remain unclear in basketball athletes of different ages. Eighty male basketball players participated in the experimental group and 80 healthy and sedentary male individuals served as controls. All participants underwent to athletic history, anthropometric measurements, 12-lead resting electrocardiogram (ECG), echocardiography, resting spirometry and cardiopulmonary exercise stress test. Left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular end-diastolic internal dimension (LVIDd), end-diastolic volume (EDV), stroke volume (SV) and interventricular septal thickness at diastole (IVSd) were significantly higher in all groups of athletes compared to controls (P<0.05). End-diastolic volume index (EDVI) was significantly higher only in adult players compared to controls (P<0.05). Posterior wall thickness at diastole (PWd) was significantly greater in groups of children and adult players compared to controls (P<0.05). Maximal oxygen uptake (V̇O<inf>2max</inf>) in relative values was higher in all groups of athletes compared to controls (P<0.05). The increased LVM is attributed to concentric hypertrophy. This is further supported by the finding that there was no relationship between V̇O<inf>2max</inf> and echo parameters. The results of the present study indicate that the cardiorespiratory adaptations caused by basketball training are mainly formed at the early age stages without further increase throughout the years of action.

TOO MUCH TESTOSTERONE CAN MAKE IT HARD TO BREATHE

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Testosterone replacement therapy for hypogonadism can be prescribed through topical/transdermal and intramuscular injections. Recognized treatment risks include prostate cancer, benign prostatic hypertrophy, erythrocytosis, and venous thromboembolism. There have been concerns for possible cardiovascular side effects from testosterone supplementation as well. Here we discuss a patient with worsening shortness of breath and subthreshold erythrocytosis in the setting of intramuscular (IM) testosterone supplementation. CASE PRESENTATION: A 43 year old man with a history of hypertension, CPAP-treated obstructive sleep apnea, and hypogonadism presented with 2 months of slowly progressive dyspnea on exertion and flushing occurring with activity or after a shower. He reported no chest pain, wheezing, cough, headache or dizziness. His physical exam was normal. Extensive evaluation included a resting echocardiogram showing preserved ejection fraction, no valvular dysfunction, and no signs of pulmonary hypertension. Cardiopulmonary exercise stress test was normal. PFTs excluded obstructive or restrictive ventilatory defects; lung volumes were normal and DLCO was 101% predicted. CT chest showed a 1 cm RML endobronchial nodule; subsequent PET scan showed no FDG uptake in the nodule or elsewhere. A hemoglobin of 17.7 g/dl, elevated compared with prior values, decreased to 14.3 g/dl over three months following cessation of IM testosterone therapy and his dyspnea improved without other changes in therapy or management. He was switched to a topical testosterone supplement with no rise in hemoglobin nor return of dyspnea. DISCUSSION: Polycythemia is a well-known side effect from testosterone injections and monitoring is advised with guidelines suggesting holding testosterone for a hemoglobin of 18 g/dl or a hematocrit of 54%. Erythrocytosis is of concern due to the increased risk of hyperviscosity syndrome whose symptoms including blurred vision, headaches, chest pain, weakness, and paresthesia. Case reports have associated IM testosterone with lower extremity edema too. This patient’s successful transition to transdermal testosterone is concordant with prior reports of a reduced risk of elevated hemoglobin with transdermal therapy. CONCLUSIONS: Testosterone supplementation requires routine monitoring due to risk of erythrocytosis and associated hyperviscosity syndrome, prostate cancer, and thromboembolism. In this patient, a new manifestation of dyspnea and subthreshold polycythemia co-occurred with IM testosterone and abated with discontinuation and transition to transdermal forms. A thorough review of other medical history and medications continues to be needed in patient on testosterone when present with cardiorespiratory symptoms to ensure accurate identification of the underlying cause. Reference #1: Keohane, C., et al. “The Diagnosis and Management of Erythrocytosis.” Bmj, vol. 347, no. nov18 1, 2013, doi:10.1136/bmj.f6667 Reference #2: Basaria, Shehzad, et al. “Adverse Events Associated with Testosterone Administration.” New England Journal of Medicine, vol. 363, no. 2, 2010, pp. 109–122., doi:10.1056/nejmoa1000485 Reference #3: Surampudi, Prasanth N., et al. “Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy.” International Journal of Endocrinology, vol. 2012, 2012, pp. 1–20., doi:10.1155/2012/625434 DISCLOSURES: Site PI for pharmaceutical trials relationship with Boehringer-Ingelheim Please note: $1001 - $5000 Added 06/01/2020 by Rebecca Bascom, source=Web Response, value=Travel Site PI for pharmaceutical study relationship with Nitto Denko Please note: $1001 - $5000 Added 06/01/2020 by Rebecca Bascom, source=Web Response, value=Travel Site PI for pharmaceutical study relationship with Galapagos Please note: $1001 - $5000 Added 06/01/2020 by Rebecca Bascom, source=Web Response, value=Travel Other relationship with Nitto Denko Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel Other relationship with Galapagos Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel attended investigator meeting relationship with Nitto Denko Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel attended investigator meeting relationship with Galapagos Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel No relevant relationships by Ibrahim Ismail-Sayed, source=Web Response No relevant relationships by Kathleen Twomey, source=Web Response

Exercise Oscillatory Ventilation is Independently Associated with Right Ventricular Systolic Dysfunction in Patients with Chronic Heart Failure

Background Exercise Oscillatory Ventilation (EOV) is a crucial marker for disease severity and prognosis in chronic heart failure (HF) patients. Although the presence of EOV in chronic HF patients has been demonstrated the association with worse left ventricular (LV) function, the evidence regarding with right ventricular (RV) function is still lacking. This study aim was to determine the association of EOV and RV systolic function in chronic heart failure patients. Method We retrospectively analyzed a cardiopulmonary exercise stress testing (CPET) database in 709 chronic HF patients at Cleveland Clinic, between April 2018 and June 2019. RV systolic dysfunction was determined by tricuspid annular plane systolic excursion (TAPSE) Results The prevalence of EOV in chronic HF patients with RV systolic dysfunction was significantly higher than those without RV systolic dysfunction (75.7% vs. 24.3%, p Conclusion In the large contemporary cohort, exercise oscillatory ventilation was independently associated with RV systolic dysfunction in chronic heart failure patients.

Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents

To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US. Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index. We analyzed data on 1829 children (average age, 13.6±2.6years; 52% male). After 12years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold. Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future.

Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.

Wearing a surgical mask does not affect the anaerobic threshold during pedaling exercise

The effect of wearing a surgical mask on cardiopulmonary function and anaerobic threshold (AT) has not been reported. Thus, we aimed to determine whether cardiopulmonary function and AT vary while wearing surgical masks. Six healthy men were enrolled and underwent the cardiopulmonary exercise (CPX) stress test under two different conditions (with and without a commercially available surgical mask) to evaluate their AT. To confirm that there was no breath leakage, a gas mask connected with a respiratory gas analyser was worn over the surgical mask when the participants performed the CPX. The AT was measured by the V-slope method. Moreover, the AT time, exercise load, oxygen consumption, and ventilation values after the CPX were determined. No significant differences were found between the two conditions. The number of complaints of respiratory distress, however, was significantly higher while wearing a surgical mask. The exercise intensity achieved by each participant was equivalent, irrespective of whether they wore the surgical mask; therefore, wearing a surgical mask does not affect cardiopulmonary function during vigorous exercise.

Predictors of Improved Aerobic Capacity in Individuals With Chronic Stroke Participating in Cycling Interventions

ObjectiveTo determine demographic and physiological factors that predict improvement in aerobic capacity among individuals with chronic stroke participating in cycling interventions. DesignSecondary analysis of data from 2 randomized clinical trials. SettingResearch laboratory. ParticipantsIndividuals with chronic stroke (N=44). InterventionsParticipants were randomized to one of the following interventions: forced aerobic exercise and upper extremity repetitive task practice (FE+UERTP, n=16), voluntary aerobic exercise and upper extremity repetitive task practice (VE+UERTP, n=15), or a nonaerobic control group (control, n=13). All interventions were time-matched and occurred 3 times per week for 8 weeks. Main Outcome MeasureAerobic capacity as measured by peak oxygen consumption per unit time (VO2peak) during maximal cardiopulmonary exercise stress testing. ResultsSignificant improvements in VO2peak were observed from baseline to postintervention in the VE+UERTP group (P<.001). Considerable variability was observed among participants relating to postintervention change in VO2peak. Among aerobic exercise participants, a multivariate regression analysis revealed that cycling cadence, baseline VO2peak, and group allocation were significant predictors of change in VO2peak. ConclusionsHigh exercise rate (cycling cadence) appears to be an important variable in improving aerobic capacity and should be considered when prescribing aerobic exercise for individuals with chronic stroke. Those with low VO2peak at baseline may benefit the most from aerobic interventions as it relates to cardiorespiratory fitness. Further investigation is warranted to understand the precise role of other exercise and demographic variables in the prescription of aerobic exercise for this population and their effects on secondary stroke prevention and mortality.

P4431Cardiopulmonary exerscise stress tests vs standard exercise stress tests in the rational prescription of physical activity in men

Abstract Background The standard exercise stress test (ET) provides direct measurement of the load tolerated by the subject, but the cardiopulmonary exercise stress test (CPET) in addition to the measurement of the work load also provides direct measurement of the corresponding oxygen consumption. Objective The aim of the present study was to estimate the differences between the estimated oxygen consumption based on the load (ET) and the one directly measured with the CPET, and to highlight and quantify the inaccuracies of the indirect estimate of oxygen consumption and its consequences on the rational prescription of physical activity. Material and method The tests performed on 7544 males from January 2007 to October 2018 were analyzed. For each test the sustained load, the consumption of direct oxygen, and the estimated oxygen consumption based on the load sustained with the use of a formula provided by the American College of Sports Medicine and reported below: VO2max (ml/kg/min) = (10.51 x Watt) + (6.35 x weight in kg) − (10.49 x Età) + 519.3. The total population of the subjects examined was divided into two groups: Group A: 1358 subjects without signs of heart disease, and Group B: 6186 subjects with heart disease. Results In the total population the oxygen consumption (VO2) estimated on the basis of the load was overestimated in 22% of subjects, underestimated in 55% of subjects and overlapping in 23% of subjects. In Group B the calculated VO2 was overestimated in 38%, underestimated in 54% and overlapping in 8% of the subjects. In group A the calculated VO2 was overestimated in 33%, underestimated in 54% and overlapping in 9% of subjects. Conclusions In subjects with heart disease the VO2 calculated on the basis of the sustained load is overestimated or underestimated in 92% of subjects. The CPET through direct measurement of oxygen consumption provides a precise estimate of functional capacity, an essential prerequisite for a correct rational prescription of physical activity. Because of this peculiarity, the CPET is absolutely irreplaceable in cardiac patients in which a correct rational prescription of physical activity is crucial.

CHRONOTROPIC INSUFFICIENCY AS CAUSE OF EXERCISE LIMITATION IN PATIENTS UNDERGOING CARDIOPULMONARY EXERCISE TESTING FOR DYSPNEA

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Chronotropic incompetence is defined as the inability of the heart to increase its rate in response to increased activity or demand. It has been recognized as predictor for major cardiovascular event, mortality and exercise intolerance.The purpose of this study was to identify the proportion of patients who underwent cardiopulmonary exercise testing(CPET) in whom chronotropic incompetence was deemed to be the primary cause of exercise limitation and to describe the characteristic exercise response in these patients. METHODS: The results of all CPET studies done in a tertiary referral center from January 2015 to May 2018 were reviewed. The results of patients in whom chronotropic incompetence was inferred to be the primary cause of exercise limitation were analyzed to describe the characteristic exercise response. RESULTS: A total of 260 CPET studies were done during the study period. Chronotropic incompetence was identified as the primary cause of exercise limitation in 37(14%) of the studies. The mean maximum oxygen uptake(VO2) was normal at 81.78%(SD 18.97), mean VO2/kg was reduced at 65%(SD 13.5%). The mean resting heart rate(HR) was 67 (SD 11). Mean maximum HR was reduced at 103 (SD 19). Mean maximum HR percent predicted was reduced at 67%(SD 9.5). Mean oxygen(O2) pulse was increased at 122% (SD 22). Mean maximum ventilation (Ve) was normal at 53.5%(SD 10.66). Mean Respiratory exchange ratio (RER) 1.14 (SD 0.12). Information about the medication use was present in 24 of the 38 patients. Of the 24, 20 patients were on beta blockers, 2 were on calcium channel blockers and 2 were not on any AV nodal blocking agents. CONCLUSIONS: Chronotropic incompetence was the reason for exercise limitation in 14% of all patients that underwent cardiopulmonary exercise testing for evaluation of their dyspnea. These patients demonstrated a characteristic exercise response with preserved maximum oxygen uptake, decreased maximum heart rate, increased oxygen pulse and normal breathing reserve.The most common cause of chronotropic incompetence in this patient population was use of AV nodal blocking agents, specifically beta blockers. CLINICAL IMPLICATIONS: Chronotropic incompetence is an under recognized and under reported cause of exercise limitation in patients presenting with dyspnea. It is easily recognizable on cardiopulmonary exercise stress testing. The most common culprit are beta blockers. Clinicians need to be aware of the characteristic exercise response. If CI is present, clinicians should consider discontinuing beta blockers unless there is a strong indication. More research is needed to see if discontinuation of the culprit medications helps with decreasing dyspnea. The exact mechanism by which chronotropic incompetence could lead to dyspnea on exertion is not well known but could be due to increased left sided end diastolic pressures during exercise. DISCLOSURES: No relevant relationships by Abhishek Agarwal, source=Web Response No relevant relationships by Melvin Pratter, source=Web Response

Tachycardia Induced Cardiomyopathy (TIC) in Patients with Postural Orthostatic Tachycardia Syndrome (POTS) and Ehlers-Danlos Syndromes (EDS)

Intro POTS is said to be a type of dysautonomia characterized by Tachycardia brought about by postural shifts in blood volume and circulation. This results in various Symptoms (Sx) including dizziness, lightheadedness, syncope, palpitations and tremulousness. POTS is often associated with EDS, a rare inherited connective tissue disorder pertaining to the production and processing of collagen. POTS causes abnormal increases in HR. If left untreated, pts can suffer from TIC indicated by an increasing Left Ventricle End Diastolic Diameter (LVEDD). Methods Electronic health records of 1300 POTS pts were reviewed retrospectively. Female pts with EDS between the ages of 20-40 who had imaging records of 3 or more echocardiograms in the past 5 yrs, with no more than 1 yr between consecutive echocardiograms were randomly selected. Our records identified 94 pts fulfilling this criteria. An assessment of the relation between associated Sx and corresponding Echocardiogram LVEDD values was made by observing pts reported Sx such as shortness of breath, chest pain, dizziness/lightheadedness, palpitations, and their overall feeling of well-being. Corresponding Functional Capacity (FC) values of each pt analyzed by reviewing Cardiopulmonary Exercise Stress Tests were also noted. Lastly, treatment modalities including drugs, exercise and I/V fluids were also monitored. A timeline with regards to changes in LVEDD was established to determine the effectiveness of various treatments. Results Of the 94 pts fulfilling the inclusion criteria: Mean age was 30 +/- 6.3 yrs. Mean LVEDD of pts reporting min Sx was 4.02 +/- 0.43. Mean LVEDD of pts reporting max Sx was 4.28 +/- 0.45. T-Test (p-value The average FC of pts experiencing min Sx was 69% while it was 63% for pts experiencing max Sx. T-Test (p-value = 0.006665) indicates that the mean of FC with least Sx is significantly higher than FC with maximum Sx. The average Decrease in FC per 0.1 cm Increase in LVEDD was 2.55% Pts with LVEDD of 4.04 +/- 0.48 were seen to have the highest FC >70%. Overall, 40 pts were seen to have >70% FC at LVEDD with the Lowest Sx. At >70% FC, 44 pts showed improvement with medication (Midodrine 20, Florinef 12, Beta Blockers 12), 25 pts with exercise and 11 on IV Fluids (including saline and/or albumin infusions). Conclusion Pts with POTS and EDS, tend to develop a worsening of Sx as LVEDD progressively increases resulting in a Tachycardia Induced Cardiomyopathy. However, aggressive management of Sx with medication and a dedicated exercise regimen can improve Sx, decrease LVEDD and cause reversal of the disease process. From the evidence collected, it can be recommended that POTS pts’ LVEDD values be maintained between 3.8 - 4.2 cm, as this range was seen to produce the least amount of Sx as well as a higher FC (>70%).

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing.

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption () on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.

High Right Ventricular Afterload is Associated with Impaired Exercise Tolerance in LVAD Patients

Purpose Exercise tolerance, measured by pVO 2 during cardiopulmonary exercise stress test (CPET), is impaired in patients with LVAD. After LVAD, the right heart is more sensitive to afterload. We hypothesize that high RV afterload during exercise is associated with lower pVO 2 . Methods At routine right heart catheterization (RHC), LVAD patients performed supine bicycle exercise to maximal effort. Hemodynamics and echocardiograms at rest and peak exercise were collected. The same patients underwent CPET on different days as part of routine post-operative monitoring. We used effective arterial elastance (Ea = systolic PAP/stroke volume) to measure RV afterload, as it incorporates both pulsatile and resistive loads. Results Between 11/17 and 9/18, 10 patients (median age 54 years) had RHC, 8 of them had CPET. Time between LVAD and RHC was 244 days (IQ 223-299) and between CPET and RHC was 55 days (IQ 35-126). Work achieved (Watts) during CPET and RHC correlated linearly (α=1.1, p=0.003, R²=0.60). Patients had low pVO 2 (13.2 L/kg/min, IQ 11-18) and high VEVCO 2 slope (34, IQ 32-43) despite normal filling pressures and cardiac output (CO) after LVAD. They had no chronotropic incompetence (reaching 89.5% of max predicted heart rate, IQ 66.4-95.4). Compared to resting state, at peak exercise, filling pressures, CO, RV stroke work index, and RV tissue Doppler (S’) increased. Notably, pVO 2 negatively correlated with Ea at peak exercise and the change in Ea from rest to stress, while VEVCO 2 slope had the inverse correlations (Figure). pVO 2 did not correlate with changes in PCWP, CO, or LVAD flow. Moderate-severe baseline RV dysfunction and mild-moderate TR are associated with worse pVO 2 and VEVCO 2 slope. Conclusion This pilot study is the first to suggest that poor baseline RV function and high RV afterload at peak exercise are associated with worse pVO 2 and VEVCO 2 slope in LVAD patients. The practice of increasing pump speed may not be adequate to improve exercise tolerance and may be harmful to RV function.

Prediction of the Wingate anaerobic mechanical power outputs from a maximal incremental cardiopulmonary exercise stress test using machine-learning approach.

The Wingate Anaerobic Test (WAnT) is a short-term maximal intensity cycle ergometer test, which provides anaerobic mechanical power output variables. Despite the physiological significance of the variables extracted from the WAnT, the test is very intense, and generally applies for athletes. Our goal, in this paper, was to develop a new approach to predict the anaerobic mechanical power outputs using maximal incremental cardiopulmonary exercise stress test (CPET). We hypothesized that maximal incremental exercise stress test hold hidden information about the anaerobic components, which can be directly translated into mechanical power outputs. We therefore designed a computational model that included aerobic variables (features), and used a new computational \\ predictive algorithm, which enabled the prediction of the anaerobic mechanical power outputs. We analyzed the chosen predicted features using clustering on a network. For peak power (PP) and mean power (MP) outputs, the equations included six features and four features, respectively. The combination of these features produced a prediction model of r = 0.94 and r = 0.9, respectively, on the validation set between the real and predicted PP/MP values (P< 0.001). The newly predictive model allows the accurate prediction of the anaerobic mechanical power outputs at high accuracy. The assessment of additional tests is desired for the development of a robust application for athletes, older individuals, and/or non-healthy populations.

NT-proBNP is a weak indicator of cardiac function and haemodynamic response to exercise in chronic heart failure.

AimsN‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) plays an important role in diagnosis and management of heart failure. The aim of the present study was to assess haemodynamic response to exercise and to evaluate the relationship between NT‐proBNP, cardiac function, and exercise tolerance in chronic heart failure.Methods and resultsA single‐centre, cross‐sectional pilot study recruited 17 patients with chronic heart failure with reduced left ventricular ejection fraction (age 67 ± 7 years) and 20 healthy volunteers (age 65 ± 12 years). The NT‐proBNP was measured in the heart failure group. All participants completed maximal graded cardiopulmonary exercise stress testing coupled with gas exchange (using metabolic analyser for determination of exercise tolerance, i.e. peak O2 consumption) and continuous haemodynamic measurements (i.e. cardiac output and cardiac power output) using non‐invasive bioreactance technology. Heart failure patients demonstrated significantly lower peak exercise cardiac function and exercise tolerance than healthy controls, i.e. cardiac power output (5.0 ± 2.0 vs. 3.2 ± 1.2 W, P < 0.01), cardiac output (18.2 ± 6.3 vs. 13.5 ± 4.0 L/min, P < 0.01), heart rate (148 ± 23.7 vs. 111 ± 20.9 beats/min, P < 0.01), and oxygen consumption (24.3 ± 9.5 vs. 16.8 ± 3.8 mL/kg/min, P < 0.01). There was no significant relationship between NT‐proBNP and cardiac function at rest, i.e. cardiac power output (r = −0.28, P = 0.28), cardiac output (r = −0.18, P = 0.50), and oxygen consumption (r = −0.18, P = 0.50), or peak exercise, i.e. cardiac power output (r = 0.18, P = 0.49), cardiac output (r = 0.13, P = 0.63), and oxygen consumption (r = −0.05, P = 0.84).ConclusionsLack of a significant and strong relationship between the NT‐proBNP and measures of cardiac function and exercise tolerance may suggest that natriuretic peptides should be considered with caution in interpretation of the severity of cardiac dysfunction and functional capacity in chronic heart failure.

Reproducibility of Inert Gas Rebreathing Method to Estimate Cardiac Output at Rest and During Cardiopulmonary Exercise Stress Testing.

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23-32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min-1, p=0.54; 114 (28) vs. 108 (15) ml beat-1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p<0.01 with coefficient of variation of 6.0%), at rest (r=0.90, p<0.01 with coefficient of variation of 5.1%), and during exercise (r=0.89, p<0.01 with coefficient of variation 3.3%). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (-1.1 to 1.8) liter min-1 and 0.5 (-2.3 to 3.3) liter min-1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands.