Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95%CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies.

Estimation of Energy Expenditure in Breeding Cows Grazing Rangelands with Different Herbage Allowance

The energy partitioning between total heat production (HP) and retained energy (RE) on the efficiency of energy use was evaluated throughout the annual production cycle (gestation-lactation) of 46 multiparous beef cows grazing on two herbage allowances (HA) of Campos grassland (4 vs. 7 kg dry matter/kg body weight; BW; LO vs. HI). Total RE was greater (P < 0.01) for HI than LO cows and presented minimum values during early gestation and maximum values during early lactation associated to the greater (P = 0.02) RE-milk in the former ones. Whole-animal HP, estimated by the heart rate-O2 pulse technique, and cow metabolized energy (ME) intake did not differ between HA treatments, but relative to BW0.75, HP was greater (P = 0.04) for LO than HI cows. Total HP and ME intake were minimum in gestation and maximum in early lactation and ME intake was greater during early lactation for HI than LO cows, and per unit of BW0.75, tended (P < 0.10) to be less for HI than LO cows in winter. The energy efficiency of the annual cycle was not affected by treatments (0.19 vs. 0.12 ± 0.02 for HI and LO respectively; P > 0.10) and there were no differences between treatments in terms of grams of calf per MJ of ME intake (P > 0.10). Management of grazing intensity of Campos grasslands with high herbage allowance improved energy balance of the beef cow-calf system through partitioning of cow ME intake towards RE instead of maintenance.

53 Exercise oxygen kinetic in hypertrophic cardiomyopathy: results from a multicentre cardiopulmonary exercise testing study

Aims Reduced cardiac output (CO) has been considered crucial in symptoms’ genesis in hypertrophic cardiomyopathy (HCM). We evaluated the cardiopulmonary exercise testing (CPET) response in HCM focusing on parameters strongly associated with stroke volume (SV) and cardiac output (CO), such as oxygen uptake (VO2) and O2-pulse, considering both their absolute values and temporal behaviour during physical exercise. Methods and results We enrolled 312 non-end stage HCM patients, divided according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva manoeuver (72% with LVOTO &lt; 30; 10% between 30 and 49; and 18% ≥50 mmHg). Peak VO2 (percent of predicted), O2-pulse, and ventilation to carbon dioxide production (VE/VCO2) slope did not change across LVOTO groups. Ninety-six (31%) HCM patients presented an abnormal O2-pulse temporal behaviour, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106 ± 45 vs. 130 ± 49 W), VO2 (74 ± 17% vs. 80 ± 20%) and O2-pulse (12 [9–14] vs. 14 [11–17]ml/beat), with higher VE/VCO2 slope (28 [25–31] vs. 27 [24–31]) (P &lt; 0.005 for all). Only two patients had an abnormal VO2/work slope. Conclusions None of CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal O2-pulse exercise behaviour, which is strongly related to inadequate SV during exercise, correlates with reduced functional capacity (peak and anaerobic threshold VO2 and workload) and increased VE/VCO2 slope, helping identifying more advanced disease irrespectively of LVOTO. Adding O2-pulse kinetics evaluation to standard CPET could lead to a potential incremental benefit in terms of HCM prognostic stratification and, then, therapeutic management.

EXPRESS: The association of six minute walk work and other clinical measures to cardiopulmonary exercise test parameters in pulmonary vascular disease

In pulmonary vascular disease (PVD) exercise abnormalities can include reduced exercise capacity, reduced oxygen pulse (O2 pulse) and elevated VE/VCO2. The association of clinical measures such as 6 minute walk work (6MWW), haemodynamics, lung function and echocardiogram to peak VO2, O2 pulse and VE/VCO2 has not been fully investigated in PVD Aims: To determine the relationship of 6MWW and other clinical measures to peak VO2, peak O2 pulse and VE/VCO2. Additionally, to investigate the ability to predict peak VO2 from 6MWW and other clinical parameters. Methods: Clinical data was retrospectively analysed from 63 chronic thromboembolic pulmonary hypertension (CTEPH) and 54 chronic thromboembolic disease (CTED) patients. 6 minute walk test measures, haemodynamics, lung function and echocardiographic measures were correlated with peak VO2, peak O2 pulse and VE/VCO2. Predictive equations were developed to predict peak V̇O2 in both CTEPH and CTED cohorts and subsequently validated. Results: A number of clinical parameters correlated to peak VO2, peak O2 pulse and VE/VCO2. 6MWW and TLCO demonstrated the strongest correlation to peak VO2 and peak O2 pulse. The validation of the predictive equations showed a variable level of agreement between measured peak VO2 and calculated peak VO2 from the predictive equations. Conclusion: 6MWW and additionally a number of clinical test parameters were associated to peak VO2, peak O2 pulse and VE/VCO2. 6MWW and TLCO were particularly highly correlated to peak VO2 and similarly to peak O2 pulse. The validation of the predictive equations showed a variable level of agreement and therefore may have limited clinical applicability.

The Effect of Voxelotor on Exercise Capacity of Youths with Sickle Cell Anemia

Background/Hypothesis: Children and adults with sickle cell anemia (SCA) exhibit decreased cardiopulmonary fitness. Anemia is directly related to oxygen carrying capacity and is one factor that affects cardiopulmonary fitness. The new sickle cell drug voxelotor raises hemoglobin in patients with SCA treated or untreated with hydroxyurea. We hypothesized that voxelotor improves exercise capacity in youths with SCA. Methods: A single-center, open-label, single-arm longitudinal interventional pilot study was conducted for patients with SCA age &gt; 12. Participants performed baseline Cardiopulmonary Exercise Testing (CPET#1), took 1500mg voxelotor for 2 months, then CPET was repeated (CPET#2). A modified Bruce Protocol using 2-minute stages was performed on a motorized treadmill, for a goal of 8-12 minutes of exercise. Breath by breath gas exchange data were collected and analyzed using a VMax Encore 29C metabolic cart. The metabolic test included standard monitoring of heart rate, EKG ST changes, arrhythmias, and O2 saturation. A respiratory quotient &gt;1.1 was used as evidence of participant effort. Peak oxygen consumption (peak VO2), anaerobic threshold (AT), O2 pulse, VE/VCO2 slope, and time exercised in CPET#1 and CPET#2 were compared for each participant. The primary endpoint was peak VO2. Hemoglobin (Hgb), reticulocyte count, and bilirubin were measured before CPET#1 and CPET#2. Pill count was used to monitor medication adherence and left shift of the P50 oxygen dissociation curve was used to document biochemical effect of voxelotor. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected at the end of the study. Statistical analysis was performed using Student's paired T-test. Results: Nine SCA patients ages 12-20, including 4 males and 5 females, completed the study. All had Hgb SS and were stably maintained on hydroxyurea, which was continued without dose change during the study. After 2 months of voxelotor, all participants demonstrated expected hematologic changes, including mean rise in Hgb +1.3 g/dL (95% C.I.= 0.8, 1.7), mean decrease in reticulocyte count -2.4% (95% C.I.= -4.1, -0.8), and mean decrease in bilirubin -0.4 mg/dL (95% C.I.= -0.8, -0.1). All participants demonstrated voxelotor adherence and leftward shift of p50 (Table 1). Oxygen consumption, measured as percent predicted peak VO2 (ml/kg/min), ranged from 52% to 80% in CPET#1 and from 55% to 71% in CPET#2. The changes in peak VO2 for individual participants ranged from -10% to +10% of predicted peak VO2, with a mean difference of -2.2% (95% CI = -7.1, 2.7), which is insignificant (p=0.3). Using +/- 6% as variability in peak VO2 measurement, 5 participants exhibited no change, 3 participants had decrease in peak VO2 of -7%, -9%, and -10%, while peak VO2 increased by +10% for a single participant, who started to exercise on his own after starting voxelotor. Changes in individuals' anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were not significant and did not correlate with changes in peak VO2. All participants achieved respiratory quotient &gt;1.1, assuring participant effort during CPET (Table 2). On the 7-point PGIC questionnaire evaluating activity limitations, symptoms, emotions, and overall quality of life, 7 out of 9 participants reported positive change, including "a great deal better," "definite," and "moderate" improvements. Two participants reported minimal to no change, and no participants reported worsening. In comparison, clinicians reported "minimal" to "much" improvement on CGIC for all participants. Overall, patient impression of improvement was higher than clinician impression of improvement. Conclusion: This pilot study demonstrated the feasibility of using CPET to evaluate exercise capacity longitudinally in youths with SCA. After addition of voxelotor to hydroxyurea for 2 months, all patients perceived global improvement. Peak VO2 did not change in 8 out of 9 participants and improved for 1 participant who exercised between the 2 CPETs. To increase peak VO2, higher Hgb increase, concurrent regular exercise, and longer exposure to voxelotor may be necessary. This study was funded by Global Blood Therapeutics Figure 1 Figure 1. Disclosures Larkin: Forma Therapeutics, Inc.: Research Funding. Dulman: Pfizer: Other: own stock. Kuypers: Forma Therapeutics, Inc.: Research Funding.

Functional capacity and gender-related differences in Fabry disease

Background Fabry disease (FD) is a rare x-linked lysosomal storage disease characterized by accumulation of glicosphingolipids in several organs, including the heart. Cardiac involvement manifests as left ventricular (LV) hypertrophy, often complicated by myocardial fibrosis. The impact of disease on functional capacity is not well defined, as well as the potential gender-related differences. Aim To evaluate the functional capacity in a cohort of FD patients with different degree of cardiac involvement. Methods Seventy-two patients were prospectively enrolled from March 2015 to December 2019. Patients underwent cardiac magnetic resonance (CMR) and cardiopulmonary exercise test (CPET) with cycle ergometer. In addition to standard CPET parameters, Chronotropic Index (CI) was calculated as (HR max − HR rest) / (HR max predicted − HR rest), adjusting with HR max predicted calculated as 119 + (HR rest/2) − (age/2) in case of beta-blockers treatment. Results CMR showed left ventricle (LV) hypertrophy (LV mass greater than normal reference value) in 36.1% of patients, LGE and reduced T1 values were detected in 30.6% and 59.7% of subjects respectively. Twenty-eight patients were males (39%), the median age was 40 (28–54) [median (25th–75th)] years and only 11 (15%) subjects were on beta-blockers. All subjects performed a maximal test [RQ max = 1.21 (1.14–1.26)] using a ramp protocol of 15 (15–20) Watt. The absolute peakVO2 was 18.2 (15.75–24.08) mL/min/kg, whilst the percentage of predicted peakVO2 was 67.7 (57.3–76.6)%. The chronotropic response of the overall population was characterized by reduced peak heart rate (HRmax) [80.3 (73.8–87.6)% of predicted], and diminished chronotropic index (CI) [0.67 (0.55–0.77) normal value: 0.80], but preserved heart rate reserve (HRR) [21 (12–28) bpm]. Ventilatory efficiency was preserved [VE/VCO2 = 25.70 (23.18–28.00)]. At gender analysis, men showed higher absolute peakVO2 [men vs females: 19.95 (17.20–28.28) vs 17.80 (15.50–21.28) mL/min/kg, p=0.02] but lower percentage of predicted [64.24 (52.58–70.61) vs 70.75 (59.05–78.02)%, p&lt;0.001] than females. No differences between genders were observed in chronotropic response [HRmax = 138 (108–154) vs 142 (135–153) bpm, p=0.38; HRR = 22 (13–36) vs 20 (11–26), p=0.097; CI: 0.67 (0.51–0.76) vs 0.67 (0.58–0.79), p=0.33], whilst females showed a lower peak O2 pulse (VO2/HR) than males [men vs females: 12.08 (10.04–13.64) vs 7.76 (6.88–9.22), p&lt;0.001], possibly related to gender differences in LV dimensions and stroke volume. Conclusions This large cohort of FD patients with different degree of cardiac involvement showed a significantly impaired functional capacity, mainly characterized by relevant chronotropic incompetence (independent from the use of beta-blockers), consistent with systemic autonomic dysfunction. The degree of chronotropic incompetence was similar between the genders, but females showed higher predicted peakVO2 despite a lower peak O2 pulse. FUNDunding Acknowledgement Type of funding sources: None.

Cardiac Autonomic Modulation of Heart Rate Recovery in Children with Spina Bifida

We aimed to analyse cardiac autonomic control by assessing the post-exercise heart rate recovery (HRR) and physical fitness in children and adolescents with spina bifida (SB), compared to participants with typical development. A total of 124 participants, 42 with spina bifida (SB group) and 82 typical developmental controls (CO group) performed the arm cranking exercise test with a gas analysis system. HRR was determined at the first (HRR_1) and second (HRR_2) minute at recovery phase. Data are shown as [mean difference (95% CI)]. The SB group showed reduced HR reserve [14.5 (7.1–22.0) bmp, P<0.01], slower HRR_1 [12.4 (7.4–17.5) bpm, P<0.01] and HRR_2 [16.3 (10.6–21.9) bpm; P<0.01], lower VO2peak [VO2peak relative: 7.3 (4.2–10.3) mL·min−1·kg−1, P<0.01; VO2peak absolute: 0.42 (0.30–0.54) L·min−1, P<0.01], and lower O2 pulse [2.5 (1.8–3.2) mL·bpm, P<0.01] and ventilatory responses [13.5 (8.8–18.1) L·min−1, P<0.01] than the CO group. VE/VO2 was not different between groups [−2.82 (−5.77– −0.12); P=0.06], but the VE/VCO2 [−2.59 (−4.40–0.78); P<0.01] and the values of the anaerobic threshold corrected by body mass [−3.2 (−5.8– −0.6) mL·min−1·kg−1, P=0.01] were higher in the SB group than in the CO group. We concluded that children and adolescents with SB have reduced physical fitness and a slower HRR response after maximal effort.

IDENTIFICATION OF SPECIFIC SELECTION CRITERIA IN YOUNG BALL SPORT PLAYERS

Background: Our study aimed to analyze body composition and spiroergometric data of young (14-15 years) elite level ball sport players. We suggested three-ball sports (handball, soccer, and basketball) share common performance indicators, as rapid intermittent movements primarily characterize each ball sport. Methods: We selected one-hundred and ten, handball (n=30), basketball (n=40), and soccer (n=40) players male and female from local clubs in Hungary. Seventy-nine males and thirty-one females participated in our study; their average age was 14.51 and 14.56, respectively. They participated in laboratory testing; the protocol included a body composition analysis and spiroergometric tests. We measured body composition and physiological parameters utilizing an In Body 720 device and a standard Bruce treadmill protocol. Although we were aware of the Bruce protocol limitations in elite athletes, we choose this protocol as a safer alternative for younger inexperienced athletes. Results and conclusions: We concluded that in young male soccer and basketball players, mean peak /load (W), peak/VE (l), peak/Vtex (l), peak/VO2 (ml/min), peak/VCO2 (ml/min), and peak/ O2 pulse (ml) data is a reliable indicator of the sport-specific performance. We may also suggest that in our male basketball and handball players' population, peak/Vtex (l) is the only variable, which is significantly different. Between groups of male handball and soccer players, peak/VO2/kg (ml/min) may be a valid performance indicator. Among female basketball and handball players, we found a significant difference in three performance variables: peak/Vtex (l), peak/VO2 (ml/min), and peak/ O2 pulse (ml).