scholarly journals Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers

2020 ◽  
Author(s):  
Maciej Tysarowski ◽  
Krzysztof Smarz ◽  
Beata Zaborska ◽  
Ewa Pilichowska-Paszkiet ◽  
Malgorzata Sikora-Frac ◽  
...  
Keyword(s):  
Exercise Capacity ◽  
Beta Blocker ◽  
Partial Correlation ◽  
Beta Blockers ◽  
Cardiopulmonary Exercise Testing ◽  
Peak Oxygen Uptake ◽  
Chronotropic Incompetence ◽  
Peak Vo2 ◽  
Aerobic Exercise Capacity ◽  
Variance Explained

Background: Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear. Methods: We retrospectively analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing. EC was expressed as peak oxygen uptake (peak VO2; mL/kg/min). Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. CI was calculated as [(HR at peak-HR at rest) / (maximum predicted HR-HR at rest)] x 100%. Results: Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), there were 113 (80.7%) patients with chronotropic incompetence. EC was lower in the group with chronotropic incompetence than the group without it, peak VO2 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. In multivariate analysis EC correlated positively with CI (β = 0.14, p < 0.001) and male gender (β = 5.12, p < 0.001), and negatively with age (β = −0.17, p < 0.001) and presence of heart failure (β = −3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI accounted for more than one-third of the variance in EC explained by the model. Conclusions: In patients taking beta-blockers, presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.

Abstract 16002: Chronotropic Incompetence Limits Exercise Capacity in Patients Taking Beta-Blockers

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Maciej Tysarowski ◽  
Krzysztof Smarz ◽  
Beata Zaborska ◽  
Ewa Pilichowska-Paszkiet ◽  
Malgorzata Sikora-Frac ◽  
...  
Keyword(s):  
Exercise Capacity ◽  
Beta Blocker ◽  
Partial Correlation ◽  
Beta Blockers ◽  
Cardiopulmonary Exercise Testing ◽  
Peak Oxygen Uptake ◽  
Male Gender ◽  
Chronotropic Incompetence ◽  
Cardiopulmonary Exercise ◽  
Variance Explained

Introduction: Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear. Hypothesis: We assessed the hypothesis that chronotropic incompetence is associated with decreased exercise capacity in patients taking beta-blockers. Methods: We retrospectively analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing. EC was expressed as peak oxygen uptake (VO 2 peak; mL/kg/min). Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. CI was calculated as [(HR at peak-resting HR) / (maximum predicted HR-resting HR)] х 100%. Results: Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), there were 113 (80.7%) patients with chronotropic incompetence. EC was lower in the group with chronotropic incompetence than the group without it, VO 2 peak 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. In multivariate analysis ( Table ), EC correlated positively with CI (β = 0.14, p < 0.001) and male gender (β = 5.12, p < 0.001), and negatively with age (β = –0.17, p < 0.001) and presence of heart failure (β = –3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI (partial R 2 = 24.7%) accounted for more than one-third of the variance in EC explained by the model (adjusted R 2 = 59.8%). Conclusions: In patients taking beta-blockers, the presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.

scholarly journals Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers: Real-Life Observation of Consecutive Patients

Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 212
Author(s):  
Krzysztof Smarz ◽  
Maciej Tysarowski ◽  
Beata Zaborska ◽  
Ewa Pilichowska-Paszkiet ◽  
Małgorzata Sikora-Frac ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Capacity ◽  
Beta Blocker ◽  
Beta Blockers ◽  
Cardiopulmonary Exercise Testing ◽  
Real Life ◽  
Peak Oxygen Uptake ◽  
Chronotropic Incompetence ◽  
Aerobic Exercise Capacity ◽  
Variance Explained

Background: Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear. Methods: We analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing to assess EC. Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. Results: Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), 64% with heart failure, chronotropic incompetence was present in 80.7%. EC assessed as peak oxygen uptake was lower in the group with chronotropic incompetence, 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. EC correlated positively with CI (β = 0.14, p < 0.001) and male gender (β = 5.12, p < 0.001), and negatively with age (β = −0.17, p < 0.001) and presence of heart failure (β = −3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI accounted for more than one-third of the variance in EC explained by the model (adjusted R2 = 59.8%). Conclusions: In patients taking beta-blockers, presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.

Abstract 17499: Addition of Myocardial Parameters to the Diagnosis of Stage B Heart Failure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tom Marwick ◽  
Wojciech Kosmala ◽  
Christine Jellis
Keyword(s):  
Heart Failure ◽  
At Risk ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Exercise Capacity ◽  
Beta Blockers ◽  
Cardiopulmonary Exercise Testing ◽  
Structural Heart Disease ◽  
Filling Pressure ◽  
Ischemic Heart

Introduction: Stage B heart failure (BHF, asymptomatic structural heart disease) is diagnosed in the presence of myocardial scar or impaired LVEF. However, the insensitivity of LVEF may lead to under-recognition of BHF in non-ischemic heart disease. This may be important, as BHF may precede the onset of HF symptoms, and necessitates the initiation of treatment. We sought the implications of using additional LV assessment to identify BHF in pts at risk of HF (stage A HF, AHF). Methods: We studied 510 asymptomatic pts (age 58±12yrs) with AHF (diabetes, hypertension or obesity), but no history of ischemic heart disease and a normal stress echo. All pts underwent echocardiography (including assessment of strain and diastolic dysfunction) and cardiopulmonary exercise testing. Results: BHF was defined as the presence of at least one of; reduced LV longitudinal strain (<18%), increased LV filling pressure (E/e’>13) or moderate-to-severe LV hypertrophy (LV mass index ≥109 g/m 2 in women and 132 g/m 2 in men) in 243 patients (47%). Reduced exercise capacity (peakVO 2 and METS) was identified in BHF compared with other AHF (Table). Using this definition, BHF was associated with lower peak VO 2 (β=-0.20, p<0.00001) and METS (β=-0.21, p<0.0001), independent of higher BMI, insulin resistance, older patient age, male sex and treatment with beta-blockers. Conclusions: LV hypertrophy, elevated LV filling pressure elevation and abnormal myocardial deformation independently contribute to lower exercise capacity in pts at risk of HF. Given the association of exercise capacity with outcome, these factors should be considered grounds for the diagnosis of BHF.

scholarly journals Mismatch between self-estimated and objectively assessed exercise capacity in patients with congenital heart disease varies in regard to complexity of cardiac defects

2020 ◽  
pp. 1-7
Author(s):  
Julius M. Woile ◽  
Stefan Dirks ◽  
Friederike Danne ◽  
Felix Berger ◽  
Stanislav Ovroutski
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Oxygen Uptake ◽  
Exercise Capacity ◽  
Congenital Heart ◽  
Cardiopulmonary Exercise Testing ◽  
Peak Oxygen Uptake ◽  
Subjective Rating ◽  
Cardiac Defects ◽  
Cardiopulmonary Exercise

Abstract Aim: Regular evaluation of physical capacity takes a crucial part in long-term follow-up in patients with congenital heart disease (CHD). This study aims to examine the accuracy of self-estimated exercise capacity compared to objective assessments by cardiopulmonary exercise testing in patients with CHD of various complexity. Methods: We conducted a single centre, cross-sectional study with retrospective analysis on 382 patients aged 8–68 years with various CHD who completed cardiopulmonary exercise tests. Peak oxygen uptake was measured. Additionally, questionnaires covering self-estimation of exercise capacity were completed. Peak oxygen uptake was compared to patient’s self-estimated exercise capacity with focus on differences between complex and non-complex defects. Results: Peak oxygen uptake was 25.5 ± 7.9 ml/minute/kg, corresponding to 75.1 ± 18.8% of age- and sex-specific reference values. Higher values of peak oxygen uptake were seen in patients with higher subjective rating of exercise capacity. However, oxygen uptake in patients rating their exercise capacity as good (mean oxygen uptake 78.5 ± 1.6%) or very good (mean oxygen uptake 84.8 ± 4.8%) was on average still reduced compared to normal. In patients with non-complex cardiac defects, we saw a significant correlation between peak oxygen uptake and self-estimated exercise capacity (spearman-rho −0.30, p < 0.001), whereas in patients with complex cardiac defects, no correlation was found (spearman-rho −0.11, p < 0.255). Conclusion: The mismatch between self-estimated and objectively assessed exercise capacity is most prominent in patients with complex CHD. Registration number at Charité Universitätsmedizin Berlin Ethics Committee: EA2/106/14.

scholarly journals Right ventricular systolic dysfunction but not dilatation correlates with prognostically significant reductions in exercise capacity in repaired Tetralogy of Fallot

2019 ◽  
Vol 21 (8) ◽  
pp. 906-913 ◽  
Author(s):  
Imran Rashid ◽  
Adil Mahmood ◽  
Tevfik F Ismail ◽  
Shamus O’Meagher ◽  
Shelby Kutty ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Tetralogy Of Fallot ◽  
Exercise Capacity ◽  
Multivariable Analysis ◽  
Cardiopulmonary Exercise Testing ◽  
Pulmonary Regurgitation ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Peak Vo2 ◽  
Repaired Tetralogy Of Fallot

Abstract Aims The optimal timing for pulmonary valve replacement in asymptomatic patients with repaired Tetralogy of Fallot (rTOF) and pulmonary regurgitation remains uncertain but is often guided by increases in right ventricular (RV) end-diastolic volume. As cardiopulmonary exercise testing (CPET) performance is a strong prognostic indicator, we assessed which cardiovascular magnetic resonance (CMR) parameters correlate with reductions in exercise capacity to potentially improve identification of high-risk patients. Methods and results In all, 163 patients with rTOF (mean age 24.5 ± 10.2 years) who had previously undergone CMR and standardized CPET protocols were included. The indexed right and left ventricular end-diastolic volumes (RVEDVi, LVEDVi), right and left ventricular ejection fractions (RVEF, LVEF), indexed RV stroke volume (RVSVi), and pulmonary regurgitant fraction (PRF) were quantified by CMR and correlated with CPET-determined peak oxygen consumption (VO2) or peak work. On univariable analysis, there was no significant correlation between RVEDVi and PRF with peak VO2 or peak work (% Jones-predicted). In contrast, RVEF and RVSVi had significant correlations with both peak VO2 and peak work that remained significant on multivariable analysis. For a previously established prognostic peak VO2 threshold of &lt;27 mL/kg/min, receiver-operating characteristic curve analysis demonstrated a Harrell’s c of 0.70 for RVEF (95% confidence interval 0.61–0.79) with a sensitivity of 88% for RVEF &lt;40%. Conclusion In rTOF, CMR indices of RV systolic function are better predictors of CPET performance than RV size. An RVEF &lt;40% may be useful to identify prognostically significant reductions in exercise capacity in patients with varying degrees of RV dilatation.

scholarly journals Can wearable technology be used to approximate cardiopulmonary exercise testing metrics?

2020 ◽  
Author(s):  
Matt Morgan ◽  
Laura Jones ◽  
Laura Tan ◽  
Suzanne Carey-Jones ◽  
Nathan Riddell ◽  
...  
Keyword(s):  
Physical Activity ◽  
High Risk ◽  
Oxygen Uptake ◽  
Anaerobic Threshold ◽  
Low Cost ◽  
Cardiopulmonary Exercise Testing ◽  
Peak Oxygen Uptake ◽  
Wearable Device ◽  
Cardiopulmonary Exercise ◽  
Peak Vo2

Abstract Background Consumer wrist-worn wearable activity monitors are widely available, low cost and are able to provide a direct measurement of several markers of physical activity. Despite this, there is limited data on their use in perioperative risk prediction. We explored whether these wearables could accurately approximate metrics (anaerobic threshold, peak oxygen uptake and peak work) derived using formalised cardiopulmonary exercise testing (CPET) in patients undergoing high-risk surgery. Methods Patients scheduled for major elective intra-abdominal surgery and undergoing CPET were included. Physical activity levels were estimated through direct measures (step count, floors climbed and total distance travelled) obtained through continuous wear of a wrist worn activity monitor (Garmin Vivosmart HR+) for 7 days prior to surgery and self-report through completion of the short International Physical Activity Questionnaire (IPAQ). Correlations and receiver operating characteristic (ROC) curve analysis explored the relationships between parameters provided by CPET and physical activity. Device selection Our choice of consumer wearable device was made to maximise feasibility outcomes for this study. The Garmin Vivosmart HR+ had the longest battery life and best waterproof characteristics of the available low-cost devices. Results Of 55 patients invited to participate, 49 (mean age 65.3 ± 13.6 years; 32 male) were enrolled; 37 provided complete wearable data for analyses and 36 patients provided full IPAQ data. Floors climbed, total steps and total travelled as measured by the wearable device all showed moderate correlation with CPET parameters of peak oxygen uptake (peak VO2) (R=0.57 (CI 0.29-0.76), R=0.59 (CI 0.31-0.77) and R=0.62 (CI 0.35-0.79) respectively), anaerobic threshold (R = 0.37 (CI 0.01-0.64), R = 0.39 (CI 0.04-0.66) and R = 0.42 (CI 0.07-0.68) respectively) and peak work (R = 0.56 (CI 0.27-0.75), R = 0.48 (CI 0.17-0.70) and R = 0.50 (CI 0.2-0.72) respectively). Receiver Operator Curve (ROC) analysis for direct and self-reported measures of 7 day physical activity could accurately approximate the ventilatory equivalent for carbon dioxide (VE/VCO2) and the anaerobic threshold. The area under these curves was 0.89 for VE/VCO2 and 0.91 for the anaerobic threshold. For peak VO2 and peak work, models fitted using just the wearable data were 0.93 for peak VO2 and 1.00 for peak work. Conclusions Data recorded by the wearable device was able to consistently approximate CPET results, both with and without the addition of patient reported activity measures via IPAQ scores. This highlights the potential utility of wearable devices in formal assessment of physical functioning and suggests they could play a larger role in pre-operative risk assessment. Ethics This study entitled “uSing wearable TEchnology to Predict perioperative high-riSk patient outcomes (STEPS)” gained favourable ethical opinion on 24/1/2017 from the Welsh Research Ethics Committee 3 reference number 17/WA/0006. It was registered on ClinicalTrials.gov with identifier NCT03328039.

scholarly journals Mechanisms of Exercise Capacity Improvement after Cardiac Rehabilitation Following Myocardial Infarction Assessed with Combined Stress Echocardiography and Cardiopulmonary Exercise Testing

2021 ◽  
Vol 10 (18) ◽  
pp. 4083
Author(s):  
Krzysztof Smarz ◽  
Tomasz Jaxa-Chamiec ◽  
Beata Zaborska ◽  
Maciej Tysarowski ◽  
Andrzej Budaj
Keyword(s):  
Myocardial Infarction ◽  
Heart Rate ◽  
Cardiac Rehabilitation ◽  
Exercise Capacity ◽  
Exercise Testing ◽  
Cardiopulmonary Exercise Testing ◽  
Oxygen Extraction ◽  
Peak Exercise ◽  
Cardiopulmonary Exercise ◽  
Peak Vo2

Cardiac rehabilitation (CR) is indicated in all patients after acute myocardial infarction (AMI) to improve prognosis and exercise capacity (EC). Previous studies reported that up to a third of patients did not improve their EC after CR (non-responders). Our aim was to assess the cardiac and peripheral mechanisms of EC improvement after CR using combined exercise echocardiography and cardiopulmonary exercise testing (CPET-SE). The responders included patients with an improved EC assessed as a rise in peak oxygen uptake (VO2) ≥ 1 mL/kg/min. Peripheral oxygen extraction was calculated as arteriovenous oxygen difference (A-VO2Diff). Out of 41 patients (67% male, mean age 57.5 ± 10 years) after AMI with left ventricular ejection fraction (LVEF) ≥ 40%, 73% improved their EC. In responders, peak VO2 improved by 27% from 17.9 ± 5.2 mL/kg/min to 22.7 ± 5.1 mL/kg/min, p < 0.001, while non-responders had a non-significant 5% decrease in peak VO2. In the responder group, the peak exercise heart rate, early diastolic myocardial velocity at peak exercise, LVEF at rest and at peak exercise, and A-VO2Diff at peak exercise increased, the minute ventilation to carbon dioxide production slope decreased, but the stroke volume and cardiac index were unchanged after CR. Non-responders had no changes in assessed parameters. EC improvement after CR of patients with preserved LVEF after AMI is associated with an increased heart rate response and better peripheral oxygen extraction during exercise.

scholarly journals Chronotropic incompetence and exercise capacity after mitral valve surgery: the importance of blood hemoglobin level

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Kanazawa ◽  
M Toyoda ◽  
T Seki ◽  
A Iguchi ◽  
S Takahashi ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Aortic Valve ◽  
Left Atrium ◽  
Valve Replacement ◽  
Exercise Capacity ◽  
Sympathetic Nerves ◽  
Chronotropic Incompetence ◽  
Blood Hemoglobin ◽  
Peak Vo2 ◽  
Ergometer Exercise

Abstract Background Chronotropic incompetence (CI) is sometimes observed during exercise training of cardiac rehabilitation in patients with cardiac surgery, however, little is known concerning the differences between patients with mitral valve (MV) and aortic valve (AV) surgery. Purpose Because the possibility exists that cardiac sympathetic nerves might be impaired by left atrium incision, we hypothesized that the incidence of CI was higher in patients with MV surgery (Mitral Valve Replacement and Mitral Valvuloplasty) as compared with patients with AV surgery (Aortic Valve Replacement). And if so, which factor determines the exercise capacity of patients after MV surgery. We thus aimed this study to elucidate the hypothesis with cardiopulmonary exercise testing (CPX). Methods We performed CPX by ramp loading with ergometer exercise in total 61 patients who had undergone elective cardiac valve operation (25 patients with MV surgery, age 59.2±9.9 years; 36 patients with AV surgery, age 64.6±12.3 years). We analyzed chronotropic response index (CRI), peak oxygen uptake (peak VO2/W), anaerobic threshold (AT), and peak oxygen pulse (peak VO2/HR) with CPX, and blood hemoglobin concentration (Hb). Results The value of CRI was significantly decreased in the patients with MV surgery compared with those with AV surgery (MV; 0.19±0.10 vs. AV; 0.41±0.17, p&lt;0.001). Peak VO2, peak VO2/HR and Hb were not significantly different between patients with MV and those with AV surgery. Patients with MV surgery showed correlations between peak VO2 and Hb (r=0.45, p&lt;0.05), AT and Hb (r=0.52, p&lt;0.01), and a strong correlation between peak VO2 and peak VO2/HR (r=0.63, p&lt;0.001), but not in those with AV surgery. Conclusions The present study demonstrated that higher incidence of CI was shown in patients with MV surgery as compared with those with AV surgery. The exercise capacity of patients with MV surgery was determined by peak VO2/HR and Hb. These results suggest that 1) left atrium incision impairs cardiac sympathetic nerves and causes CI, 2) peak VO2/HR which is consisted of arterio-venous oxygen difference and Hb is critical indicator for exercise capacity in patients with MV surgery with CI. Main results Funding Acknowledgement Type of funding source: None

Abstract 16896: Exercise Pulmonary Capillary Wedge Pressure Patterns in Patients With Normal Resting Left-sided Filling Pressures Predict Heart Failure Outcomes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Aaron S Eisman ◽  
Ravi V Shah ◽  
Bishnu P Dhakal ◽  
Stephanie M Meller ◽  
Paul P Pappagianopoulos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Capillary Wedge Pressure ◽  
Exercise Capacity ◽  
Exercise Testing ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cardiopulmonary Exercise Testing ◽  
Peak Vo2 ◽  
Pulmonary Capillary ◽  
Wedge Pressure

Introduction: Serial measurements of pulmonary capillary wedge pressure (PCWP) during exercise testing may help to improve hemodynamic (HD) classification of heart failure with preserved ejection fraction (HFpEF). However, the physiologic and prognostic significance of exercise PCWP patterns is largely unknown. Hypothesis: An elevated PCWP increment relative to cardiac output (CO) augmentation during exercise will independently predict exercise capacity and outcomes in patients with dyspnea on exertion and normal resting PCWP (DOE-nlrW). Methods: In a single center cohort of 175 patients referred for cardiopulmonary exercise testing (CPET) with invasive HD monitoring (n = 33 normal controls, n = 32 HFpEF with resting PCWP ≥ 15, and n = 110 consecutive patients with DOE-nlrW and LVEF > 0.45) 1,929 PCWP-CO points during exercise were measured. Median follow-up was 3.2 years and events consisted of HF hospitalization, CV death, or future RHC with resting PCWP ≥ 15 mmHg. Results: PCWP-CO slope of 1.2±0.4 mmHg/L/min in controls was used to establish the upper limit (mean + 2SDev) of normal of 2mmHg/L/min. HFpEF patients had a PCWP-CO slope of 3.6±1.8 mmHg/L/min. In the DOE-nlrW cohort, patients achieved a mean peak VO2 of 17±6 ml/kg/min (74±19 % predicted), mean PCWP-CO was 2.1±1.3 mmHg/L/min (Figure) with 45 of 110 patients having elevated PCWP-CO. PCWP-CO but not resting PCWP was related to peak VO2 in univariable (rho = -0.51, p < 0.01) and multi-variable linear regression adjusted for age, sex, hypertension, beta blocker use, diabetes, and resting PCWP (ß = -0.17, p = 0.03). Increased PCWP-CO also predicted worse event-free survival in univariable Cox regression (HR 1.67, p < 0.01) and after adjustment for age, sex, BMI, and resting PCWP (HR 1.56, p = 0.03). Conclusions: Elevated PCWP-CO during exercise ( > 2mmHg/L/min) is common in DOE-nlrW and predicts exercise capacity as well as outcomes, suggesting that assessment of exercise HD may help to refine early HFpEF diagnosis.

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