Prognostic Value of Maximal and Submaximal Exercise Performance in Fontan Patients < 15 Years of Age

•Oxygen uptake efficiency slope has a prognostic value in Fontan patients.•An important percentage of patients is not able to reach maximal effort.•Oxygen valid submaximal exercise parameter.•Young showed deterioration performance over time. In after completion capacity significantly reduced. Although peak oxygen consumption (VO2peak) strong factor many cardiovascular diseases, it requires the achievement effort. Therefore, parameters such as (OUES) may be value. present observational study we evaluated with and group an extracardiac conduit determined their Sixty followed up Leiden University Medical Center who have performed test were included this retrospective study. Exercise tests at median age 11 years. on average lower values for all compared reference from healthy dataset shown by %predicted values: VO2peak%:mean 66%(95%CI:64 74) OUES%:mean 72%(95%CI:67 77). Twenty percent achieve RER>1.0. RER moderate positive correlation VO2peak but OUES. There was VO2peak% OUES% OUES cardiac events follow period. impaired even young ages deteriorates age. An effort so use parameters, like OUES, should considered part evaluation. Moreover, could patients. The procedure, surgical palliation single ventricle physiology, developed original atriopulmonary connection total cavopulmonary (TCPC) either intracardiac tunnel (ILT) or (ECC). current era, survival these 10 years 95%,1Pundi KN Johnson JN Dearani JA Pundi Li Z Hinck CA Dahl SH Cannon BC O'Leary PW Driscoll DJ Cetta F. 40-year follow-up operation: long-term outcomes 1,052 patients.J Am Coll Cardiol. 2015; 66: 1700-1710Crossref PubMed Scopus (306) Google Scholar longevity morbidity mid remain challenge.1Pundi Scholar,2Atz AM Zak V Mahony L Uzark K D'Agincourt N Goldberg Williams RV Breitbart RE Colan SD Burns KM Margossian R Henderson HT Korsin Marino BS Daniels McCrindle BW Pediatric Heart Network ILongitudinal procedure.J 2017; 69: 2735-2744Crossref (114) adult decreased associated increased morbidity,2Atz Scholar, 3Fernandes SM Alexander ME Graham DA Khairy P Clair M Rodriguez E Pearson DD Landzberg MJ Rhodes J. testing identifies risk mortality following surgery.Congenit Dis. 2011; 6: 294-303Crossref (68) 4Diller GP, Giardini A, Dimopoulos K, Gargiulo G, Muller J, Derrick Giannakoulas Khambadkone S, Lammers AE, Picchio FM, Gatzoulis MA, Hager A. Predictors contemporary patients: results multicenter including cardiopulmonary 321 Eur J 2010;31:3073-3083.Google also decline major events.5Cunningham JW, Nathan AS, Shafer MJ, Opotowsky AR. Decline time predicts death transplantation adults circulation. 2017;189:184-192.Google Scholar,6Egbe AC, DJ, Khan AR, Said SS, Akintoye E, Berganza Connolly HM. Cardiopulmonary prior serial testing. Int Cardiol 2017;235:6-10.Google mostly (CPET) parameter asymptomatic patients.1Pundi Scholar,3Fernandes Scholar,4Diller Scholar,7Bossers Helbing WA, Duppen N, Kuipers IM, Schokking M, Hazekamp MG, Bogers AJ, Ten Harkel AD, Takken T. children connection: lateral versus technique. Thorac Cardiovasc Surg 2014;148:1490-1497.Google 8Hock Hacker AL, Reiner B, Oberhoffer R, Ewert P, Functional outcome tetralogy Fallot repair. Arch Dis Child 2019;104:129-133.Google 9Muller Christov F, Schreiber C, Hess capacity, quality life, daily activity univentricular heart connection. 2009;30:2915-2920.Google However, its correct interpretation, which often difficult TCPC. been only used small number studies patients.7Bossers Scholar,10Chen CA, Chen SY, Chiu HH, Wang JK, Chang CI, IS, YS, Lu CW, Lin MT, Lue HC, Hua YC, Wu MH. Prognostic data Med Sci Sports Exerc 2014;46:10-15.Google We hypothesize that parameter, useful determine future events. All ECC had CPET between 2010 -2019 Information regarding clinical echocardiographic aspects acquired electronic medical history, both during approved institutional review board need individual consent waived. If more than one CPET, first evaluated. Only measured included. CPET's electronically braked cycle ergometer (Jaeger ER900, Viasys Healthcare GmbH, Höchberg, Germany). A facemask (Hans Rudolph, Kansas City, MO, USA) connected flowmeter (Triple volume transducer) computerized gas analyser MasterScreen CPX, CareFusion Hoechberg, Germany; Vyntus Vyaire Germany) do analysis. breath-by-breath minute ventilation (VE), (VO2), carbon dioxide production (VCO2) respiratory exchange ratio (RER, defined VCO2/VO2) calculated second intervals. rate (HR) continuously monitored through twelve-lead electrocardiogram blood pressure every 2 minutes sphygmomanometry. Weight height obtained body surface area (BSA) mass index (BMI) using Dubois equation. 3 warm-up phase (unloaded cycling) continuous incremental bicycle protocol work increment 10, 15 20 W/min depending (<125cm, 125-150cm >150cm) according Godfrey protocol.11Godfrey S. Methods measuring response children. Testing Children: Applications Health Disease. London: W.B. Saunders Company Ltd, 1974.Google maintain pedalling 60 65 revolutions/min encouraged perform exhaustion. ended patient case discomfort supervising physician ECG changes, excessive breathing pattern otherwise. (RERpeak) highest consecutive achieved sec (WRpeak). WRpeak maximum finished (1 min completed) % predicted previously described.12Ten T, Van Osch-Gevers WA. Normal Prev Rehabil 2011;18:48-54.Google HR rest (HRrest) least seated position (HRpeak) WRpeak. Then formula [200-age(in years)], being abnormal <85%.13American Thoracic American College Chest P. ATS/ACCP statement Respir Crit Care 2003;167:211-277.Google reserve (HRreserve) HRpeak–HRrest. recorded 1 cessation (HR01’ HR02’). recovery (HRrecovery01’and HRrecovery02’) difference HRpeak HR01’ HR02’. relative decrement (HR01% HR02%) (HRrecovery/HRreserve) x100%. VO2 It expressed absolute (ml/min), per weight (ml/kg/min) adjusted age, gender (VO2peak).12Ten Scholar,13American VE/VCO2 VO2/WR slopes calculated. O2 pulse divided HR, (O2pulsemax) two et al12Ten calculate pulse. linear squares regression common logarithm VE equation = log (VE) + b, where constant ‘a’ coefficient OUES.14Baba Nagashima Goto Nagano Y, Yokota Tauchi Nishibata K. Oxygen slope: new cardiorespiratory functional derived relation exercise. 1996;28:1567-1572.Google Absolute values, represented. (OUES%) described formulas based normal values.15Bongers BC, Hulzebos EH, van Brussel Response profiles 2016;23:865-873.Google Follow-up collected until November 2019. Patients records reviewed (morbidity mortality). Cardiac cardiac-related hospitalization management any complications failure, arrhythmias, protein losing enteropathy plastic bronchitis. Overall noted well. SPSS Statistics software (version 25.0 IBM SPSS, Chicago, IL) Variables tested distribution Kolmogorov-Smirnov test. Continuous mean ± standard deviation (SD) third quartile [Q1-Q3] suitable. Patient relatively (100% would equal value) represented 95% confidence interval (CI). < 0.05 statistically significant. independent samples t-test Mann-Whitney test, non-normality, assess differences gender, ventricular dominance, function medication Correlations different (age, Fontan, SatO2) well Spearman distribution. Kaplan-Meier method construct outcome-free curve procedure. To whether differed sample evaluate values. General characteristics are Table 1. included; 31 them (52%) dominant left 29 right ventricle. undergone 11[10-13] years, 8[7-10] completion. subjective assessed echocardiography good 83% reasonable other general condition 88%; pacemaker because sinus node dysfunction, bronchitis enteropathy.Table 1Characteristics populationVariablen 60Men38 (63%)Dominant ventricle31 (52%)Age (years)11 [10-13]Years Fontan8 [7-10]Weight (kg)37 [30-50]Body Surface Area (m2)1.22 [1.07-1.51]Body Mass Index (kg/m2)16.87 [15.36-19.19]SatO296 [94-97]Cardiac medications Anticoagulants/antiplatelet60 (100%) ACEI6 (10%) β-blocker1 (1.7%) Sildenafil1 Diuretics1 (1.7%)Data (%), [Q1-Q3]CPET: ACEI: angiotensin-converting enzyme inhibitors. Open table tab Data CPET: depicts results. > 1.0. no adverse events, arrhythmia (near) syncope tests. Maximal dataset,12Ten Scholar,15Bongers reflected (mean 69% (95%CI: 64-74), p <0.001; 72% 67-77), <0.001). Male HRpeak%, female subjects, significant found males females. function. When analysing ventricle, ventricles (LV OUES%: 65%(95%CI 59-72) vs 79%(70-88); 0.011).Table 2Cardiopulmonary resultsVariableAll patientsMaleFemalep-value SBP basal (mmHg)120 16120 16121 160.60 (mmHg)159 27159 27158 260.85 RERpeak1.06 0.111.05 0.101.06 0.120.70Maximal exerciseN 48N= 30N 18 Work Ratepeak (W)90 [80-100]80 [79-123]93 160.357 WRpeak%70 (65-74)68 (62-74)72 (66-78)0.448 (W/kg)2.3 0.62.3 0.72.2 0.40.573 (bpm)170 18163 18180 140.002 HRpeak%90 (87-93)87 (83-91)96 (92-100)0.002 (ml/min)1187 [1079-1377]1152 [1046-1468]1234 2130.749 VO2peak%69 (64-74)68 (61-75)70 (63-76)0.744 (ml/kg/min)31.1 8.431.6 8.730.2 8.20.580 / kg70 (64-75)68 (61-76)72 (62-82)0.546 pulsemax (ml/beat)7.3 [6.5-8.3]7.5 [6.9-8.8]7 10.069 pulsemax%59 (56-62)61 (57-65)54 (50-59)0.013Submaximal exercisen 60n 38n 22 (L/min)35.9 [32.7-39.5]35.9 [32.8-39]37 5.80.81 (ml/min/log(L/min))1350 3761385 4171288 2930.34 OUES%72 (67-77)70 (64-78)74 (65-83)0.59 OUES/kg35.4 11.136.7 11.733.2 9.90.25 kg76 (70-82)75 (67-83)79 (68-89)0.51Data [Q1-Q3]. mean(95%CI).p: Independent T U.HRpeak%: exercise; pulsemax: pulse; OUES: slope; OUES; RERpeak: basal: systolic rest; peak: VCO2: production; VE: ventilation; VO2peak: VO2peak%: VO2peak; WRpeak: rate; WRpeak%: rate. mean(95%CI). p: U. HRpeak%: taking anticoagulant/antiplatelet better several (specially parameters) worse having (Table 3).Table 3Difference treatment status when performedTreatmentOnly antiaggregant/anticoagulant+ drugspMaximal 40n 8 Ratepeak173 17.8155 14.30.010 Ratepeak%92 (89-95)82 (76-88)0.011Submaximal exerciseN=51n 9 OUES%75 (69-81)57 (46-68)0.017 OUES/kg37 1229 60.011 kg79 (72-86)60 (51-69)0.001Clinical statusGoodOtherpSubmaximal 53n 7 slope27.5 [25.66-29.9]24.1 [22.8-26.8]0.021 OUES1388 3581055 4100.026 (69-80)53 (44-61)0.009Data SD, (95%CI). depicted table. drugs specified 1.HRpeak%: VO2peak. (Figure 1). Both negatively correlated 2). Figure shows data.Figure 2Correlation (years) VO2peak, peak; slope.View Large Image ViewerDownload Hi-res image Download (PPT)Figure 3Relationship peak. (PPT) Thirty six (60%) period ≥ CPET. For 4.8 [Q1-Q3: 3.5-5.8]. deaths transplantations (28%) problem. 4 related Fontan. Both, event ones without events: 1499 404 1096 337 0.007; 85% (95%CI 77-92) 67% 52-82) 0.002. No seen parameters. procedureTable 4Morbidity proceduren 10Cardiac catheterizationLeft pulmonary artery stentingExtracardiac stentingCollateral closureHeart rhythm disordersSinus dysfunctionSupraventricular tachycardiaHeart surgeryExtracardiac replacement313111The [0.5-7] (period 2010-2018). This paediatric Furthermore, excellent RERpeak whereas not. Lastly, patients, found. suggesting Previous investigations, although predominantly reduced level below 60%.1Pundi 2Atz 5Cunningham 6Egbe 7Bossers Scholar,9Muller reported.1Pundi contrast our Fontan-ECC cohorts usually types same procedure technical modifications since introduction 1971. most commonly currently ILT ECC. Bossers al studied techniques higher group.7Bossers On contrary, techniques.4Diller Scholar,16d'Udekem Cheung MM, Setyapranata Iyengar Kelly Buckland Grigg LE, Weintraub RG, Vance Brizard CP, Penny DJ. How Fontan? Quality life Fontans arrhythmias. Ann 2009;88:1961-1969.Google include homogenous indicates already starts childhood inability RER>1.0 high 20-40%.6Egbe therefore importance Hence, very usefulness further underscored fact reached. These findings extend previous subjects biventricular congenital disease patients.15Bongers Scholar,17Baba Tsuyuki Kimura Ninomiya Aihara Ebine M. measure Appl Physiol Occup 1999;80:397-401.Google 18Bongers HJ, Blank disease: validity. 2011;18:384-392.Google 19Van Laethem Bartunek Goethals Nellens Andries Vanderheyden slope, evaluating chronic failure 2005;149:175-180.Google comparable reported al, well.7Bossers Most 57%.7Bossers Several factors limit increase output, stroke near end hemodynamic limiting patients.20Hebert Jensen Mikkelsen UR, Idorn L, Sorensen KE, Thilen U, Hanseus Sondergaard L. Hemodynamic causes intolerance 2014;175:478-483.Google Scholar,21Claessen La Gerche De Bruaene Claeys Willems Dymarkowski Bogaert Claus Budts W, Heidbuchel H, Gewillig chronotropic incompetence limitation?J Assoc 2019;8:e012008.Google clear physiological lack preload rather pathological process frequencies reduce diastolic filling time.20Hebert 21Claessen 22Barber Di Sessa JS, Perloff Laks George BL, RG. responses isolated increments atrial pacing 1988;115:837-841.Google similar (90% value). function23Klimes Ovroutski Abdul-Khaliq Alexi-Meskishvili V, Kuehne Gutberlet Berger reflects Young 2009;19:340-345.Google controversial. Fernandes al. midterm demonstrate this.2Atz Recently, decrease (decline ≥3 points/year) pointed predictor did find association lacking. might explained again underscores Similarly, colleagues conclude can provide superior information predicting establishing ≤ 45% optimal threshold.10Chen As TCPC involves population, palliated ECC, they represent overall Nonetheless, represents homogeneous techniques. analyse due short follow-up. consider longitudinal longer greater necessary corroborate year. conclusion, negative demonstrated evaluation hospitalization. authors declare competing interests.