#include <StringConstants.au3> ; to declare the Constants of StringRegExp
#include <Array.au3> ; UDF needed for _ArrayDisplay and _ArrayConcatenate
Local $sRegex = "(?m)\d+\s?(women|men)"
Local $sString = "OR I GI N AL AR TI CL E" & @CRLF & _
"Home-based interval training increases endurance capacity" & @CRLF & _
"in adults with complex congenital heart disease" & @CRLF & _
"Camilla Sandberg RPT, PhD 1,2" & @CRLF & _
"| Magnus Hedstr€ om MD 1 |" & @CRLF & _
"Karin Wadell RPT, PhD 2" & @CRLF & _
"| Mikael Dellborg MD, PhD 3 | Anders Ahnfelt MD 3 |" & @CRLF & _
"Anna-Klara Zetterstr€ om RPT 4" & @CRLF & _
"| Amanda" & @CRLF & _
"€" & @CRLF & _
"Ohrn RPT 4" & @CRLF & _
"| Bengt Johansson MD, PhD 1" & @CRLF & _
"1 Heart Center and Department of Public" & @CRLF & _
"Health and Clinical Medicine, Umeå" & @CRLF & _
"University, Umeå, Sweden" & @CRLF & _
"2 Department of Community Medicine and" & @CRLF & _
"Rehabilitation, Physiotherapy, Umeå" & @CRLF & _
"University, Umeå, Sweden" & @CRLF & _
"3 Department of Molecular and Clinical" & @CRLF & _
"Medicine, Sahlgrenska Academy, University" & @CRLF & _
"of Gothenburg, Gothenburg, Sweden" & @CRLF & _
"4 Department of Physiotherapy and" & @CRLF & _
"Occupational Therapy, Sahlgrenska" & @CRLF & _
"University Hospital, Gothenburg, Sweden" & @CRLF & _
"Correspondence" & @CRLF & _
"Camilla Sandberg, RPT, PhD, Heart Center" & @CRLF & _
"and Department of Public Health and" & @CRLF & _
"Clinical Medicine, Umeå University," & @CRLF & _
"SE-90185, Umeå, Sweden." & @CRLF & _
"Email: camilla.sandberg@umu.se" & @CRLF & _
"Funding information" & @CRLF & _
"Swedish Heart-Lung Foundation, Grant/" & @CRLF & _
"Award Numbers: 20100355, 20130472;" & @CRLF & _
"Heart Foundation of Northern Sweden;" & @CRLF & _
"Research Foundation of The Swedish Heart" & @CRLF & _
"and Lung Association, Grant/Award Num-" & @CRLF & _
"ber: E116/12, E115/13, E129/14; Research" & @CRLF & _
"Foundation of Healthcare Professions" & @CRLF & _
"within Cardiology, Umeå University; Väster-" & @CRLF & _
"bottens läns landsting, Umeå, Sweden," & @CRLF & _
"Grant/Award Number: 316351; and ALF-" & @CRLF & _
"LUA grants at Sahlgrenska University Hos-" & @CRLF & _
"pital, G€ oteborg, Sweden" & @CRLF & _
"Abstract" & @CRLF & _
"Objective: The beneficial effects of exercise training in acquired heart failure and coronary artery" & @CRLF & _
"disease are well known and have been implemented in current treatment guidelines. Knowledge" & @CRLF & _
"on appropriate exercise training regimes for adults with congenital heart disease is limited, thus" & @CRLF & _
"further studies are needed. The aim of this study was to examine the effect of home-based interval" & @CRLF & _
"exercise training on maximal endurance capacity and peak exercise capacity." & @CRLF & _
"Design: Randomized controlled trial." & @CRLF & _
"Methods: Twenty-six adults with complex congenital heart disease were recruited from special-" & @CRLF & _
"ized units for adult congenital heart disease. Patients were randomized to either an intervention" & @CRLF & _
"group—12 weeks of home-based interval exercise training on a cycle ergometer (n516), or a con-" & @CRLF & _
"trol group (n510). The latter was instructed to maintain their habitual physical activities. An" & @CRLF & _
"incremental cardiopulmonary exercise test and a constant work rate cardiopulmonary exercise test" & @CRLF & _
"at 75% of peak workload were performed preintervention and postintervention." & @CRLF & _
"Results: Twenty-three patients completed the protocol and were followed (intervention n513," & @CRLF & _
"control n510). Postintervention exercise time at constant work rate cardiopulmonary exercise" & @CRLF & _
"test increased in the intervention group compared to controls (median[range] 12[–4 to 52]min vs 0" & @CRLF & _
"[–4 to 5]min, P5.001). At incremental cardiopulmonary exercise test, peak VO 2 increased 15%" & @CRLF & _
"within the intervention group (P5.019) compared to 2% within the control group (P5.8). How-" & @CRLF & _
"ever, in comparison between the groups no difference was found (285[–200 to 535] ml/min vs 17" & @CRLF & _
"[–380 to 306] ml/min, P5.10). In addition, peak workload at incremental cardiopulmonary exer-" & @CRLF & _
"cise test increased in the intervention group compared to controls (20[–10 to 70]W vs 0[–20 to" & @CRLF & _
"15]W, P5.003)." & @CRLF & _
"Conclusion: Home-based interval exercise training increased endurance capacity and peak exer-" & @CRLF & _
"cise capacity in adults with complex congenital heart disease. Aerobic endurance might be more" & @CRLF & _
"relevant than peak oxygen uptake with regard to daily activities, and therefore a more clinically rel-" & @CRLF & _
"evant measure to evaluate." & @CRLF & _
"K EY WO RD S" & @CRLF & _
"adult, cardiopulmonary exercise testing, congenital heart disease, constant work rate, exercise" & @CRLF & _
"training, interval training" & @CRLF & _
"254" & @CRLF & _
"|" & @CRLF & _
"V C 2017 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/chd Congenital Heart Disease. 2018;13:254–262." & @CRLF & _
"Received: 3 January 2017" & @CRLF & _
"|" & @CRLF & _
"Revised: 21 August 2017" & @CRLF & _
"|" & @CRLF & _
"Accepted: 19 October 2017" & @CRLF & _
"DOI: 10.1111/chd.12562" & @CRLF & _
"1" & @CRLF & _
"|" & @CRLF & _
"INTRODUCTION" & @CRLF & _
"During the past decades there have been substantial improvements" & @CRLF & _
"in survival and reduction in the need of reoperations for adults" & @CRLF & _
"with congenital heart disease (CHD), especially among those with" & @CRLF & _
"more complex lesions. 1–3 There is a well-known impairment in" & @CRLF & _
"exercise capacity in these patients compared to healthy controls. 4,5" & @CRLF & _
"To what extent this impairment is due to abnormal cardiovascular" & @CRLF & _
"physiology, per se, or to other factors such as physical inactivity or" & @CRLF & _
"lack of exercise training, that is, deconditioning, is unknown. Fur-" & @CRLF & _
"thermore, reduced exercise capacity is an important prognostic" & @CRLF & _
"predictor of cardiovascular morbidity and mortality. 6 In addition," & @CRLF & _
"impaired muscle function has been observed, especially in adults" & @CRLF & _
"with CHD that have complex lesions. 7–10 According to current rec-" & @CRLF & _
"ommendations of the European Society of Cardiology, adults with" & @CRLF & _
"CHD are encouraged to be physically active and exercise training" & @CRLF & _
"should be prescribed individually. 11 However, due largely to the" & @CRLF & _
"low numbers of studies on effects of exercise training in adults" & @CRLF & _
"with CHD, there are no specific recommendations regarding train-" & @CRLF & _
"ing mode, intensity, duration, and frequency. 12,13 Previous studies" & @CRLF & _
"show that exercise training seems to be safe and to have positive" & @CRLF & _
"effects on aerobic exercise capacity without adverse effect on ven-" & @CRLF & _
"tricular function. 14–21 Home-based continuous moderate exercise" & @CRLF & _
"training on an cycle ergometer increased the exercise capacity in" & @CRLF & _
"adults with a systemic right ventricle. 17 In patients with acquired" & @CRLF & _
"heart failure, interval training was shown to improve exercise" & @CRLF & _
"capacity more than continuous moderate exercise training. 22 Inter-" & @CRLF & _
"val training at moderate to high intensity (75%–95% of maximum" & @CRLF & _
"HR) was also reported to be safe and increase exercise capacity in" & @CRLF & _
"these patients. 15,18 To improve adherence to study protocol," & @CRLF & _
"home-based exercise training has been used in a number of previ-" & @CRLF & _
"ous studies. 17,23,24" & @CRLF & _
"Incremental cardiopulmonary exercise testing (incremental" & @CRLF & _
"CPET) on a cycle ergometer or treadmill is frequently used and often" & @CRLF & _
"considered the “gold standard” when evaluating aerobic exercise" & @CRLF & _
"capacity and change in aerobic capacity after intervention. 25,26" & @CRLF & _
"Changes in peak aerobic capacity, total exercise time and peak work" & @CRLF & _
"load are variables commonly used to report study results. 12 Constant" & @CRLF & _
"work rate CPET is a method commonly used to evaluate endurance" & @CRLF & _
"exercise capacity in patients with chronic obstructive pulmonary dis-" & @CRLF & _
"ease (COPD) 27 and it has emerged as the most responsive test" & @CRLF & _
"method to evaluate change in exercise capacity in these patients" & @CRLF & _
"after rehabilitation intervention. 28 At present, this test has not been" & @CRLF & _
"used to evaluate outcome of exercise training in the setting of adult" & @CRLF & _
"CHD." & @CRLF & _
"The present study was a randomized controlled trial that used" & @CRLF & _
"CPET aimed to evaluate the effect of home-based interval exercise" & @CRLF & _
"training on submaximal exercise capacity (endurance) and peak exercise" & @CRLF & _
"capacity (peak work load, peak oxygen uptake) in adults with complex" & @CRLF & _
"CHD. The hypothesis was that interval training increases endurance" & @CRLF & _
"capacity as well as peak exercise capacity in an intervention group" & @CRLF & _
"compared to a control group." & @CRLF & _
"2" & @CRLF & _
"|" & @CRLF & _
"METHODS" & @CRLF & _
"2.1" & @CRLF & _
"| Study population" & @CRLF & _
"Twenty-six patients (13 women) with complex CHD and reduced exer-" & @CRLF & _
"cise capacity were recruited from specialized units for adults with CHD" & @CRLF & _
"in the northern health care region (Umeå) and the region of Västra" & @CRLF & _
"G€ otaland (G€ oteborg) in Sweden. The inclusion criteria were complex" & @CRLF & _
"CHD, as defined by Erikssen et al., 1 (eg, palliated with variants of Fontan" & @CRLF & _
"procedure [Fontan/TCPC], pulmonary atresia [PA], tetralogy of Fallot" & @CRLF & _
"[ToF], congenitally corrected transposition of the great arteries [ccTGA]," & @CRLF & _
"dextro-transposition of the great arteries repaired with Mustard or Sen-" & @CRLF & _
"ning procedure [d-TGA]), clinically stable condition over the past 3" & @CRLF & _
"months, adult age (?18 years of age), and informed consent. The" & @CRLF & _
"patients with PA, as well as those with ToF, had undergone surgical" & @CRLF & _
"repair and were not cyanotic. The exclusion criteria were present strat-" & @CRLF & _
"egy for executing exercise training?2 times/week aimed at increasing" & @CRLF & _
"or sustaining exercise capacity, arrhythmia or other adverse events (eg," & @CRLF & _
"important symptoms, drop in blood pressure) at CPET, clinically relevant" & @CRLF & _
"arrhythmia, intellectual disability or mental illness affecting independent" & @CRLF & _
"decision making, extracardiac disease affecting physical activity, peak" & @CRLF & _
"VO 2 >30ml/kg/min at run-in CPET, or no internet access. At the time" & @CRLF & _
"of screening (October 25, 2012) the outpatient register of CHD in the" & @CRLF & _
"northern health care region, 391 patients were registered. Seventy-" & @CRLF & _
"seven patients met the inclusion criteria of complex CHD. Of these, 39" & @CRLF & _
"patients met at least one exclusion criteria. Thus, 38 patients were eligi-" & @CRLF & _
"ble and were asked to participate; 17 declined participation, 1 was" & @CRLF & _
"excluded due to arrhythmia (short periods of atrial fibrillation) and 1" & @CRLF & _
"was excluded due to peak VO 2 ?30 ml/kg/min at run-in CPET and 19" & @CRLF & _
"(53%) were finally included. There were no differences regarding age" & @CRLF & _
"and sex between those who declined participation and those who par-" & @CRLF & _
"ticipated. In the region of Västra G€ otaland, a convenience sample was" & @CRLF & _
"collected, that is, when patients fulfilling the inclusion criteria were" & @CRLF & _
"scheduled for a regular follow-up visit they were asked to participate." & @CRLF & _
"Thus, these patients were not strictly consecutively recruited. Eight" & @CRLF & _
"patients were tested with run-in CPET, of these 1 was excluded due to" & @CRLF & _
"arrhythmia. This gave an additional 7 patients. Finally, a total of 26" & @CRLF & _
"patients were included and were randomized to an exercise-training" & @CRLF & _
"group, that is, intervention group (n516), or a control group (n510)." & @CRLF & _
"Two patients that had been randomized to the intervention group dis-" & @CRLF & _
"continued study participation due to personal reasons. For another" & @CRLF & _
"patient, the exercise training was discontinued after 14 training sessions" & @CRLF & _
"due to the patient experiencing discomfort and possible arrhythmia." & @CRLF & _
"Therefore, 23 patients consisting of 13 in the intervention group and 10" & @CRLF & _
"in the control group were followed after intervention. All patients gave" & @CRLF & _
"their written informed consent for participation. The study was" & @CRLF & _
"approved by the regional Ethics Review Board in Umeå (Dnr 2011-51-" & @CRLF & _
"31 M, 2011-03-29, and 2012-143-32 M, 2012-04-04)." & @CRLF & _
"2.2" & @CRLF & _
"| Exercise capacity" & @CRLF & _
"At the incremental CPET peak VO 2 , peak work load, respiratory" & @CRLF & _
"exchange ratio (RER) and peak heart rate were registered. 25 To ensure" & @CRLF & _
"standardization, the participants were instructed that when rating ?17" & @CRLF & _
"SANDBERG ET AL ." & @CRLF & _
"|" & @CRLF & _
"255" & @CRLF & _
"(very hard) on the Borg Rated Perceived Exertion scale, 29 this corre-" & @CRLF & _
"sponded to perceived exertion of “not coping with an additional" & @CRLF & _
"increase of work load.” The subsequent endurance test, constant work" & @CRLF & _
"rate CPET, was performed at 75% of peak work load that had been" & @CRLF & _
"achieved at the initial incremental CPET. The exercise test duration" & @CRLF & _
"was the main outcome. 27,30 In one patient in the intervention group," & @CRLF & _
"the postintervention constant work rate CPET was not performed due" & @CRLF & _
"to technical issues. Therefore, for this patient we only used the incre-" & @CRLF & _
"mental CPET data. For pre- and postexercise tests the Jaeger Oxycon" & @CRLF & _
"Pro CareFusion (GmbH, Hoechberg, Germany) or Schiller CS-200 Ergo-" & @CRLF & _
"spirometry (Schiller AG, Baar, Switzerland) was used for analysis of" & @CRLF & _
"breathing-gases." & @CRLF & _
"2.3" & @CRLF & _
"| Randomization process" & @CRLF & _
"The present study was a two-armed randomized controlled trial." & @CRLF & _
"Patients were randomly assigned to intervention or control group in" & @CRLF & _
"the ratio of 2:1 that was applied by computer generated block random-" & @CRLF & _
"ization. The group allocation sequence was kept in an opaque, sealed," & @CRLF & _
"and stapled envelope to prevent prior knowledge, and was revealed to" & @CRLF & _
"patients and researchers after completion of run-in tests. At the first" & @CRLF & _
"center, the technicians performing the tests and the physician (MH)" & @CRLF & _
"analyzing the tests were blinded for group allocation. Furthermore, the" & @CRLF & _
"patients were instructed not to reveal their group allocation. At the" & @CRLF & _
"second center, the investigators were not blinded. However, the tests" & @CRLF & _
"strictly followed the prespecified protocol." & @CRLF & _
"2.4" & @CRLF & _
"| Exercise training protocol" & @CRLF & _
"The exercise training was home-based and was performed three times" & @CRLF & _
"a week for 12 weeks on a cycle ergometer with a manually adjusted" & @CRLF & _
"brake system (Tunturi T 20/Tunturi, Tunturi- Hellberg Oy Ltd, Åbo, Fin-" & @CRLF & _
"land or Bremshey BF3, Escalade Int. Ltd, Nottingham, UK). The time" & @CRLF & _
"between completion of the run-in tests, and start of intervention was" & @CRLF & _
"approximately 1 week due to delivery of the cycle ergometers. To indi-" & @CRLF & _
"vidually adjust the intensity of the exercise training protocol, the train-" & @CRLF & _
"ing heart rate (THR) was calculated according to the Karvonen method" & @CRLF & _
"based on the individual peak heart rate. 31 In addition to the heart rate" & @CRLF & _
"intervals, patients were instructed to achieve perceived exertion corre-" & @CRLF & _
"sponding to BORG 15–16. 29 All patients randomized to exercise train-" & @CRLF & _
"ing received one occasion with familiarization training. The exercise" & @CRLF & _
"training had an initial 8 min warm-up without load or with very low" & @CRLF & _
"load. During the first 2 weeks the protocol consisted of three intervals" & @CRLF & _
"at THR 75%-80%, and thereafter four intervals. The duration of the inter-" & @CRLF & _
"vals was also individually adjusted according to total exercise time dur-" & @CRLF & _
"ing the initial constant work rate CPET. When the total time at" & @CRLF & _
"constant work rate CPET was less than 5 minutes, the interval time" & @CRLF & _
"was calculated as total exercise time minus 1 minute. The maximum" & @CRLF & _
"interval time was 5 minutes. The intervals were separated by an active" & @CRLF & _
"recovery periods of 3 minutes without load or with very low load (Sup-" & @CRLF & _
"porting Information Figure S1). During the exercise training sessions," & @CRLF & _
"participants wore a heart rate monitor (Polar RS 300X, Polar Electro" & @CRLF & _
"Oy, Kempele, Finland). The registered heart rate was regularly" & @CRLF & _
"transferred to a personal webpage that was accessed by the physio-" & @CRLF & _
"therapist and participant. A weekly contact by phone was used to pro-" & @CRLF & _
"mote compliance, to provide feedback, and, when appropriate, to" & @CRLF & _
"increase training time if a shorter interval time than 5 minutes. The par-" & @CRLF & _
"ticipants were instructed to pay attention to symptoms such as dizzi-" & @CRLF & _
"ness, palpitations, chest pain, and other experiences of discomfort, and" & @CRLF & _
"if these occurred, abort exercise and contact investigators. The maxi-" & @CRLF & _
"mum number of training sessions was 36 and the goal was that every" & @CRLF & _
"participant should complete a minimum of 28 (78%) sessions. The" & @CRLF & _
"patients randomized to control group were instructed to continue with" & @CRLF & _
"their habitual physical activities." & @CRLF & _
"2.5" & @CRLF & _
"| Questionnaires" & @CRLF & _
"In addition to exercise test data, self-reported quality of life was eval-" & @CRLF & _
"uated using the EuroQol Vertical Visual Analogue Scale (EQ-VAS). 32" & @CRLF & _
"The Hospital Anxiety and Depression scale (HADS) 33,34 was used for" & @CRLF & _
"assessing prevalence of anxiety and depression. Finally, self-efficacy for" & @CRLF & _
"exercise was evaluated using the Exercise Self-Efficacy Scale (ESE). 35" & @CRLF & _
"All three scales are validated and were used preintervention and" & @CRLF & _
"postintervention." & @CRLF & _
"2.6" & @CRLF & _
"| Statistics" & @CRLF & _
"The data were tested for normality. Data are presented as mean 61" & @CRLF & _
"standard deviation (SD) or median with range (min-max). Differences" & @CRLF & _
"in means, ranks, and ratios were tested by Student’s t test, Mann-" & @CRLF & _
"Whitney U test, or chi-square test as appropriate. Paired samples t" & @CRLF & _
"test and Wilcoxon’s signed ranks test were applied for within group" & @CRLF & _
"comparisons. The null-hypothesis was rejected for P values<.05. All" & @CRLF & _
"calculations were performed using SPSS 22 (IBM, Armonk, NY," & @CRLF & _
"USA)." & @CRLF & _
"3" & @CRLF & _
"|" & @CRLF & _
"RESULTS" & @CRLF & _
"Twenty-three patients were analyzed after follow-up that included 13" & @CRLF & _
"in the intervention group and 10 in the control group. There were no" & @CRLF & _
"differences in baseline data between the intervention group and con-" & @CRLF & _
"trol group (Tables 1–3). In the population, the mean predicted peak" & @CRLF & _
"heart rate was 88%67.5% and the mean predicted peak VO 2 was" & @CRLF & _
"72%613.7%. Moreover, there were no differences between interven-" & @CRLF & _
"tion group and control group regarding these data." & @CRLF & _
"3.1" & @CRLF & _
"| Exercise capacity" & @CRLF & _
"The median test duration at constant work rate CPET increased 89%" & @CRLF & _
"post intervention in the intervention group compared to no change in" & @CRLF & _
"the control group (median[range] 12[–4 to 52] min vs 0[–4 to 5] min," & @CRLF & _
"P5.001). Furthermore, the peak workload (20[–10 to 70] W vs 0[–20" & @CRLF & _
"to 15] W, P5.003) at incremental CPET increased post intervention in" & @CRLF & _
"the intervention group compared to the controls. The peak VO 2 (ml/" & @CRLF & _
"min) at incremental CPET increased 15% within the intervention group" & @CRLF & _
"(P5.019) compared to no change (2%) within the control group" & @CRLF & _
"(P5.8). The results were similar regarding VO 2 indexed for body" & @CRLF & _
"256 | SANDBERG ET AL ." & @CRLF & _
"weight and peak O 2 pulse. However, in comparison between the inter-" & @CRLF & _
"vention group and control group no differences were found regarding" & @CRLF & _
"absolute peak VO 2 (ml/min) or peak VO 2 indexed to body weight (ml/" & @CRLF & _
"kg/min) (285[–200 to 535] ml/min vs 17[–380 to 306] ml/min, P5.10)" & @CRLF & _
"(3.6[–2.6 to 6.4] ml/kg/min vs 0.6[–3.5 to 4.9] ml/kg/min, P5.12)." & @CRLF & _
"Furthermore, the increase in peak O 2 pulse did not differ between" & @CRLF & _
"the groups (1.3[–1.7 to 4.2] ml/heartbeat vs 0.4[–1.2 to 2.4], P5.21" & @CRLF & _
"(Table 2, Figure 1A–D)." & @CRLF & _
"3.2" & @CRLF & _
"| EQ-VAS, HADS, and ESE" & @CRLF & _
"No differences were found within or between groups preintervention" & @CRLF & _
"and postintervention regarding self-reported QoL, prevalence of anxi-" & @CRLF & _
"ety and depression or exercise self-efficacy (Table 3)." & @CRLF & _
"3.3" & @CRLF & _
"| Compliance" & @CRLF & _
"Compliance to exercise training protocol, defined as the number of" & @CRLF & _
"completed training sessions in relation to the possible number of ses-" & @CRLF & _
"sions, was in mean 79%617 (median 83%, 47%–100%). The number" & @CRLF & _
"of registered exercise occasions ranged from 17 to 36 of 36 possible" & @CRLF & _
"occasions." & @CRLF & _
"3.4" & @CRLF & _
"| Adverse event" & @CRLF & _
"In one case, the exercise training was discontinued due to the patient" & @CRLF & _
"experiencing discomfort and possible arrhythmia during a session of" & @CRLF & _
"exercise training. No arrhythmia was detected on a subsequent exer-" & @CRLF & _
"cise test or at Holter registration. No other adverse events occurred." & @CRLF & _
"TABLE 1 Descriptive data on included patients" & @CRLF & _
"All patients (n523) Intervention group (n513) Controls (n510) P value" & @CRLF & _
"Sex" & @CRLF & _
"M n (%) 12(52) 8(62) 4(40) .31" & @CRLF & _
"F n (%) 11(48) 5(39) 6(60)" & @CRLF & _
"Age, years Median(IQR) 30.1(22.9–36.6) 31.3(26.9–36.6) 26.3(22.9–35.6) .38" & @CRLF & _
"Height, m Mean6SD 1.72(0.10) 1.72(0.09) 1.72(0.10) .85" & @CRLF & _
"Weight, kg Mean6SD 77(15) 77(10) 76(21) .90" & @CRLF & _
"BMI, kg/m 2 Mean6SD 25.8(3.9) 26.0(3.6) 25.5(4) .77" & @CRLF & _
"Diagnosis n (%)" & @CRLF & _
"ToF 5(22) 4(31) 1(10) .19" & @CRLF & _
"ccTGA 3(13) 3(23) 0(0)" & @CRLF & _
"d-TGA 5(22) 2(15) 3(30)" & @CRLF & _
"TCPC 5(22) 3(23) 2(20)" & @CRLF & _
"PA 2(9) 0(0) 2(20)" & @CRLF & _
"Complete AV-septal defect 1(4) 0(0) 1(10)" & @CRLF & _
"Ebstein 1(4) 0(0) 1(10)" & @CRLF & _
"Miscellaneous 1(4) 1(8) 0(0)" & @CRLF & _
"Surgical intervention, yes n (%) 21(91) 11(85) 10(100) .19" & @CRLF & _
"Age at intervention, years* median(IQR) 3.1(1.1–6.8) 3.6(1.2–7.6) 3.0(0.7-6.1) .74" & @CRLF & _
"PM, yes n (%) 2(9) 2(15) 0(0) .19" & @CRLF & _
"Cardiovascular medication, yes n (%) 10(44) 5(39) 5 (50) .58" & @CRLF & _
"ACE/ARB n (%) 6(26) 4(31) 2(20) .56" & @CRLF & _
"Beta-blockers n (%) 2(9) 1(8) 1(10) .85" & @CRLF & _
"Diuretics n (%) 2(9) 1(8) 1(10) .85" & @CRLF & _
"Warfarin n (%) 5(22) 3(23) 2(20) .86" & @CRLF & _
"Aspirin n (%) 3(13) 2(15) 1(10) .70" & @CRLF & _
"Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor-2 blockers; AV, atrioventricular; ccTGA, congenitally corrected transposi-" & @CRLF & _
"tion of the great arteries; d-TGA, dextro-transposition of the great arteries; F, female; IQR, interquartile range; M, male; n, number; PA, pulmonary atre-" & @CRLF & _
"sia; PM, pacemaker; TCPC, total cavo-pulmonary connection; ToF, tetralogy of Fallot." & @CRLF & _
"*Age at TCPC surgery or correction or ToF. Presented P values represent comparison between intervention group and controls. Mann-Whitney U test" & @CRLF & _
"was applied in comparison of age and age at intervention; in all other comparisons chi-square or Student’s t test was used." & @CRLF & _
"SANDBERG ET AL ." & @CRLF & _
"|" & @CRLF & _
"257" & @CRLF & _
"4" & @CRLF & _
"|" & @CRLF & _
"DISCUSSION" & @CRLF & _
"This is the first study to evaluate endurance capacity in addition to" & @CRLF & _
"peak aerobic capacity after exercise training in adults with complex" & @CRLF & _
"CHD. The present study shows that home-based high intensity interval" & @CRLF & _
"training on a cycle ergometer has a great impact on endurance capacity" & @CRLF & _
"as well as on maximum exercise capacity in adults with complex CHD." & @CRLF & _
"4.1" & @CRLF & _
"| Exercise capacity" & @CRLF & _
"Peak VO 2 (ml/min) increased within the intervention group but not in" & @CRLF & _
"comparison to the control group. However, the peak work rate for the" & @CRLF & _
"intervention group increased in comparison to the control group which" & @CRLF & _
"altogether indicates an improvement in peak aerobic capacity. The" & @CRLF & _
"increase in peak VO 2 in previous studies was approximately 8%, 14,15,18" & @CRLF & _
"and in the present study the corresponding increase within the inter-" & @CRLF & _
"vention group was 15%. An increase in aerobic capacity could be of" & @CRLF & _
"significance in daily activities. In patients with complex congenital heart" & @CRLF & _
"lesions, especially with impaired NYHA class, activities of daily living" & @CRLF & _
"might be in line with or even exceed their individual exercise capacity. 5" & @CRLF & _
"In these cases, an exercise training induced improvement of exercise" & @CRLF & _
"capacity could play an important role in coping with activities of daily" & @CRLF & _
"living. In adults with complex CHD, the central adaption to exercise" & @CRLF & _
"training is usually blunted, 36,37 which might lead peripheral mecha-" & @CRLF & _
"nisms, that is, increased muscle capillarization and oxidative capacity, to" & @CRLF & _
"play an even greater role in the response to exercise training. 38 The" & @CRLF & _
"important increase in endurance capacity may actually reflect this" & @CRLF & _
"mechanism. It is noteworthy that modest increases in peak VO 2 (ml/" & @CRLF & _
"min) and peak work rate after exercise training corresponded to a sub-" & @CRLF & _
"stantial increase in time duration at constant work rate CPET; this" & @CRLF & _
"result was previously reported in patients with COPD. 28,39 Our results" & @CRLF & _
"imply that endurance capacity might be a more clinically relevant mea-" & @CRLF & _
"sure of change in exercise capacity after exercise training in adults with" & @CRLF & _
"complex CHD." & @CRLF & _
"4.2" & @CRLF & _
"| Exercise testing" & @CRLF & _
"Peak VO 2 derived from incremental CPET is frequently used and often" & @CRLF & _
"considered the “gold standard” measure of peak aerobic exercise" & @CRLF & _
"capacity. 25,26 When assessing the peak aerobic exercise capacity, it is" & @CRLF & _
"important that the test is performed with maximum effort. The" & @CRLF & _
"RER?1.10 is considered as a measure of maximum effort being" & @CRLF & _
"reached. 25 In the present study, this limit was reached by the majority" & @CRLF & _
"of the participants (Table 2). However, in adults with complex CHD dif-" & @CRLF & _
"ficulties in reaching this limit was previously reported. 6,40 This phenom-" & @CRLF & _
"enon was to some extent also observed in our population. Pulmonary" & @CRLF & _
"limitation of the exercise capacity has been proposed to cause this lim-" & @CRLF & _
"ited ability to reach RER ?1.10. 25 Recently, submaximal outcome" & @CRLF & _
"measures calculated from the incremental CPET, that is, ventilatory" & @CRLF & _
"anaerobic threshold (VAT), oxygen uptake efficiency slope (OUES), and" & @CRLF & _
"VE/VCO 2 slope, have emerged as useful in evaluation of exercise" & @CRLF & _
"capacity and as prognostic tools. Furthermore, these parameters do not" & @CRLF & _
"require a test performed with maximum effort. 26,40,41 In our study, we" & @CRLF & _
"TABLE 2 Preintervention, postintervention, and change in cardiopulmonary exercise test data in intervention group vs control group" & @CRLF & _
"Preintervention Postintervention Change after intervention" & @CRLF & _
"Intervention group Control group P Intervention group Control group P Intervention group Control group P" & @CRLF & _
"CPET incremental" & @CRLF & _
"VO 2 peak, ml/min 1865 (1191–2355) 1601 (1215–2650) .74 1870 (1040–2642) 1688 (1326–2367) .26 285 (–200 to 535) 17 (–380 to 306) .10" & @CRLF & _
"VO 2 peak, ml/kg/min 23.4 (14.8–29.4) 23.6 (18.1–28.1) .98 26.9 (13.0–33.6) 24.8 (18.1–28.4) .23 3.6 (–2.6 to 6.4) 0.6 (–3.5 to 4.9) .12" & @CRLF & _
"Peak O 2 pulse, ml/heartbeat 10.3 (7.3–13.7) 9.5 (6.8–15.1) .99 12.0 (8.3–15.0) 10.8 (8.2–14.0) .48 1.3 (–1.7 to 8.5) 0.4 (–1.2 to 2.4) .21" & @CRLF & _
"Peak workload, W 155 (100–220) 150 (110–200) .69 170 (90–240) 140 (110–200) .07 20 (–10 to 70) 0 (–20 to 15) .003" & @CRLF & _
"RER 1.19 (0.99-1.51) 1.22 (1.02-1.36) .61 1.20 (1.13-1.40) 1.20 (0.98-1.29) .52" & @CRLF & _
"Constant work rate at 75% of peak workload:" & @CRLF & _
"Test duration min 14 (4–33) 9 (3–20) .11 28 (8–68) 9 (5–16) .001 12 (–4 to 52) 0 (–4 to 5) .001" & @CRLF & _
"Abbreviations: CPET, cardiopulmonary exercise test; RER, respiratory exchange ratio." & @CRLF & _
"Data are presented as median (range). Bold text indicates a P value<.05." & @CRLF & _
"258 | SANDBERG ET AL ." & @CRLF & _
"took this a step further and used a submaximal exercise test in addition" & @CRLF & _
"to the incremental CPET and found a substantially larger (median" & @CRLF & _
"change 12 min, 89%) increase in submaximal exercise capacity in com-" & @CRLF & _
"parison to peak VO 2 (15%). With reference to the patients’ perform-" & @CRLF & _
"ance capacity in daily activities, increased endurance might better" & @CRLF & _
"illustrate the benefits of improved aerobic capacity and thereby be a" & @CRLF & _
"more clinically relevant measure. The increase in endurance capacity" & @CRLF & _
"we found is in line with previous studies in patients with COPD. Pors-" & @CRLF & _
"zasz et al. 39 reported a mean increase of 11.668.1 minutes in duration" & @CRLF & _
"at constant work rate CPET after exercise training, while Cambach" & @CRLF & _
"et al. 42 reported a mean increase of approximately 7 minutes in dura-" & @CRLF & _
"tion. An increase of 1.6–3.3 minutes has been suggested as a minimal" & @CRLF & _
"clinically important difference in response to exercise training in" & @CRLF & _
"patients with COPD. 43,44 In our intervention group, all patients except" & @CRLF & _
"one increased the time duration at constant work rate CPET above this" & @CRLF & _
"suggested level of minimal clinical importance. This particular patient" & @CRLF & _
"did not comply fully with the exercise training protocol fulfilling only" & @CRLF & _
"17 of 36 (47%) of the possible exercise training sessions." & @CRLF & _
"4.3" & @CRLF & _
"| Exercise training protocol" & @CRLF & _
"As stated in the current recommendations on physical activity and rec-" & @CRLF & _
"reational sports in adults with CHD, exercise prescriptions should be" & @CRLF & _
"individualized. 11 We aimed to provide the patients in the intervention" & @CRLF & _
"group with an individually adjusted exercise training protocol based on" & @CRLF & _
"the results of the cardiopulmonary exercise tests. Different modes of" & @CRLF & _
"exercise training, for example, walking, interval training with step aero-" & @CRLF & _
"bics, and moderate continuous training on a cycle ergometer have been" & @CRLF & _
"used in previous studies. 17,18,23,24 The present study is the first to use" & @CRLF & _
"home-based moderate to high intensity interval exercise training on a" & @CRLF & _
"cycle ergometer in a population of adults with different complex con-" & @CRLF & _
"genital heart lesions. Studies in adults with systemic right ventricle" & @CRLF & _
"have shown that home-based exercise training is safe, feasible and" & @CRLF & _
"effective with regard to exercise capacity without negative effects on" & @CRLF & _
"the systemic right ventricle. 17,18,24 In patients with heart failure, inter-" & @CRLF & _
"val training was reported to improve exercise capacity more than a" & @CRLF & _
"moderate continuous exercise training mode. 22 The present study" & @CRLF & _
"FIGURE 1 A-D, Individual cardiopulmonary exercise test data at baseline, at 12-week follow-up and change from baseline to follow-up in" & @CRLF & _
"intervention group" & @CRLF & _
"TABLE 3 Preintervention, postintervention and change in data regarding self-reported prevalence of anxiety and depression (HADS), quality" & @CRLF & _
"of life (EQ5D VAS), and exercise self-efficacy (ESE)" & @CRLF & _
"Preintervention Postintervention Change after intervention" & @CRLF & _
"Intervention" & @CRLF & _
"group Control group P" & @CRLF & _
"Intervention" & @CRLF & _
"group" & @CRLF & _
"Control" & @CRLF & _
"group P" & @CRLF & _
"Intervention" & @CRLF & _
"group Control group P" & @CRLF & _
"HADS Anxiety 4(1–9) 4(0–7) .69 5(2–9) 6(0–8) .72 1(–3 to 3) 1(0–3) .28" & @CRLF & _
"HADS Depression 2(0–9) 2(0–5) .26 2(0–5) 2(0–6) .97 0(–4 to 2) 0(–1 to 4) .18" & @CRLF & _
"EQ-VAS 77.5(35.0–99.0) 89.5(70.0–99.0) .10 78.8(48.0–99.0) 85.5(35.0–99.0) .31 0(–21.0 to 25.0) 0(–55.0 to 9.0) .42" & @CRLF & _
"ESE 32(16–39) 30(15–40) .88 28(11–40) 29(18–40) .67 25(–12 to 8) 21(–6 to 6) .23" & @CRLF & _
"Abbreviations: EQ-VAS, EuroQol Vertical Visual Analogue Scale; ESE, Exercise Self-Efficacy Scale; HADS, Hospital and Anxiety and Depression scale." & @CRLF & _
"Data are presented as median (range)." & @CRLF & _
"SANDBERG ET AL ." & @CRLF & _
"|" & @CRLF & _
"259" & @CRLF & _
"showed that home-based interval exercise training increased endur-" & @CRLF & _
"ance capacity as well as peak aerobic exercise capacity in adults with" & @CRLF & _
"complex congenital heart lesions. The finding of markedly increased" & @CRLF & _
"endurance capacity, in addition to peak capacity, contributes important" & @CRLF & _
"information to previous exercise training studies in this population." & @CRLF & _
"4.4" & @CRLF & _
"| Quality of life" & @CRLF & _
"In CHD, self-reported quality of life is known to be associated with" & @CRLF & _
"physical activity level. 45 Here, we report that self-reported quality of" & @CRLF & _
"life remained unchanged after intervention which is in line with results" & @CRLF & _
"previously shown by others. 15 In contrast, positive effects of exercise" & @CRLF & _
"on quality of life has been reported. 23 The population in the present" & @CRLF & _
"study rated their quality of life as rather high preintervention which" & @CRLF & _
"might explain the unchanged results." & @CRLF & _
"4.5" & @CRLF & _
"| Compliance" & @CRLF & _
"As many patients with complex heart lesions are in the “middle of life”" & @CRLF & _
"and occupied with studies, work, children, and family activities, a" & @CRLF & _
"home-based exercise training protocol was chosen to improve adher-" & @CRLF & _
"ence to study protocol. In addition, participants were contacted by" & @CRLF & _
"phone every week, which probably also contributed to compliance. The" & @CRLF & _
"mean compliance in the present study (79%) was in line with previously" & @CRLF & _
"presented results (68%-77%). 14,17,18" & @CRLF & _
"4.6" & @CRLF & _
"| Limitations" & @CRLF & _
"As in previously presented studies on exercise training in adults with" & @CRLF & _
"CHD, our study population was rather small which somewhat limits the" & @CRLF & _
"generalizability of the results. However, the results are in line with pre-" & @CRLF & _
"vious studies which further strengthen exercise training as a part of the" & @CRLF & _
"rehabilitation of adults with complex CHD. Furthermore, our study" & @CRLF & _
"population consisted of patients with different complex diagnoses that" & @CRLF & _
"to a greater extent reflect the diversity seen in the clinic, thus enhanc-" & @CRLF & _
"ing the generalizability." & @CRLF & _
"This study was performed at two centers. The center recruiting 5" & @CRLF & _
"patients (22%) was not able to keep the investigators performing the" & @CRLF & _
"exercise tests strictly blinded for group allocation. However, there was" & @CRLF & _
"a prespecified protocol that was strictly followed in both centers. Fur-" & @CRLF & _
"thermore, the same center had a different recruitment strategy that" & @CRLF & _
"possibly could involve patients with more frequent clinical visits and" & @CRLF & _
"thus potentially patients with more complex lesions. However, the" & @CRLF & _
"numbers are small and the two patients performing the exercise proto-" & @CRLF & _
"col did not obviously differ from the rest of the study population." & @CRLF & _
"One concern of the constant work rate CPET that has been dis-" & @CRLF & _
"cussed previously in patients with COPD is the power/duration rela-" & @CRLF & _
"tionship. 28 This means that the endurance time varies depending on" & @CRLF & _
"the workload (power) used during the test. However, there is no con-" & @CRLF & _
"sensus on optimal power to use which complicates comparison of" & @CRLF & _
"results between studies. To standardize, we used 75% of peak work" & @CRLF & _
"rate that was used previously in COPD patients. 39,42" & @CRLF & _
"4.7" & @CRLF & _
"| Conclusions" & @CRLF & _
"Home-based interval exercise training increased the endurance" & @CRLF & _
"capacity at 75% of peak work load by 12 minutes as well as peak exer-" & @CRLF & _
"cise capacity in adults with different complex congenital heart lesions." & @CRLF & _
"Substantially increased endurance capacity in the spectrum of daily" & @CRLF & _
"activities is what most patients need. Therefore, endurance capacity" & @CRLF & _
"might be a more clinically relevant target than solely peak oxygen" & @CRLF & _
"uptake in patients with complex congenital heart lesions." & @CRLF & _
"ACKNOWLEDGMENT" & @CRLF & _
"We are grateful to the personnel at the department of Clinical Phys-" & @CRLF & _
"iology at the Heart Center, Umeå University Hospital who con-" & @CRLF & _
"ducted the exercise tests and to the staff at the GUCH-center in" & @CRLF & _
"G€ oteborg." & @CRLF & _
"CLINICAL TRIAL REGISTRATION" & @CRLF & _
"ClinicalTrials.gov, identification:NCT01671566" & @CRLF & _
"CONFLICT OF INTEREST" & @CRLF & _
"None" & @CRLF & _
"AUTHOR CONTRIBUTIONS" & @CRLF & _
"All authors read and approved the final version of the manuscript." & @CRLF & _
"Concept/design: Camilla Sandberg, Magnus Hedstr€ om, Karin Wadell," & @CRLF & _
"Mikael Dellborg, Bengt Johansson" & @CRLF & _
"Data collection: Camilla Sandberg, Magnus Hedstr€ om, Mikael Dell-" & @CRLF & _
"borg, Anders Ahnfelt, Anna-Klara Zetterstr€ om Amanda" & @CRLF & _
"€" & @CRLF & _
"Ohrn, Bengt" & @CRLF & _
"Johansson" & @CRLF & _
"Data analysis: Camilla Sandberg, Magnus Hedstr€ om, Mikael Dellborg," & @CRLF & _
"Bengt Johansson" & @CRLF & _
"Interpretation: Camilla Sandberg, Magnus Hedstr€ om, Mikael Dellborg," & @CRLF & _
"Anders Ahnfelt, Bengt Johansson" & @CRLF & _
"Drafting: Camilla Sandberg, Karin Wadell, Bengt Johansson" & @CRLF & _
"Critical revision: Camilla Sandberg, Magnus Hedstr€ om, Karin Wadell," & @CRLF & _
"Mikael Dellborg, Anders Ahnfelt, Anna-Klara Zetterstr€ om, Amanda" & @CRLF & _
"€" & @CRLF & _
"Ohrn, Bengt Johansson" & @CRLF & _
"Approval of article: Camilla Sandberg, Magnus Hedstr€ om, Karin" & @CRLF & _
"Wadell, Mikael Dellborg, Anders Ahnfelt, Anna-Klara Zetterstr€ om," & @CRLF & _
"Amanda" & @CRLF & _
"€" & @CRLF & _
"Ohrn, Bengt Johansson" & @CRLF & _
"ORCID" & @CRLF & _
"Camilla Sandberg RPT, PhD http://orcid.org/0000-0002-4043-7130" & @CRLF & _
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Local $aArray = StringRegExp($sString, $sRegex, $STR_REGEXPARRAYGLOBALFULLMATCH)
Local $aFullArray[0]
For $i = 0 To UBound($aArray) -1
_ArrayConcatenate($aFullArray, $aArray[$i])
Next
$aArray = $aFullArray
; Present the entire match result
_ArrayDisplay($aArray, "Result")
Please keep in mind that these code samples are automatically generated and are not guaranteed to work. If you find any syntax errors, feel free to submit a bug report. For a full regex reference for AutoIt, please visit: https://www.autoitscript.com/autoit3/docs/functions/StringRegExp.htm