Aneurysm CaRe ­– Randomized Controlled Feasibility Trial of Cardiac Rehabilitation versus Standard Care After Aortic Aneurysm Repair

Aneurysm CaRe ­– Randomized Controlled Feasibility Trial of Cardiac Rehabilitation versus Standard Care After Aortic Aneurysm Repair | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Aneurysm CaRe ­– Randomized Controlled Feasibility Trial of Cardiac Rehabilitation versus Standard Care After Aortic Aneurysm Repair Michal Kawka, Sandeep S Bahia, Matthew Bown, Iain Roy, Ian Loftus, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6464370/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background & Aims Abdominal and thoracic aortic aneurysms (A/TAA) are a major cause of mortality in older adults. Most deaths post-A/TAA repair result from cardiovascular events, which may be preventable with cardiac rehabilitation (CR) – a multidisciplinary approach to cardiovascular recovery. The feasibility and acceptability of CR in A/TAA patients remain unknown. Methods This 1:1, non-blinded feasibility randomised trial compared CR to standard care (SC) after elective A/TAA repair at two UK tertiary centres. Patients <50 years, diagnosed with connective tissue disorders, or deemed too unfit for CR were excluded at screening. The CR group followed an 8-week structured programme focusing on medical risk reduction, supervised exercise, and lifestyle modification. Co-primary outcomes were enrolment (target: 60.0%) and CR compliance (target: 70.0%). Secondary outcomes included major cardiac events, cardiovascular biomarkers, echocardiography, lifestyle, and quality of life metrics. This trial was supported by a British Heart Foundation Grant (PG/13/98/30490). Results From September 2014 – September 2015, 159 patients were screened, 97 were eligible, and 68 (70.1%) were randomised (SC: 34, CR: 34). CR adherence was 61.8% (n=21), with 13 withdrawals, primarily due to travel and personal commitments (69.2%). At 36 weeks, CR participants maintained higher physical activity levels (40 min vs. 30 min, p = 0.042). Conclusion Recruiting patients after A/TAA repair to CR is feasible, with good adherence. Virtual or video-based CR may help overcome barriers related to accessing CR. Trial registration ISRCTN (65746249). Cardiac & Cardiovascular Systems Figures Figure 1 Figure 2 Introduction Advances in both surgical techniques and peri-operative care have significantly reduced the short-term mortality associated with elective abdominal and thoracic aortic aneurysm (A/TAA) repair ( 1 ). However, the established enhanced short-term survival has, to date, not translated into improved long-term outcomes ( 2 ). Compared to matched contemporaries without aneurysmal disease, patients who require elective A/TAA repair experience a distinct increase in adverse cardiac events (ACE), strokes and amputation; there is an associated reduction in 5-year-survival from 81% for controls to 67% in the A/TAA repair population ( 3 , 4 ). This is also true when age-matched controls are compared with patients with aneurysmal disease; the latter have higher cardiovascular risk burden. Up to 60% of deaths in this cohort are attributable to cardiovascular disease, contributing substantially to their relative reduction in long-term survival ( 5 ). A/TAA is an uncommon but serious phenotype of the advanced atherosclerotic disease observable in this patient population. Despite this, the proportion of A/TAA repaired patients that are prescribed prognostically beneficial medications such as antiplatelets, statins and anti-hypertensive medications is sub-optimal ( 6 ). What is more, there is scope in improving their lifestyle risk factors, such as exercise level, and smoking. As such, these observations suggest that patients undergoing elective A/TAA repair might derive long-term benefit from post-operative protocolised cardiac rehabilitation. Cardiac rehabilitation (CR) is a multidisciplinary, biopsychosocial approach to the promotion of recovery from cardiovascular disease ( 7 ). The World Health Organisation (WHO) defines it as the ‘sum of activities required to influence favourably the underlying cause of the disease, as well as to provide the best possible physical, mental and social conditions, so that the patients may, by their own efforts, preserve or resume when lost, as normal a place as possible in the community’. To achieve this, CR is typically delivered over 8–12 weeks, combining supervised exercise, dietary & lifestyle modifications, smoking cessation, and optimisation of medical therapy for cardiovascular risk factors ( 8 ). CR has been shown to be an important, cost-effective intervention in the management of coronary heart disease ( 9 ), peripheral arterial disease ( 10 ), and heart failure ( 11 ). As such, a Cochrane review recommended trialled use of CR be widened to other populations with severe cardiovascular disease ( 12 ). The proven CR derived benefit in cardiothoracic patient populations is encouraging of the potential for similar benefit to be seen in A/TAA repair patients. However, the feasibility of performing CR in A/TAA repair patients is not yet known. A/TAA repair patients not only experience more major adverse cardiac events (MACE) than their counterparts without aneurysms, but are typically approximately 10 years older than patients currently recruited to CR ( 11 , 12 ). Therefore, the primary aim of this randomised feasibility study is to enrol a sufficient number of patients to ensure CR is both feasible and acceptable to patients post A/TAA repair. Secondary outcome measures include assessment of mortality, rate of MACE, biochemical markers of cardiovascular risk, behavioural and biometric changes and measures of patient quality of life (QoL). Methods Study design and participants This study was designed as a feasibility, randomised trial, comparing Cardiac Rehabilitation (CR) and Standard Care (SC) after elective A/TAA repair. Patients were enrolled from two secondary care sites in the UK: St George’s Vascular Institute in London and University Hospitals of Leicester NHS Trust according to a previous published trial protocol ( 13 ). All patients gave informed written consent. The protocol was approved by the NRES Committee (London, Bloomsbury, ref 13/LO/0395). The trial is registered with the ISRCTN: 65746249. This study was conducted according to the CONSORT statement for pilot and feasibility RCTs ( 14 ). Randomisation After informed consent was obtained, patients discharged from hospital after elective aortic aneurysm (thoracic or abdominal) repair were randomised in a 1:1 ratio into the intervention arm (CR) and the control arm (SC). A minimisation algorithm was utilised to ensure stratification variables (age, gender and study site) were balanced between groups. This was performed using a secure Internet-based central randomisation through an NIHR-accredited clinical trials unit (King’s Clinical Trials Unit) using a minimisation algorithm. Neither investigators nor patients were blinded to treatment. Intervention Patients randomised to CR were seen by a member of the Cardiac Rehabilitation team either before discharge, if possible, or at the induction CR meeting 4–6 weeks after A/TAA repair. They received a nationalised, protocolised approach to intensive medical risk factor reduction and enrolment in the local multimodal CR programme; an 8 week regime of supervised exercise, lifestyle modification, dietary interventions, psychological assessment and medical risk modification. In brief, each weekly session took 1 to 2 hours and was supervised by two nurses trained in CR, two qualified physiotherapists and one occupational therapy technician. Each session began with a blood pressure and heart rate measurement and a review of each patient’s progress to date. The group then proceeded through a supervised warm-up of 10–15 minutes, followed by the main exercise session of 45 minutes. This was followed by a warm-down, and finally further blood pressure and heart rate measurements. Patients randomised to the SC arm received routine post-operative out-patient appointments and/or follow-up scans as necessary with GP-based management of their co-existing co-morbidities (e.g. hypertension, smoking). The trial structure can be seen in Supplementary Fig. 1. Inclusion and exclusion criteria All patients discharged home after undergoing elective thoracic or abdominal aortic aneurysm repair during the recruitment period were eligible for the study. Patients were excluded if they were: Under the age of 50 years; Diagnosed with a connective tissue disease (e.g. Marfan’s and Loeys-Dietz syndromes); Unable or unwilling to consent to participation or attend CR sessions; Deemed too unfit for the CR programme by the Lead CR nurse; Undergoing expedited or emergent surgical intervention for symptomatic or ruptured aortic aneurysms. Sample size We planned to approach 140 patients for consent, and estimated the feasibility trial will recruit 84 patients, based on the assumption that at least 60% (95% CI 50.7–68.8%) of approached patients will agree to take part. The lower margin of the 95% confidence interval for this enrolment rate (50.7%) provides adequate precision to establish that at least 50% of aortic aneurysm patients will agree to participate in an RCT of CR; establishing the feasibility of a definitive multi-centre national RCT. Outcomes measures The co-primary outcome measures of the study were: Enrolment: the proportion of patients following A/TAA repair meeting the inclusion criteria and agreeing to enrolment in the trial. We expected that at least 60.0% of patients (95% CI, 50.7%-68.8%) agree to enrol. Compliance with CR therapy in the group randomised to this arm. This was defined as the proportion of patients demonstrating attendance at 100% of scheduled CR sessions over 8 weeks. We expected that 70.0% of patients (95% CI, 55%-84%) attend all CR sessions. Secondary outcome measures were: Mortality: collected using screening of patient records at their treatment hospital and validated through contact with the patient’s GP. Presence of first Major Adverse Cardiac Event (MACE); a composite end point of myocardial infarction, stroke, and cardiac or limb revascularisation. Collected using screening of patient records at their treatment hospital and validated through contact with the patient’s GP. Presence, and severity of non-cardiovascular adverse events. Change in measures of plasma biochemical cardiac risk factors; Sodium, Potassium, Creatinine, Homocysteine, Troponin, hsCRP, BNP, Fibrinogen, HbA1C, Total lipids, HDL, LDL, Triglycerides. Change in urine biochemical cardiac risk factors; urine albumin, urine creatinine, albumin: creatinine ratio. Change in echocardiographic parameters; left ventricle end systolic diameter (cm), left ventricle end diastolic diameter (cm), pulmonary artery pressure (mmHg), LV fractional shortening (%), Max Ascending Aorta Diameter (cm), LVOT Diameter (cm), Max sinus of Valsalva (cm), Max aortic arch diameter (cm), presence of regional wall motion abnormalities, presence, and severity of valvular pathologies. Change in indicators of patient behaviour and lifestyle related to cardiac risk factors; CO breath test, ABPI, Systolic BP, Diastolic BP, Toe Pressure, Heart Rate, Physical activity, Waist to Hip Ratio, BMI. Smoking habit data, including salivary contin. Change in patient reported outcome measures and quality of life; collected using the EQ5D-5L questionnaire ( 15 ). Patients that did not wish to participate in the study were surveyed to look at their reasons for non-participation using structured questionnaires. Statistical analysis Statistical analysis was performed in R Version 4.3.2 (R Core Team, 2014). Categorical variables were presented as count and compared with the chi square test (χ²). Continuous variables were presented as Median [Range], longitudinal difference was analysed using one way ANOVA for continuous variables, and Kruskal Wallis test for categorical variables. When significance was detected on longitudinal analysis, Tukey’s HSD (continuous) or Benjamini-Hochberg correction (categorical) was used to analyse pairwise comparisons between time-points. P-values of less than 0.05 were considered statistically significant. Role of funding This trial was supported by a British Heart Foundation Project Grant (PG/13/98/30490). The funder had no role in the study design, data collection, data analysis, manuscript preparation and publication decisions Results Demographics, enrolment, and compliance. Between September 2014 and September 2015, 159 patients were assessed for eligibility. Of the 159 patients, 62 were non-eligible to participate (1 patient was under age of 50, and 61 were deemed too unfit for CR programme at screening). Of the remaining 97 patients, 68 (70.1%) were randomised into SC (n = 34) or CR (n = 34), whilst 29 did not want to participate (29.9%). 13 (38.2%) individuals withdrew from the CR arm and 6 (17.6%) from the SC arm (Fig. 1). Of the 13 patients that withdrew from the CR arm 6 withdrew before any CR visits, and 7 withdrew after CR pre-assessment. 17 (81.0%) of the 21 remaining patients in the CR group attended all eight CR sessions. Figure 1 – CONSORT diagram for feasibility randomised controlled trial of cardiac rehabilitation vs. standard care after aortic aneurysm repair. Baseline demographics of both the CR and SC arms are shown in Table 1 . The groups were comparable in terms of age, sex, BMI, smoking status, ASA grade, and cardiovascular co-morbidities. Majority of patients had diagnosis of hypertension (n = 47, 69.1%), and hypercholesterolaemia (n = 50, 73.5%), with a significant proportion having previous MI (n = 16, 23.5%). Patient were taking 6.81 medications on average, with majority of patients taking an antiplatelet (n = 67, 98.5%), and a statin (n = 63, 92.6%). In the 12 month preceding surgery, patients attended 2.42 hospital appointments. Non-cardiac comorbidities, medication, and socioeconomic baseline data is presented in Supplementary Tables 1–3 . Table 1 Baseline demographics of patients randomised into the trial. SD – Standard Deviation. ASA – American Society of Anaesthesiologists. BMI – Body Mass Index. MI – Myocardial Infarction. PCI – Primary Coronary Intervention. CABG – Coronary Artery Bypass Grafting. TIA – Transient Ischaemic Attack. CVA – Cerebrovascular Accident. T1DM – Type 1 Diabetes Mellitus. T2DM – Type 2 Diabetes Mellitus Cardiac Rehab (N = 34) Standard Care (N = 34) Overall (N = 68) Age (years) Median [Min, Max] 73.4 [62.3, 87.4] 76.7 [65.6, 89.3] 74.4 [62.3, 89.3] Gender Male 33 (97.1%) 33 (97.1%) 66 (97.1%) Female 1 (2.9%) 1 (2.9%) 2 (2.9%) BMI Mean (SD) 26.9 (4.62) 27.1 (6.12) 27.0 (5.39) Median [Min, Max] 26.7 [15.5, 35.6] 28.4 [1.18, 37.7] 26.8 [1.18, 37.7] ASA Grade 1 0 (0.0%) 1 (2.9%) 1 (1.5%) 2 5 (14.7%) 3 (8.8%) 8 (11.8%) 3 19 (55.9%) 19 (55.9%) 38 (55.9%) 4 7 (20.6%) 10 (29.4%) 17 (25.0%) Missing 3 (8.8%) 1 (2.9%) 4 (5.9%) Smoking History Current 6 (17.6%) 6 (17.6%) 12 (17.6%) Ex-Smoker 18 (52.9%) 18 (52.9%) 36 (52.9%) Non Smoker 6 (17.6%) 10 (29.4%) 16 (23.5%) Missing 4 (11.8%) 0 (0.0%) 4 (5.9%) Site Leicester 9 (26.5%) 9 (26.5%) 18 (26.5%) St George’s 25 (73.5%) 25 (73.5%) 50 (73.5%) Cardiovascular Co-Morbidities Hypertension 21 (61.8%) 26 (76.5%) 47 (69.1%) Hypercholesterolemia 22 (64.7%) 27 (79.4%) 49 (72.1%) Angina 1 (2.9%) 3 (8.8%) 4 (5.9%) Previous MI 8 (23.5%) 8 (23.5%) 16 (23.5%) Previous PCI 3 (8.8%) 6 (17.6%) 9 (13.2%) Previous CABG 7 (20.6%) 8 (23.5%) 15 (22.1%) Heart Failure 1 (2.9%) 4 (11.8%) 5 (7.4%) Previous TIA 3 (8.8%) 4 (11.8%) 7 (10.3%) Previous CVA 2 (5.9%) 1 (2.9%) 3 (4.4%) T1DM 0 (0.0%) 0 (0.0%) 0 (0.0%) T2DM (Diet Only) 3 (8.8%) 2 (5.9%) 5 (7.4%) T2DM (Oral Agents) 1 (2.9%) 4 (11.8%) 5 (7.4%) T2DM (Insulin) 2 (5.9%) 0 (0.0%) 2 (2.9%) The reasons stated on non-participation questionnaire are summarised in Supplementary Fig. 2 . Patients were allowed to list multiple reasons for non-participation. Response rate was 79.3% (n = 23/29). Logistical issues pertaining to travel, and other personal commitments were the most frequently listed reasons for non-participation (n = 9/23, 39.1%), followed by other hospital appointments commitments (n = 4/23, 17.4%). Patients who were enrolled in the study but subsequently decided to withdraw, also underwent an aforementioned questionnaire (n = 19), with 68.4% response rate. Eight patients stated they withdrew was due to travel issues (n = 9/13, 69.2%), three because of other hospital commitments (23.1%), and 2 felt that CR offered them no benefit. Secondary outcome measures Death and time to death There were no deaths within the 32 weeks study period in either group. Long-term, all-cause mortality data was available for 95.9% of the patients (n = 47/49) patients. At 9.1 years (IQR 8.9–9.3 years) median follow-up from randomisation, the overall survival was 65.9% (n = 31). The median survival was 8.9 years (IQR 6.9–9.3 years). The survival in SC group (n = 14, 66.7%) and CR group (n = 17, 65.3%) were comparable (median 9.0 vs 8.8 years, p = 0.68). The Kaplan Meier curve is shown in Fig. 2 . Figure 2 – Kaplan Meier curve for overall survival from day of randomisation. Data shown up to 9 years as < 20% of patient at risk beyond year 9. CR – Red, SC – Blue. Freedom from MACE and revascularisation There were two MACE within 32 week study period, both in SC group; one MI leading to coronary artery bypass grafting and one lower limb ischemia requiring revascularisation. These occurred at post-operative day 129, and 139 post respectively. The difference between groups was not significant (p = 0.21). Other adverse events Fifty two adverse events, across 30 patients were recorded. Out of those, 8 (15.1%) were classified as serious adverse events (including the abovementioned two MACE). The prevalence of all events was comparable in both groups (CR n = 24 vs. SC n = 28), as well as prevalence of serious adverse events (19.0% vs 14.2%, p = 0.655). None of the adverse events were thought to be related to CR. None of the adverse events resulted in withdrawal from the study. Majority of the adverse events were rated as mild (n = 28, 53.8%). The list of all adverse events can be found in Supplementary Table 4 Biochemical and haematological cardiac risk biomarkers No significant longitudinal change in biochemical, or haematological cardiovascular risk factor serum marker values was found in either group, as presented in Supplementary Table 5 . This was true accorss all study time-points (0,6,18,36 weeks). Urinary cardiac risk biomarkers No significant longitudinal change in urinary risk factor values was found in either group, as presented in Supplementary Table 6 . This was true accorss all study time-points (0,6,18,36 weeks). Echocardiographic data No significant longitudinal change in echocardiographic data was found in either group, as presented in Supplementary Tables 7a&7b . This was true accorss all study time-points (0,6,18,36 weeks). The groups were comparable in terms of valvular pathology distribution at baseline. Patient behaviour and lifestyle A significant longitudinal change was found in only two out of ten studied patient behaviour and lifestyle factors as seen in Table 2 . These where toe pressure on the right and weekly self-reported physical activity (p-values 0.041 and 0.026 respectively), with both significant findings occurring in the CR groups. On pairwise comparison analysis, the right toe pressures in CR groups were significantly higher between baseline and week 18 (82.5 mmHg vs 97.0 mmHg, p = 0.014), and baseline compared with week 36 (82.5 mmHg vs 95.5mmHg, p = 0.040). Similarly, the difference in activity levels (minutes) in CR group was statistically significant between measurement on week 6 and week 36 (median 30min vs 40min, p = 0.042), demonstrating increase in activity level over time. Table 2 – Patient behaviour and lifestyle markers. Median values (IQR) where data continuous, counts (%) where data categorical. Differences across week 0 (baseline), 6, 18, and 36 week measurements tested using ANOVA. * – p < 0.05. Variable Arm Week 0 Week 6 Week 18 Week 36 P value CO Breath Test CR N/A 2 (6.7) 0 (0.0) 0 (0.0) 0.19 SC N/A 2 (6.5) 3 (9.7) 3 (9.7) 0.31 Left ABPI (mmHg) CR 1.04 (0.28) 1.07 (0.34) 1.06 (0.19) 1.04 (0.31) 0.95 SC 1.07 (0.10) 1.09 (0.16) 1.08 (0.16) 1.13 (0.19) 0.23 Right ABPI (mmHg) CR 1.03 (0.27) 1.05 (0.27) 1.07 (0.26) 1.02 (0.38) 0.40 SC 1.07 (0.22) 1.11 (0.19) 1.09 (0.10) 1.13 (0.22) 0.74 Systolic BP (mmHg) CR 130 (28) 131 (43) 141 (41) 134 (28) 0.15 SC 132 ( 18 ) 144 (33) 144 (31) 144 ( 24 ) 0.061 Diastolic BP (mmHg) CR 71 ( 7 ) 78 ( 15 ) 78 ( 14 ) 73 ( 14 ) 0.079 SC 72 ( 15 ) 79 ( 21 ) 77 ( 20 ) 78 ( 14 ) 0.13 Toe Pressure Left (mmHg) CR 85 (39) 87 (40) 92 (41) 75 (45) 0.38 SC 77 (33) 99 (37) 108 (28) 100 ( 4 ) 0.22 Toe Pressure Right (mmHg) CR 83 (41) 88 (50) 97 (31) 96 (31) 0.041* SC 91 (36) 106 (36) 101 (43) 101 (38) 0.23 Heart Rate(bpm) CR 75 ( 9 ) 71 ( 15 ) 71 ( 15 ) 70 ( 21 ) 0.39 SC 65 ( 24 ) 63 ( 17 ) 65 ( 21 ) 66 ( 19 ) 0.48 Activity (min) CR 30 (45) 30 ( 25 ) 30 (45) 40 (50) 0.026* SC 30 (40) 35 (30) 30 (45) 45 (60) 0.19 Waist to Hip Ratio CR N/A 1.02 (0.08) 1.02 (0.08) 1.02 (0.07) 0.59 SC N/A 1.00 (0.06) 1.01 (0.06) 1.03 (0.08) 0.22 BMI (kg/m 2 ) CR 26.7 (3.8) 26.2 (4.7) 26.6 (3.9) 26.5 (4.0) 0.97 SC 27.5 (5.4) 26.8 (4.1) 26.9 (5.4) 26.6 (4.8) 0.82 Smoking cessation On initial post-operative assessment, 7 patients (CR; n = 3/21, 14.3% vs SC; n = 4/28, 14.3%) declared still smoking. The amount of cigarettes smoked was comparable (CR; median 10 (IQR 10–12.5) vs CS median 10 (IQR 6.5–25). At 36 weeks, 1 patient from CS group reported quitting smoking, with all remaining 3 patients reducing their cigarette consumption (median 8 cigarettes (IQR 6.5–18). In CR group, one patient didn’t complete questionnaire, whilst the 2 remaining patients also reported reduction in cigarette consumption (median 7.5 cigarettes IQR (6.25–8.75). All salivary contin measurements, across all time points and both groups were negative (i.e. <12ng/ml). Patient reported quality of life Patient reported quality of life was measured using the EQ5D-5L questionnaire at Week 0, 6, 18 and 36. At baseline CR group had lower overall index score (64.41 vs 75.35, p = 0.024), and higher physical discomfort scores (2.10 vs 1.29, p = 0.0044), as well as level sum score (8.07 vs. 6.71, p = 0.013). However, at 32 weeks none of the subdomains, index and LSS values were significantly different between the groups. On longitudinal analysis of all timepoints, only physical discomfort shown statistically significant change across time, only in SC group (p = 0.015), increasing over time (mean score 1.29 at baseline, 1.66 at 6 weeks, 1.74 at 18 weeks, and 1.79 at 32 weeks), Supplementary Table 8 ) However, upon pairwise comparisons there was no significant differences between separate time points (p = 0.78, p = 0.96). Of note, although not statistically significant, in CR group the physical discomfort and anxiety & depression score decreased over time, whilst overall index QoL score increased (Table 3 , Supplementary Fig. 3 ). Table 3 – Wilcoxon rank sum test outcomes for CR vs SC EQ5D-5L at baseline compared to scores at 32 weeks. EQ5D Domain Arm Score at baseline p-value Score at 32 weeks p-value Index CR 64.41 ± 18.26 0.024* 75.88 ± 18.44 0.52 CS 75.35 ± 17.42 79.48 ± 14.48 Level Sum Score CR 8.07 ± 2.55 0.013* 7.67 ± 2.68 0.87 CS 6.71 ± 2.24 7.55 ± 2.56 Mobility CR 1.79 ± 0.86 0.086 1.71 ± 0.95 0.38 CS 1.53 ± 0.96 1.93 ± 1.00 Self-care CR 1.14 ± 0.44 0.90 1.21 ± 0.59 0.74 CS 1.12 ± 0.33 1.10 ± 0.31 Usual Activity CR 1.34 ± 0.72 0.71 1.54 ± 0.83 0.83 CS 1.29 ± 0.80 1.48 ± 0.87 Physical Discomfort CR 2.10 ± 1.01 0.00044* 1.83 ± 0.87 0.88 CS 1.29 ± 0.52 1.79 ± 0.82 Anxiety & Depression CR 1.69 ± 0.97 0.208 1.38 ± 0.58 0.23 CS 1.47 ± 0.93 1.24 ± 0.58 Discussion In this feasibility RCT we have shown that it is possible to recruit patients after A/TAA repair to a trial offering a structured cardiac rehabilitation programme, with 70.1% of approached patients enrolling in the study, and reaching randomisation. Moreover, 81% of patients who began cardiac rehabilitation, completed all of the planned sessions. Logistical issues pertaining to travel were cited as the biggest barrier to participation in cardiac rehabilitation programme. Poor attendance of CR has been an often-cited issue within the cardiology literature, with little change between the EUROASPIRE IV and preceding III survey ( 16 ). EUROASPIRE IV showed that of those referred, 81% attended at least half of the CR sessions prescribed. Despite initial drop-out after randomisation, the same proportion of patient have completed all eight CR sessions our study, even with the mean age in EUROASPIRE IV being 64 years compared to the 75 years in this study. Furthermore, in other non-EU based studies enrolment and participation has been as low as approximately 50% ( 17 ). Thus, the percentage achieved in this study does seem in keeping with the global experience of uptake of these programs, and thus shows similar levels of patient acceptability. Within our study travel issues, and other personal commitments, were found to be the major reason for both non-enrolment and withdrawal from the study. This is in line with existing literature on barriers to prarticipation in cardiac rehabilitation ( 18 , 19 ). It thus may be possible to achieve higher levels of recruitment if wider adoption of the standardised CR programmes occurred within regional centres, decentralising these services from tertiary services only. Another solution to overcome travel barrier is to adopt virtual, or technology-assisted approaches to cardiac rehabilitation ( 20 ). These have been shown to also improve exercise capacity and be a potential alternative to centre-based CR. In the context of the UK, these have gained popularity during COVID-19 pandemic, and their acceptability amongst patients remains high ( 21 ). Also, co-existence of other hospital appointment was a significant factor for non-participation. This is of particular importance in the A/TAA cohort, as patients are likely to be older, and more co-morbid than comparator cohort looking at CR within the literature. This highlights the need for multidisciplinary collaboration, and co-ordination with other services to ensure these patients can attend CR sessions, without logistical challenges. Whilst the majority of evidence for CR is from cardiac revascularisation population, there is increasing body of evidence of effectiveness of CR in aortic disease. CR has been shown to be beneficial following aortic dissection repair ( 22 , 23 ). CR was implemented safely in post-repair setting for both Type A and Type B dissections, with signals towards better bloods pressure control, and increased peak oxygen uptake. What is more, it has been demonstrated that cardiac rehabilitation can play a role in prevention of aneurysm expansion. Nakayama et al., shown that patients receiving CR, when matched with comparable controls, had a lower risk of needing aneurysm repair in the first instance (hazard ratio, 0.19; 95% confidence interval, 0.07–0.50; p < 0.001), and slower rate of aneurysmal expansion (2.1 ± 3.0 versus 4.5 ± 4.0 mm/y; p < 0.001) ( 24 ). We found no evidence that CR was unsafe in A/TAA population, with no significant difference in either death or MACE between the two groups. Safety is often cited as barrier to CR, due to concerns about excessive blood pressure and heart rate elevation ( 25 ). We found no difference in such parameters within this feasibility study. There was, however, statistically significant increase in the minutes of activity per week undertaken by patients in the CR group, suggesting potential benefit and long-lasting lifestyle change resulting from CR. No statistically significant change was seen in the biochemical and haematological cardiac risk biomarkers screened in either cohort over the course of this feasibility study. It worth noting, the study has not been powered to look at differences in secondary outcomes, and thus larger scale study would be needed to examine any signals. Despite poorer self-reported QoL, higher physical discomfort, depression, and anxiety scores at baseline in CR groups, at 32 weeks, the scores were comparable between SC and CR groups, suggesting potential beneficial effect of CR on quality of life, in line with existing literature on CR and QoL ( 26 ). However, due to small sample size of the study involved in this study the significance of this finding is not known. No difference was seen in other components of this score (mobility, self-care, and usual activity). This study validates a use of a standardised cardiac rehabilitation programme for patient who have undergone A/TAA. A low drop-out rate following completion of at least one session of CR suggest acceptability to patients. Only one patient each cited being concerned with intervention, and not understanding intervention as reasons for non-participation, highlighting robust enrolment, patient education strategies already in use. However, the study was limited by its feasibility character and small sample size, not being powered to detect differences in secondary outcomes. The high proportion of patients excluded before enrolment, as well as 13 patients following randomisation in the CR group also suggests robust pre-assessment is needed, alongside patient education. Finally, the high number of secondary outcomes used for exploratory analyses has also resulted in a proportion of missing data across biochemical and lifestyle outcomes. Our study shows that CR following A/TAA repair is safe and acceptable to patients. CR was associated with increase in physical activity levels, and potentially improvement in quality of life. A further larger RCT is required to determine if the benefits shown within the cardiac rehabilitation literature would translate to the older, and more co-morbid population that makes up the A/TAA patient group. However, as logistical challenges pertaining to travel, other hospital, and personal commitments remains a barrier to uptake of structured CR programmes, expansion of CR programmes to regional centres, as well as adoption of virtual CR could serve as a solutions to recruitment challenges. Declarations Funding: This trial was supported by a British Heart Foundation Project Grant (PG/13/98/30490). Category : Original Article Previous Communications: Presented at British Society of Endovascular Therapy (BSET) 2016 Meeting Conflicts of Interest / Declarations: The authors declare no conflicts of interest Data Availability Statement: Grouped (groups >10 patients), anonymised data used in the trial is available on request from the corresponding author Acknowledgements: We would like to thank Paul Seed, Ray Kausik, Michael Ussher, Jan D Poloniecki, Rajan Sharma, Robert J Hinchliffe, Matthew M Thompson and Alan Karthikesalingam for assistance with obtaining the grant funding and protocol design. CRediT statement: MK: Data Curation, Formal Analysis, Visualisation, Writing – original draft, Writing – review & editing SB: Conceptualisation, Methodology, Investigation, Writing – original draft, Writing – review & editing IR: Supervision, Formal Analysis, Writing – original draft, Writing – review & editing MB: Data Curation, Investigation, Writing – original draft, Writing – review & editing IL: Supervision, Methodology, Writing – original draft, Writing – review & editing PH: Conceptualisation, Funding Acquisition, Methodology, Investigation, Writing – original draft, Writing – review & editing JB: Data Curation, Formal Analysis, Supervision, Writing – original draft, Writing – review & editing References Lederle, FA, Freischlag J, Kyriakides T. Outcomes Following Endovascular vs Open Repair of Abdominal Aortic Aneurysm: A Randomized Trial. JAMA. 2009;(302):1535–42. Bahia SS, Holt PJE, Jackson D, Patterson BO, Hinchliffe RJ, Thompson MM, et al. Systematic Review and Meta-analysis of Long-term survival After Elective Infrarenal Abdominal Aortic Aneurysm Repair 1969–2011: 5 Year Survival Remains Poor Despite Advances in Medical Care and Treatment Strategies. Eur J Vasc Endovasc Surg. 2015 Sep;50(3):320–30. Chiew K, Roy IN, Budge J, D’Abate F, Holt P, Loftus IM. The Fate of Patients Opportunistically Screened for Abdominal Aortic Aneurysms During Echocardiogram or Arterial Duplex Scans. Eur J Vasc Endovasc Surg. 2023 Aug;66(2):188–93. Karthikesalingam A, Bahia SS, Patterson BO, Peach G, Vidal-Diez A, Ray KK, et al. The Shortfall in Long-term Survival of Patients with Repaired Thoracic or Abdominal Aortic Aneurysms: Retrospective Case–Control Analysis of Hospital Episode Statistics. Eur J Vasc Endovasc Surg. 2013 Nov;46(5):533–41. Norman PE, Semmens JB, Lawrence-Brown MMD, Holman CDJ. Long term relative survival after surgery for abdominal aortic aneurysm in Western Australia: population based study. BMJ. 1998 Sep 26;317(7162):852–6. Bahia SS, Vidal-Diez A, Seshasai SRK, Shpitser I, Brownrigg JR, Patterson BO, et al. Cardiovascular risk prevention and all-cause mortality in primary care patients with an abdominal aortic aneurysm. Br J Surg. 2016 Nov 1;103(12):1626–33. Balady GJ, Ades PA, Bittner VA, Franklin BA, Gordon NF, Thomas RJ, et al. Referral, Enrollment, and Delivery of Cardiac Rehabilitation/Secondary Prevention Programs at Clinical Centers and Beyond: A Presidential Advisory From the American Heart Association. Circulation. 2011 Dec;124(25):2951–60. Balady GJ, Williams MA, Ades PA, Bittner V, Comoss P, Foody JM, et al. Core Components of Cardiac Rehabilitation/Secondary Prevention Programs: 2007 Update: A Scientific Statement From the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation. 2007 May 22;115(20):2675–82. Fidan D, Unal B, Critchley J, Capewell S. Economic analysis of treatments reducing coronary heart disease mortality in England and Wales, 2000-2010. QJM. 2007 Mar 27;100(5):277–89. Siercke M, Jørgensen LP, Missel M, Thygesen LC, Møller SP, Sillesen H, et al. Cardiovascular Rehabilitation Increases Walking Distance in Patients With Intermittent Claudication. Results of the CIPIC Rehab Study: A Randomised Controlled Trial. Eur J Vasc Endovasc Surg. 2021 Nov;62(5):768–76. Long L, Mordi IR, Bridges C, Sagar VA, Davies EJ, Coats AJ, et al. Exercise-based cardiac rehabilitation for adults with heart failure. Cochrane Heart Group, editor. Cochrane Database Syst Rev [Internet]. 2019 Jan 29 [cited 2024 Sep 5];2019(1). Available from: http://doi.wiley.com/10.1002/14651858.CD003331.pub5 Anderson L, Oldridge N, Thompson DR, Zwisler AD, Rees K, Martin N, et al. Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease Cochrane Systematic Review and Meta-Analysis. J Am Coll Cardiol. 2016;67(1):1–12. Bahia SS, Holt PJ, Ray KK, Ussher M, Poloniecki JD, Sharma R, et al. Cardiac rehabilitation versus standard care after aortic aneurysm repair (Aneurysm CaRe): Study protocol for a randomised controlled trial. Trials. 2015;16(1):1–7. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: Extension to randomised pilot and feasibility trials. The BMJ. 2016;355. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727–36. Kotseva K, Wood D, De Bacquer D, De Backer G, Rydén L, Jennings C, et al. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol. 2016;23(6):636–48. Thomas RJ, Balady G, Banka G, Beckie TM, Chiu J, Gokak S, et al. 2018 ACC/AHA Clinical Performance and Quality Measures for Cardiac Rehabilitation: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2018;71(16):1814–37. Dunlay SM, Witt BJ, Allison TG, Hayes SN, Weston SA, Koepsell E, et al. Barriers to participation in cardiac rehabilitation. Am Heart J. 2009;158(5):852–9. Leung YW, Brual J, Macpherson A, Grace SL. Geographic issues in cardiac rehabilitation utilization: A narrative review. Health Place. 2010;16(6):1196–205. Imran HM, Baig M, Erqou S, Taveira TH, Shah NR, Morrison A, et al. Home‐Based Cardiac Rehabilitation Alone and Hybrid With Center‐Based Cardiac Rehabilitation in Heart Failure: A Systematic Review and Meta‐Analysis. J Am Heart Assoc. 2019 Aug 20;8(16):e012779. Thomas E, Gallagher R, Grace SL. Future-proofing cardiac rehabilitation: Transitioning services to telehealth during COVID-19. Eur J Prev Cardiol. 2021 Jul 10;28(7):e35–6. Fuglsang S, Heiberg J, Hjortdal VE, Laustsen S. Exercise-based cardiac rehabilitation in surgically treated type-A aortic dissection patients. Scand Cardiovasc J. 2017;51(2):99–105. Hornsby WE, Norton EL, Fink S, Saberi S, Wu X, McGowan CL, et al. Cardiopulmonary Exercise Testing Following Open Repair for a Proximal Thoracic Aortic Aneurysm or Dissection. J Cardiopulm Rehabil Prev. 2020;40(2):108–15. Nakayama A, Morita H, Nagayama M, Hoshina K, Uemura Y, Tomoike H, et al. Cardiac rehabilitation protects against the expansion of abdominal aortic aneurysm. J Am Heart Assoc. 2018;7(5):1–13. Erbel R, Aboyans V, Boileau C, Bossone E, Di Bartolomeo R, Eggebrecht H, et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases. Eur Heart J. 2014;35(41):2873–926. Shepherd CW, While AE. Cardiac rehabilitation and quality of life: a systematic review. Int J Nurs Stud. 2012;49(6):755–71. Additional Declarations The authors declare no competing interests. Supplementary Files SupplementaryFiguresTables.docx Appendix - Supplementary Figures and Tables Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6464370","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":443899409,"identity":"4efdd783-5d35-4886-bb52-a064ad0e5054","order_by":0,"name":"Michal Kawka","email":"","orcid":"https://orcid.org/0000-0002-5826-8355","institution":"School of Health \u0026 Medical Sciences, City St George’s University of London, London, UK","correspondingAuthor":false,"prefix":"","firstName":"Michal","middleName":"","lastName":"Kawka","suffix":""},{"id":443899410,"identity":"36ef3436-7937-4a33-917b-10658913a389","order_by":1,"name":"Sandeep S Bahia","email":"","orcid":"","institution":"East Kent Hospitals University NHS Foundation Trust, Kent, UK","correspondingAuthor":false,"prefix":"","firstName":"Sandeep","middleName":"S","lastName":"Bahia","suffix":""},{"id":443899411,"identity":"6ce57f9c-c2f6-47fb-8048-e69253cd4b55","order_by":2,"name":"Matthew Bown","email":"","orcid":"","institution":"Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Bown","suffix":""},{"id":443899412,"identity":"5555fe0a-3b22-4c2f-8015-9b9f597d1ff4","order_by":3,"name":"Iain Roy","email":"","orcid":"","institution":"School of Health \u0026 Medical Sciences, City St George’s University of London, London, UK","correspondingAuthor":false,"prefix":"","firstName":"Iain","middleName":"","lastName":"Roy","suffix":""},{"id":443899413,"identity":"4a64459b-024f-4378-9140-dda04839de33","order_by":4,"name":"Ian Loftus","email":"","orcid":"","institution":"St George’s Vascular Institute, St George’s Hospital, London, UK","correspondingAuthor":false,"prefix":"","firstName":"Ian","middleName":"","lastName":"Loftus","suffix":""},{"id":443899414,"identity":"25f01af4-3413-4799-9e0e-a7c9448d426e","order_by":5,"name":"Peter Holt","email":"","orcid":"","institution":"School of Health \u0026 Medical Sciences, City St George’s University of London, London, UK","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Holt","suffix":""},{"id":443899415,"identity":"e589fbb0-cc36-49bb-9038-823d42adff23","order_by":6,"name":"James Budge","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYBACxhkMDBIMDDZAJnMDWESCSC1pICaRWkAqgOgwCVqYZ/cY3vxScd5ePiKxgeFHDUPizAZCDptzxtha5sztxI03EhsYe44xJM4mZAvjjBwzacm22wmGM4C28DYwJM4jTsu/c/YgLYx/idUi+bHhAON8icQGZpAthB0251ixNcOx5MQNPA8bDssckzAm6H3D2c0bb/6osbOXb08++PBNjY3sjAOEtADNZOYBMgyAKg8QE5EM8iDH/QAxCLlnFIyCUTAKRi4AAPXPQqwwjlujAAAAAElFTkSuQmCC","orcid":"","institution":"School of Health \u0026 Medical Sciences, City St George’s University of London, London, UK","correspondingAuthor":true,"prefix":"","firstName":"James","middleName":"","lastName":"Budge","suffix":""}],"badges":[],"createdAt":"2025-04-16 14:19:27","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":true,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6464370/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6464370/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80821499,"identity":"58fee5ca-a0fa-444a-b01c-247bd9e4575d","added_by":"auto","created_at":"2025-04-17 12:17:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":97351,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT diagram for feasibility randomised controlled trial of cardiac rehabilitation vs. standard care after aortic aneurysm repair.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6464370/v1/a722fff2db7f20c7e06ca312.png"},{"id":80822279,"identity":"743c7215-fb26-4bbc-a753-d16c9341f35e","added_by":"auto","created_at":"2025-04-17 12:25:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":78067,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meier curve for overall survival from day of randomisation. Data shown up to 9 years as \u0026lt;20% of patient at risk beyond year 9. CR – Red, SC – Blue.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6464370/v1/9bf0de015d9ac4f7455ae516.png"},{"id":80822679,"identity":"38ef1d7c-0438-497c-afd2-8f151618a257","added_by":"auto","created_at":"2025-04-17 12:33:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1226642,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6464370/v1/98c48ff0-c4bc-4750-ae34-3d47e4912094.pdf"},{"id":80821495,"identity":"1e474b76-861a-44d8-9af5-6e8ddc006573","added_by":"auto","created_at":"2025-04-17 12:17:09","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":450139,"visible":true,"origin":"","legend":"\u003cp\u003eAppendix - Supplementary Figures and Tables\u003c/p\u003e","description":"","filename":"SupplementaryFiguresTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6464370/v1/20e61989565f2d9c697a9212.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eAneurysm CaRe ­– Randomized Controlled Feasibility Trial of Cardiac Rehabilitation versus Standard Care After Aortic Aneurysm Repair\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAdvances in both surgical techniques and peri-operative care have significantly reduced the short-term mortality associated with elective abdominal and thoracic aortic aneurysm (A/TAA) repair (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, the established enhanced short-term survival has, to date, not translated into improved long-term outcomes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Compared to matched contemporaries without aneurysmal disease, patients who require elective A/TAA repair experience a distinct increase in adverse cardiac events (ACE), strokes and amputation; there is an associated reduction in 5-year-survival from 81% for controls to 67% in the A/TAA repair population (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This is also true when age-matched controls are compared with patients with aneurysmal disease; the latter have higher cardiovascular risk burden. Up to 60% of deaths in this cohort are attributable to cardiovascular disease, contributing substantially to their relative reduction in long-term survival (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). A/TAA is an uncommon but serious phenotype of the advanced atherosclerotic disease observable in this patient population. Despite this, the proportion of A/TAA repaired patients that are prescribed prognostically beneficial medications such as antiplatelets, statins and anti-hypertensive medications is sub-optimal (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). What is more, there is scope in improving their lifestyle risk factors, such as exercise level, and smoking. As such, these observations suggest that patients undergoing elective A/TAA repair might derive long-term benefit from post-operative protocolised cardiac rehabilitation.\u003c/p\u003e \u003cp\u003eCardiac rehabilitation (CR) is a multidisciplinary, biopsychosocial approach to the promotion of recovery from cardiovascular disease (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The World Health Organisation (WHO) defines it as the \u0026lsquo;sum of activities required to influence favourably the underlying cause of the disease, as well as to provide the best possible physical, mental and social conditions, so that the patients may, by their own efforts, preserve or resume when lost, as normal a place as possible in the community\u0026rsquo;. To achieve this, CR is typically delivered over 8\u0026ndash;12 weeks, combining supervised exercise, dietary \u0026amp; lifestyle modifications, smoking cessation, and optimisation of medical therapy for cardiovascular risk factors (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). CR has been shown to be an important, cost-effective intervention in the management of coronary heart disease (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), peripheral arterial disease (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), and heart failure (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). As such, a Cochrane review recommended trialled use of CR be widened to other populations with severe cardiovascular disease (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe proven CR derived benefit in cardiothoracic patient populations is encouraging of the potential for similar benefit to be seen in A/TAA repair patients. However, the feasibility of performing CR in A/TAA repair patients is not yet known. A/TAA repair patients not only experience more major adverse cardiac events (MACE) than their counterparts without aneurysms, but are typically approximately 10 years older than patients currently recruited to CR (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Therefore, the primary aim of this randomised feasibility study is to enrol a sufficient number of patients to ensure CR is both feasible and acceptable to patients post A/TAA repair. Secondary outcome measures include assessment of mortality, rate of MACE, biochemical markers of cardiovascular risk, behavioural and biometric changes and measures of patient quality of life (QoL).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis study was designed as a feasibility, randomised trial, comparing Cardiac Rehabilitation (CR) and Standard Care (SC) after elective A/TAA repair. Patients were enrolled from two secondary care sites in the UK: St George\u0026rsquo;s Vascular Institute in London and University Hospitals of Leicester NHS Trust according to a previous published trial protocol (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). All patients gave informed written consent. The protocol was approved by the NRES Committee (London, Bloomsbury, ref 13/LO/0395). The trial is registered with the ISRCTN: 65746249. This study was conducted according to the CONSORT statement for pilot and feasibility RCTs (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRandomisation\u003c/h3\u003e\n\u003cp\u003e After informed consent was obtained, patients discharged from hospital after elective aortic aneurysm (thoracic or abdominal) repair were randomised in a 1:1 ratio into the intervention arm (CR) and the control arm (SC). A minimisation algorithm was utilised to ensure stratification variables (age, gender and study site) were balanced between groups. This was performed using a secure Internet-based central randomisation through an NIHR-accredited clinical trials unit (King\u0026rsquo;s Clinical Trials Unit) using a minimisation algorithm. Neither investigators nor patients were blinded to treatment.\u003c/p\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003ePatients randomised to CR were seen by a member of the Cardiac Rehabilitation team either before discharge, if possible, or at the induction CR meeting 4\u0026ndash;6 weeks after A/TAA repair. They received a nationalised, protocolised approach to intensive medical risk factor reduction and enrolment in the local multimodal CR programme; an 8 week regime of supervised exercise, lifestyle modification, dietary interventions, psychological assessment and medical risk modification. In brief, each weekly session took 1 to 2 hours and was supervised by two nurses trained in CR, two qualified physiotherapists and one occupational therapy technician. Each session began with a blood pressure and heart rate measurement and a review of each patient\u0026rsquo;s progress to date. The group then proceeded through a supervised warm-up of 10\u0026ndash;15 minutes, followed by the main exercise session of 45 minutes. This was followed by a warm-down, and finally further blood pressure and heart rate measurements.\u003c/p\u003e \u003cp\u003ePatients randomised to the SC arm received routine post-operative out-patient appointments and/or follow-up scans as necessary with GP-based management of their co-existing co-morbidities (e.g. hypertension, smoking). The trial structure can be seen in Supplementary Fig.\u0026nbsp;1.\u003c/p\u003e\n\u003ch3\u003eInclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003eAll patients discharged home after undergoing elective thoracic or abdominal aortic aneurysm repair during the recruitment period were eligible for the study. Patients were excluded if they were:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eUnder the age of 50 years;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDiagnosed with a connective tissue disease (e.g. Marfan\u0026rsquo;s and Loeys-Dietz syndromes);\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eUnable or unwilling to consent to participation or attend CR sessions;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDeemed too unfit for the CR programme by the Lead CR nurse;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eUndergoing expedited or emergent surgical intervention for symptomatic or ruptured aortic aneurysms.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e\n\u003ch3\u003eSample size\u003c/h3\u003e\n\u003cp\u003eWe planned to approach 140 patients for consent, and estimated the feasibility trial will recruit 84 patients, based on the assumption that at least 60% (95% CI 50.7\u0026ndash;68.8%) of approached patients will agree to take part. The lower margin of the 95% confidence interval for this enrolment rate (50.7%) provides adequate precision to establish that at least 50% of aortic aneurysm patients will agree to participate in an RCT of CR; establishing the feasibility of a definitive multi-centre national RCT.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes measures\u003c/h2\u003e \u003cp\u003eThe co-primary outcome measures of the study were:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eEnrolment: the proportion of patients following A/TAA repair meeting the inclusion criteria and agreeing to enrolment in the trial. We expected that at least 60.0% of patients (95% CI, 50.7%-68.8%) agree to enrol.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eCompliance with CR therapy in the group randomised to this arm. This was defined as the proportion of patients demonstrating attendance at 100% of scheduled CR sessions over 8 weeks. We expected that 70.0% of patients (95% CI, 55%-84%) attend all CR sessions.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eSecondary outcome measures were:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eMortality: collected using screening of patient records at their treatment hospital and validated through contact with the patient\u0026rsquo;s GP.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePresence of first Major Adverse Cardiac Event (MACE); a composite end point of myocardial infarction, stroke, and cardiac or limb revascularisation. Collected using screening of patient records at their treatment hospital and validated through contact with the patient\u0026rsquo;s GP.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePresence, and severity of non-cardiovascular adverse events.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eChange in measures of plasma biochemical cardiac risk factors; Sodium, Potassium, Creatinine, Homocysteine, Troponin, hsCRP, BNP, Fibrinogen, HbA1C, Total lipids, HDL, LDL, Triglycerides.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eChange in urine biochemical cardiac risk factors; urine albumin, urine creatinine, albumin: creatinine ratio.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eChange in echocardiographic parameters; left ventricle end systolic diameter (cm), left ventricle end diastolic diameter (cm), pulmonary artery pressure (mmHg), LV fractional shortening (%), Max Ascending Aorta Diameter (cm), LVOT Diameter (cm), Max sinus of Valsalva (cm), Max aortic arch diameter (cm), presence of regional wall motion abnormalities, presence, and severity of valvular pathologies.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eChange in indicators of patient behaviour and lifestyle related to cardiac risk factors; CO breath test, ABPI, Systolic BP, Diastolic BP, Toe Pressure, Heart Rate, Physical activity, Waist to Hip Ratio, BMI.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eSmoking habit data, including salivary contin.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eChange in patient reported outcome measures and quality of life; collected using the EQ5D-5L questionnaire (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003ePatients that did not wish to participate in the study were surveyed to look at their reasons for non-participation using structured questionnaires.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed in R Version 4.3.2 (R Core Team, 2014). Categorical variables were presented as count and compared with the chi square test (χ\u0026sup2;). Continuous variables were presented as Median [Range], longitudinal difference was analysed using one way ANOVA for continuous variables, and Kruskal Wallis test for categorical variables. When significance was detected on longitudinal analysis, Tukey\u0026rsquo;s HSD (continuous) or Benjamini-Hochberg correction (categorical) was used to analyse pairwise comparisons between time-points. P-values of less than 0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRole of funding\u003c/h3\u003e\n\u003cp\u003eThis trial was supported by a British Heart Foundation Project Grant (PG/13/98/30490). The funder had no role in the study design, data collection, data analysis, manuscript preparation and publication decisions\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cspan type=\"Underline\" name=\"Emphasis\"\u003eDemographics, enrolment, and compliance.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eBetween September 2014 and September 2015, 159 patients were assessed for eligibility. Of the 159 patients, 62 were non-eligible to participate (1 patient was under age of 50, and 61 were deemed too unfit for CR programme at screening). Of the remaining 97 patients, 68 (70.1%) were randomised into SC (n\u0026thinsp;=\u0026thinsp;34) or CR (n\u0026thinsp;=\u0026thinsp;34), whilst 29 did not want to participate (29.9%). 13 (38.2%) individuals withdrew from the CR arm and 6 (17.6%) from the SC arm (Fig.\u0026nbsp;1). Of the 13 patients that withdrew from the CR arm 6 withdrew before any CR visits, and 7 withdrew after CR pre-assessment. 17 (81.0%) of the 21 remaining patients in the CR group attended all eight CR sessions.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFigure 1 \u0026ndash; CONSORT diagram for feasibility randomised controlled trial of cardiac rehabilitation vs. standard care after aortic aneurysm repair.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBaseline demographics of both the CR and SC arms are shown in Table \u003cspan\u003e1\u003c/span\u003e. The groups were comparable in terms of age, sex, BMI, smoking status, ASA grade, and cardiovascular co-morbidities. Majority of patients had diagnosis of hypertension (n\u0026thinsp;=\u0026thinsp;47, 69.1%), and hypercholesterolaemia (n\u0026thinsp;=\u0026thinsp;50, 73.5%), with a significant proportion having previous MI (n\u0026thinsp;=\u0026thinsp;16, 23.5%). Patient were taking 6.81 medications on average, with majority of patients taking an antiplatelet (n\u0026thinsp;=\u0026thinsp;67, 98.5%), and a statin (n\u0026thinsp;=\u0026thinsp;63, 92.6%). In the 12 month preceding surgery, patients attended 2.42 hospital appointments. Non-cardiac comorbidities, medication, and socioeconomic baseline data is presented in \u003cem\u003eSupplementary Tables\u0026nbsp;1\u0026ndash;3\u003c/em\u003e.\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline demographics of patients randomised into the trial. SD \u0026ndash; Standard Deviation. ASA \u0026ndash; American Society of Anaesthesiologists. BMI \u0026ndash; Body Mass Index. MI \u0026ndash; Myocardial Infarction. PCI \u0026ndash; Primary Coronary Intervention. CABG \u0026ndash; Coronary Artery Bypass Grafting. TIA \u0026ndash; Transient Ischaemic Attack. CVA \u0026ndash; Cerebrovascular Accident. T1DM \u0026ndash; Type 1 Diabetes Mellitus. T2DM \u0026ndash; Type 2 Diabetes Mellitus\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCardiac Rehab\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStandard Care\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;68)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge\u0026nbsp;(years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.4 [62.3, 87.4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.7 [65.6, 89.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.4 [62.3, 89.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (97.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (97.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66 (97.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.9 (4.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.1 (6.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.0 (5.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian [Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.7 [15.5, 35.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.4 [1.18, 37.7]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.8 [1.18, 37.7]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eASA Grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (14.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (55.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (55.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (55.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (20.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking History\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurrent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEx-Smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (52.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon Smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLeicester\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (26.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (26.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (26.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSt George\u0026rsquo;s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (73.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (73.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50 (73.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiovascular Co-Morbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (61.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 (76.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47 (69.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypercholesterolemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (64.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (79.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49 (72.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAngina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious MI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious PCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (13.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious CABG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (20.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (22.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart Failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious CVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT1DM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT2DM (Diet Only)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT2DM (Oral Agents)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT2DM (Insulin)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eThe reasons stated on non-participation questionnaire are summarised in \u003cem\u003eSupplementary Fig.\u0026nbsp;2\u003c/em\u003e. Patients were allowed to list multiple reasons for non-participation. Response rate was 79.3% (n\u0026thinsp;=\u0026thinsp;23/29). Logistical issues pertaining to travel, and other personal commitments were the most frequently listed reasons for non-participation (n\u0026thinsp;=\u0026thinsp;9/23, 39.1%), followed by other hospital appointments commitments (n\u0026thinsp;=\u0026thinsp;4/23, 17.4%).\u003c/p\u003e\n\u003cp\u003ePatients who were enrolled in the study but subsequently decided to withdraw, also underwent an aforementioned questionnaire (n\u0026thinsp;=\u0026thinsp;19), with 68.4% response rate. Eight patients stated they withdrew was due to travel issues (n\u0026thinsp;=\u0026thinsp;9/13, 69.2%), three because of other hospital commitments (23.1%), and 2 felt that CR offered them no benefit.\u003c/p\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eSecondary outcome measures\u003c/h2\u003e\n \u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003eDeath and time to death\u003c/h2\u003e\n \u003cp\u003eThere were no deaths within the 32 weeks study period in either group. Long-term, all-cause mortality data was available for 95.9% of the patients (n\u0026thinsp;=\u0026thinsp;47/49) patients. At 9.1 years (IQR 8.9\u0026ndash;9.3 years) median follow-up from randomisation, the overall survival was 65.9% (n\u0026thinsp;=\u0026thinsp;31). The median survival was 8.9 years (IQR 6.9\u0026ndash;9.3 years). The survival in SC group (n\u0026thinsp;=\u0026thinsp;14, 66.7%) and CR group (n\u0026thinsp;=\u0026thinsp;17, 65.3%) were comparable (median 9.0 vs 8.8 years, p\u0026thinsp;=\u0026thinsp;0.68). The Kaplan Meier curve is shown in \u003cem\u003eFig.\u0026nbsp;2\u003c/em\u003e.\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eFigure 2 \u0026ndash; Kaplan Meier curve for overall survival from day of randomisation.\u003c/em\u003e Data shown up to 9 years as \u0026lt;\u0026thinsp;20% of patient at risk beyond year 9. \u003cem\u003eCR \u0026ndash; Red, SC \u0026ndash; Blue.\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003eFreedom from MACE and revascularisation\u003c/h2\u003e\n \u003cp\u003eThere were two MACE within 32 week study period, both in SC group; one MI leading to coronary artery bypass grafting and one lower limb ischemia requiring revascularisation. These occurred at post-operative day 129, and 139 post respectively. The difference between groups was not significant (p\u0026thinsp;=\u0026thinsp;0.21).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003eOther adverse events\u003c/h2\u003e\n \u003cp\u003eFifty two adverse events, across 30 patients were recorded. Out of those, 8 (15.1%) were classified as serious adverse events (including the abovementioned two MACE). The prevalence of all events was comparable in both groups (CR n\u0026thinsp;=\u0026thinsp;24 vs. SC n\u0026thinsp;=\u0026thinsp;28), as well as prevalence of serious adverse events (19.0% vs 14.2%, p\u0026thinsp;=\u0026thinsp;0.655). None of the adverse events were thought to be related to CR. None of the adverse events resulted in withdrawal from the study. Majority of the adverse events were rated as mild (n\u0026thinsp;=\u0026thinsp;28, 53.8%). The list of all adverse events can be found in \u003cem\u003eSupplementary Table\u0026nbsp;4\u003c/em\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\"\u003e\n \u003ch2\u003eBiochemical and haematological cardiac risk biomarkers\u003c/h2\u003e\n \u003cp\u003eNo significant longitudinal change in biochemical, or haematological cardiovascular risk factor serum marker values was found in either group, as presented in \u003cem\u003eSupplementary Table\u0026nbsp;5\u003c/em\u003e. This was true accorss all study time-points (0,6,18,36 weeks).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\"\u003e\n \u003ch2\u003eUrinary cardiac risk biomarkers\u003c/h2\u003e\n \u003cp\u003eNo significant longitudinal change in urinary risk factor values was found in either group, as presented in \u003cem\u003eSupplementary Table\u0026nbsp;6\u003c/em\u003e. This was true accorss all study time-points (0,6,18,36 weeks).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\"\u003e\n \u003ch2\u003eEchocardiographic data\u003c/h2\u003e\n \u003cp\u003eNo significant longitudinal change in echocardiographic data was found in either group, as presented in \u003cem\u003eSupplementary Tables\u0026nbsp;7a\u0026amp;7b\u003c/em\u003e. This was true accorss all study time-points (0,6,18,36 weeks). The groups were comparable in terms of valvular pathology distribution at baseline.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\"\u003e\n \u003ch2\u003ePatient behaviour and lifestyle\u003c/h2\u003e\n \u003cp\u003eA significant longitudinal change was found in only two out of ten studied patient behaviour and lifestyle factors as seen in Table \u003cspan\u003e2\u003c/span\u003e. These where toe pressure on the right and weekly self-reported physical activity (p-values 0.041 and 0.026 respectively), with both significant findings occurring in the CR groups. On pairwise comparison analysis, the right toe pressures in CR groups were significantly higher between baseline and week 18 (82.5 mmHg vs 97.0 mmHg, p\u0026thinsp;=\u0026thinsp;0.014), and baseline compared with week 36 (82.5 mmHg vs 95.5mmHg, p\u0026thinsp;=\u0026thinsp;0.040). Similarly, the difference in activity levels (minutes) in CR group was statistically significant between measurement on week 6 and week 36 (median 30min vs 40min, p\u0026thinsp;=\u0026thinsp;0.042), demonstrating increase in activity level over time.\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u0026ndash; Patient behaviour and lifestyle markers. Median values (IQR) where data continuous, counts (%) where data categorical. Differences across week 0 (baseline), 6, 18, and 36 week measurements tested using ANOVA. * \u0026ndash; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eArm\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWeek 0\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWeek 6\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWeek 18\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWeek 36\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCO Breath Test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eLeft ABPI\u003c/p\u003e\n \u003cp\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04 (0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07 (0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.06 (0.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04 (0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07 (0.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.09 (0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08 (0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13 (0.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eRight ABPI\u003c/p\u003e\n \u003cp\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.03 (0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05 (0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07 (0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07 (0.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.11 (0.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.09 (0.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.13 (0.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSystolic BP\u003c/p\u003e\n \u003cp\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e131 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e141 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e134 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e132 (\u003cspan\u003e18\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144 (\u003cspan\u003e24\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDiastolic BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71 (\u003cspan\u003e7\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78 (\u003cspan\u003e15\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78 (\u003cspan\u003e14\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73 (\u003cspan\u003e14\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72 (\u003cspan\u003e15\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79 (\u003cspan\u003e21\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77 (\u003cspan\u003e20\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78 (\u003cspan\u003e14\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eToe Pressure Left (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100 (\u003cspan\u003e4\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eToe Pressure Right (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.041*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eHeart Rate(bpm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75 (\u003cspan\u003e9\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71 (\u003cspan\u003e15\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71 (\u003cspan\u003e15\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70 (\u003cspan\u003e21\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65 (\u003cspan\u003e24\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63 (\u003cspan\u003e17\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65 (\u003cspan\u003e21\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66 (\u003cspan\u003e19\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eActivity\u003c/p\u003e\n \u003cp\u003e(min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (\u003cspan\u003e25\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eWaist to Hip Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (0.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (0.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02 (0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01 (0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.03 (0.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003cp\u003e(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.7 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.2 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.6 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.5 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.5 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.8 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.9 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.6 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\"\u003e\n \u003ch2\u003eSmoking cessation\u003c/h2\u003e\n \u003cp\u003eOn initial post-operative assessment, 7 patients (CR; n\u0026thinsp;=\u0026thinsp;3/21, 14.3% vs SC; n\u0026thinsp;=\u0026thinsp;4/28, 14.3%) declared still smoking. The amount of cigarettes smoked was comparable (CR; median 10 (IQR 10\u0026ndash;12.5) vs CS median 10 (IQR 6.5\u0026ndash;25). At 36 weeks, 1 patient from CS group reported quitting smoking, with all remaining 3 patients reducing their cigarette consumption (median 8 cigarettes (IQR 6.5\u0026ndash;18). In CR group, one patient didn\u0026rsquo;t complete questionnaire, whilst the 2 remaining patients also reported reduction in cigarette consumption (median 7.5 cigarettes IQR (6.25\u0026ndash;8.75). All salivary contin measurements, across all time points and both groups were negative (i.e. \u0026lt;12ng/ml).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\"\u003e\n \u003ch2\u003ePatient reported quality of life\u003c/h2\u003e\n \u003cp\u003ePatient reported quality of life was measured using the EQ5D-5L questionnaire at Week 0, 6, 18 and 36. At baseline CR group had lower overall index score (64.41 vs 75.35, p\u0026thinsp;=\u0026thinsp;0.024), and higher physical discomfort scores (2.10 vs 1.29, p\u0026thinsp;=\u0026thinsp;0.0044), as well as level sum score (8.07 vs. 6.71, p\u0026thinsp;=\u0026thinsp;0.013). However, at 32 weeks none of the subdomains, index and LSS values were significantly different between the groups. On longitudinal analysis of all timepoints, only physical discomfort shown statistically significant change across time, only in SC group (p\u0026thinsp;=\u0026thinsp;0.015), increasing over time (mean score 1.29 at baseline, 1.66 at 6 weeks, 1.74 at 18 weeks, and 1.79 at 32 weeks), \u003cem\u003eSupplementary Table\u0026nbsp;8\u003c/em\u003e) However, upon pairwise comparisons there was no significant differences between separate time points (p\u0026thinsp;=\u0026thinsp;0.78, p\u0026thinsp;=\u0026thinsp;0.96). Of note, although not statistically significant, in CR group the physical discomfort and anxiety \u0026amp; depression score decreased over time, whilst overall index QoL score increased (Table \u003cspan\u003e3\u003c/span\u003e, \u003cem\u003eSupplementary Fig.\u0026nbsp;3\u003c/em\u003e).\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003e\u0026ndash; Wilcoxon rank sum test outcomes for CR vs SC EQ5D-5L at baseline compared to scores at 32 weeks.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEQ5D Domain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eArm\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eScore at baseline\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eScore at 32 weeks\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eIndex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.41\u0026thinsp;\u0026plusmn;\u0026thinsp;18.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.88\u0026thinsp;\u0026plusmn;\u0026thinsp;18.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.35\u0026thinsp;\u0026plusmn;\u0026thinsp;17.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79.48\u0026thinsp;\u0026plusmn;\u0026thinsp;14.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eLevel Sum Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.07\u0026thinsp;\u0026plusmn;\u0026thinsp;2.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.013*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.71\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eMobility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSelf-care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eUsual Activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ePhysical Discomfort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00044*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eAnxiety \u0026amp; Depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this feasibility RCT we have shown that it is possible to recruit patients after A/TAA repair to a trial offering a structured cardiac rehabilitation programme, with 70.1% of approached patients enrolling in the study, and reaching randomisation. Moreover, 81% of patients who began cardiac rehabilitation, completed all of the planned sessions. Logistical issues pertaining to travel were cited as the biggest barrier to participation in cardiac rehabilitation programme.\u003c/p\u003e \u003cp\u003ePoor attendance of CR has been an often-cited issue within the cardiology literature, with little change between the EUROASPIRE IV and preceding III survey (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). EUROASPIRE IV showed that of those referred, 81% attended at least half of the CR sessions prescribed. Despite initial drop-out after randomisation, the same proportion of patient have completed all eight CR sessions our study, even with the mean age in EUROASPIRE IV being 64 years compared to the 75 years in this study. Furthermore, in other non-EU based studies enrolment and participation has been as low as approximately 50% (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Thus, the percentage achieved in this study does seem in keeping with the global experience of uptake of these programs, and thus shows similar levels of patient acceptability.\u003c/p\u003e \u003cp\u003eWithin our study travel issues, and other personal commitments, were found to be the major reason for both non-enrolment and withdrawal from the study. This is in line with existing literature on barriers to prarticipation in cardiac rehabilitation (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). It thus may be possible to achieve higher levels of recruitment if wider adoption of the standardised CR programmes occurred within regional centres, decentralising these services from tertiary services only. Another solution to overcome travel barrier is to adopt virtual, or technology-assisted approaches to cardiac rehabilitation (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These have been shown to also improve exercise capacity and be a potential alternative to centre-based CR. In the context of the UK, these have gained popularity during COVID-19 pandemic, and their acceptability amongst patients remains high (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Also, co-existence of other hospital appointment was a significant factor for non-participation. This is of particular importance in the A/TAA cohort, as patients are likely to be older, and more co-morbid than comparator cohort looking at CR within the literature. This highlights the need for multidisciplinary collaboration, and co-ordination with other services to ensure these patients can attend CR sessions, without logistical challenges.\u003c/p\u003e \u003cp\u003eWhilst the majority of evidence for CR is from cardiac revascularisation population, there is increasing body of evidence of effectiveness of CR in aortic disease. CR has been shown to be beneficial following aortic dissection repair (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). CR was implemented safely in post-repair setting for both Type A and Type B dissections, with signals towards better bloods pressure control, and increased peak oxygen uptake. What is more, it has been demonstrated that cardiac rehabilitation can play a role in prevention of aneurysm expansion. Nakayama et al., shown that patients receiving CR, when matched with comparable controls, had a lower risk of needing aneurysm repair in the first instance (hazard ratio, 0.19; 95% confidence interval, 0.07\u0026ndash;0.50; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and slower rate of aneurysmal expansion (2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0 versus 4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 mm/y; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe found no evidence that CR was unsafe in A/TAA population, with no significant difference in either death or MACE between the two groups. Safety is often cited as barrier to CR, due to concerns about excessive blood pressure and heart rate elevation (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). We found no difference in such parameters within this feasibility study. There was, however, statistically significant increase in the minutes of activity per week undertaken by patients in the CR group, suggesting potential benefit and long-lasting lifestyle change resulting from CR. No statistically significant change was seen in the biochemical and haematological cardiac risk biomarkers screened in either cohort over the course of this feasibility study. It worth noting, the study has not been powered to look at differences in secondary outcomes, and thus larger scale study would be needed to examine any signals.\u003c/p\u003e \u003cp\u003eDespite poorer self-reported QoL, higher physical discomfort, depression, and anxiety scores at baseline in CR groups, at 32 weeks, the scores were comparable between SC and CR groups, suggesting potential beneficial effect of CR on quality of life, in line with existing literature on CR and QoL (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). However, due to small sample size of the study involved in this study the significance of this finding is not known. No difference was seen in other components of this score (mobility, self-care, and usual activity).\u003c/p\u003e \u003cp\u003eThis study validates a use of a standardised cardiac rehabilitation programme for patient who have undergone A/TAA. A low drop-out rate following completion of at least one session of CR suggest acceptability to patients. Only one patient each cited being concerned with intervention, and not understanding intervention as reasons for non-participation, highlighting robust enrolment, patient education strategies already in use. However, the study was limited by its feasibility character and small sample size, not being powered to detect differences in secondary outcomes. The high proportion of patients excluded before enrolment, as well as 13 patients following randomisation in the CR group also suggests robust pre-assessment is needed, alongside patient education. Finally, the high number of secondary outcomes used for exploratory analyses has also resulted in a proportion of missing data across biochemical and lifestyle outcomes.\u003c/p\u003e \u003cp\u003eOur study shows that CR following A/TAA repair is safe and acceptable to patients. CR was associated with increase in physical activity levels, and potentially improvement in quality of life. A further larger RCT is required to determine if the benefits shown within the cardiac rehabilitation literature would translate to the older, and more co-morbid population that makes up the A/TAA patient group. However, as logistical challenges pertaining to travel, other hospital, and personal commitments remains a barrier to uptake of structured CR programmes, expansion of CR programmes to regional centres, as well as adoption of virtual CR could serve as a solutions to recruitment challenges.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis trial was supported by a British Heart Foundation Project Grant (PG/13/98/30490).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e: Original Article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrevious Communications:\u003c/strong\u003e Presented at British Society of Endovascular Therapy (BSET) 2016 Meeting\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest / Declarations:\u003c/strong\u003e The authors declare no conflicts of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u0026nbsp;\u003c/strong\u003eGrouped (groups \u0026gt;10 patients), anonymised data used in the trial is available on request from the corresponding author\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Paul Seed, Ray Kausik, Michael Ussher, Jan D Poloniecki, Rajan Sharma, Robert J Hinchliffe, Matthew M Thompson\u0026nbsp;and Alan Karthikesalingam for assistance with obtaining the grant funding and protocol design.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eCRediT statement:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMK: Data Curation, Formal Analysis, Visualisation, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eSB: Conceptualisation, Methodology, Investigation, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eIR: Supervision, Formal Analysis, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eMB: Data Curation, Investigation, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eIL: Supervision, Methodology, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003ePH: Conceptualisation, Funding Acquisition, Methodology, Investigation, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eJB: Data Curation, Formal Analysis, Supervision, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLederle, FA, Freischlag J, Kyriakides T. Outcomes Following Endovascular vs Open Repair of Abdominal Aortic Aneurysm: A Randomized Trial. JAMA. 2009;(302):1535\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eBahia SS, Holt PJE, Jackson D, Patterson BO, Hinchliffe RJ, Thompson MM, et al. Systematic Review and Meta-analysis of Long-term survival After Elective Infrarenal Abdominal Aortic Aneurysm Repair 1969\u0026ndash;2011: 5 Year Survival Remains Poor Despite Advances in Medical Care and Treatment Strategies. Eur J Vasc Endovasc Surg. 2015 Sep;50(3):320\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eChiew K, Roy IN, Budge J, D\u0026rsquo;Abate F, Holt P, Loftus IM. The Fate of Patients Opportunistically Screened for Abdominal Aortic Aneurysms During Echocardiogram or Arterial Duplex Scans. Eur J Vasc Endovasc Surg. 2023 Aug;66(2):188\u0026ndash;93. \u003c/li\u003e\n\u003cli\u003eKarthikesalingam A, Bahia SS, Patterson BO, Peach G, Vidal-Diez A, Ray KK, et al. The Shortfall in Long-term Survival of Patients with Repaired Thoracic or Abdominal Aortic Aneurysms: Retrospective Case\u0026ndash;Control Analysis of Hospital Episode Statistics. Eur J Vasc Endovasc Surg. 2013 Nov;46(5):533\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eNorman PE, Semmens JB, Lawrence-Brown MMD, Holman CDJ. Long term relative survival after surgery for abdominal aortic aneurysm in Western Australia: population based study. BMJ. 1998 Sep 26;317(7162):852\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eBahia SS, Vidal-Diez A, Seshasai SRK, Shpitser I, Brownrigg JR, Patterson BO, et al. Cardiovascular risk prevention and all-cause mortality in primary care patients with an abdominal aortic aneurysm. Br J Surg. 2016 Nov 1;103(12):1626\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eBalady GJ, Ades PA, Bittner VA, Franklin BA, Gordon NF, Thomas RJ, et al. Referral, Enrollment, and Delivery of Cardiac Rehabilitation/Secondary Prevention Programs at Clinical Centers and Beyond: A Presidential Advisory From the American Heart Association. Circulation. 2011 Dec;124(25):2951\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003eBalady GJ, Williams MA, Ades PA, Bittner V, Comoss P, Foody JM, et al. Core Components of Cardiac Rehabilitation/Secondary Prevention Programs: 2007 Update: A Scientific Statement From the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation. 2007 May 22;115(20):2675\u0026ndash;82. \u003c/li\u003e\n\u003cli\u003eFidan D, Unal B, Critchley J, Capewell S. Economic analysis of treatments reducing coronary heart disease mortality in England and Wales, 2000-2010. QJM. 2007 Mar 27;100(5):277\u0026ndash;89. \u003c/li\u003e\n\u003cli\u003eSiercke M, J\u0026oslash;rgensen LP, Missel M, Thygesen LC, M\u0026oslash;ller SP, Sillesen H, et al. Cardiovascular Rehabilitation Increases Walking Distance in Patients With Intermittent Claudication. Results of the CIPIC Rehab Study: A Randomised Controlled Trial. Eur J Vasc Endovasc Surg. 2021 Nov;62(5):768\u0026ndash;76. \u003c/li\u003e\n\u003cli\u003eLong L, Mordi IR, Bridges C, Sagar VA, Davies EJ, Coats AJ, et al. Exercise-based cardiac rehabilitation for adults with heart failure. Cochrane Heart Group, editor. Cochrane Database Syst Rev [Internet]. 2019 Jan 29 [cited 2024 Sep 5];2019(1). Available from: http://doi.wiley.com/10.1002/14651858.CD003331.pub5\u003c/li\u003e\n\u003cli\u003eAnderson L, Oldridge N, Thompson DR, Zwisler AD, Rees K, Martin N, et al. Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease Cochrane Systematic Review and Meta-Analysis. J Am Coll Cardiol. 2016;67(1):1\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eBahia SS, Holt PJ, Ray KK, Ussher M, Poloniecki JD, Sharma R, et al. Cardiac rehabilitation versus standard care after aortic aneurysm repair (Aneurysm CaRe): Study protocol for a randomised controlled trial. Trials. 2015;16(1):1\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eEldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: Extension to randomised pilot and feasibility trials. The BMJ. 2016;355. \u003c/li\u003e\n\u003cli\u003eHerdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727\u0026ndash;36. \u003c/li\u003e\n\u003cli\u003eKotseva K, Wood D, De Bacquer D, De Backer G, Ryd\u0026eacute;n L, Jennings C, et al. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol. 2016;23(6):636\u0026ndash;48. \u003c/li\u003e\n\u003cli\u003eThomas RJ, Balady G, Banka G, Beckie TM, Chiu J, Gokak S, et al. 2018 ACC/AHA Clinical Performance and Quality Measures for Cardiac Rehabilitation: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2018;71(16):1814\u0026ndash;37. \u003c/li\u003e\n\u003cli\u003eDunlay SM, Witt BJ, Allison TG, Hayes SN, Weston SA, Koepsell E, et al. Barriers to participation in cardiac rehabilitation. Am Heart J. 2009;158(5):852\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eLeung YW, Brual J, Macpherson A, Grace SL. Geographic issues in cardiac rehabilitation utilization: A narrative review. Health Place. 2010;16(6):1196\u0026ndash;205. \u003c/li\u003e\n\u003cli\u003eImran HM, Baig M, Erqou S, Taveira TH, Shah NR, Morrison A, et al. Home‐Based Cardiac Rehabilitation Alone and Hybrid With Center‐Based Cardiac Rehabilitation in Heart Failure: A Systematic Review and Meta‐Analysis. J Am Heart Assoc. 2019 Aug 20;8(16):e012779. \u003c/li\u003e\n\u003cli\u003eThomas E, Gallagher R, Grace SL. Future-proofing cardiac rehabilitation: Transitioning services to telehealth during COVID-19. Eur J Prev Cardiol. 2021 Jul 10;28(7):e35\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eFuglsang S, Heiberg J, Hjortdal VE, Laustsen S. Exercise-based cardiac rehabilitation in surgically treated type-A aortic dissection patients. Scand Cardiovasc J. 2017;51(2):99\u0026ndash;105. \u003c/li\u003e\n\u003cli\u003eHornsby WE, Norton EL, Fink S, Saberi S, Wu X, McGowan CL, et al. Cardiopulmonary Exercise Testing Following Open Repair for a Proximal Thoracic Aortic Aneurysm or Dissection. J Cardiopulm Rehabil Prev. 2020;40(2):108\u0026ndash;15. \u003c/li\u003e\n\u003cli\u003eNakayama A, Morita H, Nagayama M, Hoshina K, Uemura Y, Tomoike H, et al. Cardiac rehabilitation protects against the expansion of abdominal aortic aneurysm. J Am Heart Assoc. 2018;7(5):1\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eErbel R, Aboyans V, Boileau C, Bossone E, Di Bartolomeo R, Eggebrecht H, et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases. Eur Heart J. 2014;35(41):2873\u0026ndash;926. \u003c/li\u003e\n\u003cli\u003eShepherd CW, While AE. Cardiac rehabilitation and quality of life: a systematic review. Int J Nurs Stud. 2012;49(6):755\u0026ndash;71. \u003cstrong\u003e\u003cstrong\u003e\u003c/strong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"British Heart Foundation","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6464370/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6464370/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u0026amp; Aims\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbdominal and thoracic aortic aneurysms (A/TAA) are a major cause of mortality in older adults. Most deaths post-A/TAA repair result from cardiovascular events, which may be preventable with cardiac rehabilitation (CR) – a multidisciplinary approach to cardiovascular recovery. The feasibility and acceptability of CR in A/TAA patients remain unknown.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u0026nbsp;\u0026nbsp;\u003c/strong\u003eThis 1:1, non-blinded feasibility randomised trial compared CR to standard care (SC) after elective A/TAA repair at two UK tertiary centres. Patients \u0026lt;50 years, diagnosed with connective tissue disorders, or deemed too unfit for CR were excluded at screening. The CR group followed an 8-week structured programme focusing on medical risk reduction, supervised exercise, and lifestyle modification. Co-primary outcomes were enrolment (target: 60.0%) and CR compliance (target: 70.0%). Secondary outcomes included major cardiac events, cardiovascular biomarkers, echocardiography, lifestyle, and quality of life metrics. This trial was supported by a British Heart Foundation Grant (PG/13/98/30490).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u0026nbsp;\u003c/strong\u003eFrom September 2014 – September 2015, 159 patients were screened, 97 were eligible, and 68 (70.1%) were randomised (SC: 34, CR: 34). CR adherence was 61.8% (n=21), with 13 withdrawals, primarily due to travel and personal commitments (69.2%). At 36 weeks, CR participants maintained higher physical activity levels (40 min vs. 30 min, \u003cem\u003ep\u003c/em\u003e = 0.042).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u0026nbsp;\u003c/strong\u003eRecruiting patients after A/TAA repair to CR is feasible, with good adherence. Virtual or video-based CR may help overcome barriers related to accessing CR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e \u0026nbsp;\u0026nbsp;ISRCTN (65746249).\u003c/p\u003e","manuscriptTitle":"Aneurysm CaRe ­– Randomized Controlled Feasibility Trial of Cardiac Rehabilitation versus Standard Care After Aortic Aneurysm Repair","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 12:17:02","doi":"10.21203/rs.3.rs-6464370/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"64836d0e-0f23-4566-8075-32c86b009dfb","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47299318,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2025-04-17T12:17:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-17 12:17:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6464370","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6464370","identity":"rs-6464370","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}