Ventilatory efficiency as a prognostic factor for postoperative complications in patients undergoing elective major surgery: a systematic review.

BACKGROUND: Major surgery is associated with high complication rates. Several risk scores exist to assess individual patient risk before surgery but have limited precision. Novel prognostic factors can be included as additional building blocks in existing prediction models. A candidate prognostic factor, measured by cardiopulmonary exercise testing, is ventilatory efficiency (VE/VCO2). The aim of this systematic review was to summarise evidence regarding VE/VCO2 as a prognostic factor for postoperative complications in patients undergoing major surgery. METHODS: A medical library specialist developed the search strategy. No database-provided limits, considering study types, languages, publication years, or any other formal criteria were applied to any of the sources. Two reviewers assessed eligibility of each record and rated risk of bias in included studies. RESULTS: From 10,082 screened records, 65 studies were identified as eligible. We extracted adjusted associations from 32 studies and unadjusted from 33 studies. Risk of bias was a concern in the domains 'study confounding' and 'statistical analysis'. VE/VCO2 was reported as a prognostic factor for short-term complications after thoracic and abdominal surgery. VE/VCO2 was also reported as a prognostic factor for mid- to long-term mortality. Data-driven covariable selection was applied in 31 studies. Eighteen studies excluded VE/VCO2 from the final multivariable regression owing to data-driven model-building approaches. CONCLUSIONS: This systematic review identifies VE/VCO2 as a predictor for short-term complications after thoracic and abdominal surgery. However, the available data do not allow conclusions about clinical decision-making. Future studies should select covariables for adjustment a priori based on external knowledge. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022369944).

Effect of a physical activity intervention on lower body bone health in childhood cancer survivors: A randomized controlled trial (SURfit).

It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, <16 years at diagnosis and ≥5 years in remission were identified from the national Childhood Cancer Registry. Participants randomized to the intervention group were asked to perform an additional ≥2.5 hours of intense physical activity/week, controls continued exercise as usual. Bone health was assessed as a secondary trial endpoint at baseline and after 12-months. We measured tibia bone mineral density (BMD) and morphology by peripheral quantitative computed tomography and lumbar spine, hip and femoral neck BMD by dual-energy x-ray absorptiometry. We performed intention-to-treat, per protocol, and an explorative subgroup analyses looking at low BMD using multiple linear regressions. One hundred fifty-one survivors (44% females, 7.5 ± 4.9 years at diagnosis, 30.4 ± 8.6 years at baseline) were included. Intention-to-treat analysis revealed no differences in changes between the intervention and control group. Per protocol analyses showed evidence for an improvement in femoral neck and trabecular BMD between 1.5% and 1.8% more in participants being compliant with the exercise program. Trabecular BMD increased 2.8% more in survivors of the intervention group with BMD z-score ≤-1 compared to those starting at z-score >-1. A nonstandardized personalized exercise programs might not be specific enough to promote bone health in CCS, although those compliant and those most in need may benefit. Future trials should include bone stimulating exercise programs targeting risk groups with reduced bone health and motivational features to maximize compliance.

High impact physical activity and bone health of lower extremities in childhood cancer survivors: A cross-sectional study of SURfit.

Childhood cancer survivors (CCS) are at risk of reduced bone health and premature osteoporosis. As physical activity with high impact loading (IL-PA) is known to promote bone health, we compared bone densitometry and microstructure between groups of CCS who performed different amounts of physical activities in their daily life. We used baseline data of a single-center PA trial including 161 CCS from the Swiss Childhood Cancer Registry, aged <16 at diagnosis, ≥16 at study and ≥5 years since diagnosis. Lower body bone health was assessed with peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA). Daily IL-PA (duration in activities >2 g acceleration and numbers of vertical impacts/hr >2 g) was captured using hip-worn accelerometers (1-3 weeks). For both IL-PA approaches, we formed low, middle and high activity groups based on tertiles. Bone health of the high and middle active groups was compared to the low active group. 63% of CCS had indication of at least one bone mineral density z-score ≤ -1 measured by pQCT or DXA. The high IL-PA group performing 2.8 min/day or 19.1 impact peaks/hr > 2 g (median) showed about 3-13% better microstructural and densitometric bone health as compared to the low IL-PA group with 0.38 min/day or 0.85 peaks/hr > 2 g. Just a few minutes and repetitions of high IL-PA as easily modifiable lifestyle factor may be sufficient to improve bone health in adult CCS. Future longitudinal research is needed to better understand pattern and dosage of minimal impact loading needed to strengthen bone in growing and adult CCS.

Clinical outcomes after cardiac rehabilitation in elderly patients with and without diabetes mellitus: The EU-CaRE multicenter cohort study.

BACKGROUND: The prevalence of patients with concomitant cardiovascular disease and diabetes mellitus (DM) is increasing rapidly. We aimed to compare the effectiveness of current cardiac rehabilitation (CR) programs across seven European countries between elderly cardiac patients with and without DM. METHODS: 1633 acute and chronic coronary artery disease (CAD) patients and patients after valve intervention with an age 65 or above who participated in comprehensive CR (3 weeks to 3 months, depending on centre) were included. Peak oxygen uptake (VO2 peak), body mass index, resting systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), and glycated haemoglobin (HbA1c) were assessed before start of CR, at termination of CR (variable time point), and 12 months after start of CR, with no intervention after CR. Baseline values and changes from baseline to 12-month follow-up were compared between patients with and without DM using mixed models, and mortality and hospitalisation rates using logistic regression. RESULTS: 430 (26.3%) patients had DM. Patients with DM had more body fat, lower educational level, more comorbidities, cardiovascular risk factors, and more advanced CAD. Both groups increased their VO2 peak over the study period but with a significantly lower improvement from baseline to follow-up in patients with DM. In the DM group, change in HbA1c was associated with weight change but not with change in absolute VO2 peak. 12-month cardiac mortality was higher in patients with DM. CONCLUSIONS: While immediate improvements in VO2 peak after CR in elderly patients with and without DM were similar, 12-month maintenance of this improvement was inferior in patients with DM, possibly related to disease progression. Glycemic control was less favourable in diabetic patients needing insulin in the short- and long-term. Since glycemic control was only related to weight loss but not to increase in exercise capacity, this highlights the importance of weight loss in obese DM patients during CR. Trial registration NTR5306 at trialregister.nl; trial registered 07/16/2015; https://www.trialregister.nl/trial/5166.

A partially supervised physical activity program for adult and adolescent survivors of childhood cancer (SURfit): study design of a randomized controlled trial [NCT02730767].

BACKGROUND: Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today's survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). Primary outcome of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. Secondary outcomes are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety). METHODS: A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant. DISCUSSION: The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients. TRIAL REGISTRATION: Prospectively registered in clinicaltrials.gov [ NCT02730767 ], registration date: 10.12.2015.

Sex differences in heart rate variability: a longitudinal study in international elite cross-country skiers.

PURPOSE: Exercise-related sudden cardiac deaths (SCD) occur with a striking male predominance. A higher sympathetic tone in men has been suggested as risk factor for SCD. Elite athletes have the highest risk for exercise-related SCD. We aimed to analyze the autonomic nervous system of elite cross-country skiers from Norway, Russia and Switzerland in supine position and after orthostatic challenge in various training periods (TP). METHOD: Measurements of heart rate variability (HRV) were performed on a weekly basis over 1 year using an orthostatic challenge test with controlled breathing. Main outcome parameters were the high-frequency power in supine position (HFsupine) as marker of cardiac parasympathetic activity and the low-frequency/high-frequency power ratio after orthostatic challenge (LF/HFstand) as marker of cardiac sympathetic activation. Training intensity and duration were recorded daily and expressed as training strain. The training year was divided into three TPs. An average of weekly HRV measurements was calculated for each TP. RESULT: Female (n = 19, VO2max 62.0 ± 4.6 ml kg(-1) min(-1), age 25.8 ± 4.3 years) and male (n = 16, VO2max 74.3 ± 6.3 ml kg(-1) min(-1), age 24.4 ± 4.2 years) athletes were included. Training strain was comparable between sexes (all p > 0.05) and changed between TPs (all p < 0.05) while no HRV parameters changed over time. There were no sex differences in HFsupine while the LF/HFstand was significantly higher in male athletes in all TPs. CONCLUSION: For a comparable amount of training, male athletes showed constantly higher markers of sympathetic activity after a provocation maneuver. This may explain part of the male predominance in sports-related SCD.

Good reproducibility of heart rate variability after orthostatic challenge in patients with a history of acute coronary syndrome.

BACKGROUND: Several parameters of heart rate variability (HRV) have been shown to predict the risk of sudden cardiac death (SCD) in cardiac patients. There is consensus that risk prediction is increased when measuring HRV during specific provocations such as orthostatic challenge. For the first time, we provide data on reproducibility of such a test in patients with a history of acute coronary syndrome. METHODS: Sixty male patients (65 ± 8 years) with a history of acute coronary syndrome on stable medication were included. HRV was measured in supine (5 min) and standing (5 min) position on 2 occasions separated by two weeks. For risk assessment relevant time-domain [standard deviation of all R-R intervals (SDNN) and root mean squared standard differences between adjacent R-R intervals (RMSSD)], frequency domain [low-frequency power (LF), high-frequency power (HF) and LF/HF power ratio] and short-term fractal scaling component (DF1) were computed. Absolute reproducibility was assessed with the standard errors of the mean (SEM) and 95% limits of random variation, and relative reproducibility by the intraclass correlation coefficient (ICC). RESULTS: We found comparable SEMs and ICCs in supine position and after an orthostatic challenge test. All ICCs were good to excellent (ICCs between 0.636 and 0.869). CONCLUSIONS: Reproducibility of HRV parameters during orthostatic challenge is good and comparable with supine position.

Reproducibility of peripheral arterial tonometry measurements in male cardiovascular patients.

BACKGROUND: Assessment of endothelial function of the microvasculature by peripheral arterial tonometry (EndoPAT(®)) has gained increasing popularity in patients with cardiovascular risk factors. Only limited knowledge about its reproducibility in patients with coronary artery disease (CAD) is available. We therefore aimed to quantify reproducibility of EndoPAT(®) parameters in patients with stable CAD. DESIGN: EndoPAT(®) measurements were performed repeatedly in 78 male patients (age 66 ± 8 years) with CAD on stable medication. We calculated overall mean, standard deviation (SD), coefficient of variation (CV) and intraclass correlation coefficient (ICC) of the following parameters: reactive hyperemic index (RHI), PAT ratio of the postocclusion period 90-150 s as used for calculation of the RHI (PAT ratio90-150 s) and 90-120 s (PAT ratio90-120 s) as used for the often employed Framingham RHI (F-RHI), as well as PAT ratio of the peak hyperemic response (PAT ratiopeak response). Additionally, least significant changes (LSC) for individual subjects and minimum sample sizes for parallel and cross-over design studies were calculated. RESULTS: Mean RHI was 1·84 (SD 0·36). For RHI, PAT ratio90-150 s , PAT ratio90-120 s , and PAT ratiopeak response the CVs were 17·0%, 25·4%, 26·1%, and 25·0%, respectively. The ICCs were 0·45, 0·49, 0·48 and 0·51, respectively, and LSC for RHI was 47·2%. CONCLUSIONS: CV of RHI in our population was moderate; however, we consider this precision insufficient to monitor changes in individual patients, as they would need to exceed 47% to show a significant change. Further, the poor ICCs reflect the difficulty of detecting treatment effects in homogenous populations, such as patients with stable CAD.

Interdisciplinary cardiovascular and neurologic outpatient rehabilitation in patients surviving transient ischemic attack or stroke with minor or no residual deficits.

OBJECTIVE: To evaluate the feasibility and effectiveness of a comprehensive outpatient rehabilitation program combining secondary prevention and neurorehabilitation to improve vascular risk factors, neurologic functions, and health-related quality of life (HRQOL) in patients surviving a transient ischemic attack (TIA) or stroke with minor or no residual deficits. DESIGN: Prospective interventional single-center cohort study. SETTING: University hospital. PARTICIPANTS: Consecutive consenting patients having sustained a TIA or stroke with 1 or more vascular risk factors (N=105) were included. INTERVENTIONS: Three-month hospital-based secondary prevention and neurorehabilitation outpatient program with therapeutic and educational sessions twice a week. Patients were evaluated at entry and program end. MAIN OUTCOME MEASURES: Impact on vascular risk factors, neurological outcome, and HRQOL. RESULTS: A total of 105 patients entered the program and 95 patients completed it. Exercise capacity (P<.000), smoking status (P=.001), systolic (P=.001) and diastolic (P=.008) blood pressure, body mass index (P=.005), low-density lipoprotein cholesterol (P=.03), and triglycerides (P=.001) improved significantly. Furthermore, the 9-Hole-Peg-Test (P<.000), Six-minute Walking Test (P<.000), and One Leg Stand Test (P<.011) values as well as HRQOL improved significantly. The program could be easily integrated into an existing cardiovascular prevention and rehabilitation center and was feasible and highly accepted by patients. CONCLUSIONS: Comprehensive combined cardiovascular and neurologic outpatient rehabilitation is feasible and effective to improve vascular risk factors, neurologic functions, and HRQOL in patients surviving TIA or stroke with minor or no residual deficits.

Qualitative assessment of expectations on the content, form and way of delivery of a prehabilitation programme in patients with lung resection surgery - A Swiss tertiary centre experience.

Objective: To assess the interest in a prehabilitation programme of patients awaiting lung resection and to identify expectations from such a programme. Introduction: At present, in Switzerland, there are no multimodal clinical prehabilitation programmes for lung resection patients awaiting surgery. Methods: Semi-structured face-to-face interviews were conducted with patients who have had or were awaiting lung resection at a Swiss tertiary centre. Thematic analysis was performed to identify common prespecified themes. Results: Twenty-two patients (45.5% female, age 70.6 ± 16.6 years) were interviewed. Seventy-seven percent were interested in a prehabilitation programme. Sixty-two percent, 67% and 90% were interested in endurance, strength and respiratory training, respectively. Six patients (27%) were active smokers, of whom two (one-third) were interested in a smoking cessation programme. Seventy-six percent were interested in nutrition counselling and 90% in receiving education on risk factor management. Forty percent preferred centre-based training/counselling sessions, 20% preferred home-based training/counselling and 30% found both forms acceptable. Patients were willing to perform prehabilitation activities on 2.6 days/week for a total of 162 min/week. Participating in peer groups was desired by only 25%. Conclusions: Patients with lung resection were highly interested in participating in prehabilitation, albeit only for a mean time cost of 2.7 h per week. Offering a prehabilitation programme with a combination of in-hospital group sessions and home-based training seems feasible.

Timing of cardio-oncological rehabilitation and cardiorespiratory fitness in patients receiving cardiotoxic chemotherapy: a longitudinal observational study.

AIMS: Anthracycline-based chemotherapy has well-known cardiotoxic effects, butmay also cause skeletal muscle myopathy and negatively affect cardiorespiratory fitness and quality of life. The effectiveness of exercise training in improving cardiorespiratory fitness and quality of life during chemotherapy is highly variable. We set out to determine how the effect of exercise training on cardiorespiratory fitness (primary outcome) and quality of life (secondary outcome) in cancer patients is affected by the type of therapy they receive (cardiotoxic therapy with or without anthracyclines; non-cardiotoxic therapy) and the timing of the exercise training (during or after therapy). METHODS: Consecutive patients with cancer who participated in an exercise-based cardio-oncology rehabilitation programme at a university hospital in Switzerland between January 2014 and February 2022 were eligible. Patients were grouped based on chemotherapy (anthracycline vs non-anthracycline) and timing of exercise training (during vs after chemotherapy). Peak oxygen uptake (VO2) was assessed with cardiopulmonary exercise testing (n = 200), and quality of life with the Functional Assessment of Cancer Therapies questionnaire (n = 77). Robust linear models were performed for change in peak VO2 including type and timing of cardiotoxic therapies, age, training impulse and baseline peak VO2; change in quality of life was analysed with cumulative linked models. RESULTS: In all patients with valid VO2 (n = 164), median change in peak VO2 from before to after exercise training was 2.3 ml/kg/min (range: -10.1-15.9). The highest median change in peak VO2 was 4.1 ml/kg/min (interquartile range [IQR]: 0.7-7.7) in patients who completed exercise training during non-anthracycline cardiotoxic or non-cardiotoxic therapies, followed by 2.8 ml/kg/min (IQR: 1.2-5.3) and 2.3 ml/kg/min (IQR: 0.1-4.6) in patients who completed exercise training after anthracycline and after non-anthracycline cardiotoxic or non-cardiotoxic therapies, respectively. In patients who completed exercise training during anthracycline therapy, peak VO2 decreased by a median of -2.1 ml/kg/min (IQR: -4.7-2.0). In the robust linear model, there was a significant interaction between type and timing of cancer treatment for anthracycline therapy, with greater increases in peak VO2 when exercise training was performed after anthracycline therapy. For quality of life, higher baseline scores were negatively associated with changes in quality of life. CONCLUSION: In our cohort, the increase in cardiorespiratory fitness was diminished when exercise training was performed concurrently with anthracyclines. For patients with cardiotoxic treatments other than anthracyclines, cardiorespiratory fitness and quality of life was not associated with timing of exercise training.

High-volume sports club participation and autonomic nervous system activity in children.

BACKGROUND: Sixty minutes of daily moderate-to-vigorous physical activity (PA) are recommended for children. This study investigated the additional impact of high-volume sports club participation on the autonomic nervous system in active children, while controlling for acute effects of short-term PA. MATERIALS AND METHODS: Forty-nine children (29 females) aged 10-13 years were investigated. Sports club participation was assessed with a validated questionnaire. Short-term PA and night-time autonomic tone (spectral power and nonlinear analysis of heart rate variability) were measured with an ambulatory device (Actiheart(®) ). Children were dichotomized into two groups, based on their individual weekly time spent in a sports club: low-volume group < 180 min/week (N = 26) and high-volume group ≥ 180 min/week (N = 23). RESULTS: Children in the high-volume group exhibited higher indices of vagal tone compared with the children in the low-volume group. Short-term moderate PA had a significant impact on the night course of autonomic activity. Boys showed a linear increase in vagal activity over the night course in relation to volumes of short-term moderate PA of the previous day. A similar but nonsignificant trend was observed for girls. CONCLUSIONS: In active children, higher volumes of sports club participation have an additional benefit on indices of autonomic tone.

Physical activity intensity and surrogate markers for cardiovascular health in adolescents.

We examined the impact of physical activity (PA) on surrogate markers of cardiovascular health in adolescents. 52 healthy students (28 females, mean age 14.5 ± 0.7 years) were investigated. Microvascular endothelial function was assessed by peripheral arterial tonometry to determine reactive hyperemic index (RHI). Vagal activity was measured using 24 h analysis of heart rate variability [root mean square of successive normal-to-normal intervals (rMSSD)]. Exercise testing was performed to determine peak oxygen uptake ([Formula: see text]) and maximum power output. PA was assessed by accelerometry. Linear regression models were performed and adjusted for age, sex, skinfolds, and pubertal status. The cohort was dichotomized into two equally sized activity groups (low vs. high) based on the daily time spent in moderate-to-vigorous PA (MVPA, 3,000-5,200 counts(.)min(-1), model 1) and vigorous PA (VPA, >5,200 counts(.)min(-1), model 2). MVPA was an independent predictor for rMSSD (ß = 0.448, P = 0.010), and VPA was associated with maximum power output (ß = 0.248, P = 0.016). In model 1, the high MVPA group exhibited a higher vagal tone (rMSSD 49.2 ± 13.6 vs. 38.1 ± 11.7 ms, P = 0.006) and a lower systolic blood pressure (107.3 ± 9.9 vs. 112.9 ± 8.1 mmHg, P = 0.046). In model 2, the high VPA group had higher maximum power output values (3.9 ± 0.5 vs. 3.4 ± 0.5 W kg(-1), P = 0.012). In both models, no significant differences were observed for RHI and [Formula: see text]. In conclusion, in healthy adolescents, PA was associated with beneficial intensity-dependent effects on vagal tone, systolic blood pressure, and exercise capacity, but not on microvascular endothelial function.

Adolescent blood pressure hyperreactors have a higher reactive hyperemic index at the fingertip.

PURPOSE: The use of peripheral arterial tonometry (PAT) to assess microvascular endothelial function is getting increasingly popular in the pediatric population. The aim of the present study was to examine the impact of blood pressure (BP) hyperreactivity on microvascular hyperemic reaction in healthy, normotensive adolescents. METHODS: Fifty-two adolescents with a mean age of 14.5 ± 0.7 years were investigated. Microvascular endothelial function was assessed at rest and after exhaustive cycling exercise using PAT to determine the reactive hyperemic index (RHI, primary endpoint). Hyperreactors were identified according to their cardiovascular response to a cold pressor test. Indices of autonomic tone were assessed with an ambulatory electrocardiograph and cardiopulmonary exercise testing was performed on a cycle ergometer. Physical activity was measured using accelerometry. ANOVA with repeated measures and Tukey HSD post hoc tests were applied to determine differences between BP hyperreactors and controls (normal reactors). RESULTS: Sixteen adolescents were identified as hyperreactors and matched with regard to age, sex, pubertal status, and height with 16 normal reactors. At rest, hyperreactors had a significantly higher RHI than normal reactors (2.1 ± 0.4 vs. 1.6 ± 0.4, P = 0.003). After exhaustive cycling exercise, the differences in RHI were abolished. No differences between these two groups existed in physical activity levels, exercise capacity and indices of autonomic tone. CONCLUSIONS: Our data suggest that normotensive hyperreactors have a markedly higher RHI compared to normal reactors. Future studies using PAT to assess microvascular endothelial function should bare in mind the large effect of vascular hyperreactivity.

Multimodal prehabilitation for major surgery in elderly patients to lower complications: protocol of a randomised, prospective, multicentre, multidisciplinary trial (PREHABIL Trial).

INTRODUCTION: The global volume of surgery is growing and the population ageing, and economic pressure is rising. Major surgery is associated with relevant morbidity and mortality. Postoperative reduction in physiological and functional capacity is especially marked in the elderly, multimorbid patient with low fitness level, sarcopenia and malnutrition. Interventions aiming to optimise the patient prior to surgery (prehabilitation) may reduce postoperative complications and consequently reduce health costs. METHODS AND ANALYSIS: This is a multicentre, multidisciplinary, prospective, 2-arm parallel-group, randomised, controlled trial with blinded outcome assessment. Primary outcome is the Comprehensive Complications Index at 30 days. Within 3 years, we aim to include 2×233 patients with a proven fitness deficit undergoing major surgery to be randomised using a computer-generated random numbers and a minimisation technique. The study intervention consists of a structured, multimodal, multidisciplinary prehabilitation programme over 2-4 weeks addressing deficits in physical fitness and nutrition, diabetes control, correction of anaemia and smoking cessation versus standard of care. ETHICS AND DISSEMINATION: The PREHABIL trial has been approved by the responsible ethics committee (Kantonale Ethikkomission Bern, project ID 2020-01690). All participants provide written informed consent prior to participation. Participant recruitment began in February 2022 (10 and 8 patients analysed at time of submission), with anticipated completion in 2025. Publication of the results in peer-reviewed scientific journals are expected in late 2025. TRIAL REGISTRATION NUMBER: NCT04461301.

Supervised exercise training in patients with cancer during anthracycline-based chemotherapy to mitigate cardiotoxicity: a randomized-controlled-trial.

Background: Exercise training (ET) has been shown to mitigate cardiotoxicity of anthracycline-based chemotherapies (AC) in animal models. Data from randomized controlled trials in patients with cancer are sparse. Methods: Patients with breast cancer or lymphoma receiving AC were recruited from four cancer centres and randomly assigned to 3 months supervised ET. Primary outcome was change in left ventricular global longitudinal strain (GLS) from baseline (before AC) to post AC (AC-end) compared between the EXduringAC group, who participated in an exercise intervention during AC including the provision of an activity tracker, and the control group EXpostAC, who received an activity tracker only. Secondary outcome parameters were changes in high sensitivity Troponin T (hsTnT), NT-pro-brain natriuretic peptide (NT-proBNP), peak oxygen consumption (peak VO2) and objectively measured physical activity (PA) during this same time-period. All assessments were repeated at a 12-week follow-up from AC-end, when also the EXpostAC group had completed the ET, that started after AC. In exploratory analyses, robust linear models were performed to assess the association of PA with changes in echocardiographic parameters and biomarkers of LV function. Results: Fifty-seven patients (median age 47 years; 95% women) were randomized to EXduringAC (n = 28) and EXpostAC (n = 29) group. At AC-end, GLS deteriorated in both study groups (albeit insignificantly) with 7.4% and 1.0% in EXduringAC (n = 18) and EXpostAC (n = 18), respectively, and hsTnT and NT-proBNP significantly increased in both groups, without difference between groups for any parameter. Change in peak VO2 (-1.0 and -1.1 ml/kg/min) at AC-end was also similar between groups as was duration of moderate-to-vigorous PA (MVPA) with a median of 33 [26, 47] min/day and 32 [21, 59] min/day in the EXduringAC and EXpostAC group, respectively. In the robust linear model including the pooled patient population, MVPA was significantly associated with a more negative GLS and lesser increase in hsTnT at AC-end. Conclusion: In this small scale RCT, supervised ET during AC was not superior to wearing a PA tracker to mitigate cardiotoxicity. The dose-response relationship between PA and cardioprotective effects during AC found in our and previous data supports the notion that PA should be recommended to patients undergoing AC. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03850171.

Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction-modification with exercise-based cardiac rehabilitation and prognostic value.

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

Puberty and microvascular function in healthy children and adolescents.

OBJECTIVE: To determine the role of pubertal status on microvascular function in healthy children and adolescents. STUDY DESIGN: Children and adolescents (n = 112; age 10-16 years) were investigated in 2 separate prospective cross-sectional studies. The main outcome measure was microvascular function, assessed by peripheral arterial tonometry to determine the reactive hyperemic index (RHI). Physical activity was assessed using 7-day recall in one study and accelerometry in the other study. Subjects were grouped based on their self-assessed pubertal status according to Tanner stage: group 1 (prepuberty, Tanner I), group 2 (mid-puberty, Tanner II/III), and group 3 (late puberty, Tanner IV/V). Stepwise multiple regression analysis was performed to identify independent predictors of the RHI. RESULTS: Complete data were available for 94 subjects (55 females) with a median (IQR) age of 14 (3.0) years and a mean body mass index of 19.0 ± 3.63 kg·m(-2). Significant correlations with RHI were observed for Tanner stage (r = 0.569; P < .001), age (r = 0.567; P < .001), stature (r = 0.553; P < .001), systolic blood pressure (r = 0.494; P < .001), and body mass index (r = 0.309; P = .001), but not for sex and moderate-to-vigorous physical activity. In stepwise regression analysis, pubertal status was the only independent predictor of microvascular function (R(2) = 0.242; ß = 0.492; P < .001). Prepubertal children (group 1) had a significantly lower RHI [1.14 (0.24)] compared with group 2 [1.65 (0.57)] and group 3 [1.70 (0.75)] (all P < .001). CONCLUSION: Pubertal status was the main predictor of microvascular function in healthy children and adolescents. Future studies investigating microvascular function in this age group should assess and control for pubertal maturation.

Validation of open-source step-counting algorithms for wrist-worn tri-axial accelerometers in cardiovascular patients.

BACKGROUND: Accurate quantification of daily steps in a cardiovascular patient population is of high importance for primary and secondary prevention. While sensor derived step counts have been sufficiently validated for hip-worn devices and commercial wrist-worn devices, there is a lack of knowledge on validity of freely available step counting algorithms for raw acceleration data collected at the wrist. RESEARCH QUESTION: How accurate are step-counting algorithms for wrist worn tri-axial accelerometers in a cardiac rehabilitation training setting? METHODS: Two step counting algorithms (Windowed Peak Detection, Autocorrelation) for tri-axial accelerometers (Axivity AX-3), were tested. Steps were recorded by chest-mounted GoPro video cameras as gold standard. Cardiovascular patients without neurological impairments enrolled in an ambulatory rehabilitation program were recruited. Recordings were performed during one 45-90 min outdoor physical therapy session of which 5-min segments of six movement categories, namely Walking, Running, Nordic, Stairs, Arm Movement [AM] With [+] and Without [-] Walking [W] were identified and analyzed. Mean absolute difference and mean absolute percentage error [MAPE] with regard to true steps measured from video are reported to report accuracy. RESULTS: Training sessions of 22 patients were recorded and analyzed. Steps were overestimated during AM-W and underestimated during Walking, Running and Stairs. Windowed Peak Detection algorithm was more accurate during AM+W and AM-W and Autocorrelation performed better during Nordic. A MAPE of close or below 10% was achieved by both algorithms for the categories: Walking, Running, Stairs and Nordic. SIGNIFICANCE: Both algorithms provided accurate results for estimation of step counts in a controlled setting of a cardiovascular patient population. The quantification of daily number of steps recorded by wrist-worn accelerometers delivering raw data analyzed by freely available algorithms is a cost-effective option for research studies.

Young endurance training starting age in non-elite athletes is associated with higher proximal aortic distensibility.

OBJECTIVE: Decreased proximal aortic distensibility (AD) is known to significantly predict all-cause mortality and cardiovascular events among individuals without overt cardiovascular disease. This cross-sectional study investigated the association of endurance training (ET) parameters, namely, ET starting age, ET years and yearly ET volume with AD in non-elite endurance athletes. METHODS: Healthy, normotensive, male Caucasian participants of a 10-mile race were assessed with a 2D echocardiogram and comprehensive interview. Ascending aortic diameters were measured simultaneously with pulse pressure. Aortic strain, AD and aortic stiffness index were calculated. Predictors of AD were investigated among training parameters by linear regression models corrected for age, resting heart rate, stroke volume index and mean blood pressure. RESULTS: Ninety-two of 121 athletes (aged 42±8 years) had sufficient echocardiogram quality and were used for analysis. ET starting age (range 6-52 years) and years of ET (range 2-46 years) were highly collinear and used in two separate models for AD. Significant factors for AD were ET starting age, 10-mile race time and resting heart rate in model I, and age, years of ET, 10-mile race time and heart rate in model II (all p<0.01). CONCLUSIONS: In our cohort of healthy, non-elite, middle-aged runners, AD was significantly higher in athletes with younger ET starting age or more years of ET (in the model adjusted for confounders). In the model with years of ET, age had a negative contribution to AD, suggesting that with older age, the benefit of more years of ET on AD decreased. Future studies assessing the effect of exercise training on arterial properties should include training starting age.