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.

Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: The EU-CaRE study.

AIMS: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients. METHODS: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center. RESULTS: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001). CONCLUSIONS: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs.

This study explores the association between exercise capacity and the well-being of elderly cardiac patients participating in a cardiac rehabilitation program, focusing on health-related quality of life (HRQoL), anxiety, and depression. Key Findings:Women, despite having higher percentages of predicted exercise capacity, consistently reported poorer HRQoL, anxiety, and depression scores compared to men at all assessed time points.Improvements in exercise capacity were strongly associated with positive changes in HRQoL and mental health, with these associations being more pronounced in men.

Calabi-Yau Meets Gravity: A Calabi-Yau Threefold at Fifth Post-Minkowskian Order.

We study geometries occurring in Feynman integrals that contribute to the scattering of black holes in the post-Minkowskian (PM) expansion. These geometries become relevant to gravitational-wave production from binary mergers through the classical conservative potential. At 4PM, a K3 surface is known to occur in a three-loop integral, leading to elliptic integrals in the result. In this Letter, we identify a Calabi-Yau threefold in a four-loop integral, contributing at 5PM. The presence of this Calabi-Yau geometry indicates that completely new functions occur in the full analytical results.

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).

Ultra-Cycling- Past, Present, Future: A Narrative Review.

BACKGROUND: Ultra-endurance events are gaining popularity in multiple exercise disciplines, including cycling. With increasing numbers of ultra-cycling events, aspects influencing participation and performance are of interest to the cycling community. MAIN BODY: The aim of this narrative review was, therefore, to assess the types of races offered, the characteristics of the cyclists, the fluid and energy balance during the race, the body mass changes after the race, and the parameters that may enhance performance based on existing literature. A literature search was conducted in PubMed, Scopus, and Google Scholar using the search terms 'ultracycling', 'ultra cycling', 'ultra-cycling', 'ultra-endurance biking', 'ultra-bikers' and 'prolonged cycling'. The search yielded 948 results, of which 111 were relevant for this review. The studies were classified according to their research focus and the results were summarized. The results demonstrated changes in physiological parameters, immunological and oxidative processes, as well as in fluid and energy balance. While the individual race with the most published studies was the Race Across America, most races were conducted in Europe, and a trend for an increase in European participants in international races was observed. Performance seems to be affected by characteristics such as age and sex but not by anthropometric parameters such as skin fold thickness. The optimum age for the top performance was around 40 years. Most participants in ultra-cycling events were male, but the number of female athletes has been increasing over the past years. Female athletes are understudied due to their later entry and less prominent participation in ultra-cycling races. A post-race energy deficit after ultra-cycling events was observed. CONCLUSION: Future studies need to investigate the causes for the observed optimum race age around 40 years of age as well as the optimum nutritional supply to close the observed energy gap under consideration of the individual race lengths and conditions. Another research gap to be filled by future studies is the development of strategies to tackle inflammatory processes during the race that may persist in the post-race period.

Accurate Prediction Equations for Ventilatory Thresholds in Cardiometabolic Disease When Gas Exchange Analysis is Unavailable: Development and Validation.

AIMS: To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains. METHODS: Cross-sectional study involving 2,868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). 'Adjusted' percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1,893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland-Altman analyses, intraclass correlation coefficients (ICC). RESULTS: HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), 'good' ICC for VT1 (0.81, 0.82) and 'excellent' for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8%-21.3%, VT2: 5.1%-16.7%), 'poor' to 'good' ICC for VT1, and 'poor' to 'excellent' for VT2, indicating inconsistencies related to specific VTs across guidelines. CONCLUSION: Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.

Equations to predict heart rate at ventilatory thresholds were developed and externally validated, offering a new perspective when a cardiopulmonary exercise test is unavailable to accurately determine the aerobic exercise intensity domains. Additionally, an adjusted range for exercise intensity prescription based on the percentage of heart rate reserve (%HRR) was provided, utilizing a large sample from eight countries. The proposed equations and the range-adjusted %HRR significantly outperformed the guideline-directed methods for determining exercise intensity, exhibiting higher accuracy, agreement, and reliability. Exercise intensity prescription based on the percentage of heart rate peak showed higher errors, raising concerns about its clinical applicability. Our study may enhance the efficacy of exercise training and physical activity advice when gas exchange analysis is unavailable, potentially leading to improved clinical outcomes, even in low-resource settings. Employing these approaches in research could facilitate more tailored and consistent interventions, introducing a contemporary perspective for studies comparing exercise intensity prescriptions.

European Society of Cardiology Core Curriculum for cardio-oncology.

Cardio-oncology is a rapidly growing field of cardiovascular (CV) medicine that has resulted from the continuously increasing clinical demand for specialized CV evaluation, prevention and management of patients suffering or surviving from malignant diseases. Dealing with CV disease in patients with cancer requires special knowledge beyond that included in the general core curriculum for cardiology. Therefore, the European Society of Cardiology (ESC) has developed a special core curriculum for cardio-oncology, a consensus document that defines the level of experience and knowledge required for cardiologists in this particular field. It is structured into 8 chapters, including (i) principles of cancer biology and therapy; (ii) forms and definitions of cancer therapy-related cardiovascular toxicity (CTR-CVT); (iii) risk stratification, prevention and monitoring protocols for CTR-CVT; (iv) diagnosis and management of CV disease in patients with cancer; (v) long-term survivorship programmes and cardio-oncology rehabilitation; (vi) multidisciplinary team management of special populations; (vii) organization of cardio-oncology services; (viii) research in cardio-oncology. The core curriculum aims at promoting standardization and harmonization of training and evaluation in cardio-oncology, while it further provides the ground for an ESC certification programme designed to recognize the competencies of certified specialists.

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.

Bootstrapping Elliptic Feynman Integrals Using Schubert Analysis.

The symbol bootstrap has proven to be a powerful tool for calculating polylogarithmic Feynman integrals and scattering amplitudes. In this Letter, we initiate the symbol bootstrap for elliptic Feynman integrals. Concretely, we bootstrap the symbol of the twelve-point two-loop double-box integral in four dimensions, which depends on nine dual-conformal cross ratios. We obtain the symbol alphabet, which contains 100 logarithms as well as nine simple elliptic integrals, via a Schubert-type analysis, which we equally generalize to the elliptic case. In particular, we find a compact, one-line formula for the (2,2) coproduct of the result.

Exercise benefits in cardiovascular diseases: from mechanisms to clinical implementation.

There is a pandemic of physical inactivity that appears to parallel the widespread prevalence of cardiovascular disease (CVD). Yet, regular physical activity (PA) and exercise can play an important role not only in primary cardiovascular prevention but also in secondary prevention. This review discusses some of the main cardiovascular effects of PA/exercise and the mechanisms involved, including a healthier metabolic milieu with attenuation of systemic chronic inflammation, as well as adaptations at the vascular (antiatherogenic effects) and heart tissue (myocardial regeneration and cardioprotection) levels. The current evidence for safe implementation of PA and exercise in patients with CVD is also summarized.

Antipodal Self-Duality for a Four-Particle Form Factor.

We bootstrap the symbol of the maximal-helicity-violating four-particle form factor for the chiral part of the stress-tensor supermultiplet in planar N=4 super-Yang-Mills theory at two loops. When minimally normalized, this symbol involves only 34 letters and obeys the extended Steinmann relations in all partially overlapping three-particle momentum channels. In addition, the remainder function for this form factor exhibits an antipodal self-duality: It is invariant under the combined operation of the antipodal map defined on multiple polylogarithms-which reverses the order of the symbol letters-and a simple kinematic map. This self-duality holds on a four-dimensional parity-preserving kinematic hypersurface. It implies the antipodal duality recently noticed between the three-particle form factor and the six-particle amplitude in this theory.

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.

The need for long-term personalized management of frail CVD patients by rehabilitation and telemonitoring: A framework.

Due to advances in cardiovascular medicine and preventive cardiology, patients benefit from a better prognosis, even in case of significant disease burden such as acute and chronic coronary syndromes, advanced valvular heart disease and chronic heart failure. These advances have allowed CVD patients to increase their life expectancy, but on the other hand also experience aging-related syndromes such as frailty. Despite being underrecognized, frailty is a critical, common, and co-existent condition among older CVD patients, leading to exercise intolerance and compromised adherence to cardiovascular rehabilitation (CR). Moreover, frail patients need a different approach for CR and are at very high risk for adverse events, but yet are underrepresented in conventional CR. Fortunately, recent advances have been made in technology, allowing remote monitoring, coaching and supervision of CVD patients in secondary prevention programs with promising benefits. Similarly, we hypothesized that such programs should also be implemented to treat frailty in CVD patients. However, considering frail patients' particular needs and challenges, telerehabilitation interventions should thus be appropriately adapted. Our purpose is to provide, for the first time and based on expert opinions, a framework of how such a cardiac telerehabilitation program could be developed and implemented to manage a prevention and rehabilitation program for CVD patients with frailty.

How to optimize the adherence to a guideline-directed medical therapy in the secondary prevention of cardiovascular diseases: a clinical consensus statement from the European Association of Preventive Cardiology.

A key factor to successful secondary prevention of cardiovascular disease (CVD) is optimal patient adherence to treatment. However, unsatisfactory rates of adherence to treatment for CVD risk factors and CVD have been observed consistently over the last few decades. Hence, achieving optimal adherence to lifestyle measures and guideline-directed medical therapy in secondary prevention and rehabilitation is a great challenge to many healthcare professionals. Therefore, in this European Association of Preventive Cardiology clinical consensus document, a modern reappraisal of the adherence to optimal treatment is provided, together with simple, practical, and feasible suggestions to achieve this goal in the clinical setting, focusing on evidence-based concepts.

Objectively measured adherence to physical activity among patients with coronary artery disease: Comparison of the 2010 and 2020 World Health Organization guidelines and daily steps.

Background: Tailored recommendations for patients after percutaneous coronary interventions (PCI) need physical activity (PA) to be objectively measured and assessed for adherence to guidelines. The recent WHO guidelines removed the daily recommended bout duration, while the potential impact of this change on patients after PCI remains unclear. Aim: We evaluated prevalence estimates of adherence to PA recommendations among patients after PCI across the 2010 [≥30 min moderate- to vigorous-intensity PA (MVPA) at ≥ 10-min bout duration] and 2020 WHO guidelines (≥30 min of MVPA of any bout duration), as well as 7,500 and 10,000 steps. Methods: We conducted an observational longitudinal single-center study with patients after PCI for chronic or acute coronary syndrome (ACS); maximal age 80 years. Wrist-worn accelerometers recorded participants' PA data from the evening of hospital discharge over the next 18 days. Results: We analyzed data from 282 participants with sufficient minimum wear time (7 days of ≥12 h), including 45 (16%) women; and 249 (88%) with ACS. Median wear time was 18 (17, 18) days. Median participant age was 62 (55, 69) years. Fifty-two participants (18.4%) fulfilled 2010 WHO guidelines and 226 (80.1%) fulfilled the 2020 WHO guidelines. Further, 209 (74.1%) participants achieved ≥7,500 steps/day and 155 (55.0%) performed ≥10,000 steps/day. Conclusion: Among participants after PCI, most MVPA was accumulated in bouts <10 min, leading to a fourfold discrepancy between participants fulfilling the 2010 and 2020 WHO PA recommendations. The number of steps/day may be a valid proxy to recent WHO PA recommendations as it is not dependent on the bout-length definition. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04663373].

Prognostic impact of physical activity patterns after percutaneous coronary intervention. Protocol for a prospective longitudinal cohort. The PIPAP study.

Introduction: Current guidelines recommend wearable activity trackers to detect insufficient physical activity (PA) and help increase PA to prevent or ameliorate cardiovascular disease. However, there is a paucity of data regarding how objectively measured PA trajectories, patterns, and sedentary time, are associated with mortality and recurrent events after percutaneous coronary intervention (PCI) in patients with established coronary artery disease (CAD). Additionally, it remains unclear if early PA and sedentary time after PCI are associated with such outcomes. Therefore, in the present study (ClinicalTrials.gov Identifier: NCT04663373), we aim to establish the associations of objectively measured PA with major adverse cardiac events and mortality at one-year follow-up. Methods and analysis: In this single-centre observational study, patients with CAD will be prospectively recruited immediately after PCI. All the information from the clinical history, baseline characteristics, and outcomes during follow-up will be obtained from the CARDIOBASE registry. Accelerometer data will be collected for 18 days following hospital discharge and 14 days at one-year follow-up. PA trajectories will be identified by group-based trajectory modeling. Major adverse cardiac events and mortality will be prospectively monitored up to 1 year after PCI. All data will be collected using Research Electronic Data Capture.

Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study.

Background: Type 2 diabetes (T2D) is associated with limitation in physical performance. Results from animal studies report enhancement of physical performance in T2D rodents treated with sodium glucose cotransporter 2 inhibitors (SGLT2is). However, in human patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk, the impact of guideline directed SGLT2i medication on physical performance has not been sufficiently examined. Objectives: The main objectives of this study are thus firstly, to assess the changes in physical performance after 4 weeks of exercise therapy in patients with established ASCVD or high cardiovascular risk categorized into three groups according to their glycemic control at baseline. Secondly, to investigate the association of glycemic control at baseline and new guideline directed antidiabetic treatment (inadequate glycemic control and diabetes + new SGLT2i vs. adequate glycemic control and diabetes vs. no diabetes) with change in physical performance. Methods and design: This is a 4-week prospective observational study of 450 participants with established ASCVD or high cardiovascular risk with or without T2D and without previous SGLT2i medication undergoing exercise therapy during inpatient rehabilitation in a single center in Switzerland. Upon admission, participants are categorized into 3 groups of 150 participants each according to their glycemic control. Group I consisting of participants with inadequately controlled T2D defined as mean fasting plasma glucose (FPG) of ≥7 mmol/L, who are consequently administered new treatment with an SGLT2i. Group II comprises of participants with adequately controlled T2D with mean FPG of <7 mmol/L requiring no antidiabetic medication change. Group III consists of participants with no diabetes and mean FPG of ≤ 5.5 mmol/L. Primary outcomes are 6-min walk distance and rate of perceived exertion. Secondary outcomes are echocardiographic parameters (left ventricular mass index; global longitudinal strain average; end-diastolic volume), fatigue, muscle, metabolic, and anthropometric measures. Ethics and dissemination: This study is conducted in accordance with the Declaration of Helsinki with ethical approval from the Cantonal Ethical Commission of Bern, Switzerland. The results will be published in a peer-reviewed journal. The implementation and reporting will be according to the SPIRIT guidelines. Study protocol registration: https://www.clinicaltrials.gov/, identifier: NCT03422263.

Short- and Long-Term Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Left Ventricular Remodeling in Patients Early After ST-Segment Elevation Myocardial Infarction-The HIIT-EARLY Randomized Controlled Trial.

Aim: Due to insufficient evidence on the safety and effectiveness of high-intensity interval training (HIIT) in patients early after ST-segment elevation myocardial infarction (STEMI), we aimed to compare short- and long-term effects of randomized HIIT or moderate-intensity continuous training (MICT) on markers of left ventricular (LV) remodeling in STEMI patients receiving optimal guideline-directed medical therapy (GDMT). Materials and Methods: Patients after STEMI (<4 weeks) enrolled in a 12-week cardiac rehabilitation (CR) program were recruited for this randomized controlled trial (NCT02627586). During a 3-week run-in period with three weekly MICT sessions, GDMT was up-titrated. Then, the patients were randomized to HIIT or isocaloric MICT for 9 weeks. Echocardiography and cardiopulmonary exercise tests were performed after run-in (3 weeks), end of CR (12 weeks), and at 1-year follow-up. The primary outcome was LV end-diastolic volume index (LVEDVi) at the end of CR. Secondary outcomes were LV global longitudinal strain (GLS) and cardiopulmonary fitness. Results: Seventy-three male patients were included, with the time between STEMI and start of CR and randomization being 12.5 ± 6.3 and 45.8 ± 10.8 days, respectively. Mixed models revealed no significant group × time interaction for LVEDVi at the end of CR (p = 0.557). However, there was a significantly smaller improvement in GLS at 1-year follow-up in the HIIT compared to the MICT group (p = 0.031 for group × time interaction). Cardiorespiratory fitness improved significantly from a median value of 26.5 (1st quartile 24.4; 3rd quartile 1.1) ml/kg/min at randomization in the HIIT and 27.7 (23.9; 31.6) ml/kg/min in the MICT group to 29.6 (25.3; 32.2) and 29.9 (26.1; 34.9) ml/kg/min at the end of CR and to 29.0 (26.6; 33.3) and 30.6 (26.0; 33.8) ml/kg/min at 1 year follow-up in HIIT and MICT patients, respectively, with no significant group × time interactions (p = 0.138 and 0.317). Conclusion: In optimally treated patients early after STEMI, HIIT was not different from isocaloric MICT with regard to short-term effects on LVEDVi and cardiorespiratory fitness. The worsening in GLS at 1 year in the HIIT group deserves further investigation, as early HIIT may offset the beneficial effects of GDMT on LV remodeling in the long term.