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The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond the heart. The authors provide a framework using the oxygen pathway to understand the impact of cancer treatment on peak oxygen uptake, a marker of integrative cardiopulmonary function and CVD risk. Peripheral toxicities and the impact on oxygen transport are discussed. Consideration for the broad effects of cancer therapies will improve the prediction and identification of cancer survivors at risk for CVD, functional disability, and premature mortality and those who would benefit from therapeutic intervention, ultimately improving patient outcomes.

Abstract Approximately 1–2 per 100,000 young athletes die from sudden cardiac death (SCD) and extreme exercise may be associated with myocardial scar and arrhythmias. Racehorses have a high prevalence of atrial fibrillation (AF) and SCD but the presence of myocardial scar and inflammation has not been evaluated. Cardiac tissues from the left (LAA) and right (RAA) atrial appendages, left ventricular anterior (LVAPM) and posterior (LVPPM) papillary muscles, and right side of the interventricular septum (IVS-R) were harvested from racehorses with sudden cardiac death (SCD, n = 16) or other fatal injuries (OFI, n = 17), constituting the athletic group (ATH, n = 33), and compared to sedentary horses (SED, n = 10). Horses in the ATH group had myocyte hypertrophy at all sites; increased fibrosis at all sites other than the LAA; increased fibroblast infiltration but a reduction in the overall extracellular matrix (ECM) volume in the RAA, LVAPM, and IVS-R compared to SED horses. In this horse model, athletic conditioning was associated with myocyte hypertrophy and a reduction in ECM. There was an excess of fibrocyte infiltration and focal fibrosis that was not present in non-athletic horses, raising the possibility of an exercise-induced pro-fibrotic substrate.

Background Cardiac screening of elite athletes is widely recommended by Australasian sporting federations, but data are not structured to be shared. Data are lacking from underrepresented groups to inform ECG interpretation guidelines. The ARENA (Australasian Registry of Screening ECGs in National Athletes) project is a retrospective and prospective, multicenter, longitudinal, observational registry of athlete cardiac screening results and outcomes. The aim is to create a repository to improve our understanding of the diagnoses and outcomes of screening. Methods Participating sports that conduct cardiac screening of athletes will contribute data. This includes an initial collection (retrospective data, waiver of consent) and future prospective data (opt‐out consent). Data include sex, age, sport/event, screening date, ECG findings, cardiac test results, follow‐up details, sport participation status, cardiac diagnoses, and major cardiovascular outcomes defined as sudden cardiac arrest/death, cardiac syncope or implanted cardioverter defibrillator shock, cardiac hospitalization, and arrhythmias requiring intervention. Comparisons will be made between diagnoses, outcomes, and ECG features and analyzed by sport and sex. The ARENA project was developed in collaboration with sporting bodies, team physicians, and players association representatives and endorsed by the Australasian College of Sport & Exercise Physicians and Sports Medicine Australia. Conclusions The ARENA project will provide a long‐term international data repository to improve our understanding of ECG interpretation, cardiac screening and diagnoses, and the prevalence of cardiovascular outcomes in screened athletes. A unique aim is to address evidence gaps in underrepresented athlete groups, specifically female athletes and Indigenous populations. Results will inform screening policies and guidelines.

Background: Women are at greater risk for heart failure with preserved ejection fraction (HFpEF). Objectives: The aim of the study was to compare sex differences in the pathophysiology of exertional breathlessness in patients with high vs low HFpEF likelihood. Methods: This cohort study evaluated consecutive patients (n = 1,936) with unexplained dyspnea using cardiopulmonary exercise testing and simultaneous echocardiography and quantified peak oxygen uptake (peak VO2) and its determinants. HFpEF was considered likely when the H2FPEF or HFA-PEFF score was ≥6 or ≥5, respectively. Sex differences were evaluated with the Student’s t-test or Mann-Whitney U test and determinants of exercise capacity with a multivariable linear regression. Results: The cohort included 1,963 patients (49% women and 28% [n = 555] with a high HFpEF likelihood). HFpEF likelihood did not impact the magnitude of sex differences in peak VO2 and its determinants. Overall, women had lower peak VO2 (mean difference −4.4 mL/kg/min [95% CI: −3.7 to −5.1 mL/kg/min]) secondary to a reduced O2 delivery (−0.5 L/min [95% CI: −0.4 to −0.6 L/min]) and less oxygen extraction (−2.9 mL/dL [95% CI: −2.5 to −3.2 mL/dL]). Reduced O2 delivery was due to lower hemoglobin (−1.2 g/dL [95% CI: −0.9 to −1.5 g/dL]) and smaller stroke volume (−15 mL [95% CI: −14 to −17 mL]). Women demonstrated increased mean pulmonary artery pressure/cardiac output slope (+0.5 mm Hg/L/min [95% CI: 0.3-0.7 mm Hg/L/min]) and left ventricular ejection fraction (+1% [95% CI: 1%-2%]), while they had smaller left ventricular end-diastolic volumes (−9 mL/m2 [95% CI: −8 to −11 mL/m2]) and mass (−12 g/m2 [95% CI: −9 to −14 g/m2]) and more often iron deficiency (55% vs 33%; P < 0.001). Conclusions: Women with unexplained dyspnea had significantly lower peak VO2, regardless of HFpEF likelihood, attributed to both lower peak exercise O2 delivery and extraction. This suggests that physiologic sex differences, and not HFpEF likelihood, are an important factor contributing to functional limitations in females with exertional breathlessness.

Background Studies reporting on the incidence of sudden cardiac arrest and/or death (SCA/D) in athletes commonly lack methodological and reporting rigor, which has implications for screening and preventative policy in sport. To date, there are no tools designed for assessing study quality in studies investigating the incidence of SCA/D in athletes. Methods and Results The International Criteria for Reporting Study Quality for Sudden Cardiac Arrest/Death tool (IQ‐SCA/D) was developed following a Delphi process. Sixteen international experts in sports cardiology were identified and invited. Experts voted on each domain with subsequent moderated discussion for successive rounds until consensus was reached for a final tool. Interobserver agreement between a novice, intermediate, and expert observer was then assessed from the scoring of 22 relevant studies using weighted and unweighted κ analyses. The final IQ‐SCA/D tool comprises 8 domains with a summated score of a possible 22. Studies are categorized as low, intermediate, and high quality with summated IQ‐SCA/D scores of ≤11, 12 to 16, and ≥17, respectively. Interrater agreement was “substantial” between all 3 observers for summated IQ‐SCA/D scores and study categorization. Conclusions The IQ‐SCA/D is an expert consensus tool for assessing the study quality of research reporting the incidence of SCA/D in athletes. This tool may be used to assist researchers, reviewers, journal editors, and readers in contextualizing the methodological quality of different studies with varying athlete SCA/D incidence estimates. Importantly, the IQ‐SCA/D also provides an expert‐informed framework to support and guide appropriate design and reporting practices in future SCA/D incidence trials.

Abstract Background Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations for high-risk patients who should be monitored in a pediatric cardio-oncology clinic have previously been developed by expert Delphi consensus by our group. In 2022 we opened our first multidisciplinary pediatric cardio-oncology clinic adhering to these recommendations in surveillance and management. Objectives Our pediatric cardio-oncology clinic aimed to: (i) Document cardiovascular toxicities observed within a pediatric cardio-oncology clinic and. (ii) Evaluate the applicability of the Australian and New Zealand Pediatric Cardio-Oncology recommendations. Methods Monthly multidisciplinary cardio-oncology clinics were conducted in an Australian tertiary pediatric hospital. Structured standardised approaches to assessment were built into the electronic medical record (EMR). All patients underwent baseline echocardiogram and electrocardiogram assessment together with vital signs in conjunction with standard history and examination. Results Nineteen (54%) individuals had a documented cardiovascular toxicity or pre-existing risk factor prior to referral. The two most common cardiovascular toxicities documented during clinic review included Left Ventricular Dysfunction (LVD) and hypertension. Of note 3 (8.1%) patients had CTCAE grade III LVD. An additional 10 (27%) patients reviewed in clinic had CTCAE grade I hypertension. None of these patients had hypertension noted within their referral. Cascade testing for cardiac history was warranted in 2 (5.4%) of patients. Conclusions Pediatric cardio-oncology clinics are likely beneficial to documenting previously unrecognised cardiotoxicity and relevant cardiac family histories, whilst providing an opportunity to address lifestyle risk factors.

Background: Previous studies have suggested that females experiencing out-of-hospital cardiac arrest (OHCA) receive lower rates of both bystander cardiopulmonary resuscitation (CPR) and defibrillation compared to males. Whether this disparity has improved over time is unknown. Methods: A state-wide OHCA registry in Victoria, Australia collected data over twenty years (2002–2021) regarding rates of bystander interventions in OHCA. Characteristics and outcomes of each OHCA were compared with logistic regression according to sex and time (defined in two-year periods). Results: 32,502 OHCAs were included (69.7% male). Both bystander CPR and defibrillation rates increased for females over time (p

Abstract Background Atrial fibrillation (AF) is the most common performance limiting arrhythmia in racehorses. High dose exercise and airway disease promote AF in humans. Few studies have investigated epidemiological factors associated with AF in horses. Objectives Explore variables relating to performance, exercise volume and postrace endoscopic findings in horses with AF. Animals A total of 164 horses with poor race performance and postrace AF were compared to 321 horses with poor performance without AF (PP) and 314 horses performing to expectation (TE). Methods Horse‐level and race‐level variables for horses racing in Australia and Hong Kong from 2009 to 2021 were compared using univariable and multivariable logistic regression. Postrace endoscopic exercise‐induced pulmonary hemorrhage (EIPH) and tracheal mucus accumulation (TMA) grades for AF and PP horses were compared using chi‐squared analysis. Results Variables that were significant in the multivariable model of AF compared to TE were distance (lengths) behind the winner, (odds ratio [OR]; 95% confidence interval [95% CI], 1.41 [1.32‐1.51], P

Abstract Premature cardiovascular mortality is increased in long-term allogeneic stem cell transplant (allo-SCT) survivors, but little information exists regarding subclinical cardiovascular dysfunction in this population. We compared peak oxygen uptake ( $${{\dot{\mathrm V}}}$$ V ˙ O2peak), a prognostic cardiovascular marker, and its determinants between long-term allo-SCT survivors and non-cancer controls. Fourteen allo-SCT survivors (mean ± SD, 44 ± 15 years, 50% male, median time since allo-SCT: 6.5 years [range 2–20]) and 14 age- and sex-matched controls (46 ± 13 years, 50% male) underwent cardiopulmonary exercise testing to quantify $${{\dot{\mathrm V}}}$$ V ˙ O2peak. Resting echocardiography (left-ventricular ejection fraction and strain), exercise cardiac MRI (peak cardiac and stroke volume index [CIpeak, SVIpeak]), biochemistry (hemoglobin, troponin-I, B-natriuretic peptide), dual-energy x-ray absorptiometry (lean [LM] and fat [FM] mass, percent body fat [%BF]) and Fick-principal calculation (arteriovenous oxygen difference) were also performed. Survivors exhibited impaired $${{\dot{\mathrm V}}}$$ V ˙ O2peak as compared with controls (25.9 ± 5.1 vs. 33.7 ± 6.5 ml kg−1 min−1, p = 0.002), which coincided with reduced CIpeak (6.6 ± 0.8 vs. 8.6 ± 1.9 L min−1 m−2; p = 0.001) secondary to reduced SVIpeak (48 ± 4 vs. 61 ± 8 ml m−2; p

Abstract Aims The contribution of adverse ventricular interdependence remains undervalued in heart failure or pulmonary vascular disease, and not much is known about its dynamic nature during exercise and respiration. In this study, we evaluated ventricular interaction during exercise in patients with heart failure with preserved ejection fraction (HFpEF) and patients with chronic thromboembolic pulmonary hypertension (CTEPH) as compared with healthy controls. Methods and results Forty‐six subjects (10 controls, 19 CTEPH patients, and 17 HFpEF patients) underwent cardiac magnetic resonance imaging during exercise. Ventricular interaction was determined through analysis of the septal curvature (SC) of a mid‐ventricular short‐axis slice at end‐diastole, end‐systole, and early‐diastole, both in expiration and inspiration. Exercise amplified ventricular interaction in CTEPH patients and to a lesser extent in HFpEF patients (P