Background: Advances in cancer therapeutics have improved overall survival and prognosis in this patient population, however this has come at the expense of cardiotoxicity including arrhythmia. Summary: Cancer and its therapies are associated with cardiotoxicity via several mechanisms including inflammation, cardiomyopathy, and off-target effects. Among cancer therapies, anthracyclines and tyrosine kinase inhibitors (TKIs) are particularly known for their pro-arrhythmia effects. In addition to cardiomyopathy, anthracyclines may be pro-arrhythmogenic via reactive oxygen species (ROS) generation and altered calcium handling. TKIs may mediate their cardiotoxicity via inhibition of off-target tyrosine kinases. Ibrutinib-mediated inhibition of CSK may be responsible for the increased prevalence of atrial fibrillation (AF). Further investigation is warranted to further elucidate the mechanisms behind arrhythmias in cancer therapies. Key Messages: Arrhythmias are a common cardiotoxicity of cancer therapies. Cancer therapies may induce arrhythmias via off-target effects. Understanding the mechanisms underlying arrhythmogenesis associated with cancer therapies may help design cancer therapies that can avoid these toxicities.

No abstract

BackgroundIsolated small airway abnormalities may be demonstrable at rest in patients with normal spirometry; however, the relationship of these abnormalities to exertional symptoms remains uncertain. This study uses an augmented cardiopulmonary exercise test (CPET) to include evaluation of small airway function during and following exercise to unmask abnormalities not evident with standard testing in individuals with dyspnoea and normal spirometry.MethodsThree groups of subjects were studied: 1) World Trade Center (WTC) dust exposure (n=20); 2) Clinical Referral (n=15); and Control (n=13). Baseline evaluation included respiratory oscillometry. Airway function during an incremental workload CPET was assessed by: 1) tidal flowversusvolume curves during exercise to assess for dynamic hyperinflation and expiratory flow limitation; and 2) post-exercise spirometry and oscillometry to evaluate for airway hyperreactivity.ResultsAll subjects demonstrated normal baseline forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). Dyspnoea was reproduced during CPET in WTC and Clinical Referral groupsversusControl without abnormality in respiratory pattern and minute ventilation. Tidal flow–volume curves uncovered expiratory flow limitation and/or dynamic hyperinflation with increased prevalence in WTC and Clinical ReferralversusControl (55%, 87%versus15%; p<0.001). Post-exercise oscillometry uncovered small airway hyperreactivity with increased prevalence in WTC and Clinical ReferralversusControl (40%, 47%versus0%, p<0.05).ConclusionsWe uncovered mechanisms for exertional dyspnoea in subject with normal spirometry that was attributable to either small airway dysfunction during exercise and/or small airway hyperreactivity following exercise. The similarity of findings in WTC environmentally exposed and clinically referred cohorts suggests broad relevance for these evaluations.

Opinion StatementPatients with cancer are at risk of developing cardiovascular disease (CVD) including atherosclerotic heart disease (AHD), valvular heart disease (VHD), and atrial fibrillation (AF). Advances in percutaneous catheter-based treatments, including percutaneous coronary intervention (PCI) for AHD, percutaneous valve replacement or repair for VHD, and ablation and left atrial appendage occlusion devices (LAAODs) for AF, have provided patients with CVD significant benefit in the recent decades. However, trials and registries investigating outcomes of these procedures often exclude patients with cancer. As a result, patients with cancer are less likely to undergo these therapies despite their benefits. Despite the inclusion of cancer patients in randomized clinical trial data, studies suggest that cancer patients derive similar benefits of percutaneous therapies for CVD compared with patients without cancer. Therefore, percutaneous interventions for CVD should not be withheld in patients with cancer, as they may still benefit from these procedures.