No abstract

Purpose of Review Immune checkpoint inhibitors (ICIs) have improved the survival of several cancers. However, they may cause a wide range of immune-related adverse events (irAEs). While most irAEs are manageable with temporary cessation of ICI and immunosuppression, cardiovascular toxicity can be associated with high rates of morbidity and mortality. As ICIs evolve to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of ICI-associated cardiotoxicity may be even higher. Recent Findings Several cardiovascular toxicities such as myocarditis, stress cardiomyopathy, and pericardial disease have been reported in association with ICIs. Recent findings also suggest an increased risk of atherosclerosis with ICI use. ICI-associated myocarditis usually occurs early after initiation and can be fulminant. A high index of suspicion is required for timely diagnosis. Prompt treatment with high-dose corticosteroids is shown to improve outcomes. Summary Although the overall incidence is rare, ICI cardiotoxicity, particularly myocarditis, is associated with significant morbidity and mortality, making it a major therapy-limiting adverse event. Early recognition and prompt treatment with the cessation of ICI therapy and initiation of high-dose corticosteroids are crucial to improve outcomes. Cardio-oncologists will need to play an important role not just in the management of acute cardiotoxicity but also to reduce the risk of long-term sequelae.

Purpose of review Contemporary anticancer immunotherapy, particularly immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell therapy, has changed the landscape of treatment for patients with a variety of malignancies who historically had a poor prognosis. However, both immune checkpoint inhibitors and CAR T cell therapy are associated with serious cardiovascular adverse effects. As immunotherapy evolves to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of its associated cardiotoxicity will be even higher. Recent findings ICI can cause myocarditis, which usually occurs early after initiation, can be fulminant, and prompt treatment with high-dose corticosteroids is crucial. CAR T cell therapy frequently leads to cytokine release syndrome, which is associated with cardiomyopathy or arrhythmia development and may also result in circulatory collapse. Supportive treatment, as well as tocilizumab, an anti-interleukin-6 receptor antibody, is the cornerstone of treatment. Recent findings suggest that preexisting cardiovascular risk factors and disease may increase the risk of such cardiotoxicity, and prompt recognition, as well as treatment, may favorably alter the outcomes. Summary ICI and CAR T cell therapy have improved cancer-related outcomes; however, they both are associated with potentially therapy-limiting cardiotoxicity. Cardio-oncologists are required to play an important role in patient selection, pretherapy cardiovascular optimization, and prompt recognition and treatment of cardiotoxicity.

Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.

Background: Acute kidney injury (AKI) is a significant complication of Coronavirus Disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analog, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. Methods: We implemented a quasi-experimental design with non-random, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline estimated glomerular filtration rate <15 ml/min/1.73m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or renal replacement therapy (RRT). Results: 38/90 B3 patients and 62/111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR 0.64, 95% CI 0.40 to 1.00, p=0.05), an association driven by patients with KDIGO stage 2/3 AKI (HR 0.29, 95% CI 0.13 to 0.65, p=0.03; p interaction with KDIGO stage 0.03). Total mortality also followed this pattern (HR 0.17, 95% CI 0.05-0.52 in KDIGO 2/3 patients, p=0.002). Serum creatinine following AKI increased by 0.20 (SE 0.08) mg/dL/day among non-B3 patients with KDIGO 2/3 AKI but was stable among comparable B3 patients (+0.01 (SE 0.06) mg/dL/day; p interaction 0.03). Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.

Background Though the incidence of atrial fibrillation (AF) is increased in patients with cancer, the effectiveness of catheter ablation (CA) for AF in patients with cancer is not well studied. Methods We conducted a retrospective cohort study of patients who underwent CA for AF. Patients with a history of cancer within 5-years prior to, or those with an exposure to anthracyclines and/or thoracic radiation at any time prior to the index ablation were compared to patients without a history of cancer who underwent AF ablation. The primary outcome was freedom from AF [with or without anti-arrhythmic drugs (AADs), or need for repeat CA at 12-months post-ablation]. Secondary endpoints included freedom from AF at 12 months post-ablation with AADs and without AADs. Safety endpoints included bleeding, pulmonary vein stenosis, stroke, and cardiac tamponade. Multivariable regression analysis was performed to identify independent risk predictors of the primary outcome. Results Among 502 patients included in the study, 251 (50%) had a history of cancer. Freedom from AF at 12 months did not differ between patients with and without cancer (83.3% vs 72.5%, p 0.28). The need for repeat ablation was also similar between groups (20.7% vs 27.5%, p 0.29). Multivariable regression analysis did not identify a history of cancer or cancer-related therapy as independent predictors of recurrent AF after ablation. There was no difference in safety endpoints between groups. Conclusion CA is a safe and effective treatment for AF in patients with a history of cancer and those with exposure to potentially cardiotoxic therapy.

PURPOSE Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer.

Background: Though the incidence of atrial fibrillation (AF) is increased in patients with cancer, the effectiveness of catheter ablation (CA) for AF in patients with cancer is not well studied. Methods: We conducted a retrospective cohort study of patients who underwent CA for AF. Patients with a history of cancer within 5-years prior to, or those with an exposure to anthracyclines and/or thoracic radiation at any time prior to the index ablation were compared to patients without a history of cancer who underwent AF ablation. The primary outcome was freedom from AF, with or without anti-arrhythmic drugs (AADs), and need for repeat CA at 12-months post-ablation. Secondary endpoints included freedom from AF at 12 months post-ablation with AADs and without AADs. Safety endpoints included bleeding, pulmonary vein stenosis, stroke, and cardiac tamponade. Multivariable regression analysis was performed to identify independent risk predictors of the primary outcome. Results: Among 502 patients included in the study, 251 (50%) had a history of cancer. Freedom from AF at 12 months did not differ between patients with and without cancer (83.3% vs 72.5%, p 0.28). Need for repeat ablation was also similar between groups (20.7% vs 27.5%, p 0.29). Multivariable regression analysis did not identify a history of cancer or cancer-related therapy as independent predictors of recurrent AF after ablation. There was no difference in safety endpoints between groups. Conclusion: CA is a safe and effective treatment for AF in patients with a history of cancer and those with exposure to potentially cardiotoxic therapy.