Aims Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio‐oncology has not yet been systematically evaluated. This meta‐analysis aims to determine whether cardiac troponins and (N‐terminal pro) brain natriuretic peptide (BNP/NT‐proBNP) predict cancer therapy‐related left ventricular (LV) dysfunction. Methods and results Scientific databases were searched for studies that assessed troponins or BNP/NT‐proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0–34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR 11.9, 95% CI 4.4–32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT‐proBNP levels were increased in patients post‐treatment (standardized mean difference 0.6, 95% CI 0.3–0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7–4.2; n = 197). β‐blocker and angiotensin‐converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7–9.8; n = 466). Conclusion Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio‐oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.

Key Points Question What is the rate of cardiovascular adverse events among patients with melanoma treated with BRAF and MEK inhibitors compared with patients treated with BRAF inhibitor monotherapy? Findings In this systematic review and meta-analysis of 5 randomized clinical trials including 2317 patients, treatment with BRAF and MEK inhibitors was associated with a higher risk of pulmonary embolism, decrease in left ventricular ejection fraction, and arterial hypertension compared with treatment with BRAF inhibitor monotherapy. The risks of myocardial infarction, atrial fibrillation, and QTc prolongation were similar between groups. Meaning These findings demonstrate an association of cardiovascular adverse events with BRAF and MEK inhibitor therapy, which may guide clinical cardio-oncological management.

BackgroundThe monoclonal antibody bevacizumab effectively inhibits angiogenesis in several types of cancers by blocking vascular endothelial growth factor. However, life‐threatening cardiovascular adverse effects could limit its use and may warrant specific follow‐up strategies.Methods and ResultsWe systematically searched MEDLINE, Cochrane, EMBASE, and Web of Science for randomized controlled trials published until November 2016 that assessed patients with cancer treated with or without bevacizumab in addition to standard chemotherapy. A total of 20 050 patients with a broad range of cancer types from 22 studies were included in this analysis (10 394 in the bevacizumab group and 9656 in the control group). The risks of arterial and venous adverse events were higher in the bevacizumab groups (relative risk [RR], 1.37; 95% CI, 1.10–1.70 [P=0.004] and RR, 1.29; 95% CI, 1.12–1.47 [P<0.001], respectively), and more arterial adverse events occurred in patients taking high‐dose bevacizumab regimens. Bevacizumab treatment was associated with the highest risk of cardiac and cerebral ischemia in the high‐dose bevacizumab groups (RR, 4.4; 95% CI, 1.59–12.70 [P=0.004] and RR, 6.67; 95% CI, 2.17–20.66 [P=0.001], respectively). In addition, the risk of bleeding and arterial hypertension were higher in the bevacizumab groups (RR, 2.74; 95% CI, 2.38–3.15 [P<0.001] and RR, 4.73; 95% CI, 4.15–5.39 [P<0.00001], respectively), with higher values for patiens taking high‐dose regimens.ConclusionsTreatment with bevacizumab increases the risk of arterial adverse events, particularly cardiac and cerebral ischemia, venous adverse events, bleeding, and arterial hypertension. This risk is additionally increased with high doses of bevacizumab. Further studies should determine the appropriate options for cardio‐oncology management.Clinical Trial Registration URL: https://www.crd.york.ac.uk. Unique identifier: PROSPERO(CRD42016054305).

Aims Conventional cytotoxic chemotherapy is still among the most effective treatment options for many types of cancer. However, cardiotoxicity, notably the decrease in left ventricular function under these regimens, can impair prognosis. Thus, prevention and treatment of cardiotoxicity are crucial. The present meta‐analysis aims to assess the efficacy of beta‐blockers or angiotensin‐converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) for prevention of cardiotoxicity. Methods and results We systematically searched Pubmed, Cochrane, EMBASE, and Web of Science databases for randomized controlled trials published until February 2019. The analysis included randomized studies that reported on left ventricular ejection fraction (LVEF) after 6 months of chemotherapy in cancer patients who received beta‐blockers or ACE inhibitors/ARBs for prevention of cardiotoxicity compared with controls. Studies on combination cardioprotective therapies were excluded from the analysis. The primary endpoint was prevention of a decrease in LVEF as defined by the individual study and as assessed by either transthoracic echocardiography or magnetic resonance imaging. We here show that patients under anthracycline‐based chemotherapy have a moderate yet significant benefit in LVEF from beta‐blockers or ACEs/ARBs. The beta‐blocker analysis included 769 cancer patients, and the ACE inhibitors/ARBs analysis included a total of 581 cancer patients. The mean LVEF difference between the beta‐blocker group and the control group was 2.57% (95% confidence interval 0.63–4.51, P = 0.009). The mean difference for ACE inhibitors/ARBs was 4.71% (95% confidence interval 0.38–9.03, P = 0.03). However, the beneficial effects throughout the studies were variable as documented by significant heterogeneity between the studies. Conclusions Systematic evidence is needed to solidly found recommendations for cardioprotective prevention during chemotherapy. Likewise, trials on other neurohumoral drugs (spironolactone) and lipid‐lowering approaches are required to improve protection for cardio‐oncology patients.

Aims Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients. Methods and results PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53). Conclusions BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.