br history should be performed before any cancer therapy
history should be performed before any cancer therapy. Coronary artery disease may result from accelerated atherosclerosis (radiation), coro-nary endothelial dysfunction, arterial thromboembolism (e.g. VEGF in-hibitors), and coronary vasospasm (e.g. 5-fluoruracil, Supplementary Table 1) in combination with the systemic inflammation resulting from cancer. Some cancer drugs (e.g. tamoxifen in breast cancer) appear to have beneficial effects on ischemic 606-58-6 disease particularly when compared to aromatase inhibitors . However, cancer patients have been largely excluded from clinical trials on acute and chronic coronary artery disease. Current evidence is therefore limited and patients largely require individualized treatments due to e.g. frailty, clinical need for cancer therapy due to high symptom burden, low platelet counts and access site complications. Acute chest pain requires diagnostic follow-up according to current guidelines, including percutaneous coronary in-tervention (PCI) and dual anti-platelet therapy. Interventional proce-dures should be individually tailored in close interaction with the oncologist. Anti-platelet therapy is particularly problematic when mye-losuppressive therapies with resulting low platelet counts are planned. In the absence of prospective data, catheterization and dual antiplatelet therapy appear feasible in patients with platelet counts N 30,000/μl . Most PCI procedures can be performed safely with platelet counts of 40– 50,000/μl. Of note, novel drug eluting stents may provide the opportu-nity for shorter dual antiplatelet therapy. Radial access is preferred, but a femoral approach can be considered in patients with a history of multiple arterial lines or in breast cancer patients following mastec-tomy. Calcium channel antagonists or organic nitrates can be used to prevent vasospasm .
5.4. Valvular heart disease
Aortic and mitral valve disease may develop as late toxicities from radiation and result in stenosis or regurgitation . Long-term cancer survivors (N10 years) are at particularly high risk. Clinical and echocar-diography assessment is therefore recommended in the long-term follow-up of these patients. Treatment strategies must consider co-morbidities and clinical status.
Clinical signs of heart failure include dyspnea, edema and fatigue. Anthracyclines and HER2-targeting agents (e.g. trastuzumab, lapatinib) are widely recognized to induce potentially irreversible heart failure . We have therefore outlined a treatment algorithm for the assessment and treatment of heart failure, notably in a breast cancer cohort of our center's cardio-oncology unit. Many other agents can induce reversible or irreversible heart failure (Supplementary Table 1) through yet in-completely characterized mechanisms . Diagnosis of heart failure is based on patient history, clinical examination, biomarkers (NT-proBNP, troponin) and echocardiography. Therapy follows current AHA/ACC/ESC guidelines in order to help patients complete their cancer therapy and to reduce morbidity and mortality.
Arrhythmic events during cancer therapy include the complete spectrum from bradycardias to tachyarrhythmias [3,15]. The underlying cause may be a specific agent (e.g. atrial fibrillation during ibrutinib therapy ) or multi-faceted (electrolyte imbalance, fluid overload, QT prolongation, co-medication, tumor infiltration of the heart). The in-cidence of arrhythmias increases with advanced cancer stages, age, sep-sis and pain . Targeted inhibitors of signal transduction may induce arrhythmias, however prevention and treatment has not been system-atically tested . Therefore, therapy must follow current guidelines, but discussion in multidisciplinary teams with cardiologists and oncol-ogists is advised, including correction of electrolyte imbalance, treat-ment of sepsis, use of antiarrhythmic drugs and anticoagulation. Of
note, standard scoring systems and pharmacological approaches have not been tested in cancer patients, including the need for anticoagulation.
6. Diagnostic and therapeutic algorithms for specific cardio-oncology patients
Diagnosis and treatment algorithms in cardio-oncology are incom-plete and largely based on expert consensus. Below, we discuss specific strategies for three typical cancer cohorts, which frequently report to our and other cardio-oncology units. This includes patients treated with cytotoxic chemotherapy including anthracyclines, patients receiv-ing targeted therapies and the growing cohort of cancer patients under ICI therapy.
6.1. Breast cancer patients undergoing classical chemotherapy
Breast cancer is the most common cancer in females, and thus breast cancer patients comprise the largest group of cardio-oncology patients. Generally, breast cancers have a favorable stage-dependent prognosis, with 5- and 10-year survival rates of 89% and 83%, respectively . Most patients live for 20 more years or longer. With increasing numbers of breast cancer survivors, cardiovascular diseases secondary to cancer therapy become more relevant, sometimes many years after therapy [103,104]. A systematic analysis of N1.2 million breast cancer survivors revealed an 1.9-fold increased risk of death from cardiovascular disease over that in an age-matched population . Risk factors for heart fail-ure include anthracyclines, HER2-targeting agents, and/or radiation. The risk for the development of heart failure is not limited to the period of treatment but sustained for decades following therapy, and cardio-vascular risk factors augment this risk . The prevention of cardio-vascular disease in breast cancer patients is based on an elaborate pre-selection of patients and risk-reducing treatment protocols, treatment of cardiovascular risk factors and early detection and treatment of ad-verse effects. Fig. 2 proposes an algorithm for the management of these patients based on recent recommendations from cardiological [3,8] and oncological [6,106] societies. After assessment of baseline car-diac function using cardiovascular history and echocardiography, pa-tients with normal baseline ejection fraction are monitored over the following months for early signs of cardiotoxicity (e.g. every CTCAE grade for heart failure, Supplementary Table 2). Follow-up is recom-mended 6–12 months after completion of chemotherapy [6,106]. Long-term survivors are re-evaluated for cardiovascular risk factors and signs of cardiovascular disease (hypertension, coronary artery dis-ease, heart failure and/or arrhythmias) at 5-year intervals [14,15]. Chemotherapy protocols avoiding high-risk agents are considered for patients with pre-existing moderate-to-severe heart failure, includ-ing use of pegylated liposomal doxorubicin or concomitant use of dexrazoxane. Dexrazoxane was developed to protect from anthracycline-induced cardiotoxicity by reduced ROS formation . Dexrazoxane is now increasingly used for cardioprotection.