br Fig Algorithm for the assessment of patients
Fig. 2. Algorithm for the assessment of patients receiving classical chemotherapy. Initial evaluation is recommended in all patients scheduled for Heparin sodium failure-inducing agents, particularly anthracyclines and HER2-targeting agents such as trastuzumab. Current cut-off values for ejection fraction (EF; as measured in 3D) are set to 50%. Cardiotoxicity is defined when EF declines by N10% to values below 50% or if GLS is impaired by N15%. Treatment is recommended with ACE inhibitors and ß-blockers, but evidence from randomized trials is scarce. Heart failure with reduced ejection fraction is defined by EF below 40%. Cessation or alternative therapies are then recommended, including lower doses or second line therapies. However, individual treatment decisions are required since otherwise many patients would be excluded from highly effective therapies (3D EF = 3-dimensional ejection fraction, ACE = ACE inhibitor, BB = β blocker, echo = echocardiography. ECG = electrocardiogram, GLS = global longitudinal strain).
mandatory. For acute coronary syndromes, a 1 month interruption of ICI therapy has been proposed .
7. Development and standard procedures of a cardio-oncology unit
The cardio-oncology unit of the West German Heart and Vascular Center, notably its Department of Cardiology and Vascular Medicine treats patients in a multidisciplinary approach together with the depart-ments and institutes of the West German Cancer Center, including the
Departments of Medical Oncology, Hematology, Bone Marrow Trans-plantation, Radiation Oncology, Gynecology and Dermatology. The De-partment of Cardiology and Vascular Medicine is a tertiary care center with certified chest pain, coronary care, heart failure and intensive care units. The cardio-oncology service has established a close collabo-ration with the imaging institutes (radiology and nuclear medicine). All state-of the heart diagnostic and therapeutic tools are available, in-cluding PET/CT and PET/MRI. An institutional communication has been established through an online system for consultants, and daily
Fig. 3. Recommended algorithm for the evaluation of patients with targeted therapy. Adverse cardiovascular effects from BRAF/MEK inhibition include heart failure and QTc prolongation to a level with increased risk of torsades des pointes. 3D ejection fraction is monitored before and during therapy. A decline in EF by 10–20% warrants an interruption of therapy with evaluation of heart failure medication. If heart failure persists or EF remains reduced by 10–20%, therapy with BRAF/MEK should be re-evaluated and discussed. However, therapy termination may exclude patients from this therapy and its benefits. Individualized decisions by the multi-disciplinary cardio-oncology team and repeated echocardiographic assessment are therefore required. Persistent QTc prolongation may require BRAF/MEK withdrawal (*temporary QTc elongation should be treated by correction of magnesium and potassium levels and then re-evaluated, ECG = electrocardiography. Echo = echocardiography 3DEF = 3-dimensional ejection fraction).
consultations are performed. With support from the University Hospi-tal, experimental and clinical research trials have been initiated in the cardio-oncology unit. The education of personnel is provided through regular case conferences and tutorials. Together with the oncology de-partments, standard operating procedures have been implemented. Breast cancer patients scheduled for anthracycline therapy, myeloma patients, and patients receiving ICI are among the most frequently re-ferred to the cardio-oncology service.
Breast cancer patients receiving anthracyclines (in conjunction with HER2-inhibitors) are monitored at the cardio-oncology unit at three time-points: before the initiation of chemotherapy and following three and six months. The gynecology department automatically refers all respective patients following a tumor board decision. Each patient receives an echocardiography, including 3DEF and GLS, blood test for troponin, NT-proBNP, lipid profile and ECG. All parameters are tested during follow-up visits for signs of subclinical cardiotoxicity [16,82,117,118]. Whenever signs of cardiotoxicity become evident (ele-vated troponin, impaired LVEF/GLS) the interruption of chemotherapy is discussed with the treating oncologist. Beta-blockers and ACE-inhibitors are routinely used to treat toxic cardiomyopathy. Statins are recommended according to guideline recommendations. The clinical status, including echocardiography, is re-assessed at least every four weeks in patients with cardiotoxicity. Additional consultations may be
necessary upon signs of cardiotoxicity, including: angina, dyspnea, arrhythmia including QT N 500 ms, pericardial effusion, edema, conges-tion, acute coronary syndrome, hypertension, hypotension and syncope. Severe heart failure and cardiogenic shock are occasionally observed due to anthracycline therapy. Left ventricular assist devices (Impella, LVAD) have been implanted in selected cases for temporary or perma-nent support. We recommend that all breast cancer survivors are re-evaluated by a cardiologist in case of a planned pregnancy.