br Myeloma patients are referred to the
Myeloma patients are referred to the cardio-oncology service from the hematology department. Proteasome inhibitors, including bortezomib and carfilzomib, come along with an increased risk of heart failure. Due to the high number of referred patients, we routinely assess all patients before and six months after initiation of therapy. A clinical registry has been established for the systematic assessment of clinical status and vascular and left ventricular functions. We recom-mend ambulatory blood pressure tests in all patients to monitor for pos-sible hypertension or hypotension. In cases of cardiotoxicity, beta-blockers and ACE-inhibitors can be given but may worsen hypotension. Mineral corticoid receptor antagonists are an alternative option.
ICI may induce multiple cardiotoxic adverse events, including myo-carditis, pericarditis, pericardial effusion, acute coronary syndromes and advance conduction abnormalities (second and third degree AV Block). Baseline assessments, including clinical history, examination and ECG
Fig. 4. Recommended algorithm for the evaluation of patients with immune checkpoint inhibitor therapy. A cardiac reaction to immune therapy is a rare, but fulminant condition. Clinical signs are dyspnea, arrhythmia (particularly advanced conduction disease) and angina. Electrocardiography (ECG) and troponin (high-sensitive troponin I or T) measurement identify early stages of such myocarditis and are recommended in weeks 1–4 of treatment or when cardiotoxicity is suspected. An acute coronary syndrome is evaluated according to current guidelines and may require coronary angiography. Persistent symptoms should be evaluated despite negative troponin and ECG in cardio-oncology units. Holter-ECG and imaging, including echocardiography, magnetic resonance imaging, possibly in combination with positron emission tomography, are helpful to confirm myocarditis. Severe cases of heart failure with rapid progression should be evaluated by endomyocardial biopsy to confirm immune therapy-related adverse events and exclude other causes. Glucocorticosteroids are the first choice treatment . (ACS, acute coronary syndrome, CT = computed tomography, ECG = electrocardiogram, EMB = endomyocardial biopsy, PET = positron emission tomography, MRI = magnetic resonance imaging).
are performed by the oncologists. The patients are served by clinical consultation together with ECG and troponin tests once in the first four weeks of treatment. In cases of signs of dyspnea, Haloperidol and ar-rhythmia or positive ECG/troponin tests, patients are referred to the cardio-oncology unit via the online system. If myocarditis is suspected, we discuss termination of ICI therapy until myocarditis is ruled-out def-initely. The further work-up includes echocardiography and nuclear im-aging (PET/CT or PET/MRI) and in indecisive cases endomyocardial biopsy. Proven myocarditis is treated with 1 mg/kg prednisone as first-line option. Whenever myocarditis has been ruled-out, ICI is only re-challenged after consultation with the oncologist and repeated test-ing at least once four weeks after the initial visit.
8. Adult survivors of childhood, adolescent and young adult malignancies
Advances in the treatment of childhood, adolescent and young adult (CAYA) malignancies have yielded substantially increased survival [119,120]. As adults, many of these patients experience premature car-diovascular disease. By the age of 35 years, cancer recurrence and
cardiovascular disease increase morbidity and mortality as compared to age-matched controls [11,121]. A 15-fold increased risk of heart fail-ure and a 7-fold increased of premature cardiac death were reported . Cardiovascular morbidity and mortality are particularly associ-ated with anthracycline-based chemotherapy and chest irradiation [12,18,119,122]. More than 20 years after therapy, nearly 40% of pa-tients have coronary lesions as detected by computed tomography angi-ography . Whether these dramatic figures still hold true with current highly sophisticated treatment planning and radiotherapy op-tions is still an open question. Symptoms may often be uncharacteristic and include fatigue, palpitations, and syncope. Classical signs of struc-tural heart disease, including exertional dyspnea and angina, may be ab-sent. Therefore particularly careful examination of childhood cancer survivors is warranted. The development of cardiovascular risk factors must be closely monitored beginning two years after exposure to cancer therapies [119,120]. According to current recommendations [119,120], symptomatic patients should be referred to cardiological evaluation. Asymptomatic patients are to be monitored every 5 years by clinical as-sessment, electrocardiography and/or alternative imaging modalities. When subclinical signs of cardiovascular disease are detected, patients