Cardiovascular risk factors and diseases—risk assessment prior to tumour therapy
Classic risk factors
Pre-existing or concomitant cardiovascular diseases
Cardiotoxic risk induced by prior cancer treatment
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Before scheduled oncological therapy, cardiovascular risk factors and the prior history of potentially cardiotoxic therapies are decisive for individual risk assessment.
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Patients with cardiovascular risk factors. These patients have an increased risk of cardiovascular side effects associated with cancer therapy.
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Patients who have undergone prior systemic therapy or radiotherapy of the chest are at risk of developing cardiotoxicity.
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All patients who undergo a therapy with known potential cardiotoxicity require an accurate baseline cardiac examination and close surveillance.
Radiotherapy
Management of patients after radiotherapy
Conventional chemotherapy
Immune checkpoint inhibitor-induced myocarditis
Clinical symptoms
ECG changes
Biomarkers
Cardiac imaging
Diagnostics for suspected ICI-induced myocarditis
Histopathology | CMR | Echocardiogram with new WMA | Increased cardiac biomarkers relative to previous values | |
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Definitive | Pathology results conclusive | CMR + M syndrome + increased cardiac biomarkers or ECG changes | WMA + M syndrome + increased cardiac biomarkers + ECG changes + absence of obstructive coronary heart disease | |
Probable | CMR without M syndrome without increased cardiac biomarkers and without ECG changes | WMA + M syndrome + increased cardiac biomarkers or ECG changes | ||
Inconclusive CMR findings + M syndrome or increased cardiac biomarkers or ECG changes | ||||
Possible | Ambiguous CMR findings without M syndrome without increased cardiac biomarkers without ECG changes | WMA + M syndrome or ECG changes | Increased cardiac biomarkers + M syndrome or ECG changes |
Supplementary diagnostics
Fundamentals of ICI-induced myocarditis therapy
Target structure | Half-life | |
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Ipilimumab | CTLA-4 | 15 days |
Atezolizumab | PD-L1 | 27 days |
Avelumab | 6.1 days | |
Durvalumab | 21 days | |
Nivolumab | PD-1 | 25 days |
Pembrolizumab | 27.3 days | |
Cemiplimab | 19 days |
Basic diagnostics and monitoring of ICI therapy patients
Targeted therapies: conventional antibodies and ‘small-molecule’ tyrosine kinase inhibitors
Indication | Peri-/myocardial disease | Arrhythmias | Vascular diseases | Monitoring | |
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Small-molecule tyrosine kinase inhibitors | |||||
BCR-ABL | |||||
Imatinib (PDGFR, KIT) | CML, ALL, gastrointestinal stromal tumours, chronic eosinophilic leukaemia | – | – | – | – |
Dasatinib (Src) | CML, ALL | HF, pericardial effusion | QTc prolongation | HTN, PAH | ECG |
Nilotinib (KIT, PDGFR) | CML | – | QTc prolongation, AF, AV block | ATE, HTN | Lipids, ECG |
Bosutinib (Src) | CML | Pericardial effusion | QTc prolongation | HTN | ECG |
Ponatinib (VEGFR, PDGFR, Src) | CML, ALL | HF, pericardial effusion | AF | HTN, VTE, ATE | BP |
BRAF | |||||
Vemurafenib | Melanoma, hairy cell leukaemia, multiple myeloma | – | QTc prolongation | Vasculitis | ECG, Electrolytes |
Dabrafenib | Melanoma, NSCLC | LV dysfunction | – | HTN | |
Encorafenib | Melanoma | LV dysfunction | SVT | HTN, VTE | TTE, ECG, Electrolytes |
MEK | |||||
Trametinib | Melanoma, NSCLC | LV dysfunction | Bradycardia | HTN | TTE, BP |
Cobimetinib | Melanoma | LV dysfunction | – | HTN | TTE |
Binimetinib | Melanoma | LV dysfunction | – | HTN, VTE | BP, TTE |
ALK, MET | |||||
Crizotinib | NSCLC | HF | Bradycardia, QTc prolongation | – | ECG, Electrolytes, BP |
Alectinib | NSCLC | – | Bradycardia | – | |
Brigatinib | NSCLC | – | Tachycardia, bradycardia, QTc prolongation | HTN | HR/BP |
Ceritinib | NSCLC | Pericarditis | Bradycardia, QTc prolongation | – | ECG |
Bruton | |||||
Ibrutinib | CLL, mantle cell lymphoma, Waldenström's macroglobulinaemia | – | AF, ventr. tachyarrhythmias | – | ECG |
Acalabrutinib | Lymphoplasmacytic lymphoma, mantle cell lymphoma, CLL | – | – | – | – |
EGFR | |||||
Erlotinib | NSCLC, pancreatic cancer | – | – | – | – |
Gefitinib | NSCLC | – | – | – | – |
Lapatinib (HER2) | Breast Ca. | LV dysfunction | – | – | TTE, ECG |
Afatinib | NSCLC | – | – | – | – |
Osimertinib | NSCLC | – | – | – | – |
Neratinib (HER2) | Breast Ca. | – | – | – | – |
Multi-Target | |||||
Sorafenib (RAF-1/B-RAF, VEGFR2, PDGFR) | HCC, RCC, follicular thyroid Ca. | HF | – | MI, HTN | BP |
Sunitinib (VEGFR, PDGFR, KIT) | GIST, RCC, neuroendocrine pancreatic tumour | LV dysfunction | – | Ischaemia, HTN, VTE | BP |
Pazopanib (VEGFR, PDGFR, KIT) | RCC, soft-tissue sarcoma | LV dysfunction | – | HTN, VTE | BP, ECG, Electrolytes |
Vandetanib (VEGFR, EGFR) | Medullary thyroid Ca. | – | QTc prolongation | HTN | ECG, Electrolytes, BP |
Lenvatinib (VEGF, FGFR, PDGF, KIT, RET) | HCC, RCC, follicular thyroid Ca. | HF | QTc prolongation | HTN, MI, VTE | BP, ECG, Electrolytes |
Regorafenib (VEGFR) | Colorectal, GIST, HCC | – | – | HTN | BP |
Vandetanib (VEGFR, EGFR) | RCC | HF | – | HTN, VTE, MI | BP |
Nintedanib (VEGFR, FGFR, PDGFR) | NSCLC | – | – | – | – |
Cabozantinib (VEGFR, MET, RET) | RCC, HCC, medullary thyroid Ca. | – | – | HTN, VTE, ATE | BP, ECG, Electrolytes |
Antibodies | |||||
HER2 | |||||
Pertuzumab | Breast Ca. | LV dysfunction | – | – | TTE, troponin |
Trastuzumab | Breast Ca., gastric Ca. | LV dysfunction/HF | – | – | ECG, TTE, troponin |
Ado-trastuzumab emtansine | Breast Ca. | LV dysfunction | – | – | TTE, troponin |
VEGF | |||||
Bevacizumab | Colon Ca., breast Ca., NSCLC, RCC, ovarian Ca., cervical Ca. | HF | SVT | HTN, VTE, ATE | BP |
Ramucirumab | Gastric, colorectal, NSCLC | – | – | HTN | BP |
Aflibercept | Colorectal | – | – | HTN, VTE, ATE | BP, TTE |
EGFR | |||||
Panitumumab | Colorectal | – | Tachycardia | VTE, HTN | |
Cetuximab | Colorectal, squamous cell carcinoma of the pharynx/larynx | – | – | – | – |
Necitumumab | Squamous cell Ca., NSCLC | – | – | VTE, ATE | – |
Multi-target tyrosine kinase inhibitors
BCR-ABL inhibitors
BRAF and MEK inhibitors
ALK inhibitors
Bruton's tyrosine kinase inhibitor
HER2 inhibitors/EGF2-dependent therapeutics
VEGFR inhibitors
New haematological therapies
Active ingredient group | Active ingredient | Currently approved for* | Potential cardiac side effects |
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Proteasome inhibitors | Bortezomib | Multiple myeloma | Heart failure |
Carfilzomib | Multiple myeloma | Heart failure | |
HDAC inhibitors | Vorinostat | Cutaneous T-cell lymphoma, multiple myeloma | QTc prolongation |
Panobinostat | Multiple myeloma | QTc prolongation | |
Romidepsin | QTc prolongation | ||
Immunomodulatory drugs | Lenalidomide | Multiple myeloma | Arterial venous thrombosis, arterial hypertension, heart failure |
Pomalidomide | Multiple myeloma | Arterial venous thrombosis |
Proteasome inhibitors
The clinical data
Recommendation concerning cardiotoxicity
Procedures for suspected cardiotoxicity
Histone deacetylase (HDAC) inhibitors
Immunomodulatory drugs
Chimeric antigen receptor (CAR) T-cell therapies
Childhood and adolescent cancers and their long-term sequelae
Background
Cardiovascular burden following therapy in childhood and adolescence
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A high cumulative anthracycline dose
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A high single dose
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Repeated dosage
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Pre-existing cardiac diseases
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Additional radiotherapy
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Lower age
Transition and aspects of lifelong follow-up care
Survivorship programmes
Risk group | Electrocardiogram and echocardiography | Cardiovascular risk factors | |
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High | Doxo ≥ 250 mg/m2 | After the completion of therapy Optional: 12 months after the end of therapy 24 months after the end of therapy 5 years after the end of therapy Every 5 years At any time if symptoms appear | Blood pressure at least annually Lipid profile and HbA1c at least every 3 years, especially after RTx Adjust modifiable risk factors: Nicotine Weight, BMI, WHR Explain individual risk profile Educate patient regarding lifestyle |
RTx ≥ 35 Gy | |||
Doxo < 250 mg/m2 + RTx ≥ 15 Gy | |||
Therapy at age < 5 years | |||
Moderate | Doxo < 250 mg/m2 | After the completion of therapy Optional: 12 months after the end of therapy 5 years after the end of therapy Every 5 years At any time if symptoms appear | |
RTx ≥ 15 – < 35 Gy | |||
Other agents | Cisplatin | On a single basis | |
(High-dose) cyclophosphamide | |||
Mitoxantrone |
Follow-up observation after anthracycline therapy
Radiotherapy follow-up observation
Onco-cardiology teams
Structure
Basic structure/basic care | Advanced patient care/maximum care | Specialised centres | |
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Number of patients | < 10 patients/week | > 10 patients/week | > 20 patients/week |
Hospital structure | Cardiology department Oncology department General intensive care unit | Cardiology department Haematology/oncology/radiotherapy clinic Haematology department | Departments as for maximum care providers Heart failure programme Cardiology intensive care unit |
Multidisciplinary teams | |||
Organisation | Basic onco-cardiology team or specialised cardiologist General cardiology care | Onco-cardiology team | Onco-cardiology team Cardiac rehabilitation centre Heart failure unit Valve team Research focus |
Onco-cardiology outpatient clinic | Recommended | Available | Available |
24/7 | Recommended | Available for inpatients | Available for inpatients |
Structured clinical procedures | Available | Available | Available |
Cancer follow-up programme | Available | Available | |
Structured further education | Implemented for staff | Implemented for staff and patients | |
Technical requirements | |||
Standard echocardiography | Available | Available | Available |
Strain/3D strain | Not mandatory | Available | Available |
CMR, CT | Not mandatory | Available | Available |
Laboratory tests (cardiac biomarkers) | Available | Available | Available/genetic/new biomarkers |
Procedures | |||
Cardiac catheters/electrophysiological examinations/heart surgery/cardiac device therapy | Network with larger, regional onco-cardiology centres | Available | + Care for terminal heart failure patients |
Review of data | |||
Databases and research programme | Not mandatory | Strongly recommended | Implemented onco-cardiological research focus |
Coordination of patient routing
Basic structure
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ECG
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24-h ECG
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echocardiography, if necessary, 3D LVEF, strain and, if necessary, 3D strain
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laboratory diagnostics, including cardiac serum parameters
Central structures (highest level of care)
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cardiac MRI
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CT
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right heart catheterisation
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left heart catheterisation with the option of coronary intervention and myocardial biopsy
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PET-CT (previously restricted to trials)
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if necessary, facilities for diagnostic and therapeutic catheter ablation
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device therapies
Training
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reduced LVEF
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CAD
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arrhythmias
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arterial hypertension
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PAD
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pulmonary arterial hypertension
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myocarditis
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pericarditis
Selection of patients
Prior to cancer treatment | During cancer treatment | After cancer treatment | |
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Identification of high-cardiovascular-risk patients | Monitoring of high-cardiovascular-risk patients | Cardiological care of patients after potentially cardiotoxic therapy | |
Identification of high-cardiac-risk therapies | Monitoring of high-cardiac-risk oncology patients | ||
Treatment of patients with increased cardiac biomarkers or cardiac symptoms | |||
Responsibilities of the onco-cardiologist: | Further diagnostics and/or initiation of therapy providing advice to the oncologist | Diagnosis and therapy of pathological cardiac conditions | Initiating a cardiac therapy or initiating further cardiac diagnostics |
Patients prior to scheduled cancer therapy
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Anthracyclines
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Immune checkpoint inhibitors
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BRAF inhibitors
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Proteasome inhibitors
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Alkylating agents
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BTK inhibitors