2022 ESC Guidelines on Cardio-Oncology PDF

European Heart Journal (2022) 43, 4229–4361 ESC GUIDELINES https://doi.org/10.1093/eurheartj/ehac244 2022 ESC Guidelines on cardio-oncology developed in collaboration wit...

European Heart Journal (2022) 43, 4229–4361 ESC GUIDELINES https://doi.org/10.1093/eurheartj/ehac244 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS) Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC) Authors/Task Force Members: Alexander R. Lyon*† (Chairperson) (United Kingdom), Teresa López-Fernández*† (Chairperson) (Spain), Liam S. Couch (Task Force Coordinator) (United Kingdom), Riccardo Asteggiano (Italy), Marianne C. Aznar1 (United Kingdom), Jutta Bergler-Klein (Austria), Giuseppe Boriani (Italy), Daniela Cardinale (Italy), Raul Cordoba2 (Spain), Bernard Cosyns (Belgium), David J. Cutter (United Kingdom), Evandro de Azambuja (Belgium), Rudolf A. de Boer (Netherlands), Susan F. Dent3 (United States of America), Dimitrios Farmakis (Cyprus), Sofie A. Gevaert (Belgium), Diana A. Gorog (United Kingdom), Joerg Herrmann3 (United States of America), Daniel Lenihan3 (United States of America), Javid Moslehi (United States of America), Brenda Moura (Portugal), Sonja S. Salinger (Serbia), Richard Stephens (United Kingdom), Thomas M. Suter (Switzerland), Sebastian Szmit (Poland), Juan Tamargo (Spain), Paaladinesh Thavendiranathan (Canada), Carlo G. Tocchetti (Italy), Peter van der Meer (Netherlands), Helena J.H. van der Pal (Netherlands), and ESC Scientific Document Group *Corresponding authors: Alexander R. Lyon, National Heart and Lung Institute, Imperial College London and Cardio-Oncology Service, Royal Brompton Hospital, London, United Kingdom. Tel: +44 207 352 8121, E-mail: [email protected]. Teresa López-Fernández, Cardiology Department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, Spain. Tel: +34 619 227 076, E-mail: [email protected]. † The two chairpersons contributed equally to the document and are joint corresponding authors. Author/Task Force Member affiliations are listed in Author information. 1 Representing the European Society for Therapeutic Radiology and Oncology (ESTRO); 2representing the European Hematology Association (EHA); 3representing the International Cardio-Oncology Society (IC-OS). ESC Clinical Practice Guidelines (CPG) Committee: listed in the Appendix. ESC subspecialty communities having participated in the development of this document: Associations: Association for Acute CardioVascular Care (ACVC), European Association of Cardiovascular Imaging (EACVI), European Association of Preventive Cardiology (EAPC), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA). Councils: Council of Cardio-Oncology, Council on Hypertension, Council on Valvular Heart Disease. Working Groups: Aorta and Peripheral Vascular Diseases, Cardiovascular Pharmacotherapy, e-Cardiology, Myocardial Function, Pulmonary Circulation and Right Ventricular Function, Thrombosis. Patient Forum 4230 ESC Guidelines Document Reviewers: Patrizio Lancellotti (CPG Review Coordinator) (Belgium), Franck Thuny (CPG Review Coordinator) (France), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Berthe Aleman1 (Netherlands), Joachim Alexandre (France), Ana Barac3 (United States of America), Michael A. Borger (Germany), Ruben Casado-Arroyo (Belgium), Jennifer Cautela (France), Jolanta Čelutkienė (Lithuania), Maja Cikes (Croatia), Alain Cohen-Solal (France), Kreena Dhiman (United Kingdom), Stéphane Ederhy (France), Thor Edvardsen (Norway), Laurent Fauchier (France), Michael Fradley3 (United States of America), Julia Grapsa (United Kingdom), Sigrun Halvorsen (Norway), Michael Heuser2 (Germany), Marc Humbert (France), Tiny Jaarsma (Sweden), Thomas Kahan (Sweden), Aleksandra Konradi (Russian Federation), Konstantinos C. Koskinas (Switzerland), Dipak Kotecha (United Kingdom), Bonnie Ky3 (United States of America), Ulf Landmesser (Germany), Basil S. Lewis (Israel), Ales Linhart (Czech Republic), Gregory Y.H. Lip (United Kingdom), Maja-Lisa Løchen (Norway), Katarzyna Malaczynska-Rajpold (United Kingdom), Marco Metra (Italy), Richard Mindham (United Kingdom), Marie Moonen (Belgium), Tomas G. Neilan (United States of America), Jens Cosedis Nielsen (Denmark), Anna-Sonia Petronio (Italy), Eva Prescott Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 (Denmark), Amina Rakisheva (Kazakhstan), Joe-Elie Salem (France), Gianluigi Savarese (Sweden), Marta Sitges (Spain), Jurrien ten Berg (Netherlands), Rhian M. Touyz (Canada/United Kingdom), Agnieszka Tycinska (Poland), Matthias Wilhelm (Switzerland), and Jose Luis Zamorano (Spain) All experts involved in the development of these Guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the Guidelines. The report is also available on the ESC website www.escardio.org/Guidelines See the European Heart Journal online for supplementary data that includes background information and detailed discussion of the data that have provided the basis of the guidelines. ------------------------------------------------------------------------------------------------------------------------------------------------------------ Keywords Guidelines Androgen deprivation therapy Anthracycline Atrial fibrillation Arrhythmias Biomarkers Cancer Cancer survivors Carcinoid syndrome Amyloid light-chain cardiac amyloidosis Cardiac magnetic resonance Cardiac tumour Cardio-oncology Cardiotoxicity Coronary artery disease Chemotherapy Echocardiography Fluoropyrimidine Heart failure Haematopoietic stem cell transplantation Hormone therapy Hypertension Immunotherapy Ischaemic heart disease Myocarditis Pericardial disease Pulmonary hypertension Thrombosis Risk stratification Trastuzumab Valvular heart disease Vascular endothelial growth factor inhibitors (VEGFi) Venous thromboembolism Pericardial disease Proteasome inhibitors QTc prolongation Radiotherapy Strain The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC ([email protected]). Disclaimer: The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgement, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strat- egies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consid- eration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription. This article has been co-published with permission in the European Heart Journal and the European Heart Journal – Cardiovascular Imaging. © The European Society of Cardiology 2022. All rights reserved. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article. For permissions please e-mail: [email protected]. ESC Guidelines 4231 Table of contents 6.1. Cancer therapy-related cardiac dysfunction.......................... 4282 6.1.1. Anthracycline chemotherapy-related cardiac 1. Preamble........................................................................................................ 4236 dysfunction......................................................................................... 4282 2. Introduction................................................................................................. 4238 6.1.2. Human epidermal receptor 2-targeted therapy- 2.1. Cancer and cardiovascular needs of patients with cancer 4238 related cardiac dysfunction......................................................... 4284 2.2. Role of cardio-oncology services............................................... 4238 6.1.3. Immune checkpoint inhibitor-associated 2.3. General principles of cardio-oncology..................................... 4239 myocarditis and non-inflammatory heart failure............... 4286 3. Cancer therapy-related cardiovascular toxicity definitions..... 4242 6.1.4. Chimeric antigen receptor T cell and tumour- 4. Cardiovascular toxicity risk stratification before anticancer infiltrating lymphocytes therapies and heart dysfunction 4290 therapy................................................................................................................. 4244 6.1.5. Heart failure during haematopoietic stem cell 4.1. General approach to cardiovascular toxicity risk in patients transplantation................................................................................. 4291 with cancer................................................................................................... 4244 6.1.6. Takotsubo syndrome and cancer................................ 4291 4.2. History and clinical examination................................................. 4249 6.2. Coronary artery disease................................................................. 4291 Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 4.3. Electrocardiogram............................................................................. 4249 6.2.1. Acute coronary syndromes............................................ 4291 4.4. Cardiac serum biomarkers............................................................ 4251 6.2.2. Chronic coronary syndromes....................................... 4293 4.5. Cardiovascular imaging................................................................... 4252 6.3. Valvular heart disease...................................................................... 4293 4.6. Cardiopulmonary fitness assessment....................................... 4253 6.4. Cardiac arrhythmias......................................................................... 4294 4.7. Cardiovascular risk evaluation before cancer surgery...... 4254 6.4.1. Atrial fibrillation................................................................... 4294 4.8. Genetic testing................................................................................... 4254 6.4.2. Long corrected QT interval and ventricular 5. Prevention and monitoring of cardiovascular complications arrhythmias........................................................................................ 4298 during cancer therapy................................................................................... 4254 6.4.3. Bradyarrhythmias................................................................ 4300 5.1. General principles............................................................................. 4254 6.5. Arterial hypertension....................................................................... 4300 5.2. Primary prevention strategies...................................................... 4256 6.6. Thrombosis and thromboembolic events.............................. 4303 5.2.1. Primary prevention of cancer therapy-related 6.6.1. Venous thromboembolism............................................. 4303 cardiovascular toxicity during anthracycline 6.6.2. Arterial thromboembolism............................................ 4304 chemotherapy.................................................................................. 4256 6.6.3. Intracardiac thrombosis................................................... 4304 5.2.2. Primary prevention of radiation-induced 6.6.4. Anticoagulation therapy................................................... 4305 cardiovascular toxicity.................................................................. 4256 6.7. Bleeding complications.................................................................... 4306 5.3. Secondary prevention strategies................................................ 4257 6.7.1. High-risk patients................................................................ 4306 5.4. Cardiovascular surveillance during cancer therapies......... 4257 6.7.2. Antiplatelet therapy........................................................... 4306 5.4.1. Cardiac serum biomarkers............................................. 4257 6.7.3. Management of bleeding.................................................. 4306 5.4.2. Cardiac imaging.................................................................... 4257 6.8. Peripheral artery disease................................................................ 4307 5.5. Cancer therapy-related cardiovascular toxicity monitoring 6.9. Pulmonary hypertension................................................................ 4307 protocols....................................................................................................... 4259 6.10. Pericardial diseases......................................................................... 4308 5.5.1. Anthracycline chemotherapy......................................... 4259 6.10.1. Pericarditis........................................................................... 4308 5.5.2. HER2-targeted therapies................................................. 4259 6.10.2. Pericardial effusion........................................................... 4308 5.5.3. Fluoropyrimidines............................................................... 4261 7. End-of-cancer therapy cardiovascular risk assessment............. 4309 5.5.4. Vascular endothelial growth factor inhibitors........ 4261 7.1. Cardiovascular evaluation during the first year after 5.5.5. Multitargeted kinase inhibitors targeting BCR-ABL 4264 cardiotoxic anticancer therapy............................................................ 4309 5.5.6. Bruton tyrosine kinase inhibitors................................. 4267 7.2. Which cancer survivors require cardiovascular surveillance 5.5.7. Multiple myeloma therapies........................................... 4268 in the first year after cancer treatment?.......................................... 4309 5.5.8. Rapidly accelerated fibrosarcoma and mitogen- 7.3. Management of cancer therapy-related cardiac dysfunction activated extracellular signal-regulated kinase inhibitor at the end-of-therapy assessment...................................................... 4310 treatment............................................................................................ 4271 7.4. Cardiopulmonary exercise testing and fitness during the 5.5.9. Immune checkpoint inhibitors...................................... 4273 end-of-therapy assessment.................................................................... 4310 5.5.10. Androgen deprivation therapies for prostate 7.5. The role of cardiac rehabilitation............................................... 4310 cancer................................................................................................... 4274 8. Long-term follow-up and chronic cardiovascular complications 5.5.11. Endocrine therapies for breast cancer................... 4276 in cancer survivors.......................................................................................... 4312 5.5.12. Cyclin-dependent kinase 4/6 inhibitors.................. 4276 8.1. Cancer survivors................................................................................ 4312 5.5.13. Anaplastic lymphoma kinase inhibitors................... 4277 8.1.1. Adult survivors of childhood and adolescent 5.5.14. Epidermal growth factor receptor inhibitors...... 4277 cancer................................................................................................... 4312 5.5.15. Chimeric antigen receptor 8.1.2. Adult cancer survivors...................................................... 4313 T cell and tumour-infiltrating lymphocytes therapies..... 4278 8.2. Myocardial dysfunction and heart failure................................ 4315 5.5.16. Radiotherapy...................................................................... 4279 8.3. Coronary artery disease................................................................. 4316 5.5.17. Haematopoietic stem cell transplantation............ 4279 8.4. Valvular heart disease...................................................................... 4317 5.5.18. Other cancer treatments............................................. 4282 8.5. Peripheral artery disease and stroke........................................ 4317 6. Diagnosis and management of acute and subacute 8.6. Pericardial complications................................................................ 4317 cardiovascular toxicity in patients receiving anticancer treatment 4282 8.7. Arrhythmias and autonomic disease......................................... 4318 4232 ESC Guidelines 8.8. Metabolic syndrome, lipid abnormalities, diabetes mellitus, Recommendation Table 12 — Recommendations for baseline and hypertension........................................................................................ 4318 risk assessment and monitoring during Bruton tyrosine kinase 8.9. Pregnancy in cancer survivors..................................................... 4318 inhibitor therapy.............................................................................................. 4267 8.10. Pulmonary hypertension.............................................................. 4319 Recommendation Table 13 — Recommendations for baseline 9. Special populations.................................................................................... 4319 risk assessment and monitoring during multiple myeloma 9.1. Cardiac tumours................................................................................ 4319 therapies..................................................................................................... 4271 9.2. Pregnant patients with cancer..................................................... 4319 Recommendation Table 14 — Recommendations for baseline 9.2.1. Left ventricular dysfunction and heart failure........ 4320 risk assessment and monitoring during combined rapidly 9.2.2. Venous thromboembolism and pulmonary accelerated fibrosarcoma and mitogen-activated extracellular embolism..................................................................................... 4320 signal-regulated kinase inhibitor therapy............................................... 4272 9.3. Carcinoid valvular heart disease................................................. 4323 Recommendation Table 15 — Recommendations for baseline 9.4. Amyloid light-chain cardiac amyloidosis.................................. 4324 risk assessment and monitoring during immunotherapy............... 4274 9.5. Cardiac implantable electronic devices.................................... 4326 Recommendation Table 16 — Recommendations for baseline Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 10. Patient information, communication, and self-management 4330 risk assessment and monitoring during androgen deprivation 11. The role of scientific societies in the promotion and therapy for prostate cancer....................................................................... 4276 development of cardio-oncology in modern medicine.................. 4331 Recommendation Table 17 — Recommendations for baseline 12. Key messages............................................................................................ 4331 risk assessment and monitoring during endocrine therapy for 13. Future needs.............................................................................................. 4332 breast cancer.................................................................................................... 4276 14. Gaps in evidence...................................................................................... 4333 Recommendation Table 18 — Recommendations for baseline 15. ‘What to do’ and ‘what not to do’ messages from the risk assessment and monitoring during cyclin-dependent kinase Guidelines........................................................................................................... 4333 4/6 inhibitor therapy...................................................................................... 4277 16. Quality indicators for cardio-oncology.......................................... 4342 Recommendation Table 19 — Recommendations for baseline 17. Supplementary data................................................................................ 4342 risk assessment and monitoring during anaplastic lymphoma 18. Data availability statement................................................................... 4342 kinase and epidermal growth factor receptor inhibitors............... 4277 19. Author information................................................................................ 4342 Recommendation Table 20 — Recommendations for baseline 20. Appendix..................................................................................................... 4342 risk assessment and monitoring in patients receiving chimeric 21. References.................................................................................................. 4343 antigen receptor T cell and tumour-infiltrating lymphocytes therapies............................................................................................................. 4279 Recommendation Table 21 — Recommendations for baseline Tables of Recommendations risk assessment of patients before radiotherapy to a volume including the heart.......................................................................................... 4279 Recommendation Table 1 — Recommendations for a general Recommendation Table 22 — Recommendations for baseline approach to cardiovascular toxicity risk categorization................. 4249 risk assessment in haematopoietic stem cell transplantation Recommendation Table 2 — Recommendations for patients................................................................................................................ 4281 electrocardiogram baseline assessment................................................ 4251 Recommendation Table 23 — Recommendation for the Recommendation Table 3 — Recommendation for cardiac management of cardiovascular disease and cancer biomarker assessment prior to potentially cardiotoxic therapies. 4252 therapy-related cardiovascular toxicity in patients receiving Recommendation Table 4 — Recommendations for cardiac anticancer treatment..................................................................................... 4282 imaging modalities in patients with cancer.......................................... 4253 Recommendation Table 24 — Recommendations for the Recommendation Table 5 — Recommendations for management of cancer treatment-related cardiac dysfunction primary prevention of cancer therapy-related cardiovascular during anthracycline chemotherapy........................................................ 4284 toxicity......................................................................................................... 4256 Recommendation Table 25 — Recommendations for the Recommendation Table 6 — Recommendation for secondary management of cancer treatment-related cardiac dysfunction prevention of cancer therapy-related cardiovascular toxicity..... 4257 during human epidermal receptor 2-targeted therapies............... 4286 Recommendation Table 7 — Recommendations for baseline risk Recommendation Table 26 — Recommendations for the assessment and monitoring during anthracycline chemotherapy diagnosis and management of immune checkpoint and in the first 12 months after therapy.............................................. 4259 inhibitor-associated myocarditis............................................................... 4289 Recommendation Table 8 — Recommendations for baseline risk Recommendation Table 27 — Recommendations for the assessment and monitoring during human epidermal receptor diagnosis and management of Takotsubo syndrome in patients 2-targeted therapies and in the first 12 months after therapy... 4260 with cancer........................................................................................................ 4291 Recommendation Table 9 — Recommendations for baseline risk Recommendation Table 28 — Recommendations for the assessment and monitoring during fluoropyrimidine therapy..... 4261 management of acute coronary syndromes in patients receiving Recommendation Table 10 — Recommendations for baseline anticancer treatment..................................................................................... 4292 risk assessment and monitoring during vascular endothelial Recommendation Table 29 — Recommendation for the growth factor inhibitors............................................................................... 4264 management of chronic coronary syndromes in patients receiving Recommendation Table 11 — Recommendations for baseline anticancer treatment..................................................................................... 4293 risk assessment and monitoring during second- and Recommendation Table 30 — Recommendations for the third-generation breakpoint cluster region–Abelson oncogene management of valvular heart disease in patients receiving locus tyrosine kinase inhibitors................................................................. 4267 anticancer treatment..................................................................................... 4293 ESC Guidelines 4233 Recommendation Table 31 — Recommendations for the Table 6 Factors that could influence peri-operative risk during management of atrial fibrillation in patients receiving anticancer cancer surgery and preventive strategies............................................. 4254 treatment............................................................................................................ 4297 Table 7 Cancer treatments that predispose to acute coronary Recommendation Table 32 — Recommendations for the syndromes.......................................................................................................... 4291 management of long corrected QT interval and ventricular Table 8 Risk factors for drug-induced QT prolongation and arrhythmias in patients receiving anticancer treatment................. 4300 torsade de pointes.......................................................................................... 4298 Recommendation Table 33 — Recommendations for the Table 9 Classification of corrected QT interval prolongation management of arterial hypertension in patients receiving induced by cancer drug therapy............................................................... 4298 anticancer treatment..................................................................................... 4302 Table 10 Risk factors for future cardiovascular disease at the Recommendation Table 34 — Recommendations for the end-of-cancer therapy cardiovascular risk assessment................... 4310 management of venous thromboembolism in patients receiving Table 11 Risk categories for asymptomatic adults who are anticancer treatment..................................................................................... 4305 childhood and adolescent cancer survivors......................................... 4313 Recommendation Table 35 — Recommendations for venous Table 12 Risk categories for asymptomatic adult cancer survivors 4314 Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 thromboembolism prophylaxis during anticancer treatment...... 4306 Table 13 Management strategies and surgery indications for Recommendation Table 36 — Recommendation for management symptomatic and asymptomatic patients with benign and of peripheral artery disease during anticancer treatment.................. 4307 malignant cardiac tumours.......................................................................... 4321 Recommendation Table 37 — Recommendations for the management of pulmonary hypertension during anticancer treatment............................................................................................................ 4308 List of figures Recommendation Table 38 — Recommendations for the Figure 1 Video 1 Central Illustration: Dynamics of management of pericardial diseases in patients receiving cardiovascular toxicity risk of patients with cancer over their anticancer treatment..................................................................................... 4309 therapy continuum.................................................................................. 4239 Recommendation Table 39 — Recommendations for Figure 2 Cardio-oncology care pathways............................................. 4240 end-of-cancer therapy cardiovascular risk assessment................... 4312 Figure 3 Baseline cardiovascular toxicity risk assessment checklist 4241 Recommendation Table 40 — Recommendations for Figure 4 Dimensions of cancer therapy-related cardiovascular cardiovascular surveillance in asymptomatic adults who are toxicity risk and disease severity.............................................................. 4242 childhood and adolescent cancer survivors......................................... 4313 Figure 5 Baseline cardiovascular toxicity risk assessment before Recommendation Table 41 — Recommendations for anticancer therapy.......................................................................................... 4245 cardiovascular surveillance in asymptomatic adult cancer survivors 4314 Figure 6 General cardio-oncology approach after Heart Failure Recommendation Table 42 — Recommendations for adult Association–International Cardio-Oncology Society cancer survivors who develop cancer therapy-related cardiac cardiovascular toxicity risk assessment................................................ 4248 dysfunction late after cardiotoxic cancer therapy............................ 4316 Figure 7 Baseline screening recommendations for patients with Recommendation Table 43 — Recommendations for adult cancer treated with potentially cardiotoxic drugs............................ 4250 cancer survivors with coronary artery disease.................................. 4316 Figure 8 Recommended transthoracic echocardiography and Recommendation Table 44 — Recommendations for adult cardiac magnetic resonance imaging parameters in the evaluation of cancer survivors with valvular heart disease....................................... 4317 patients with cancer............................................................................................... 4252 Recommendation Table 45 — Recommendation for adult cancer Figure 9 Primary and secondary cancer therapy-related survivors with pericardial complications............................................... 4318 cardiovascular toxicity prevention.................................................................. 4255 Recommendation Table 46 — Recommendations for Figure 10 Cardiovascular toxicity monitoring in patients receiving cardiovascular monitoring in cancer survivors during pregnancy 4319 anthracycline chemotherapy...................................................................... 4258 Recommendation Table 47 — Recommendations for cardiovascular Figure 11 Cardiovascular toxicity monitoring in patients receiving assessment and monitoring of pregnant women with cancer............. 4323 human epidermal receptor 2-targeted therapies.............................. 4260 Recommendation Table 48 — Recommendations for carcinoid Figure 12 Vascular endothelial growth factor inhibitors-related valvular heart diseases................................................................................... 4323 cardiovascular toxicities............................................................................... 4262 Recommendation Table 49 — Recommendations for amyloid Figure 13 Cardiovascular toxicity monitoring in patients receiving light-chain cardiac amyloidosis diagnosis and monitoring.............. 4326 vascular endothelial growth factor inhibitors..................................... 4263 Recommendation Table 50 — Recommendations for risk Figure 14 Breakpoint cluster region–Abelson oncogene locus stratification and monitoring for patients with cardiac implantable tyrosine kinase inhibitor-related cardiovascular toxicities............ 4265 electronic devices undergoing radiotherapy.................................................... 4330 Figure 15 Second- and third-generation breakpoint cluster region–Abelson oncogene locus tyrosine kinase inhibitors surveillance protocol..................................................................................... 4266 List of tables Figure 16 Multiple myeloma drug-related cardiovascular toxicities 4268 Figure 17 Cardiovascular monitoring in patients with multiple Table 1 Classes of recommendations.................................................... 4237 myeloma receiving proteasome inhibitors........................................... 4269 Table 2 Levels of evidence.......................................................................... 4237 Figure 18 Risk factors for venous thromboembolic events in Table 3 Cancer therapy-related cardiovascular toxicity definitions 4243 patients with multiple myeloma............................................................... 4270 Table 4 Heart Failure Association–International Cardio-Oncology Figure 19 Rapidly accelerated fibrosarcoma and mitogen-activated Society baseline cardiovascular toxicity risk stratification............... 4246 extracellular signal-regulated kinase inhibitor-related cardiovascular Table 5 Anthracycline equivalence dose............................................... 4247 toxicities........................................................................................................................ 4272 4234 ESC Guidelines Figure 20 Cardiovascular surveillance in patients treated with immune checkpoint inhibitors................................................................... 4273 Abbreviations and acronyms Figure 21 Androgen deprivation therapy-related cardiovascular 2D Two-dimensional toxicities.............................................................................................................. 4275 3D Three-dimensional Figure 22 Anaplastic lymphoma kinase and epidermal growth 5-FU 5-fluorouracil factor receptor inhibitor-related cardiovascular toxicities........... 4278 5HIAA 5-hydroxyindoleacetic acid Figure 23 Radiotherapy mean heart dose and associated a′ Late diastolic velocity of mitral annulus cardiovascular toxicity risk.......................................................................... 4280 obtained by tissue Doppler imaging Figure 24 Risk factors and cardiovascular surveillance in patients ABC Atrial fibrillation Better Care referred for haematopoietic stem cell transplantation.................. 4281 ABI Ankle–brachial index Figure 25 Management of anthracycline chemotherapy-related AC Anthracycline chemotherapy cardiac dysfunction......................................................................................... 4283 ACE-I Angiotensin-converting enzyme inhibitors Figure 26 Management of human epidermal receptor 2-targeted ACS Acute coronary syndromes Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 therapy-related cardiac dysfunction........................................................ 4285 ADT Androgen deprivation therapy Figure 27 Direct and indirect immune checkpoint ADVANCE Action in Diabetes and Vascular Disease: inhibitor-related cardiovascular toxicity................................................ 4287 Preterax and Diamicron-MR Controlled Figure 28 Diagnosis and management of immune checkpoint Evaluation inhibitor-related myocarditis...................................................................... 4288 AF Atrial fibrillation Figure 29 Diagnosis and management workup in cancer-related AI Aromatase inhibitors Takotsubo syndrome.................................................................................... 4290 AL-CA Amyloid light-chain cardiac amyloidosis Figure 30 Pathophysiology of atrial fibrillation associated with ALK Anaplastic lymphoma kinase cancer................................................................................................................... 4295 ANS Autonomic nervous system Figure 31 Structured approach to anticoagulation for atrial ARB Angiotensin receptor blockers fibrillation in patients with cancer............................................................ 4296 ARISTOTLE Apixaban for Reduction in Stroke and Other Figure 32 Corrected QT interval monitoring before and during Thromboembolic Events in Atrial Fibrillation treatment with corrected QT interval-prolonging anticancer drugs 4299 ASCVD AtheroSclerotic Cardiovascular Disease Figure 33 Recommended threshold for asymptomatic ASPIRE Carfilzomib, Lenalidomide, and hypertension treatment in different clinical scenarios.................... 4301 Dexamethasone vs. Lenalidomide and Figure 34 Treatment of arterial hypertension in patients with Dexamethasone for the Treatment of cancer................................................................................................................... 4302 Patients with Relapsed Multiple Myeloma Figure 35 Risk factors for venous thromboembolism in patients ASTCT American Society for Transplantation and with cancer........................................................................................................ 4303 Cellular Therapy Figure 36 Structured approach to anticoagulation for venous ATAC ‘Arimidex’ and Tamoxifen Alone or in thromboembolism in patients with active cancer............................ 4304 Combination Figure 37 Management of cancer therapy-related cardiac ATE Arterial thromboembolism dysfunction after cancer therapy............................................................. 4311 AV Atrioventricular Figure 38 Long-term follow-up in cancer survivors......................... 4315 BB Beta-blockers Figure 39 Location of primary and secondary cardiac tumours. 4320 BC Breast cancer Figure 40 Diagnostic algorithm for cardiac masses.......................... 4321 BCR-ABL Breakpoint cluster region–Abelson oncogene Figure 41 Cardiac monitoring protocol for pregnant women locus receiving anthracycline-based chemotherapy..................................... 4322 BIG Breast International Group Figure 42 Carcinoid heart disease: clinical features and diagnostic BLEED Increased bleeding risk tests....................................................................................................................... 4324 BMI Body mass index Figure 43 Non-invasive diagnosis of amyloid light-chain cardiac BNP B-type natriuretic peptide amyloidosis......................................................................................................... 4325 BP Blood pressure Figure 44 Risk stratification in patients with a cardiac implantable BTK Bruton tyrosine kinase electronic device undergoing radiotherapy......................................... 4327 C Chemotherapy cycle Figure 45 Management of patients with a cardiac implantable CABG Coronary artery bypass graft electronic device located in the radiotherapy treatment beam. 4328 CAD Coronary artery disease Figure 46 Management of patients with a cardiac implantable CARDIOTOX CARDIOvascular TOXicity induced by electronic device located outside the radiotherapy treatment cancer-related therapies volume................................................................................................................. 4329 CAR-T Chimeric antigen receptor T cell Figure 47 Patient information, communication, and CCB Calcium channel blockers self-management.............................................................................................. 4330 CCS Chronic coronary syndromes Figure 48 The role of scientific societies in the promotion and CCTA Coronary computed tomography development of cardio-oncology............................................................. 4331 angiography ESC Guidelines 4235 CCU Coronary care unit ESC-CCO European Society of Cardiology Council of CDK Cyclin-dependent kinase Cardio-Oncology CHA2DS2-VASc Congestive heart failure, Hypertension, Age ESH European Society of Hypertension ≥ 75 years (2 points), Diabetes mellitus, EuroSCORE European System for Cardiac Operative Stroke (2 points)—Vascular disease, Age Risk Evaluation 65–74 years, Sex category (female) FAC Fractional area change CIED Cardiac implantable electronic device FDA Food and Drug Administration CML Chronic myeloid leukaemia FLT3 FMS-like tyrosine kinase 3 CMR Cardiac magnetic resonance FWLS Free wall longitudinal strain COMPASS-CAT Prospective COmparison of Methods for GI Gastrointestinal thromboembolic risk assessment with clinical GLS Global longitudinal strain Perceptions and AwareneSS in real-life GnRH Gonadotropin-releasing hormone patients—Cancer Associated Thrombosis GU Genitourinary Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 CPET Cardiopulmonary exercise testing GVHD Graft vs. host disease CrCl Creatinine clearance Gy Gray CRF Cardiorespiratory fitness HAS-BLED Hypertension, Abnormal renal and liver CRS Cytokine release syndrome function, Stroke, Bleeding Labile CS Cancer survivors international normalized ratio, Elderly, CT Computed tomography Drugs or alcohol CTLA-4 Cytotoxic T lymphocyte-associated HbA1c Glycated haemoglobin antigen-4 HDU High-dependency unit cTn Cardiac troponin HER2 Human epidermal receptor 2 CTRCD Cancer therapy-related cardiac HF Heart failure dysfunction HFA Heart Failure Association CTR-CVT Cancer therapy-related cardiovascular HFmrEF Heart failure with mildly reduced ejection toxicity fraction CV Cardiovascular HFpEF Heart failure with preserved ejection fraction CVD Cardiovascular disease HFrEF Heart failure with reduced ejection fraction CVRF Cardiovascular risk factors HG Hyperglycaemia DAPT Dual antiplatelet therapy HIIT High-intensity interval training DASISION DASatinib vs. Imatinib Study In HSCT Haematopoietic stem cell transplantation treatment-Naïve chronic myeloid hs-cTn High-sensitivity cardiac troponin leukaemia patients HTN Hypertension DL Dyslipidaemia ICD Implantable cardioverter defibrillator DM Diabetes mellitus ICI Immune checkpoint inhibitors DNR Do not resuscitate ICOS International Cardio-Oncology Society DVT Deep vein thrombosis ICU Intensive care unit E Mitral inflow early diastolic velocity IHD Ischaemic heart disease obtained by pulsed wave IMiD Immunomodulatory drugs e′ Early diastolic velocity of the mitral annulus i.v. Intravenous obtained by tissue Doppler imaging IVC Inferior vena cava EACTS European Association for Cardio-Thoracic IVS Intraventricular septum Surgery LA Left atrial EBC Early breast cancer LAA Left atrial appendage ECG Electrocardiogram LGE Late gadolinium enhancement Echo Echocardiography LIMA Left internal mammary artery ECV Extracellular volume fraction LMWH Low-molecular-weight heparins eGFR Estimated glomerular filtration rate LQTS Long QT syndrome EGFR Epidermal growth factor receptor LS Longitudinal strain EMA European Medicines Agency LV Left ventricular EMB Endomyocardial biopsy LVD Left ventricular dysfunction ENGAGE AF-TIMI 48 Effective Anticoagulation with Factor LVEDD Left ventricular end diastolic diameter Xa Next Generation in Atrial Fibrillation- LVEF Left ventricular ejection fraction Thrombolysis in Myocardial Infarction 48 LVV Left ventricular volume ENOXACAN Enoxaparin and Cancer M Months EoL End of life MACE Major adverse cardiovascular events ERS European Respiratory Society MCS Mechanical circulatory support ESC European Society of Cardiology MDT Multidisciplinary team 4236 ESC Guidelines MedDRA Medical dictionary for regulatory activities SMART Second manifestations of arterial disease MEK Mitogen-activated extracellular sPAP Systolic pulmonary artery pressure signal-regulated kinase SPEP Serum protein electrophoresis MHD Mean heart dose STEMI ST-segment elevation myocardial infarction MI Myocardial infarction STIR Short tau inversion recovery MM Multiple myeloma STS PROM Society of Thoracic Surgeons – Predicted MUGA Multigated acquisition nuclear imaging Risk of Mortality N No SVT Supraventricular tachycardia NOAC Non-vitamin K antagonist oral SYNTAX SYNergy between percutaneous coronary anticoagulants intervention with TAXus and cardiac surgery NP Natriuretic peptides TAPSE Tricuspid annular plane systolic excursion NSTE-ACS Non-ST-segment elevation acute coronary TAVI Transcatheter aortic valve implantation syndromes TBIP Thromboembolic risk, Bleeding risk, drug– Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 NT-proBNP N-terminal pro-B-type natriuretic peptide drug Interactions, Patient preferences PAD Peripheral artery disease TdP Torsade de pointes PAH Pulmonary arterial hypertension TIL Tumour-infiltrating lymphocytes PAP Pulmonary arterial pressure TKI Tyrosine kinase inhibitors PCI Percutaneous coronary intervention TRV Tricuspid regurgitation velocity PD-1 Programmed death-1 TTE Transthoracic echocardiography PD-L1 Programmed death-ligand 1 TTS Takotsubo syndrome PE Pulmonary embolism tx Treatment Peric-E Pericardial effusion ULN Upper limit of normal PET Positron emission tomography UPEP Urine protein electrophoresis PH Pulmonary hypertension VA Ventricular arrhythmias PI Proteasome inhibitors VascTox Vascular toxicity Pleu-E Pleural effusion VEGF Vascular endothelial growth factor PRECISE-DAPT PREdicting bleeding Complications In VEGFi Vascular endothelial growth factor inhibitors patients undergoing Stent implantation and VH Very high risk subsEquent Dual Anti Platelet Therapy VHD Valvular heart disease PRONOUNCE A Trial Comparing Cardiovascular Safety VKA Vitamin K antagonists of Degarelix Versus Leuprolide in Patients VTE Venous thromboembolism With Advanced Prostate Cancer and Y Yes Cardiovascular Disease PW Left ventricular posterior wall QI Quality indicator 1. Preamble ↑QTc Corrected QT interval prolongation QTc Corrected QT interval Guidelines summarize and evaluate available evidence with the aim of QTcF Corrected QT interval using Fridericia assisting health professionals in proposing the best management strat- correction egies for an individual patient with a given condition. Guidelines and RA Right atrial their recommendations should facilitate decision making of health pro- RAF Rapidly accelerated fibrosarcoma fessionals in their daily practice. However, guidelines are not a substi- RCT Randomized controlled trial tute for the patient’s relationship with their practitioner. The final RIMA Right internal mammary artery decisions concerning an individual patient must be made by the re- ROCKET AF Rivaroxaban Once Daily Oral Direct Factor sponsible health professional(s), based on what they consider to be Xa Inhibition Compared with Vitamin K the most appropriate in the circumstances. These decisions are Antagonism for Prevention of Stroke and made in consultation with the patient and caregiver as appropriate. Embolism Trial in Atrial Fibrillation Guidelines are intended for use by health professionals. To ensure RT Radiotherapy that all users have access to the most recent recommendations, the RV Right ventricular ESC makes its Guidelines freely available. The ESC warns readers RVEF Right ventricular ejection fraction that the technical language may be misinterpreted and declines any RVV Right ventricular volume responsibility in this respect. s′ Systolic velocity of tricuspid annulus A great number of guidelines have been issued in recent years by the obtained by doppler tissue imaging ESC. Because of their impact on clinical practice, quality criteria for the SBr Sinus bradycardia development of guidelines have been established to make all decisions SCORE2 Systematic Coronary Risk Estimation 2 transparent to the user. The recommendations for formulating and is- SCORE2-OP Systematic Coronary Risk Estimation 2— suing ESC Guidelines can be found on the ESC website (https://www. Older Persons escardio.org/Guidelines). The ESC Guidelines represent the official pos- SEER Surveillance, Epidemiology, and End Results ition of the ESC on a given topic and are regularly updated. ESC Guidelines 4237 Table 1 Classes of recommendations Definition Wording to use Classes of recommendations Class I Evidence and/or general agreement Is recommended or is indicated that a given treatment or procedure is beneficial, useful, effective. Class II Conflicting evidence and/or a divergence of opinion about the usefulness/ efficacy of the given treatment or procedure. Class IIa Weight of evidence/opinion is in Should be considered favour of usefulness/efficacy. Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 Class IIb Usefulness/efficacy is less well May be considered established by evidence/opinion. Class III Evidence or general agreement that the Is not recommended given treatment or procedure is not ©ESC 2022 useful/effective, and in some cases may be harmful. Table 2 Levels of evidence Level of Data derived from multiple randomized clinical trials evidence A or meta-analyses. Level of Data derived from a single randomized clinical trial evidence B or large non-randomized studies. Level of Consensus of opinion of the experts and/or small studies, ©ESC 2022 evidence C retrospective studies, registries. In addition to the publication of Clinical Practice Guidelines, the ESC Consideration was given to diversity and inclusion, notably with respect carries out the EURObservational Research Programme of internation- to gender and country of origin. A critical evaluation of diagnostic and al registries of cardiovascular diseases and interventions, which are es- therapeutic procedures was performed, including assessment of the sential to assess diagnostic/therapeutic processes, use of resources risk–benefit ratio. The level of evidence and the strength of the recom- and adherence to guidelines. These registries aim at providing a better mendation of particular management options were weighed and scored understanding of medical practice in Europe and around the world, according to predefined scales, as outlined below. The Task Force fol- based on high-quality data collected during routine clinical practice. lowed the ESC voting procedures. All recommendations subject to a Furthermore, the ESC develops sets of quality indicators (QIs), vote achieved at least 75% among voting members. which are tools to evaluate the level of implementation of the guide- The experts of the writing and reviewing panels provided declar- lines and may be used by the ESC, hospitals, healthcare providers and ation of interest forms for all relationships that might be perceived as professionals to measure clinical practice, and in educational pro- real or potential sources of conflicts of interest. Their declarations of grammes, alongside the key messages from the guidelines, to im- interest were reviewed according to the ESC declaration of interest prove quality of care and clinical outcomes. rules and can be found on the ESC website (http://www.escardio.org/ The Members of this Task Force were selected by the ESC to re- Guidelines) and have been compiled in a report and published in a present professionals involved with the medical care of patients with supplementary document simultaneously to the guidelines. this pathology. The selection procedure aimed to ensure that there is This process ensures transparency and prevents potential biases in a representative mix of members predominantly from across the whole the development and review processes. Any changes in declarations of the ESC region and from relevant ESC Subspecialty Communities. of interest that arise during the writing period were notified to the 4238 ESC Guidelines ESC and updated. The Task Force received its entire financial support after their cancer treatments with respect to their cardiovascular (CV) from the ESC without any involvement from the healthcare industry. health and wellness. This guideline provides guidance on the definitions, The ESC CPG supervises and coordinates the preparation of new diagnosis, treatment, and prevention of cancer therapy-related CV guidelines. The Committee is also responsible for the approval pro- toxicity (CTR-CVT), and the management of CV disease (CVD) cess of these guidelines. The ESC Guidelines undergo extensive re- caused directly or indirectly by cancer. This area of medicine has lim- view by the CPG and external experts, including a mix of ited trials and evidence on which to base decision-making and, members from across the whole of the ESC region and from relevant where evidence is limited, this guideline provides the consensus of ESC Subspecialty Communities and National Cardiac Societies. After expert opinion to guide healthcare professionals. appropriate revisions, the guidelines are signed off by all the experts This guideline includes the definitions of CTR-CVT (Section 3),1 and involved in the Task Force. The finalized document is signed off by provides a personalized approach to care based upon the baseline the CPG for publication in the European Heart Journal. The guidelines CV toxicity risk assessment (Section 4) and new protocols for CV sur- were developed after careful consideration of the scientific and med- veillance during cancer treatment (Section 5). The management of acute ical knowledge and the evidence available at the time of their writing. CTR-CVT is addressed in Section 6, where patients with active cancer are Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 The task of developing ESC Guidelines also includes the creation of those receiving anticancer treatment. Throughout these sections, educational tools and implementation programmes for the recommen- decision-making depends upon the risk/benefit balance of oncology dations, including condensed pocket guideline versions, summary slides, treatment efficacy and the severity and impact of CTR-CVT. Guidance summary cards for non-specialists and an electronic version for digital is provided for the first 12 months after completion of cardiotoxic treat- applications (smartphones, etc.). These versions are abridged and thus, ments (Section 7), when subacute CVD can emerge, and when patients for more detailed information, the user should always access the full- who developed CTR-CVT during cancer treatment are reviewed. text version of the guidelines, which is freely available via the ESC web- Diagnosis and management of the long-term CV complications of previ- site and the European Heart Journal. The National Cardiac Societies of ous oncology treatments, beyond 12 months after completing the cardi- the ESC are encouraged to endorse, adopt, translate and implement all otoxic treatments, and integration into the overall survivorship strategy ESC Guidelines. Implementation programmes are needed because it for cancer survivors (CS) is presented in Section 8 with new long-term has been shown that the outcome of disease may be favourably influ- surveillance recommendations for high-risk patients. enced by the thorough application of clinical recommendations. In Section 9, we address special populations where CVDs are dir- Health professionals are encouraged to take the ESC Guidelines ectly caused by the cancer, or where special considerations are re- fully into account when exercising their clinical judgement, as well quired. Section 10 provides information for patients’ involvement in as in the determination and the implementation of preventive, diag- their own care. The final section highlights the role of the ESC and nostic or therapeutic medical strategies. However, the ESC the ESC Council of Cardio-Oncology (ESC-CCO). Guidelines do not override in any way whatsoever the individual re- CTR-CVT risk is a dynamic variable, and the risk changes through- sponsibility of health professionals to make appropriate and accurate out the pathway of care (Figure 1, Video 1). Absolute risk of decisions in consideration of each patient’s health condition and in CTR-CVT is important to understand and balance against the abso- consultation with that patient or the patient’s caregiver where ap- lute benefit of the cancer treatment before and during treatment. propriate and/or necessary. It is also the health professional’s re- However, CTR-CVT risk can be influenced by several variables, in- sponsibility to verify the rules and regulations applicable in each cluding implementation of primary prevention treatments, optimiza- country to drugs and devices at the time of prescription and to re- tion of pre-existing CVD, dose, frequency, and duration of oncology spect the ethical rules of their profession. treatment, emergence of CV complications during treatment and Off-label use of medication may be presented in this guideline if their severity, and in CS, the overall cumulative treatment received, sufficient level of evidence shows that it can be considered medically the time since treatment, and the interaction with other CVDs. appropriate to a given condition and if patients could benefit from the recommended therapy. However, the final decisions concerning 2.1. Cancer and cardiovascular needs of an individual patient must be made by the responsible health profes- sional giving special consideration to: patients with cancer Since the 1990s, there has been a steady decline in cancer-related (1) the specific situation of the patient. In this respect, it is specified mortality mirrored by a steady increase in CS.2,3 In this context, that, unless otherwise provided for by national regulations, off- treatment-related side effects have gained more significance. label use of medication should be limited to situations where it Management of CTR-CVT has a tremendous impact on the type of is in the patient’s interest to do so, with regard to the quality, anticancer therapies that patients can receive as well as the long-term safety and efficacy of care, and only after the patient has been in- morbidity and mortality outcomes of patients with cancer. Effective formed and has provided consent; management of patients with both cancer and CVD requires the un- (2) country-specific health regulations, indications by governmental ique interest and expertise of healthcare providers, which has led to drug regulatory agencies and the ethical rules to which health the formation of a new discipline: cardio-oncology.4,5 A recently pub- professionals are subject, where applicable. lished ESC-CCO document describes appropriate criteria for the or- ganization and implementation of cardio-oncology services.5 2. Introduction This is the first European Society of Cardiology (ESC) guideline on 2.2. Role of cardio-oncology services cardio-oncology. The aim of this guideline is to help all the healthcare The overarching goal of the cardio-oncology discipline is to allow pa- professionals providing care to oncology patients before, during, and tients with cancer to receive the best possible cancer treatments safely, ESC Guidelines 4239 Baseline During cardiotoxic D Long-term foll f ow-up after risk cancer therappy cancer treatment Primary and Cancer treatment CTR-CVT secondary surveillance Cancer survivorship programmes risk prevention Early CTR-CVT strategies management High risk Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 Low risk Time Figure 1 Video 1 Central Illustration: Dynamics of cardiovascular toxicity risk of patients with cancer over their therapy continuum. CS, cancer survivors; CTR-CVT, cancer therapy-related cardiovascular toxicity; CV, cardiovascular; CVD, cardiovascular disease; CVRF, cardiovascular risk fac- tors; CTR-CVT risk is a dynamic variable that changes through the pathway of care, and is influenced by several conditions including age, cancer history, pre-existing CVRF or CVD, and previous cardiotoxic cancer therapy. The CTR-CVT risk changes during and after treatment according to type, dose, frequency, and duration of oncology treatment (blue solid line). Pre-existing CVRF, CVD, or previous cancer treatments may increase the magnitude of acute and long-term CV toxicity risk (purple solid line). CTR-CVT risk remains variable in extent during anticancer treatment and may or may not gradually increase over time (dotted lines). Cardio-oncology strategy may reduce the magnitude of CTR-CVT by: (1) optimizing CVD and CVRF management (green arrows); (2) considering cardioprotective strategies in high-risk patients (green arrows); (3) organizing cancer treat- ment surveillance; and (4) introducing early cardioprotection after the detection of subclinical CTR-CVT (purple arrows). CV risk assessment within the first year after completion of cardiotoxic cancer therapy identifies CS who require long-term follow-up. Cancer survivorship programmes that include annual CV risk assessment and CVRF/CVD management are recommended to minimize long-term CV adverse events (brown arrows). minimizing CTR-CVT across the entire continuum of cancer care.5 therapies with CV toxicity risk, surveillance should continue until the Before initiation of cancer therapies with a known CV toxicity profile, treatment is finished.6–8 There is also the need for re-assessment of the cardio-oncology team should identify and treat CV risk factors CV risks in patients requiring treatment for secondary malignancies. (CVRF) and pre-existing CVDs and define an appropriate prevention and surveillance plan for early identification and appropriate manage- ment of potential CV complications (Figure 2). Another important as- 2.3. General principles of pect is the participation in interdisciplinary discussions regarding the cardio-oncology benefits and risks of certain cancer treatments and their continuation A guiding principle of cardio-oncology is the integration of clinical dis- or interruption should side effects become apparent. After cancer ciplines. Cardio-oncology providers must have knowledge of the treatment has been completed, the focus shifts to co-ordination of broad scope of cardiology, oncology, and haematology management.5 long-term follow-up and treatment. For patients on long-term cancer Recommendations are formed regarding the most permissible (from a 4240 ESC Guidelines Cardio-Oncology Care Pathways New cancer During cancer First year after Long term diagnosis treatmenta cancer treatmentb follow-up Informing, advising, and supporting patients to promote a healthy lifestyle Baseline CV toxicity risk assessmentc Management of CVRF and CVD according to ESC Guidelines Downloaded from https://academic.oup.com/eurheartj/article/43/41/4229/6673995 by guest on 24 July 2023 Annual CVRF Assessment at 1 year assessmente Low risk Standard after completion of patients surveillance cancer therapy Reassessment if new CV signs/symptoms Annual CVRF assessmente Assessment at 1 year CV toxicity re-stratification Moderate risk at 5 years Cardiology referral d after completion of patients cancer therapy TTE every 5 years Assessment at 3 Annual CVRF High and d months and 1 year assessmente Cardiology referral very high risk after completion of CVD prevention TTE at years 1, 3, 5 and patients cancer therapy every 5 years Cardiology referrald if new CV signs/symptoms or CTR-CVT develop Class 1 Class 1Ia Class 1Ib Figure 2 Cardio-oncology care pathways. BP, blood pressure; CS, cancer survivors; CTR-CVT, cancer therapy-related cardiovascular toxicity; CV, cardiovascular; CVD, cardiovascular disease; CVRF, cardiovascular risk factors; ECG, electrocardiogram; ESC, European Society of Cardiology; HbA1c, glycated haemoglobin; HFA, Heart Failure Association; ICOS, International Cardio-Oncology Society; NP, natriuretic pep- tides; RT, radiotherapy; TTE, transthoracic echocardiography. aCV surveillance according to baseline CV toxicity risk, type of cancer, cancer stage, and cancer therapy. bCTR-CVT risk assessment is recommended during the first year after cardiotoxic cancer treatment to establish a long-term follow-up care plan. cThe use of HFA-ICOS risk assessment tools should be considered to assess CTR-CVT risk in patients with can- cer scheduled to receive cardiotoxic anticancer therapy. Clinical assessment and ECG are recommended at baseline in all patients with cancer and echocardiography, cardiac biomarkers, or other cardiac imaging tests in selected patients according to baseline CV toxicity risk and cancer treatment type (see Figure 7). dCardio-oncology referral is recommended when available, alternatively patients should be referred to a specia- lized cardiologist with expertise in managing CVD in patients with cancer. eAnnual CV risk assessment (including clinical review, BP, lipid profile, HbA1c, ECG, and NP) and CVRF management is recommended in CS who were treated with a potentially cardiotoxic cancer drug or RT to a volume exposing the heart. CVD perspective) and the most effective (from an oncological per- scope of CV therapies, including healthy lifestyle promotion and spective) cancer treatment. Adjudication of CV events occurring in pa- pharmacological, device, and surgical treatments.4,9,10 tients on active therapy is another important aspect of The principle underlying the dynamic course of CTR-CVT develop- cardio-oncology practice.1,3 This is in addition to recommendations ment in patients with cancer is that the absolute risk depends on their on best treatment and management practices. This includes the full baseline risk and changes with exposure to cardiotoxic therapies over ESC Guidelines 4241 Baseline CV toxicity risk assessment checklist Age, sex, genetics