European Journal of Preventive Cardiology (2022) 00, 1–10 REVIEW
https://doi.org/10.1093/eurjpc/zwac170 Cardiovascular disease
Management and treatment of cardiotoxicity
due to anticancer drugs: 10 questions
Downloaded from https://academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwac170/6658185 by guest on 27 August 2022
and answers
Michela Chianca 1, Iacopo Fabiani 2*, Annamaria Del Franco1,2,
Chrysanthos Grigoratos2, Alberto Aimo 1,2, Giorgia Panichella1,
Alberto Giannoni 1,2, Vincenzo Castiglione 3, Francesco Gentile 3,
Claudio Passino 1,2, Carlo Maria Cipolla4, Daniela Maria Cardinale4,
and Michele Emdin1,2
1
Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa 56127, Italy; 2Cardiology Division, Fondazione Toscana Gabriele Monasterio, Viale G. Moruzzi, 1–56100 Pisa, Italy;
3
Cardiology Division, Pisa University Hospital, Pisa 56124, Italy; and 4Cardioncology Unit, Cardiology Division, European Institute of Oncology, I.R.C.C.S, Milan 20141, Italy
Received 19 April 2022; editorial decision 3 August 2022; accepted 4 August 2022; online publish-ahead-of-print 8 August 2022
Since the introduction of anthracyclines into clinical practice in the 1960s, chemotherapy has always been associated with cardiotoxicity. Patients
on cardiotoxic drugs can develop a wide range of cardiovascular diseases, including left ventricular (LV) systolic dysfunction and heart failure (HF),
arrhythmias, hypertension, and coronary artery disease (CAD). The rising number of cancer patients, population ageing, and the frequent overlap
of cardiovascular and oncological diseases have highlighted the importance of close collaboration between cardiologists and oncologists. As a
result, in 1995, cardiologists at the IEO (European Institute of Oncology) coined the term cardioncology, a new discipline focused on the dy-
namics of cardiovascular disease in cancer patients. Given the complex scenario characterized by a constant dialogue between the oncological
condition and cardiovascular comorbidity, it is essential for the clinician to get the knowledge to properly fulfill the needs of the oncological pa-
tient under cardiotoxic treatment. Through the answer to 10 questions, we aim to describe the complex issue of cardiotoxicity by addressing the
main critical points and current evidence related to the assessment, management, treatment, and surveillance of cancer patients under
chemotherapy.
------------------------------------------------------------------------------------------------------------------------------------------------------------
* Corresponding author. Tel: +39 50 3152216, Fax: +39 50 3153229, Email:
© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email:
.
, 2 M. Chianca et al.
Graphical Abstract
Downloaded from https://academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwac170/6658185 by guest on 27 August 2022
.........................................................................................................................................................................................
Keywords Cardiotoxic • Cardiac biomarker • Ventricular function • Chemotherapy • Cardio protection • Heart failure
Introduction of providing a valuable tool for clinicians in managing patients who are
at risk of developing cardiotoxicity. Given the many open issues in the
The development of cardiotoxicity from antitumour drugs was first re- field of cardionocology and the growing interest in this branch, we will
cognized in the early ‘60s, with the introduction of anthracyclines into try to bring the growing problem of cardiotoxicity from chemother-
clinical practice. Over the following decades, earlier diagnosis and ad- apy to the attention of non-specialist physicians so that they can pro-
vances in cancer therapy have led to a significant improvement of out- vide proper treatment and prevention to their patients.
comes. The increasing number of cancer survivors, together with the
use of combination treatments with synergistic cardiotoxic effects, How is cardiotoxicity defined and
makes cardiotoxicity a relevant limitation of many anticancer agents.
classified?
The manifestations of cancer drug cardiotoxicity are broad, in-
The American Society of Echocardiography and the European
cluding left ventricular (LV) systolic dysfunction and heart failure
Association of Cardiovascular Imaging (EACVI) have defined cardio-
(HF), arrhythmias, hypertension, and coronary artery disease toxicity (or CTRCD) as LVEF decrease ≥10% to a value of <53%, as
(CAD). Nonetheless, the current definition focus on cancer assessed by either two- or three-dimensional echocardiography, car-
therapy-related cardiac dysfunction (CTRCD).1 diac magnetic resonance (CMR), or multi-gated acquisition scan.1
Patients who are candidates to cardiotoxic therapies should be fol- Hypertension, vascular toxicity, cardiac dysfunction, myocarditis,
lowed closely to detect a cardiotoxic damage before it becomes clin- and arrhythmias are the five basic signs of cardiotoxicity mentioned
ically evident. Echocardiography is a useful tool to assess parameters in the Intentional Cardio-Oncology Society (IC-OS) consensus state-
such as LV ejection fraction (LVEF) and global longitudinal strain ment.4 Hypertension is identified as any increase in systolic and/or
(GLS), the latter to detect subclinical cardiac damage. Cardiac biomar- diastolic blood pressure following the start of cancer treatment, with-
kers, natriuretic peptides, and high-sensitivity (hs) troponins are gaining out any other contributory alterations, above the diagnostic threshold
interest as they offer the possibility to detect cardiotoxic damage in an of 130/80 mmHg. Vascular toxicity, which comprises a variety of dis-
early phase and possibly to predict future development of CTRCD.2,3 eases (including stroke, pheripheral ischaemia, thromboembolic event,
In the present review, we will dissect the major principles of cardi- etc.), is characterized by the induction or exacerbation of vascular
otoxicity by answering 10 questions (Graphical Abstract), with the goal pathology produced by chemotherapy. According to accepted criteria,
https://doi.org/10.1093/eurjpc/zwac170 Cardiovascular disease
Management and treatment of cardiotoxicity
due to anticancer drugs: 10 questions
Downloaded from https://academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwac170/6658185 by guest on 27 August 2022
and answers
Michela Chianca 1, Iacopo Fabiani 2*, Annamaria Del Franco1,2,
Chrysanthos Grigoratos2, Alberto Aimo 1,2, Giorgia Panichella1,
Alberto Giannoni 1,2, Vincenzo Castiglione 3, Francesco Gentile 3,
Claudio Passino 1,2, Carlo Maria Cipolla4, Daniela Maria Cardinale4,
and Michele Emdin1,2
1
Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa 56127, Italy; 2Cardiology Division, Fondazione Toscana Gabriele Monasterio, Viale G. Moruzzi, 1–56100 Pisa, Italy;
3
Cardiology Division, Pisa University Hospital, Pisa 56124, Italy; and 4Cardioncology Unit, Cardiology Division, European Institute of Oncology, I.R.C.C.S, Milan 20141, Italy
Received 19 April 2022; editorial decision 3 August 2022; accepted 4 August 2022; online publish-ahead-of-print 8 August 2022
Since the introduction of anthracyclines into clinical practice in the 1960s, chemotherapy has always been associated with cardiotoxicity. Patients
on cardiotoxic drugs can develop a wide range of cardiovascular diseases, including left ventricular (LV) systolic dysfunction and heart failure (HF),
arrhythmias, hypertension, and coronary artery disease (CAD). The rising number of cancer patients, population ageing, and the frequent overlap
of cardiovascular and oncological diseases have highlighted the importance of close collaboration between cardiologists and oncologists. As a
result, in 1995, cardiologists at the IEO (European Institute of Oncology) coined the term cardioncology, a new discipline focused on the dy-
namics of cardiovascular disease in cancer patients. Given the complex scenario characterized by a constant dialogue between the oncological
condition and cardiovascular comorbidity, it is essential for the clinician to get the knowledge to properly fulfill the needs of the oncological pa-
tient under cardiotoxic treatment. Through the answer to 10 questions, we aim to describe the complex issue of cardiotoxicity by addressing the
main critical points and current evidence related to the assessment, management, treatment, and surveillance of cancer patients under
chemotherapy.
------------------------------------------------------------------------------------------------------------------------------------------------------------
* Corresponding author. Tel: +39 50 3152216, Fax: +39 50 3153229, Email:
© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email:
.
, 2 M. Chianca et al.
Graphical Abstract
Downloaded from https://academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwac170/6658185 by guest on 27 August 2022
.........................................................................................................................................................................................
Keywords Cardiotoxic • Cardiac biomarker • Ventricular function • Chemotherapy • Cardio protection • Heart failure
Introduction of providing a valuable tool for clinicians in managing patients who are
at risk of developing cardiotoxicity. Given the many open issues in the
The development of cardiotoxicity from antitumour drugs was first re- field of cardionocology and the growing interest in this branch, we will
cognized in the early ‘60s, with the introduction of anthracyclines into try to bring the growing problem of cardiotoxicity from chemother-
clinical practice. Over the following decades, earlier diagnosis and ad- apy to the attention of non-specialist physicians so that they can pro-
vances in cancer therapy have led to a significant improvement of out- vide proper treatment and prevention to their patients.
comes. The increasing number of cancer survivors, together with the
use of combination treatments with synergistic cardiotoxic effects, How is cardiotoxicity defined and
makes cardiotoxicity a relevant limitation of many anticancer agents.
classified?
The manifestations of cancer drug cardiotoxicity are broad, in-
The American Society of Echocardiography and the European
cluding left ventricular (LV) systolic dysfunction and heart failure
Association of Cardiovascular Imaging (EACVI) have defined cardio-
(HF), arrhythmias, hypertension, and coronary artery disease toxicity (or CTRCD) as LVEF decrease ≥10% to a value of <53%, as
(CAD). Nonetheless, the current definition focus on cancer assessed by either two- or three-dimensional echocardiography, car-
therapy-related cardiac dysfunction (CTRCD).1 diac magnetic resonance (CMR), or multi-gated acquisition scan.1
Patients who are candidates to cardiotoxic therapies should be fol- Hypertension, vascular toxicity, cardiac dysfunction, myocarditis,
lowed closely to detect a cardiotoxic damage before it becomes clin- and arrhythmias are the five basic signs of cardiotoxicity mentioned
ically evident. Echocardiography is a useful tool to assess parameters in the Intentional Cardio-Oncology Society (IC-OS) consensus state-
such as LV ejection fraction (LVEF) and global longitudinal strain ment.4 Hypertension is identified as any increase in systolic and/or
(GLS), the latter to detect subclinical cardiac damage. Cardiac biomar- diastolic blood pressure following the start of cancer treatment, with-
kers, natriuretic peptides, and high-sensitivity (hs) troponins are gaining out any other contributory alterations, above the diagnostic threshold
interest as they offer the possibility to detect cardiotoxic damage in an of 130/80 mmHg. Vascular toxicity, which comprises a variety of dis-
early phase and possibly to predict future development of CTRCD.2,3 eases (including stroke, pheripheral ischaemia, thromboembolic event,
In the present review, we will dissect the major principles of cardi- etc.), is characterized by the induction or exacerbation of vascular
otoxicity by answering 10 questions (Graphical Abstract), with the goal pathology produced by chemotherapy. According to accepted criteria,
