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. 2023 Mar 31;12(10):11396–11407. doi: 10.1002/cam4.5854

Prevalence of cancer therapy cardiotoxicity as assessed by imaging procedures: A scoping review

Valeria Cantoni 1, Roberta Green 1, Roberta Assante 1, Adriana D'Antonio 1, Francesca Maio 1, Emanuele Criscuolo 1, Roberto Bologna 1, Mario Petretta 2, Alberto Cuocolo 1, Wanda Acampa 1,
PMCID: PMC10242861  PMID: 36999824

Abstract

Background

Advances in treatment and optimization of chemotherapy protocols have greatly improved survival in cancer patients. Unfortunately, treatment can cause a reduction in left ventricular (LV) ejection fraction (EF) leading to cancer therapy‐related cardiac dysfunction (CTRCD). We conducted a scoping review of published literature in order to identify and summarize the reported prevalence of cardiotoxicity evaluated by noninvasive imaging procedures in a wide‐ranging of patients referred to cancer treatment as chemotherapy and/or radiation therapy.

Methods

Different databases were checked (PubMed, Embase, and Web of Science) to identify studies published from January 2000 to June 2021. Articles were included if they reported data on LVEF evaluation in oncological patients treated with chemotherapeutic agents and/or radiotherapy, measured by echocardiography and/or nuclear or cardiac magnetic resonance imaging test, providing criteria of CTRCD evaluation such as the specific threshold for LVEF decrease.

Results

From 963 citations identified, 46 articles, comprising 6841 patients, met the criteria for the inclusion in the scoping review. The summary prevalence of CTRCD as assessed by imaging procedures in the studies reviewed was 17% (95% confidence interval, 14–20).

Conclusions

The results of our scoping review endorse the recommendations regarding imaging modalities to ensure identification of cardiotoxicity in patients undergoing cancer therapies. However, to improve patient management, more homogeneous CTRCD evaluation studies are required, reporting a detailed clinical assessment of the patient before, during and after treatment.

Keywords: cancer therapy, cardiotoxicity, imaging

1. INTRODUCTION

Lately, early diagnosis, progress in cancer treatment and optimization of chemotherapy protocols have improved survival in cancer patients in a meaningful way. Nevertheless, conventional and oncologic therapies have a broad range of adverse cardiac events, including myocardial toxicity. 1 Cardio‐oncology is a relatively new area of interest focusing on the identification, monitoring, and treatment of cardiovascular disease that occurs as a side effect of cancer treatments. 2 Heart failure (HF) and ventricular dysfunction represent the most troubling adverse effects. The prevalence of subclinical left ventricular (LV) dysfunction may be found as far as 42% of cancer patients in recruited treatment groups. 3 HF and LV dysfunction due to therapy for cancer are associated with a 3.5‐fold increase in the mortality risk. 4 However, the frequency of cardiotoxicity depends on several variables related to cancer treatment and to patient characteristics. 5

Cancer therapy‐related cardiac dysfunction (CTRCD) has been commonly defined as a reduction in LV ejection fraction (EF) ≥10% to a value of <50% or as a reduction in LVEF below 53% or an absolute decrease in LVEF >20%. 6 , 7 , 8 However, the categorization of the severity of HF and LV dysfunction as markers of cancer therapy cardiotoxicity is extensively heterogeneous. 9 Endomyocardial biopsy is the gold standard for the diagnosis of cardiomyocyte damage, but this procedure is hardly used due to the invasiveness and low availability. 10 Noninvasive diagnostic imaging techniques as echocardiography, cardiac magnetic resonance (CMR), and nuclear testing have been widely used for the evaluation of CTRCD. 11

Several studies focused on the role of noninvasive diagnostic imaging techniques such as echocardiography, CMR, and nuclear cardiology in the evaluation of CTRCD. 11 The large volume and the heterogeneity of published studies, related to type of cancer patients, clinical characteristics of patients, treatment adopted, CRTD definition, and the method used for the diagnosis of CRTD highlight a relevant need to organize and summarize findings so that the most current and accurate information can be easily accessed. In this scenario, we conducted a scoping review of published literature designed in order to identify and summarize the available data on prevalence of cardiotoxicity evaluated by noninvasive imaging procedures in a wide‐ranging of oncological patients treated with chemotherapy or radiation therapy, in order to give an updated picture of what is known about.

2. MATERIALS AND METHODS

We performed a review of the medical literature using the standard methodology for scoping literature review as published by the Cochrane Collaboration, and according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement (see the Appendix S1 for PRISMA Checklist). 12

PubMed, Embase, and Web of Science databases were screened to identify studies published from January 2000 to June 2021. Articles search was limited to data retrieved in humans and adults and was performed adopting the following keywords: “cardio‐oncology, cardiotoxicity, chemotherapy, radiotherapy, cardio‐imaging, left ventricular ejection fraction, echocardiography, ultrasound, cardiac magnetic resonance (OR CMR), nuclear imaging.” The complete search strategy is depicted in the Appendix S2. A screening for appropriateness of the title and abstract of potentially pertinent articles was conducted by two reviewers (V.C. and R.G.) before retrieval of the full article, and disagreements were resolved by consensus. The full‐published studies of the abstracts identified by the reviewers were downloaded, and they individually conducted the final selection relying on the eligibility criteria; disagreements were solved by consensus. Moreover, the bibliographies of retrieved studies were manually screened for further citations.

Each article was identified evaluating journal, authors, and year of publication. To harmonize the predictors of interest, a publication was considered eligible if all of the following criteria were met: (1) the study reported LVEF data in patients with cancers treated with chemotherapeutic agents and/or radiotherapy; (2) the study provided LVEF data by echocardiography and/or nuclear test and/or CMR evaluated before and after chemotherapeutic agents and/or radiotherapy; (3) the study provided criteria of CTRCD evaluation such as the specific threshold for the LVEF decrease; and (4) follow‐up was at least 3 months after therapy completion. Articles were included if data were obtained from retrospective, prospective, or observational studies. In case of different studies from the same research team, potential patient population duplication was prevented by including the largest cohort only.

Patient population data were retrieved on age and on prevalence of female gender, cancer type, anticancer therapies, cardiac assessment modality, follow‐up time, and cardiovascular risk factors such as diabetes, hypertension, dyslipidemia, smoking, family history of coronary artery disease (CAD), and history of CAD (including previous myocardial infarction and coronary revascularization). All articles were evaluated for methodological quality by the use of Joanna Briggs Institute Prevalence Critical Appraisal Tool. 13

The criteria observe the following issues: representative sample ensured, appropriate recruitment ensured, adequate sample size, appropriate description and reporting of study subjects and setting, data of the identified sample adequate, the condition was measured reliably and objectively, appropriate statistical analysis, confounding factors, subgroups, differences identified and accounted for. There are four possible responses for these questions: yes, no, unclear, or not applicable. 13 Two reviewers (V.C. and R.G.) assessed the risk of bias in each eligible article individually. Disagreements were solved by consensus. If the answers to all the signal problems were “yes,” a low risk of bias was attributed to the study; if the answers to all the signal problems had one or more “no” or “unclear” values, an unclear risk of bias was used; if the answers to all the signal problems contained at least one “no” but no “yes” answers, a high risk of bias was attributed.

Given the disparity of study designs, treatment, and population in the literature considered, a descriptive summary approach was used with the results presented in narrative form and in tables. However, a quantitative synthesis was also performed to calculate a summary estimate of the prevalence of cardiotoxicity. A quantitative synthesis was also performed to calculate a summary estimate of the prevalence of cardiotoxicity in overall population and according to the year of publication (between 2000–2010 and 2011–2021). The logit transformation was used to pool individual studies proportions and to present in a forest plot weighted estimates with inverse‐variance weights obtained from a random‐effects model; study specific 95% confidence intervals (CI) were calculated using the exact method. 14 The I‐squared statistic was used to assess the heterogeneity of included studies. 15

3. RESULTS

The PRISMA flowchart is depicted in Figure 1. The databases search identified 1251 potentially eligible records. Among these, 288 were duplicates and then discharged, leaving 963 citations. The reviewers removed 884 citations evaluating the appropriateness of titles and abstracts of these studies, leaving 79 articles. Then, each reviewer blindly evaluated the full text of these articles, excluding 33 articles. Finally, 46 articles including 6841 patients were analyzed.

FIGURE 1.

FIGURE 1

Study selection process.

The quality assessment of included were summarized in Figure 2. The domains that showed an unclear risk of bias were “study subjects and setting” and “sample target population.” The domain that showed a high risk of bias was “sample size.” These results could be due to the lack of description of patient characteristics and small number of patients evaluated in some studies.

FIGURE 2.

FIGURE 2

Methodological quality of the included studies assessed with Joanna Briggs Institute Critical Appraisal tool for risk of bias and applicability concerns. The green circle represents low risk of bias, the yellow circle unclear risk of bias, and the red circle high risk of bias.

Table 1 showed the demographic data and clinical characteristics of patients. 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 Cancer type, treatment, and imaging technique for each study are reported in Table 2. 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 Patient population ranged from 28 to 2625 subjects. Mean age ranged from 44 to 62 years, with the prevalence of women ranging from 29% to 100%. Mean follow‐up was 9.7 ± 1.3 months.

TABLE 1.

Demographic data and clinical characteristics of patients.

Patients (n) Female (%) Age (year) Hypertension (%) Dyslipidemia (%) Smoking (%) Family history of CAD (%) Diabetes (%) Prior CAD (%)
Nousiainen et al. 16 28 39 53 14 3
Limat et al. 17 135 43 59
Belham et al. 18 51 29 50 ± 18 10 2 3
Abu‐Khalaf et al. 19 32 100 57
Wadhwa et al. 20 152 100 52 ± 10 11 13 17 20 7 2
Dodos et al. 21 100 52 46 ± 1 18
Yoon et al. 22 88 53 52 32 26 17 7
Stoodley et al. 23 52 100 49 ± 9 25 21 25 4 6
Fatima et al. 24 42 74 44 ± 10 0 0
Fallah‐Rad et al. 25 42 100 47 ± 9 12 36 17 29 14
Cochet et al. 26 118 100 58 9 13.5 7
Sawaya et al. 27 81 100 50 ± 10 32 22 7 1
Kang et al. 28 75 59 53 ± 13 13 29 4
Dores et al. 29 51 100 55 ± 14 35 25 5 19 11
Negishi et al. 30 159 80 49 ± 14 20 18 38 6
Florescu et al. 31 40 100 51 ± 8 0 12 30 0
Cardinale et al. 32 2625 74 50 ± 13 23 7.5 18 7 4 3
Dogru et al. 33 50 46 45 ± 13 53 20 26 6
Reuvekamp et al. 34 77 100 53 ± 9 14 16 4
Tan et al. 35 29 100 50 ± 10 24 21 10 0
Guerra et al. 36 69 96 56 ± 13 42 19 16 29 6
Mele et al. 37 30 99 53 ± 11 30 30 20 33 7
Shaikh et al. 38 80 45 62 ± 14 52 43 26 16
Zhang et al. 39 82 50 50 ± 12
Narayan et al. 40 135 100 48 27 17 6 8
Barthur et al. 41 41 100 52 ± 11 24 7 24 10 2
Meléndez et al. 42 112 70 52 ± 14 41 29 28 17 1
Mizia‐Stec et al. 43 67 46 58 42 44.8 43 13 10
Antolín et al. 44 142 100 49 21 17
Nowsheen et al. 45 428 100 53 ± 12 33 18 16 11 14
Klein et al. 46 146 98 61 ± 12 29 8 6 2 9 1
Bergamini et al. 47 162 100 59 ± 12 35 15 4
Mahjoob et al. 48 52 78 44 14
Keramida et al. 49 101 100 54 ± 11 15 1
Yu et al. 50 47 100 52 17 11 30 9 0
Suerken et al. 51 71 68 54 ± 4 50 11 12 17 4
Ben Abdallah et al. 52 66 100 47 ± 9
Laufer‐Perl et al. 53 237 70 62 38 23 31 22 12
Sandamali et al. 54 196 100 54 ± 11 0 0
Wang et al. 55 65 52 51 ± 13 32 31 15
Coutinho Cruz et al. 56 105 100 54 ± 12 0 0 0
Shamai et al. 57 43 60.5 58 ± 16 37 19 26 15 2
Zito et al. 58 146 98 56 ± 11 35 25 20 16
Giusca et al. 59 61 82 54 ± 15 36 15 7 7

Abbreviation: CAD, coronary artery disease.

TABLE 2.

Cancer type, treatment, and imaging technique for each study.

Cancer type Treatment Imaging Definition of CTRCD
Nousiainen et al. 16 LNH ANT + RT Nuclear Decrease of LVEF >10% to ≤50%
Limat et al. 17 LNH ANT + RT Nuclear Decrease of LVEF ≥15% or decrease of LVEF to <50%
Belham et al. 18 Different ANT Echo Decrease of LVEF >10%
Abu‐Khalaf et al. 19 Breast ANT + TAX + RT Nuclear LVEF ≤50%
Wadhwa et al. 20 Breast TZB + RT Nuclear Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Dodos et al. 21 Different ANT Echo Decrease of LVEF >20% or decrease of LVEF >10% to <55% or HF
Yoon et al. 22 Different ANT + TZB Echo‐Nuclear LVEF <55%
Stoodley et al. 23 Breast ANT Echo Decrease of LVEF ≥10% to <50%
Fatima et al. 24 Different ANT Echo‐Nuclear Decrease of LVEF ≥10% to <50%
Fallah‐Rad et al. 2011 25 Breast ANT + TZB + RT CMR Decrease of LVEF >10% to <55% with signs or symptoms of HF
Cochet et al. 2011 26 Breast ANT + 5FU + TAX + TZB + RT Nuclear

Decrease of LVEF ≥10% but <20% of baseline

Decrease of LVEF <50% or ≥20% of baseline or HF

Sawaya et al. 27 Breast ANT + TZB + RT + TAX Echo Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Kang et al. 28 LNH ANT (CHOP) Echo Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Dores et al. 29 Breast ANT + TAX + TZB Echo LVEF <55% or decrease of LVEF >10%
Negishi et al. 30 Different ANT + TZB + RT Echo Decrease of LVEF >10% to <55%
Florescu et al. 31 Breast ANT Echo Decrease of LVEF ≥10% to <55% without signs or symptoms
Cardinale et al. 32 Different ANT + RT Echo Decrease of LVEF >10% to <50%
Dogru et al. 33 LYM; Breast ANT Echo LVEF <55%
Reuvekamp et al. 34 Breast ANT + RT + TZB Nuclear LVEF <50% or a drop of ≥10%
Tan et al. 35 Breast ANT + RT + TZB + TAX Echo Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Guerra et al. 36 Breast ANT + TAX Echo Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Mele et al. 37 Breast ANT + TAX + TZB + RT Echo Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Shaikh et al. 38 AML MITOXANTRONE Echo Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Zhang et al. 39 LNH ANT Nuclear Decrease of LVEF ≥10% to <50%
Narayan et al. 40 Breast ANT + TZB + RT Echo Decrease of LVEF ≥10% to <50%
Barthur et al. 41 Breast ANT + TZB + TAX + RT CMR Decrease of LVEF ≥10% to <55% or decrease of LVEF ≥5% to <55% with signs or symptoms of HF
Meléndez et al. 42 Different ANT + TAX + TZB + ALK CMR Decrease of LVEF >10% to <50%
Mizia‐Stec et al. 43 LNH ANT (CHOP) + RT Echo Decrease of LVEF ≥10%
Antolín et al. 44 Breast ANT + RT Echo LVEF <50%
Nowsheen et al. 45 Breast ANT + TZB Echo Decrease of LVEF ≥10% to <53%
Klein et al. 46 Breast ANT + TZB + RT Nuclear Decrease of LVEF <50% or decrease of LVEF >10%
Bergamini et al. 47 Breast ANT + TZB Echo Decrease of LVEF <50% or decrease of LVEF >10% with or without symptoms
Mahjoob et al. 48 Different ANT Echo Decrease of LVEF >10% to <53%
Keramida et al. 49 Breast TZB + RT Echo Decrease of LVEF ≥10% to <50%
Yu et al. 50 Breast RT + CHT Echo Decrease of LVEF ≥10% to <53% or decrease of LVEF >16%
Suerken et al. 51 Different ANT + TAX + TZB + CYCP CMR Decrease of LVEF ≥5% or a drop <50% or decrease of LVEF >10% to <53%
Ben Abdallah et al. 52 Breast ANT + 5 FU + RT + TAX Echo Decrease of LVEF >10% to <53%
Laufer‐Perl et al. 53 Different CHT + RT + TZB Echo Decrease of LVEF >10% to <53%
Sandamali et al. 54 Breast ANT + RT Echo Decrease of LVEF >10%
Wang et al. 55 LNH ANT Echo Decrease of LVEF >10% to <53%
Coutinho Cruz et al. 56 Breast ANT + RT Echo Decrease of LVEF >10% to <54%
Shamai et al. 57 Sarcoma ANT Echo Decrease of LVEF >10% to <53%
Zito et al. 58 Breast ANT Echo Decrease of LVEF ≥10% to <50%
Giusca et al. 59 Different ANT + TZB + RT + TAX + CYCP CMR Decrease of LVEF >10% to <53%

Abbreviations: ALK, alkylating agents; ANT, anthracycline; CHOP, cyclophosphamide, doxorubicin, oncovin and prednisone; CHT, different type of treatment; CMR, cardiac magnetic resonance; CTRCD, cancer therapeutics related cardiac dysfunction; CYCP, cyclophosphamide; Echo, echocardiography; FU, fluorouracil; HF, heart failure; LNH, lymphoma non Hodgkin; LVEF, left ventricular ejection fraction; LYP, lymphoma; RT, radiotherapy; TAX, taxane; TZB, trastuzumab.

The summary prevalence of CTRCD assessed by imaging procedures in the studies reviewed was 17% (95% CI, 14–20) and the heterogeneity was 96% (Figure 3). The prevalence of CTRCD for studies published from 2011 to 2021 (16%; 95% CI, 13–19) was lower (p < 0.05) compared with studies published from 2000 to 2010 (22%; 95% CI, 14–29).

FIGURE 3.

FIGURE 3

Forest plot of cancer therapeutics related cardiac dysfunction (CTRCD) prevalence in the overall studies. Horizontal lines represent 95% confidence interval (CI) of the point estimates. The diamond represents the pooled estimate (size of the diamond = 95% CI). The dashed vertical line represents the overall point estimate.

4. DISCUSSION

In our scoping review, we aimed to identify the incidence of cardiotoxicity in oncological patients by noninvasive imaging procedures in order to support clinicians in assessment and management of cardiotoxicity in oncological patients. As shown in Figure 3, the summary prevalence of cardiotoxicity in the studied population is around 17%.

Diagnosis of cardiac functional impairment plays a key role for clinical decision‐making in oncological patients referred to chemotherapy and/or radiation therapy. Moreover, a challenge for the diagnostic procedures should be the early assessment of cardiotoxicity. The Imaging and Cardio‐Oncology Study Groups of the HF Association analyzed the timely evidence for the role of cardiovascular imaging, such as echocardiography, CMR, CT, and nuclear testing, before and after cancer treatment. 11 In addition, The International Cardio‐Oncology Society has recently developed criteria in the identification of CTRCD based on LVEF, echocardiographic global longitudinal strain, and blood biomarkers. 9 In these documents, it was outlined that echocardiography is the first‐step imaging technique for the identification of cardiotoxicity through the evaluation of LVEF. 10 Other echocardiographic indices, such as the global longitudinal LV strain, have been more recently introduced for the early identification of cardiac toxicity. 24 Those indications have been confirmed and detailed by the recently published ESC guidelines, which have reported a clear scheduled timing follow‐up by prechemotherapy CAD patients' risk assessment and type of administrated chemotherapy showing the 3D echocardiography as the gold standard, using CRM and radionuclide angiography only when echocardiography is not available or not diagnostic. 60

Recent evidence about the need of early diagnosis and rigorous follow‐up in cancer patients who underwent chemotherapy or radiotherapy led an incrementing effort in the definition of new protocols, within each diagnostic method, providing a timely diagnosis and a better patient management to cardiologists and oncologists. 61 , 62

Scoping reviews are a type of systematic review, focusing on large and heterogeneous body of literature relative to a research topic of interest. They are particularly useful for knowledge synthesis in case of lack of understanding of key conceptions within a topic and when a research topic is of a complex nature. In the field of cardio‐oncology, the large volume and the disparateness of published work, related to type of cancer patients, clinical characteristics of patients, the treatment adopted, CRTD definition, and the method used for the diagnosis of CRTD highlight a relevant need to organize and summarize findings so that the most current and accurate information can be easily accessed.

Our review indicated as a main issue the overall low quality of the included studies (Figure 2), mostly related to patient sample size and study design. Most of the included and analyzed studies enrolled a small number of patients. Moreover, most of them considered a prevalent female population undergoing chemotherapy for breast cancer, limiting the external validity for patients with other type of cancer and for male patients. Additionally, the patients' cohorts are characterized by heterogeneous cancer type and different chemotherapy protocol with different treatment duration time.

From our study, it also emerged that the summary prevalence of CTRCD was slightly lower for studies published from 2011 to 2020 as compared to those published from 2000 to 2010 (16% vs. 22%). It should be considered that the chemotherapies have significantly changed over time, especially those for breast cancer. Indeed, the large majority of studies evaluating CTRCD in breast cancer included in our search were published after 2010 where the therapy regiment reached an optimization in terms of pharmaceutical type, doses, cycles, and combined therapy. Furthermore, the improvement in regime treatments as well the evolution in the methods linked to each imaging procedure could have had a significant role in the reduction of CTRCD prevalence observed after 2010. 63 , 64

Taking into account the above‐quoted guidelines, more homogeneous CTRCD evaluation studies should be designed in the future, reporting a detailed clinical assessment of the patient before, during, and after treatment. Moreover, standardized imaging modality and follow‐up for each chemotherapy scheme are imperative to obtain homogenous data for a useful analysis. Limitations of our study may include the searching MEDLINE, which could not include all the studies published in the literature, even if we have chosen the most various patter of keywords on the topic. We decided to exclude from our MEDLINE search studies published before the 2000, to reach as much as possible the most recent clinical and imaging overview in the CTRCD evaluation. This literature analyses may be used as a starting point for future studies, which aim to analyze CTRCD in oncologic patients, understanding which kind of clinical and methodological errors should be avoided to reach a strong conclusion that may lead the ordinary clinical practice.

5. CONCLUSIONS

The findings of this scoping review endorse the recommendations regarding imaging modalities to ensure identification of cardiotoxicity in patients undergoing cancer therapies. However, to improve patient management, more homogeneous CTRCD evaluation studies are required, reporting a detailed clinical assessment of the patient before, during, and after treatment.

AUTHOR CONTRIBUTIONS

Valeria Cantoni: Data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); software (equal); writing – original draft (equal). Roberta Green: Data curation (equal); formal analysis (equal); investigation (equal); methodology (equal); software (equal); writing – original draft (equal). Roberta Assante: Data curation (equal); investigation (equal); methodology (equal); writing – original draft (equal); writing – review and editing (equal). Adriana D'Antonio: Data curation (equal); investigation (equal); writing – original draft (equal). Francesca Maio: Data curation (equal); investigation (equal); methodology (equal); writing – original draft (equal); writing – review and editing (equal). Emanuele Criscuolo: Data curation (equal); methodology (equal). Roberto Bologna: Data curation (equal); methodology (equal). Mario Petretta: Data curation (lead); formal analysis (lead); methodology (lead); software (lead); supervision (lead); writing – original draft (lead); writing – review and editing (lead). Alberto Cuocolo: Data curation (lead); methodology (lead); supervision (lead); writing – original draft (lead); writing – review and editing (lead). Wanda Acampa: Conceptualization (lead); data curation (lead); formal analysis (lead); investigation (lead); methodology (lead); supervision (lead); writing – original draft (lead); writing – review and editing (lead).

CONFLICT OF INTEREST STATEMENT

The authors made no disclosures.

Supporting information

Appendix S1.

Appendix S2.

ACKNOWLEDGMENTS

We thank the Department of Advanced Biomedical Science, University of Naples, Federico II for the technical and scientific support.

Cantoni V, Green R, Assante R, et al. Prevalence of cancer therapy cardiotoxicity as assessed by imaging procedures: A scoping review. Cancer Med. 2023;12:11396‐11407. doi: 10.1002/cam4.5854

Valeria Cantoni and Roberta Green have contributed equally as first authors.

DATA AVAILABILITY STATEMENT

Not applicable.

REFERENCES

  • 1. Chen‐Scarabelli C, McRee C, Leesar MA, Hage FG, Scarabelli TM. Comprehensive review on cardio‐oncology: role of multimodality imaging. J Nucl Cardiol. 2017;24:906‐935. doi: 10.1007/s12350-016-0535-y [DOI] [PubMed] [Google Scholar]
  • 2. Taylor J. Heart disease and cancer: the new discipline of cardioncology. Eur Heart J. 2012;33:151‐152. doi: 10.1093/eurheartj/ehs105 [DOI] [PubMed] [Google Scholar]
  • 3. Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215‐1221. doi: 10.1200/JCO.2002.20.5.1215 [DOI] [PubMed] [Google Scholar]
  • 4. Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long‐term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342:1077‐1084. doi: 10.1056/NEJM200004133421502 [DOI] [PubMed] [Google Scholar]
  • 5. Cardinale D, Biasillo G, Salvatici M, Sandri MT, Cipolla CM. Using biomarkers to predict and to prevent cardiotoxicity of cancer therapy. Expert Rev Mol Diagn. 2017;17:245‐256. doi: 10.1080/14737159.2017.1283219 [DOI] [PubMed] [Google Scholar]
  • 6. Curigliano G, Lenihan D, Fradley M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31:171‐190. doi: 10.1016/j.annonc.2019.10.023 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Zamorano JL, Lancellotti P, Rodriguez Munoz D, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology. Eur Heart J. 2016;37:2768‐2801. doi: 10.1093/eurheartj/ehw211 [DOI] [PubMed] [Google Scholar]
  • 8. Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014;27:911‐939. doi: 10.1016/j.echo.2014.07.012 [DOI] [PubMed] [Google Scholar]
  • 9. Herrmann J, Lenihan D, Armenian S, et al. Defining cardiovascular toxicities of cancer therapies: an International Cardio‐Oncology Society (IC‐OS) consensus statement. Eur Heart J. 2022;43:280‐299. doi: 10.1093/eurheartj/ehab674 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Mason JW, Bristow MR, Billingham ME, Daniels JR. Invasive and noninvasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy. Cancer Treat Rep. 1978;62:857‐864. [PubMed] [Google Scholar]
  • 11. Celutkien J, Pudil R, Lopez‐Fernandez T, et al. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio‐Oncology Council of the European Society of Cardiology. Eur J Heart Fail. 2020;22:1504‐1524. doi: 10.1002/ejhf.1957 [DOI] [PubMed] [Google Scholar]
  • 12. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group . Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi: 10.1371/journal.pmed.1000097 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Munn Z, Moola S, Riitano D, Lisy K. The development of a critical appraisal tool for use in systematic reviews addressing questions of prevalence. Int J Health Policy Manag. 2014;3:123‐128. doi: 10.15171/ijhpm.2014.71 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika. 1934;26:404‐413. doi: 10.1093/biomet/26.4.404 [DOI] [Google Scholar]
  • 15. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Stat Med. 2002;21:1539‐1558. doi: 10.1002/sim.1186 [DOI] [PubMed] [Google Scholar]
  • 16. Nousiainen T, Jantunen E, Vanninen E, Hartikainen J. Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients. Br J Cancer. 2002;86:1697‐1700. doi: 10.1038/sj.bjc.6600346 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Limat S, Demesmay K, Voillat L, et al. Early cardiotoxicity of the CHOP regimen in aggressive non‐Hodgkin's lymphoma. Ann Oncol. 2003;14:277‐281. doi: 10.1093/annonc/mdg070 [DOI] [PubMed] [Google Scholar]
  • 18. Belham M, Kruger A, Mepham S, Faganello G, Pritchard C. Monitoring left ventricular function in adults receiving anthracycline‐containing chemotherapy. Eur J Heart Fail. 2007;9:409‐414. doi: 10.1016/j.ejheart.2006.09.007 [DOI] [PubMed] [Google Scholar]
  • 19. Abu‐Khalaf MM, Juneja V, Chung GG, et al. Long‐term assessment of cardiac function after dose‐dense and ‐intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer. Breast Cancer Res Treat. 2007;104:341‐349. doi: 10.1007/s10549-006-9413-7 [DOI] [PubMed] [Google Scholar]
  • 20. Wadhwa D, Fallah‐Rad N, Grenier D, et al. Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study. Breast Cancer Res Treat. 2009;117:357‐364. doi: 10.1007/s10549-008-0260-6 [DOI] [PubMed] [Google Scholar]
  • 21. Dodos F, Halbsguth T, Erdmann E, Hoppe UC. Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline‐induced cardiotoxicity in adults. Clin Res Cardiol. 2008;97:318‐326. doi: 10.1007/s00392-007-0633-6 [DOI] [PubMed] [Google Scholar]
  • 22. Yoon GJ, Telli ML, Kao DP, Matsuda KY, Carlson RW, Witteles RM. Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally? J Am Coll Cardiol. 2010;56:1644‐1650. doi: 10.1016/j.jacc.2010.07.023 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Stoodley PW, Richards DA, Hui R, et al. Two‐dimensional myocardial strain imaging detects changes in left ventricular systolic function immediately after anthracycline chemotherapy. Eur J Echocardiogr. 2011;12:945‐952. doi: 10.1093/ejechocard/jer187 [DOI] [PubMed] [Google Scholar]
  • 24. Fatima N, Zaman MU, Hashmi A, Kamal S, Hameed A. Assessing adriamycin‐induced early cardiotoxicity by estimating left ventricular ejection fraction using technetium‐99m multiple‐gated acquisition scan and echocardiography. Nucl Med Commun. 2011;32:381‐385. doi: 10.1097/MNM.0b013e328343ceb9 [DOI] [PubMed] [Google Scholar]
  • 25. Fallah‐Rad N, Walker JR, Wassef A, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II‐positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011;57:2263‐2270. doi: 10.1016/j.jacc.2010.11.063 [DOI] [PubMed] [Google Scholar]
  • 26. Cochet A, Quilichini G, Dygai‐Cochet I, et al. Baseline diastolic dysfunction as a predictive factor of trastuzumab‐mediated cardiotoxicity after adjuvant anthracycline therapy in breast cancer. Breast Cancer Res Treat. 2011;130:845‐854. doi: 10.1007/s10549-011-1714-9 [DOI] [PubMed] [Google Scholar]
  • 27. Sawaya H, Sebag IA, Plana JC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012;5:596‐603. doi: 10.1161/CIRCIMAGING.112.973321 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Kang Y, Xu X, Cheng L, et al. Two‐dimensional speckle tracking echocardiography combined with high‐sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine‐based chemotherapy. Eur J Heart Fail. 2014;16:300‐308. doi: 10.1002/ejhf.8 [DOI] [PubMed] [Google Scholar]
  • 29. Dores H, Abecasis J, Correia MJ, et al. Detection of early sub‐clinical trastuzumab‐induced cardiotoxicity in breast cancer patients. Arq Bras Cardiol. 2013;100:328‐332. doi: 10.5935/abc.20130050 [DOI] [PubMed] [Google Scholar]
  • 30. Negishi K, Negishi T, Haluska BA, Hare JL, Plana JC, Marwick TH. Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection. Eur Heart J Cardiovasc Imaging. 2014;15:324‐331. doi: 10.1093/ehjci/jet159 [DOI] [PubMed] [Google Scholar]
  • 31. Florescu M, Magda LS, Enescu OA, Jinga D, Vinereanu D. Early detection of epirubicin‐induced cardiotoxicity in patients with breast cancer. J Am Soc Echocardiogr. 2014;27:83‐92. doi: 10.1016/j.echo.2013.10.008 [DOI] [PubMed] [Google Scholar]
  • 32. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;2(131):1981‐1988. doi: 10.1161/CIRCULATIONAHA.114.013777 [DOI] [PubMed] [Google Scholar]
  • 33. Dogru A, Cabuk D, Sahin T, Dolasik I, Temiz S, Uygun K. Evaluation of cardiotoxicity via speckle‐tracking echocardiography in patients treated with anthracyclines. Onkologie. 2013;36:712‐716. doi: 10.1159/000356850 [DOI] [PubMed] [Google Scholar]
  • 34. Reuvekamp EJ, Bulten BF, Nieuwenhuis AA, et al. Does diastolic dysfunction precede systolic dysfunction in trastuzumab‐induced cardiotoxicity? Assessment with multigated radionuclide angiography (MUGA). J Nucl Cardiol. 2016;23:824‐832. doi: 10.1007/s12350-015-0164-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Tan TC, Bouras S, Sawaya H, et al. Time trends of left ventricular ejection fraction and myocardial deformation indices in a cohort of women with breast cancer treated with anthracyclines, taxanes, and trastuzumab. J Am Soc Echocardiogr. 2015;28:509‐514. doi: 10.1016/j.echo.2015.02.001 [DOI] [PubMed] [Google Scholar]
  • 36. Guerra F, Marchesini M, Contadini D, et al. Speckle‐tracking global longitudinal strain as an early predictor of cardiotoxicity in breast carcinoma. Support Care Cancer. 2016;24:3139‐3145. doi: 10.1007/s00520-016-3137-y [DOI] [PubMed] [Google Scholar]
  • 37. Mele D, Malagutti P, Indelli M, et al. Reversibility of left ventricle longitudinal strain alterations induced by adjuvant therapy in early breast cancer patients. Ultrasound Med Biol. 2016;42:125‐132. doi: 10.1016/j.ultrasmedbio.2015.09.008 [DOI] [PubMed] [Google Scholar]
  • 38. Shaikh AY, Suryadevara S, Tripathi A, et al. Mitoxantrone‐induced cardiotoxicity in acute myeloid leukemia‐a velocity vector imaging analysis. Echocardiography. 2016;33:1166‐1177. doi: 10.1111/echo.13245 [DOI] [PubMed] [Google Scholar]
  • 39. Zhang CJ, Pei XL, Song FY, et al. Early anthracycline‐induced cardiotoxicity monitored by echocardiographic doppler parameters combined with serum hs‐cTnT. Echocardiography. 2017;34:1593‐1600. doi: 10.1111/echo.13704 [DOI] [PubMed] [Google Scholar]
  • 40. Narayan HK, French B, Khan AM, et al. Noninvasive measures of ventricular‐arterial coupling and circumferential strain predict cancer therapeutics‐related cardiac dysfunction. JACC Cardiovasc Imaging. 2016;9:1131‐1141. doi: 10.1016/j.jcmg.2015.11.024 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Barthur A, Brezden‐Masley C, Connelly KA, et al. Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study. J Cardiovasc Magn Reson. 2017;19:44. doi: 10.1186/s12968-017-0356-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Meléndez GC, Sukpraphrute B, D'Agostino RB Jr, et al. Frequency of left ventricular end‐diastolic volume‐mediated declines in ejection fraction in patients receiving potentially cardiotoxic cancer treatment. Am J Cardiol. 2017;15(119):1637‐1642. doi: 10.1016/j.amjcard.2017.02.008 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Mizia‐Stec K, Elżbieciak M, Wybraniec MT, et al. Chemotherapy and echocardiographic indices in patients with non‐Hodgkin lymphoma: the ONCO‐ECHO study. Med Oncol. 2017;35:14. doi: 10.1007/s12032-017-1075-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. Antolín S, Acea B, Albaina L, et al. Primary systemic therapy in HER2‐positive operable breast cancer using trastuzumab and chemotherapy: efficacy data, cardiotoxicity and long‐term follow‐up in 142 patients diagnosed from 2005 to 2016 at a single institution. Breast Cancer. 2018;11:29‐42. doi: 10.2147/BCTT.S179750 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Nowsheen S, Aziz K, Park JY, et al. Trastuzumab in female breast cancer patients with reduced left ventricular ejection fraction. J Am Heart Assoc. 2018;7:e008637. doi: 10.1161/JAHA.118.008637 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Klein R, Nadouri D, Osler E, Johnson C, Dent S, Dwivedi G. Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab‐based therapy. Nucl Med Commun. 2019;40:22‐29. doi: 10.1097/MNM.0000000000000941 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47. Bergamini C, Dolci G, Rossi A, et al. Left atrial volume in patients with HER2‐positive breast cancer: one‐step further to predict trastuzumab‐related cardiotoxicity. Clin Cardiol. 2018;41:349‐353. doi: 10.1002/clc.22872 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48. Mahjoob MP, Sheikholeslami SA, Dadras M, et al. Prognostic value of cardiac biomarkers assessment in combination with myocardial 2D strain echocardiography for early detection of anthracycline‐related cardiac toxicity. Cardiovasc Hematol Disord Drug Targets. 2020;20:74‐83. doi: 10.2174/1871529X19666190912150942 [DOI] [PubMed] [Google Scholar]
  • 49. Keramida K, Farmakis D, Bingcang J, et al. Longitudinal changes of right ventricular deformation mechanics during trastuzumab therapy in breast cancer patients. Eur J Heart Fail. 2019;21:529‐535. doi: 10.1002/ejhf.1385 [DOI] [PubMed] [Google Scholar]
  • 50. Yu AF, Ho AY, Braunstein LZ, et al. Assessment of early radiation‐induced changes in left ventricular function by myocardial strain imaging after breast radiation therapy. J Am Soc Echocardiogr. 2019;32:521‐528. doi: 10.1016/j.echo.2018.12.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51. Suerken CK, D'Agostino RB Jr, Jordan JH, et al. Simultaneous left ventricular volume and strain changes during chemotherapy associate with 2‐year post chemotherapy measures of left ventricular ejection fraction. J Am Heart Assoc. 2020;9:e015400. doi: 10.1161/JAHA.119.015400 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52. Ben Abdallah I, Ben Nasr S, Chourabi C, et al. The predictive value of 2D myocardial strain for Epirubicin‐induced cardiotoxicity. J Oncol. 2020;2020(30):5706561. doi: 10.1155/2020/5706561 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53. Laufer‐Perl M, Arnold JH, Mor L, et al. The association of reduced global longitudinal strain with cancer therapy‐related cardiac dysfunction among patients receiving cancer therapy. Clin Res Cardiol. 2020;109:255‐262. doi: 10.1007/s00392-019-01508-9 [DOI] [PubMed] [Google Scholar]
  • 54. Sandamali JAN, Hewawasam RP, Fernando MACSS, et al. Anthracycline‐induced cardiotoxicity in breast cancer patients from southern Sri Lanka: an echocardiographic analysis. Biomed Res Int. 2020;2020:1847159. doi: 10.1155/2020/1847159 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55. Wang B, Yu Y, Zhang Y, et al. Speckle tracking echocardiography in the early detection and prediction of anthracycline cardiotoxicity in diffuse large B‐cell lymphoma treated with (R)‐CHOP regimen. Echocardiography. 2020;37:421‐428. doi: 10.1111/echo.14622 [DOI] [PubMed] [Google Scholar]
  • 56. Coutinho Cruz M, Moura Branco L, Portugal G, et al. Three‐dimensional speckle‐tracking echocardiography for the global and regional assessments of left ventricle myocardial deformation in breast cancer patients treated with anthracyclines. Clin Res Cardiol. 2020;109:673‐684. doi: 10.1007/s00392-019-01556-1 [DOI] [PubMed] [Google Scholar]
  • 57. Shamai S, Rozenbaum Z, Merimsky O, et al. Cardio‐toxicity among patients with sarcoma: a cardio‐oncology registry. BMC Cancer. 2020;20:609. doi: 10.1186/s12885-020-07104-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58. Zito C, Manganaro R, Cusmà Piccione M, et al. Anthracyclines and regional myocardial damage in breast cancer patients. A multicentre study from the Working Group on Drug Cardiotoxicity and Cardioprotection, Italian Society of Cardiology (SIC). Eur Heart J Cardiovasc Imaging. 2021;22(22):406‐415. doi: 10.1093/ehjci/jeaa339 [DOI] [PubMed] [Google Scholar]
  • 59. Giusca S, Korosoglou G, Montenbruck M, et al. Multiparametric early detection and prediction of cardiotoxicity using myocardial strain, T1 and T2 mapping, and biochemical markers: a longitudinal cardiac resonance imaging study during 2 years of follow‐up. Circ Cardiovasc Imaging. 2021;14:e012459. doi: 10.1161/CIRCIMAGING.121.012459 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60. Lyon AR, López‐Fernández T, Couch LS, et al. 2022 ESC guidelines on cardio‐oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio‐Oncology Society (IC‐OS). Eur Heart J. 2022;43:4229‐4361. doi: 10.1093/eurheartj/ehac244 [DOI] [PubMed] [Google Scholar]
  • 61. Madonna R, Cadeddu C, Deidda M, et al. Cardioprotection by gene therapy: a review paper on behalf of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology. Int J Cardiol. 2015;191:203‐210. doi: 10.1016/j.ijcard.2015.04.232 [DOI] [PubMed] [Google Scholar]
  • 62. Madonna R, Cadeddu C, Deidda M, et al. Improving the preclinical models for the study of chemotherapy‐induced cardiotoxicity: a position paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection. Heart Fail Rev. 2015;20:621‐631. doi: 10.1007/s10741-015-9497-4 [DOI] [PubMed] [Google Scholar]
  • 63. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271‐289. doi: 10.3322/caac.21349 [DOI] [PubMed] [Google Scholar]
  • 64. Hennigs A, Riedel F, Marmé F, et al. Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat. 2016;160:491‐499. doi: 10.1007/s10549-016-4016-4 [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Appendix S1.

Appendix S2.

Data Availability Statement

Not applicable.


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