Abstract
Purpose
To compare left ventricular ejection fraction (LVEF) measured with echocardiography and cardiac MRI in individuals with cancer and suspected cardiotoxicity and assess the potential effect on downstream clinical decision-making.
Materials and Methods
In this prospective, single-center observational cohort study, participants underwent same-day two-dimensional (2D) echocardiography and cardiac MRI between 2011 and 2021. Participants with suboptimal image quality were excluded. A subset of 74 participants also underwent three-dimensional (3D) echocardiography. The agreement of LVEF derived from each modality was assessed using Bland-Altman analysis and at relevant thresholds for cardiotoxicity.
Results
A total of 745 participants (mean age, 60 years ± 5 [SD]; 460 [61.7%] female participants) underwent same-day echocardiography and cardiac MRI. According to Bland-Altman analysis, the mean bias was –3.7% ± 7.6 (95% limits of agreement [LOA]: –18.5% to 11.1%) for 2D echocardiography versus cardiac MRI. In 74 participants who underwent cardiac MRI, 3D echocardiography, and 2D echocardiography, the mean LVEFs were 60.0% ± 10.4, 58.4% ± 9.4, and 57.2% ± 8.9, respectively (P < .001). At the 50% LVEF threshold for detection of cardiotoxicity, there was disagreement for 9.3% of participants with 2D echocardiography and cardiac MRI. Agreement was better with 3D echocardiography and cardiac MRI (mean bias, –1.6% ± 6.3 [95% LOA: –13.9% to 10.7%]) compared with 2D echocardiography and cardiac MRI (mean bias, –2.8% ± 6.3 [95% LOA: –15.2% to 9.6%]; P = .016).
Conclusion
Two-dimensional echocardiography had variations of ±15% for LVEF measurement compared with cardiac MRI in participants with cancer and led to misclassification of approximately 10% of participants for cardiotoxicity detection. Three-dimensional echocardiography had better agreement with cardiac MRI and should be used as first-line imaging.
Keywords: Echocardiography, MR Functional Imaging, Cardiac
Supplemental material is available for this article.
© RSNA, 2024
An earlier incorrect version appeared online. This article was corrected on January 18, 2024.
Keywords: Echocardiography, MR Functional Imaging, Cardiac
Summary
Two-dimensional echocardiography showed large variations compared with reference standard cardiac MRI for left ventricular ejection fraction measurement, which may lead to downstream impact on clinical decision-making for cardio-oncology patients.
Key Points
■ This prospective study of 745 participants with cancer who underwent same-day two-dimensional (2D) echocardiography and cardiac MRI demonstrated a mean bias of -3.7% ± 7.6 and wide limits of agreement (-18.5% to 11.1%) between the two modalities for left ventricular ejection fraction (LVEF) measurement.
■ Two-dimensional echocardiography led to misclassification of approximately 10% of participants as having cardiotoxicity according to current cardio-oncology guidelines.
■ In a substudy, three-dimensional echocardiography had better agreement with cardiac MRI for LVEF measurement compared with 2D echocardiography and cardiac MRI (P = .016).
Introduction
Left ventricular ejection fraction (LVEF) is an important biomarker for the detection of cancer therapy−related cardiac dysfunction (CTRCD) in patients receiving anticancer therapies. The measurement of LVEF is recommended in guidelines for patients at risk for cardiotoxicity (1−3) and is important for clinical decision-making to initiate cardioprotective therapy. Therefore, the accurate and reproducible measurement of LVEF is of great importance in patients receiving anticancer therapies.
Cardiac MRI is the reference standard for assessment of left ventricular volumes and ejection fraction (4), but transthoracic echocardiography remains the most widely used imaging modality because of its widespread accessibility and lower cost. Various thresholds of LVEF have been used to define cardiotoxicity based on position papers and guidelines. These include a reduction in LVEF from baseline to less than 55%, less than 53%, and, most recently, less than 50% (1,3,5−8). The magnitude of reduction in LVEF in early cardiotoxicity may be relatively small, leading to measurements close to the lower limits of the normal range, typically in the region of 50%−55%. As a result, small absolute changes in LVEF may have important downstream consequences on the clinical management of patients with cancer.
Several studies have compared echocardiography-derived versus cardiac MRI−derived LVEF measurements (9). However, there is a paucity of data regarding how these imaging modalities compare in patients with cancer who are suspected of having cardiotoxicity and the potential effect on clinical decision-making. The aims of this study were to (a) determine the agreement of two-dimensional (2D) echocardiography−, three-dimensional (3D) echocardiography−, and cardiac MRI−derived LVEF in individuals with cancer who are suspected of having cardiotoxicity and (b) assess the effect of discordant findings on clinically relevant thresholds for cardiotoxicity, in real-world practice.
Materials and Methods
Study Participants
In this single-center study, we prospectively collected demographic and imaging biomarker data in consecutive participants referred to the Royal Brompton Hospital, part of Guy’s and St Thomas’ Hospital NHS Trust, London, United Kingdom, cardio-oncology service for suspected cardiotoxicity during a 10-year period between 2011 and 2021. Participants were excluded if image quality was suboptimal. To minimize the biologic temporal variation of LVEF measurements, only participants who underwent echocardiography and cardiac MRI on the same day were included in the analysis. The study was approved by the institutional review boards at Guy’s and St Thomas’ Hospital and the Health Research Authority.
From an initial cohort of 1290 consecutive participants, after screening and exclusions, 745 participants were included in the analysis of 2D echocardiography−derived and cardiac MRI−derived LVEF. In a subset of 74 participants, LVEF measurements were also available from 3D echocardiography. A flowchart is provided in Figure 1, which details the reasons for exclusions.
Figure 1:
Flowchart summarizes participant selection. LVEF = left ventricular ejection fraction, 3D = three-dimensional.
Image Acquisition and Analysis
Echocardiography was performed by operators consisting of physiologists or cardiologists, who were accredited by the British Society of Echocardiography, according to the society guidelines for transthoracic echocardiography (10). Two-dimensional echocardiography was performed according to guidelines recommended for image acquisition, and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and LVEF were derived using the modified Simpson biplane method (10). This involved manual tracing of the left ventricular endocardial borders from one side of the mitral valve annulus to the other side in the apical four-chamber and two-chamber views at end diastole and end systole, with inclusion of the papillary muscles as part of the blood pool. The 3D echocardiography data were acquired from multibeat full-volume data sets with an X5-1 matrix array transducer (Philips; frequency, 5−1 MHz) using the tissue harmonic mode with electrocardiography-gated acquisition. Images were acquired from apical four-chamber views with a breath hold of 6 seconds. Care was taken to maximize the frame rate and adjust depth and width for left ventricle optimization. In participants with arrhythmia, multiple acquisitions were performed until a data set with no appreciable translation artifact was obtained.
Cardiac MRI was performed at 1.5 T (Sonata or Avanto; Siemens) or 3 T (Vida; Siemens) using a steady-state free precession sequence according to recommended guidelines (11). Long-axis views were obtained along with contiguous short-axis sections from the base to apex of the heart. LVEDV and LVESV were calculated by manual contouring of the left ventricle endocardium in short axis, with exclusion of the papillary muscles by use of blood pool thresholding as previously described (12). Analysis was performed by cardiologists or radiologists who were level III accredited in reporting of cardiac MRI scans using CMRtools (CMRtools; Cardiovascular Imaging Solutions), and data were reported according to recommended guidelines (11,13).
For both imaging modalities, LVEF was calculated as (LVEDV − LVESV)/(LVEDV) × 100.
Statistical Analysis
Statistical analyses were performed using SPSS Statistics 27 (IBM). All data are presented as means ± SDs unless specified. Normality of data was determined using Kolmogorov-Smirnov tests. Parametric data were compared with the Student t test for unpaired data and using paired samples t tests for paired data. Nonparametric data were compared with the Wilcoxon signed rank test for paired data and the Mann-Whitney U test for unpaired data. Agreement of LVEF was determined at Bland-Altman analysis to calculate mean bias and 95% limits of agreement (14). Agreement was also assessed using intraclass correlation coefficients (ICCs) with a two-way mixed effects for single measurements for absolute agreement (<0.50 as poor, between 0.50 and 0.75 as moderate, between 0.75 and 0.90 as good, and >0.90 as excellent) (15). Multiple groups with matched LVEF and volumes were compared using a repeated-measures analysis of variance test, with a Tukey post hoc analysis for multiple comparisons with adjusted P values, for parametric data. Agreement of categorical data based on clinically relevant thresholds for cardiotoxicity were analyzed using Cohen κ. Multiple group comparisons of unrelated groups were performed using Kruskal-Wallis H test, with multiple group comparison with Bonferroni correction applied, for nonparametric data. Two-tailed P values less than .05 were considered to indicate statistically significant differences.
Results
Participant Characteristics
Among the 745 participants included, 460 (61.7%) were female and 285 (38.3%) were male; the mean participant age was 60 years ± 5. The demographic characteristics, cardiovascular risk factors, and prevalence of primary malignancy types are provided in Table 1.
Table 1:
Characteristics of Study Participants
Two-dimensional Echocardiography and Cardiac MRI
The LVEF measured with 2D echocardiography was significantly lower than that measured with cardiac MRI, with a median of 60% (IQR, 54%−65%) versus 63% (IQR, 56%−69%), respectively (P < .001). Bland-Altman analysis demonstrated a mean bias of −3.7% ± 7.6 (95% limits of agreement: −18.5% to 11.1%) for 2D echocardiography−derived versus cardiac MRI−derived LVEF (Fig 2). Overall, there was moderate agreement between the two measurements, with an ICC of 0.72 (95% CI: 0.56, 0.80; P < .0001). Subgroup analysis at different mean LVEF ranges demonstrated small overall biases but consistently wide 95% limits of agreement throughout all ranges (Table 2).
Figure 2:
Bland-Altman analysis of same-day left ventricular ejection fraction (LVEF) with two-dimensional (2D) echocardiography (echo) and cardiac MRI on the whole cohort (n = 745). Dashed blue line represents mean bias. Dashed red lines represent 95% upper and lower limits of agreement.
Table 2:
Two-dimensional Echocardiography– versus Cardiac MRI–derived LVEF
Evaluation of the differences in echocardiography-derived LVEF according to sex showed that female participants had a statistically greater LVEF compared with male participants (58.8% ± 10.0 vs 56.9% ± 10.0, respectively; P = .007). A similar difference was observed for cardiac MRI−derived LVEF (63.1% ± 11.5 for female participants vs 59.5% ± 11.3 for male participants; P < .001).
We evaluated agreement between 2D echocardiography and cardiac MRI on predefined LVEF thresholds for cardiotoxicity to determine the potential clinical effect. The levels of agreement were moderate across these ranges of thresholds, as summarized in Table 3.
Table 3:
Agreement of LVEF Derived from 2D Echocardiography and Cardiac MRI according to Clinically Relevant Thresholds to Define Cardiotoxicity
Further analyses of the main cohort showed a similar magnitude of difference between LVEF derived from 2D echocardiography and cardiac MRI between the different subgroups (χ2(2) = 4.21; P = .52) (Fig 3). Post hoc analysis with Wilcoxon signed rank tests was conducted with a Bonferroni correction applied, resulting in a significance level set at a P value less than .0083. There were no statistically significant differences between the groups.
Figure 3:
Box plot (median and IQR) and whiskers (minimum and maximum) for the difference in left ventricular ejection fraction (LVEF) between two-dimensional (2D) echocardiography (echo) and cardiac MRI at the clinically relevant thresholds for cardio-oncology and heart failure.
According to the different thresholds for cardiotoxicity, there were varying levels of disagreement (Table 4). The level of disagreement for a contemporary clinical LVEF threshold of 50% was 9.3%, as illustrated in Figure 4.
Table 4:
Disagreement in Classification of Cardiotoxicity according to Different LVEF Thresholds
Figure 4:
Diagram shows the disagreement in classification of cardiotoxicity using two-dimensional (2D) echocardiography (echo)–derived versus cardiac MRI–derived left ventricular ejection fraction (LVEF) (n = 745) at the 50% LVEF threshold for cardiotoxicity.
Two-dimensional Echocardiography, 3D Echocardiography, and Cardiac MRI Substudy
A subset of 74 participants underwent cardiac MRI, 3D echocardiography, and 2D echocardiography, with mean LVEF measurements of 60.0% ± 10.4, 58.4% ± 9.4, and 57.2% ± 8.9, respectively (Fig 5). A repeated-measures analysis of variance with a Greenhouse-Geisser correction showed that LVEF significantly differed between modalities (F(1.67, 121.928) = 8.907; P < .001). Post hoc analysis with a Bonferroni adjustment revealed that LVEF was significantly lower with 2D echocardiography than with cardiac MRI (−2.8% [95% CI: −4.6, −1.0]; P < .001) and with 2D echocardiography compared with 3D echocardiography (−1.2% [95% CI: −2.4, −0.1]; P = .047), but not between 3D echocardiography and cardiac MRI (−1.6% [95% CI: −3.4 to 0.2]; P = .11).
Figure 5:
Left ventricular ejection fraction (LVEF) measurements for cardiac MRI, three-dimensional (3D) echocardiography (echo), and two-dimensional (2D) echocardiography in the predefined substudy (n = 74). ns = not significant, * = P < .05, *** = P < .001.
There was good agreement between 3D echocardiography−derived and cardiac MRI−derived LVEF (ICC, 0.79 [95% CI: 0.69, 0.87]; P < .001) and between 2D echocardiography−derived and cardiac MRI−derived LVEF (ICC, 0.76 [95% CI: 0.60, 0.85]; P < .001). There was very good agreement between 2D echocardiography and 3D echocardiography (ICC, 0.89 [95% CI: 0.82, 0.93]).
Bland-Altman analysis demonstrated an absolute mean bias of −1.6% ± 6.3 (95% limits of agreement: −13.9% to 10.7%) for 3D echocardiography−derived versus cardiac MRI−derived LVEF (Fig 6A). There was a mean bias of −2.8% ± 6.3 (95% limits of agreement: −15.2% to 9.6%) for 2D echocardiography−derived versus cardiac MRI−derived LVEF (Fig 6B). The LVEF difference between 3D echocardiography and cardiac MRI was −1.6% ± 6.3 compared with a difference between 2D echocardiography and cardiac MRI of −2.8% ± 6.3, which was statistically significant (P = .016).
Figure 6:
Bland-Altman plots demonstrate the mean bias (blue lines) and 95% limits of agreement (red lines) for (A) three-dimensional (3D) echocardiography–derived (echo) versus cardiac MRI–derived left ventricular ejection fraction (LVEF) and (B) two-dimensional (2D) echocardiography–derived versus cardiac MRI–derived LVEF.
A breakdown of the differences in left ventricular volumes between the different modalities is provided in Appendix S1.
Discussion
Cardiovascular imaging remains the cornerstone for the assessment of CTRCD secondary to cancer therapies such as anthracyclines and antihuman epidermal growth factor receptor 2 therapy (16−18). Current guidelines recommend echocardiography or cardiac MRI to derive LVEF; therefore, the accurate measurement of LVEF is of paramount importance to detect cardiotoxicity and guide subsequent management (3). In this prospective study, we performed same-day echocardiography and cardiac MRI in the largest reported oncologic cohort suspected of having cardiotoxicity to determine the absolute bias and variation in measurements of LVEF. We found that 2D echocardiography underestimated LVEF compared with cardiac MRI by approximately 3% and, more important, that measurements varied widely between cardiac MRI and 2D echocardiography (by ±15%).
The implications of the variability in measurements of LVEF are highly relevant for clinical practice and design of clinical trials, given classification of CTRCD at thresholds based on LVEF (3). Although we found moderate agreement in LVEF measurements, there was also significant discordance at the relevant clinical thresholds. Using cardiac MRI as the reference standard, there was a disagreement in the diagnosis of cardiotoxicity in approximately 10% of participants with 2D echocardiography when LVEF thresholds of 50% were used for cardiotoxicity. Nevertheless, this is lower than the degree of misclassification reported between radionuclide multiple-gated acquisition scanning and cardiac MRI, ranging between 20% and 35% depending on the LVEF threshold used to define cardiotoxicity (19).
Previous studies have demonstrated that 3D echocardiography is a better imaging technique to assess LVEF given the reduced temporal variability of around 6% compared with 10% for 2D echocardiography (20). In our substudy, 3D echocardiography showed better agreement with cardiac MRI compared with 2D echocardiography for quantification of LVEF in patients with cancer. Thus, our study supports the recent guidelines that LVEF should be measured with 3D echocardiography as first line where feasible and available in cardio-oncology patients (1,3).
The measurement of LVEF has proven prognostic value in patients with heart failure (21). Several previous studies have compared different imaging modalities for the assessment of LVEF. In a prospective study of participants with chronic stable heart failure (n = 52), there was a mean bias of −2%, with large limits of agreement (−24% to 20%) between cardiac MRI and 2D echocardiography (9). In a substudy of the multicenter study of the Surgical Treatment for Ischemic Heart Failure (STICH) trial (n = 204), the mean bias was 2.5%, with wide limits of agreement (20% to −15%) (22). In another study (n = 55), 2D echocardiography underestimated LVEF compared with cardiac MRI, again with a broader range of LVEF and wide limits of agreement (−21.6% to 20.1%) (23). In a meta-analysis comparing 2D echocardiography and cardiac MRI, there was a small overall underestimation of LVEF by 2D echocardiography versus cardiac MRI (24). The findings of our main study are in keeping with these previous studies; although there has been small overall bias, as reported in previous studies, the limits of agreement are substantial. Our study adds to the literature because the effect of this variation must be carefully considered in the assessment of cardio-oncology patients, which may trigger an alteration in clinical management depending on LVEF thresholds for cardiotoxicity.
Our findings have important implications for clinical practice because the definition of CTRCD is heavily dependent on the accurate measurement of LVEF at baseline and during surveillance in asymptomatic patients with cancer. This may affect the downstream management of patients with cancer if 2D echocardiography alone is used. For instance, an incorrect diagnosis of cardiotoxicity in a patient with a true normal LVEF may lead to a delay in the use of highly effective cancer therapies or the deferral to other agents that are considered less cardiotoxic but are also less effective cancer treatments (25). In addition, such a situation may lead to the inappropriate initiation of cardiac medications, such as angiotensin-converting enzyme inhibitors, which require additional blood tests and clinic visits (26). Furthermore, incorrect assignment of CTRCD may lead to unnecessary long-term surveillance, with additional hospital visits and diagnostic investigations. On the other hand, the misclassification of a patient with true underlying cardiotoxicity and an apparently normal LVEF may provide false reassurance and miss the opportunity to initiate cardioprotective therapy and minimize the risk of symptomatic heart failure and adverse outcomes (27). These effects are likely to be associated with unnecessary, increased health care costs and adverse clinical outcomes.
Pertinent clinical evidence for prognostic heart failure drug therapies and device therapies has relied on data derived from LVEF thresholds obtained from echocardiography (28,29). Such prospective studies are unlikely to be repeated again in these cohorts of patients given the well-established prognostic data. However, given the greater accuracy and precision of cardiac MRI−derived LVEF, future studies using cardiac MRI end points, which may include other features of cardiac MRI (eg, multiparametric mapping and late gadolinium enhancement), could be considered in prospective cardio-oncology studies.
Several reasons could explain the discrepancies in measurements shown in this study. An echocardiography-derived modified Simpson biplane LVEF is based on two orthogonal 2D images of the heart. The major limitations of this approach are as follows: (a) A mathematical model is used, which assumes that the left ventricular geometry is elliptical in shape; (b) the true apex may not be adequately visualized because of foreshortening; and (c) myocardial trabeculations may be included in the tracing of endocardial contours because the true blood pool may not be properly visualized. The latter limitation can be overcome by the use of US contrast agents, but these are not used in routine transthoracic echocardiography unless the endocardium is inadequately visualized. The use of 3D echocardiography has overcome the limitation of apical foreshortening and use of geometric assumptions but is not yet established in conjunction with contrast agents for full visualization of the true blood pool in the left ventricle cavity, where myocardial trabeculations are present. Cardiac MRI avoids apical foreshortening, visualizes the true blood pool, and derives LVEF based on the summation of volumes of short-axis discs; therefore, it allows a better representation of the left ventricular geometric and morphologic features than does 2D echocardiography. One other potential explanation for the differences observed is that in this study, the cardiac MRI−derived left ventricular volumes were derived with exclusion of the papillary muscles, whereas in echocardiography, the papillary muscles are included as part of the left ventricular volumes. However, the effect of this may be small because the difference would affect the LVEDV and LVESV, with subsequent small overall effect to the LVEF. Finally, although the scans were obtained on the same day, there may be potential for biologic variation in measurements because it is impossible to undertake echocardiography and cardiac MRI simultaneously.
The findings of a higher LVEF measured in female participants compared with male participants in our study is in keeping with previous findings from the Dallas Heart Study (30). In addition, the findings of greater left ventricular volumes in diastole and systole with cardiac MRI compared with echocardiography are also consistent with previous published work in this area (31).
In clinical practice, LVEF is not the sole indicator of cardiotoxicity; the assessment of patient symptoms and the measurement of global longitudinal strain and serum biomarkers, such as troponin and brain natriuretic peptide, are also important (32). However, LVEF remains the most commonly used imaging measurement for the assessment of CTRCD, and our study supports the recent guidelines that recommend 3D echocardiography as first line in cardio-oncology patients (3). The routine use of more advanced echocardiographic techniques, such as contrast echocardiography and myocardial strain imaging, may enhance the assessment of cardiotoxicity in the future. Measurement of global longitudinal strain using echocardiography has been shown to be a more sensitive marker of early subclinical myocardial dysfunction in patients with cancer receiving potentially cardiotoxic therapies (33). The use of global longitudinal strain−guided care has been shown to result in better-preserved LVEF in patients who receive cardioprotective therapy and less CTRCD at follow-up (34). More recently, in a serial comparison of echocardiography- and cardiac MRI−derived LVEF and strain in individuals with breast cancer, the use of 2D echocardiography−derived global longitudinal strain provided higher incremental value for the detection of CTRCD (35). The use of these techniques in the cardio-oncology setting requires further investigation.
This study had some important limitations. First, this was an observational study of standard clinical practice without specific research protocols for undertaking image acquisition; thus, it reflects real-world practice. Echocardiography was performed and the findings interpreted by several different operators in a physiologist-led service typical of standard U.K. practice, and this could have affected the increased variability of LVEF measurements with echocardiography. Second, this was a single-center study, although this had the benefit of standardized in-house protocols for imaging. Third, the evaluation of LVEF was not blinded to the operator undertaking the analysis and thus is more representative of real-world practice. In addition, we included only patients referred to our cardio-oncology service rather than all patients with cancer, which may have introduced referral bias. Nevertheless, by evaluating many patients over a wide range of oncologic diseases, we anticipate that the findings apply to the wider scientific and clinical community. We did not undertake repeatability studies in this current study to determine interstudy reproducibility because this value has been reported as 2.5%−4.8% for cardiac MRI (36), 6% for 3D echocardiography, and 10% for 2D echocardiography (20).
In this prospective observational study of standard clinical practice, 2D echocardiography−derived LVEF measurements were lower than cardiac MRI−derived LVEF as the reference standard, and measurements varied widely. There was a discordance of approximately 10% between 2D echocardiography−derived and cardiac MRI−derived LVEF when cardiotoxicity was defined on the basis of different thresholds of LVEF. In a subset of patients who underwent 3D echocardiography, there was better agreement between 3D echocardiography−derived and cardiac MRI−derived LVEF than between 2D echocardiography and cardiac MRI, supporting recent guidelines recommending the use of 3D echocardiography in patients with cancer. These findings have important clinical implications in patients receiving anticancer therapies because an accurate assessment of LVEF is crucial in defining presence or absence of cardiotoxicity and thus guiding clinical decision-making and management for patients with cancer. Future work must be performed to evaluate strain with different imaging modalities as an early marker of CTRCD.
The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust and by the NIHR MedTech Co-operative for Cardiovascular Disease at Guy’s and St Thomas’ NHS Foundation Trust. M.S.N. supported by a NIHR Clinical Lectureship (CL-2019-17-001). S. Plein supported by the British Heart Foundation (BHF) (grant CH/16/2/32089). A.R.L. supported by the Fondation Leducq Network of Excellence in Cardio-Oncology. The Royal Brompton Cardio-Oncology Centre of Excellence supported by the The Big Heart Foundation. The views expressed are those of the authors and not necessarily those of the BHF, NHS, or the NIHR.
Disclosures of conflicts of interest: M.S.N. No relevant relationships. J.O. No relevant relationships. T.M. No relevant relationships. M.S.A. No relevant relationships. S.R. No relevant relationships. S.D.R. Participation in Orion 4 trial (Oxford University/Novartis); lecture fees from AstraZeneca and Boehringer. A.C. No relevant relationships. S. Plein No relevant relationships. S. Prasad No relevant relationships. R.M. No relevant relationships. D.J.P. Grant from the British Heart Foundation; deputy editor of JACC: Cardiovascular Imaging. A.J.B. No relevant relationships. R.K. No relevant relationships. A.R.L. Speaker, advisory board or consultancy fees and/or research grants from Janssens-Cilag, Astellas Pharma, Pfizer, Novartis, Servier, AstraZeneca, Bristol Myers Squibb, GSK, Amgen, Takeda, Roche, Clinigen Group, Eli Lily, Eisai, Ferring Pharmaceuticals, Boehringer Ingelheim, Akcea Therapeutics, Myocardial Solutions, iOWNA Health, and Heartfelt Technologies.
Abbreviations:
- CTRCD
- cancer therapy–related cardiac dysfunction
- ICC
- intraclass correlation coefficient
- LVEDV
- left ventricular end-diastolic volume
- LVEF
- left ventricular ejection fraction
- LVESV
- left ventricular end-systolic volume
- 3D
- three-dimensional
- 2D
- two-dimensional
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