2021 Volume 85 Issue 4 Pages 393-396
Background: Cardiac magnetic resonance (CMR) imaging is the golden standard used for the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). The consistency of cardiac computed tomography (CCT) in CTRCD cases using CMR imaging is investigated in this study.
Methods and Results: In 7 clinically confirmed CTRCD patients, focal late enhancement was confirmed on both CCT and CMR for 4 patients. Myocardial extracellular volume (ECV) values measured by CCT and CMR were elevated in all patients, suggesting the presence of diffuse myocardial damage.
Conclusions: The study findings indicated that CCT could provide adequate information about late myocardial enhancement and ECV quantification, indicating the effective evaluation of CTRCD by CCT.
Cardiac magnetic resonance (CMR) imaging is useful for assessing cardiac structure and function and has the advantage of being non-invasive and free of radiation exposure in assessing myocardial damage in cancer patients. However, because the evaluation of cardiotoxicity needs to be repeated, the high cost of examination becomes a problem in the medical economy. In addition, restrictions on use, patient indications (claustrophobia, breath-holding, and long examination time), and patients with indwelling internal metals such as non-CMR-conditional cardiac devices cannot be examined, and there are many problems in terms of ease of use and convenience.
We have already reported that cardiac computed tomography (CCT) enables comprehensive assessment for a non-invasive evaluation of patients with takotsubo cardiomyopathy1 and achieves extracellular volume (ECV) quantification using CCT in takotsubo cardiomyopathy patients.2 Recently, we reported a similarity between CCT and CMR in a case of cancer therapy-related cardiac dysfunction (CTRCD) in terms of consistency between the ECV map from CCT and the ECV map from CMR and between late iodine enhancement (LIE) in CCT and late gadolinium enhancement (LGE) in CMR.3 We investigated the consistency of CCT in CTRCD cases with CMR imaging.
A decrease in the left ventricular ejection fraction (LVEF) determined by echocardiography of >10 percentage points, to a value <53% was defined as CTRCD, according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging Expert Consensus.4
In this report, we performed CCT and CMR in 7 clinically confirmed CTRCD patients. The patient characteristics are shown in the Table. In all patients, obstructive coronary artery disease was excluded by CCT angiography. All patients were scanned with a 320-detector row CT scanner (Aquilion One Geneis Edition; Canon Medical Systems, Otawara, Tochigi, Japan) and a 3.0-T MRI scanner (Ingenia CX, Philips Healthcare, Best, The Netherlands). ECV quantification by CCT and CMR was analyzed with a postprocessing workstation (Ziostation 2; Ziosoft, Tokyo, Japan). The Figure shows myocardial late enhancement images and ECV maps obtained by CCT and CMR. Focal late enhancement confined to the right ventricular insertion into the septum, which represents focal myocardial fibrosis, was confirmed on both CCT and CMR for 4 patients (patient nos. 1, 3, 6 and 7). Myocardial ECV values measured by CCT and CMR were elevated in all patients, suggesting the presence of diffuse myocardial damage. These findings indicated that CCT could give adequate information about late myocardial enhancement and ECV quantification, in comparison to the findings obtained by using CMR, enabling the effective evaluation of CTRCD.
| No. | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
|---|---|---|---|---|---|---|---|
| Age (years)† | 65 | 64 | 53 | 52 | 62 | 49 | 31 |
| Sex | Female | Female | Female | Female | Female | Female | Female |
| Cancer site | Breast | Leukemia | Breast | Breast | Breast | Breast | Breast |
| Dox-converted doses (mg/m2) | 280 | 178 | 252 | 252 | 280 | 480 | 280 |
| Doxorubicin (mg/m2) | 200 | ||||||
| Epirubicin (mg/m2) | 400 | 360 | 360 | 400 | 400 | 400 | |
| Daunorubicin (mg/m2) | 237 | ||||||
| Alkylating agents | + | − | + | + | + | + | + |
| Immuno- or targeted- therapy | + | + | + | + | + | − | − |
| LVEF determined by UCG (%)‡ | 27.2 | 23.6 | 46.1 | 20.3 | 39.8 | 43.1 | 35 |
| AC treatment to CTRCD (days) | 467 | 33 | 646 | 2,700 | 313 | 1,360 | 84 |
| CTRCD onset to investigate (days) | 1 | 6 | 117 | 329 | 640 | 657 | 1,001 |
| Symptom† | Dyspnea | Dyspnea | None | None | None | None | None |
| Troponin T level (ng/mL)† | 0.0410 | 0.0161 | 0.0030 | 0.0038 | 0.0030 | 0.0087 | 0.0033 |
| BNP level (pg/mL)† | 55.5 | 311.8 | 9.3 | 18.3 | 7.5 | 43.2 | 16 |
| CCT-ECV (%) | 35.8 | 38.3 | 32.1 | 30.1 | 30.5 | 31.3 | 32.2 |
| CCT-LIE | + | − | + | − | − | + | + |
| CMR-ECV (%) | 35.3 | 37.7 | 32.7 | 29.5 | 31.6 | 32.3 | 31.6 |
| CMR-LGE | + | − | + | − | − | + | + |
| Reference number | [3] | [10] |
†At investigation. ‡At the onset of CTRCD. AC, anthracycline; BNP, plasma brain natriuretic peptide; CCT, cardiac computed tomography; CMR, cardiac magnetic resonance; CTRCD, cancer therapy-related cardiac dysfunction; DOX, doxorubicin; ECV, extracellular volume; LGE, late gadolinium enhancement; LIE, late iodine enhancement; LVEF, left ventricular ejection fraction; UCG, echocardiography.
Cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) imaging. Arrows and arrowheads indicate late iodine and gadolinium enhancements, respectively. ECV, extracellular volume.
All procedures were conducted in accordance with the Declaration of Helsinki and its amendments. The study protocol was approved by the Institutional Review Board of Kumamoto University (Approval No. Rinri 1730), and written informed consent was obtained from each patient or the family of the patient.
Recent advances in cancer treatment have led to an increase in the number of cancer survivors; at the same time, various cardiovascular complications associated with cancer treatment have become apparent, and a cardio-oncology program has been established. The main role of the cardio-oncologist is “risk stratification, prevention, diagnosis and treatment” of cardiovascular complications in cancer patients. Various guidelines have been published regarding cardiotoxicity caused by anticancer drugs,5–8 and it is recommended that all guidelines evaluate cardiac function before administration of anticancer agents.
There are many clinical guidelines that recommend echocardiography. Echocardiography is the most common method of assessing cardiac function. The advantages are that it is non-invasive, does not require radiation exposure, can be performed repeatedly and is less expensive than other imaging tests for the evaluation of cardiac function, such as heart morphology and size, LV contractility and diastolic function. In addition, much information can be obtained, such as valvular disease, pulmonary hypertension, and the presence of pericardial effusion. However, it has become clear that there is a limit to identifying cardiotoxicity by echocardiographic LVEF measurement.9 The 2014 American Echocardiography Expert Consensus recommends LV deformation index (strain) and blood cardiac troponin measurements in addition to LVEF in identifing cardiotoxicity.4 The myocardial strain method is a tool that can quantitatively evaluate cardiac function, and global longitudinal strain, in particular, is able to detect cardiotoxicity more sensitively than LVEF. Recently, we reported that left atrium reservoir function determined by echocardiography may be an optimal indicator of CTRCD.10 However, evaluation by echocardiography includes major limitations such as interobserver variability, intraobserver variability, test-retest variability, intervendor variability, image quality, and technical requirements.5
The cardiotoxicity of anthracyclines may be detected in acute, early (within the first year of treatment) or late (after several years) phases.5 However, no imaging features, at least in terms of ECV value or the presence of late contrast enhancement, could be found for each CTRCD onset phase. Hence, further pathophysiological studies are required.
We have shown the usefulness of CCT in the diagnosis of CTRCD. If the problems of radiation exposure and contrast medium use (renal function + allergy) are overcome, it will be an extremely useful tool in the cardio-oncology field. Moreover, this novel CT imaging can be performed in conjunction with standard coronary artery evaluation and cancer follow up, possibly contributing to a cost reduction of examination. Functional evaluation by CCT involves an increase in radiation dose, and it has little functional information over echocardiography in spite of increased radiation exposure. It can be important to effectively identify patients with suspected CTRCD by echocardiographic functional evaluation and then assess the myocardial tissue characterization by CCT. Although low-contrast visibility of myocardial lesions has been a problem for LIE in CT compared with LGE in CMR, it has been solved by technological progress, including iterative reconstruction algorithms and dual-energy CT technologies, suggesting that it now may become available as an alternative to CMR.
Study LimitationsThe present study has several limitations. First, all cases in this study had anthracycline-induced cardiotoxicity. Thus, verification of CTRCD by using other drug classes, such as trastuzumab, is mandatory. Moreover, the effects of concomitant agents must be verified. Second, it was a single-center design with a very small sample. Therefore, a larger multiracial and multicenter study is required. Furthermore, it is unclear which factors contribute, and the extent of their contribution, to this classification (acute, chronic early onset, and chronic late onset) and the prognosis of CTRCD. Hence, further pathophysiological and molecular physiological studies, including animal experiments, are warranted. Additional detailed, large-scale clinical studies may be required to verify our theories.
Despite these limitations, we have clearly, and for the first time, demonstrated a consistency between CCT and CMR in the identification of CTRCD in patients. We believe that this novel method could be useful for the ‘one-stop shop’ evaluation of CTRCD, providing new insight into cardio-oncology.
We thank all the paramedical staff and clinical secretaries for their kind support during this work.
This study was supported, in part, by a Grant-in-Aid for Scientific Research (#20K17087) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
K.T. is a member of Circulation Journal’s Editorial Team. The other authors declare no conflicts of interest.
