Many authors subsequently focused their efforts on this topic, and all of these studies may be grouped based on the four main features addressed72: identification of CTX in patients previously treated with oncologic therapies; serial evaluations for the prospective early recognition of myocardial damage; prediction of late CTX development; and planning of cardioprotection strategies.
The first group of studies demonstrated that 2D STE was more sensitive than LVEF reduction for the early recognition of asymptomatic left ventricle systolic dysfunction caused by chemotherapy in children and adults. 2D STE detected subclinical systolic myocardial abnormalities in children with acute lymphoblastic leukaemia and adult patients with breast cancer when no significant alterations were detected in conventional echocardiographic parameters.74–76
Although few data on evaluations of cardioprotection using 2D STE are available, Negishi et al. 82 recently demonstrated that LVEF and GLS improved in patients receiving anthracycline, trastuzumab or both after approximately 1 year of beta-blocker treatment. These results suggest a protective role of this therapy in these patients, but the results should be evaluated in larger populations.
There is only limited experience with the use of rotational and torsional indices in this setting. Mornos et al. 83 tried to combine GLS and left ventricle twisting to obtain a new index to evaluate cardiac function before and after 6, 12, 24 and 52 weeks of anthracycline treatment, and they identified an early deterioration of GLS multiplied by left ventricle twisting as the best predictor of later CTX. 3D STE enables the derivation of an index of left ventricle global performance that incorporates left ventricle 3D strain, dyssynchrony and torsion for the sensitive detection of altered left ventricle mechanics in childhood cancer survivors,84 although rotational indexes are currently used only for research, and further studies are needed to establish their role in the detection of CTR-CD.
In conclusion, the use the same vendor's machine and software version is presently recommended to compare individual patients with cancer when using 2D STE for the serial evaluation of systolic function.85
3D echocardiography is more accurate than the 2D modality for left ventricle volume and ejection fraction measurements, and it exhibits a precision that is comparable to CMR (Fig. 5).86 Advantages include better accuracy in LVEF measurements below the lower normal limits, superior reproducibility and lower temporal variability. The improved accuracy of 3D over 2D echocardiography for the detection of LVEF less than 50% was observed in survivors of childhood cancer.87 The preeminence of 3D echocardiography may be explained by the fact that it is less affected by acquisition differences from one scan to the next. Moreover, the use of an automated or semiautomated method for the identification of the left ventricle endocardium, compared with the manual tracing of endocardial contour that is required by the 2D method, provides a more accurate estimation of left ventricle volumes.88,89 Notably, 3D echocardiography is the technique of choice for the monitoring of the cardiac effects of chemotherapy. Serial 3D echocardiographic calculations of LVEF should be encouraged for the monitoring of cardiac toxicity where available,2 although it is important to realise that this technology needs high-quality images and training and expertise of operators for clinical application in the oncological setting. These concerns limit the widespread application of 3D echocardiography in the oncological setting.
Other imaging modalities, such as radionuclide angiography (MUGA), were referred to as the ‘gold standard’ to evaluate left ventricle systolic function in patients undergoing chemotherapy for many years.90 Serial imaging using MUGA effectively monitors anthracyclines-related damage because of its high accuracy and reproducibility of LVEF measurements. The main disadvantage of MUGA is radiation exposure, which reduces its use given the increasing availability of other imaging techniques. MUGA also does not provide comprehensive information on right ventricle function, left and right atrial size, and the presence or absence of valvular or pericardial disease. Therefore, it is frequently used as an adjunct and complementary technique to echocardiography.
CMR is currently considered the reference standard in assessing left ventricle and right ventricle volumes and function, and it was recently used more extensively to detect the acute and chronic complications of cardiotoxic chemotherapeutic agents.91 CMR is superior to echocardiography for its wide field of view, flexible scanning planes, and lack of ionising radiation.92 Contrast-enhanced CMR offers a unique capability to assess myocardial tissue characteristics because it possesses an excellent ability to outline myocardial oedema, hyperaemia, iron and necrosis/fibrosis, although this method has several limitations, such as low availability and a higher operational cost, compared with echocardiography. Issues with claustrophobia and hazards associated with ferromagnetic devices in some patients with cancer (e.g. breast tissue expanders used for breast reconstruction after mastectomy) must be considered.
The use of different imaging techniques, such as echocardiography, MUGA and CMR, to evaluate left ventricle volumes and LVEF values in the same patient is not suggested because of the significant difference in results across the techniques. Therefore, the choice of a single tool for the serial monitoring of LVEF during chemotherapy is preferred. Much evidence suggests that CMR should be considered in situations in which the discontinuation of chemotherapeutic regimens secondary to CTX is entertained or when the estimation of the LVEF is controversial or unreliable because of the low quality of echocardiographic images.2,93
International scientific societies finally began to state positions on the issue of echocardiographic monitoring during the course of chemotherapy in response to the growing evidence that the evaluation of the LVEF alone is no longer sufficient to identify chemotherapy-related early myocardial damage.
The two largest scientific societies of echocardiography, the ASE and EACVI, worked together to produce a shared document for the first time and stated positions on the role of various echocardiographic indices in this setting.2
Echocardiography was identified as the method of choice to evaluate patients before, during and after cancer therapy, and ejection fraction remained the first and irreplaceable technique. Ejection fraction should be performed using the best available method in the echocardiography laboratory (ideally 3D) in combination with the calculation of the wall motion score index.
LVEF failed to predict the development of CTR-CD. Therefore, a deeper echocardiographic investigation was strongly suggested, when available, to integrate the standard examination with data from different imaging techniques, such as TDI and STE.
The use of diastolic indices was not useful for the early detection of CTX because of their inability to predict subsequent heart failure.
Many studies during chemotherapy demonstrated reductions in all three myocardial layers, but neither radial nor circumferential strains were predictive of subsequent dysfunction. Therefore, the joint ASE/EACVI consensus suggests only the use of GLS by STE for a sensitive diagnosis of CTR-CD, and the same vendor-specific ultrasound machine should be used for serial examinations.
Patients who must undergo chemotherapy should first be evaluated by echocardiography and should be followed during and after the treatment with serial echocardiograms performed with a timing decided according to single patient's clinical conditions.
The first examination should be as complete as possible and must include the study of the: systolic function, by LVEF and GLS, diastolic function, heart valves, pericardium and right chambers.
Later checks ought to have to be guided by the results of the baseline examination. In each case, the assessment of systolic function and the pericardium must always be included. 3D echocardiography should be preferred when available for the calculation of volumes and ejection fraction. Is preferable that serial examinations are carried out always with the same echocardiographic system. The evidence of CTR-CD should be discussed with oncologist to decide whether the discontinuation of therapy is needed.
The issue of the diagnosis of CTR-CD is absolutely topical. Recent evidence of the importance of early diagnosis and strict follow-up in these patients have produced in an increasing effort to define a protocol to provide cardiologists and oncologists a prompt diagnosis and better patient management, including eventual cardioprotection therapy.94,95 Echocardiography plays a first-line role in cases with such a pressing indication.
There are no conflicts of interest.
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