**4. Cancer therapy-related cardiac dysfunction (CTRCD) and echocardiography**

#### **4.1 LV systolic function**

The need for a timely diagnosis of subclinical and clinical heart failure by using cardiac imaging has been addressed by the Expert Consensus of the ASE and EACVI [6] and more recently reinforced by the ESC Position Paper on cancer treatments and cardiovascular toxicity [4]. The quickest and most available imaging tool in detecting cancer therapy-related cardiac dysfunction (CTRCD) is transthoracic echocardiography.

Exposure to potentially cardiotoxic chemotherapeutic agents is a well-recognised indication for baseline and longitudinal evaluation of LV function [9, 10]. The most commonly used parameter for monitoring LV function with echocardiography is LVEF. Traditionally, an echo determination of LVEF is requested by the oncologists in all cancer patients at baseline and in any situation in which the suspicion of heart failure is plausible, during and after completion of the anti-cancer therapy. 2D-derived LVEF is also used to start cardio protection and to establish the interruption from anti-cancer therapies. The calculation of LVEF should be done with the best method available as per the skills and experience of the operators in a given echocardiography department. The same method needs to be maintained for surveillance during and after treatment. Importantly, the digital images obtained should be available for visually comparison with the previous studies and further discussion at multimodality echocardiographic and cardio-oncology team meetings. According to joint recommendations from the ASE/EACVI, the method of choice for LV volume quantification and LVEF calculation is the modified biplane

Simpson's technique by 2D echocardiography, with an LVEF of ≥55% as a normal reference range. Calculation of LVEF should be also combined with assessment of the wall motion score index, which is based on a 16-segment model of the left ventricle [11]. Resting wall motion score index based on a 16-segment model of the left ventricle has been demonstrated to be a more sensitive marker of anthracyclineinduced CTRCD than relying on the LVEF alone [12]. When two contiguous LV segments are not well visualised on non-contrast apical images, the use of myocardial contrast agents is recommended [13].

Although LVEF is a commonly accepted measure of cardiac systolic function and an accepted indicator of prognosis in patients with heart failure [14], it has low sensitivity for the detection of small changes in LV function. LVEF measurement using the 2D biplane technique has a temporal coefficient of variation of 7.4% [15], which is important to highlight because the measurement variability is close to the definition of CRTCD (drop in LVEF of 10% or more). This variability is the result of a number of factors including the operator's skills and the geometric assumptions used to estimate three-dimensional (3D) volumes from 2D images. 3D echocardiography has been shown to be more accurate than the 2D echocardiography in the measurement of the LV volumes [16]. However, the feasibility of the 3D technique can be reduced in some cancer patients because of the negative influence of factors such as concomitant radiotherapy (breast cancer and lymphoma) and surgery (mastectomies of left breast cancer, breast expanders or implants), which makes the ultrasound windows under these circumstances suboptimal [17]. The ASE recommends 3D echocardiography as the preferred technique for monitoring LV function and detecting CRTCD. However, it is important to realise that this technology has several limitations as well. It is recommended that calculation of LVEF by 2D biplane Simpson's method also be included in all the oncologic patients echocardiographic report to allow comparison with previous studies if this method was used.

To minimise the risk of irreversible cardiomyopathy, the goal is to identify signs of toxicity as early as possible. Echocardiography-based deformation imaging techniques (strain) have become an essential tool to detect CRTCD. Changes in strain are more sensitive, appear prior to LVEF reduction and before the CRTCD manifests as symptomatic heart failure. Global longitudinal strain (GLS) is of particular interest because it can be incorporated into a clinical echocardiographic examination relatively efficiently with currently available technology [18]. The EACVI and ASE recommend assessing GLS as a routine component of clinical echocardiograms in patients at risk for type 1 or type 2 cardiotoxicity [6]. A relative percentage decrease in GLS > 15% is indicative of subclinical LV dysfunction and could be utilised as the starting point for timely cardio protection therapy.

#### **4.2 LV diastolic function**

A comprehensive assessment of LV diastolic function, including grading of diastolic function and providing an estimate of LV filling pressure (by using the E/e′ ratio), should be performed in addition to the assessment of LV systolic function [19]. Although abnormal diastolic function parameters may reflect subclinical LV dysfunction, it has not been found to be prognostic of cardiotoxicity, and its clinical significance remains uncertain.

#### **4.3 Right ventricular (RV) function**

The frequency of the RV dysfunction during cancer therapy-related cardiotoxicity has not been accurately examined. As early studies of CRTCD included

**65**

and obesity).

**7. Pericardial disease**

secondary to cardiac metastasis.

*Cardio-Oncology: The Role of Echocardiography in Cancer Patients*

RV biopsies, there is a suggestion that the RV is affected by cancer therapies [20]. However, the prognostic value of RV dysfunction at the time of cardiotoxicity

The diagnostic capability of rest echocardiography in CAD is limited to the assessment of the presence and magnitude of regional wall motion abnormalities. Stress echocardiography, an established technique for the detection and prognostication of stable CAD as recommended by guidelines, may be useful in the evaluation of patients who are undergoing regimens that may be associated with ischemia, as fluoropyrimidines, platinum compounds (cisplatin), vascular endothe-

Stress echocardiography is also being used to unmask subclinical abnormalities of the LV function induced by chemotherapeutic agents. Although both exercise [12] and dobutamine stress echocardiography [21–23] have been applied to patients with cancer for the identification of anthracycline-induced CTRCD, the results of these studies appear to be inconclusive and contradictory. Further studies are needed to better understand the prognostic role of stress echocardiography, before

Patients who have received radiation therapy are at risk of long-term cardiovascular toxicity including radiation-induced heart valve disease, pericardial disease

Transthoracic echocardiography is the main tool to identify valvular damage in these patients. There are distinct echocardiographic characteristics of radiotherapyinduced valvular disease. The main distinguishing features between radiotherapyinduced valvular heart disease and rheumatic heart disease are the presence of commissural fusion after radiotherapy, while the involvement of the mitral leaflet

The EACVI and ASE expert consensus statement recommendations for longterm follow-up after radiation therapy suggest a yearly physical examination to assess for symptoms or signs of radiation-induced heart disease, which if present should prompt further evaluation. In asymptomatic patients, a transthoracic echocardiogram is recommended 5 years after exposure in high-risk individuals and 10 years after exposure in all others [24]. High risk individuals are defined the patients who received anterior or left-side chest irradiation and have at least one additional risk factor (smoking, diabetes mellitus, hypertension, hyperlipidemia

Pericardial disease in cancer patients is relatively common. Pericardial effusion,

cardiac tamponade and pericarditis can appear during several types of chemotherapy (anthracyclines [25], cyclophosphamide [26] and cytarabine [27]) but are especially due to radiotherapy. Constrictive pericarditis is more often associated with radiation-induced cardiotoxicity [28]. Additionally, pericardial disease may be

*DOI: http://dx.doi.org/10.5772/intechopen.93085*

**5. Coronary artery disease (CAD)**

lial growth factor inhibitors and radiotherapy.

can be routinely used into clinical practice.

tips is an indication of rheumatic disease.

**6. Valvular disease**

and coronary artery disease.

warrants further investigation.

RV biopsies, there is a suggestion that the RV is affected by cancer therapies [20]. However, the prognostic value of RV dysfunction at the time of cardiotoxicity warrants further investigation.
