Anticancer Treatments and Cardiotoxicity

Mechanisms, Diagnostic and Therapeutic Interventions

Patrizio Lancellotti,Jose L Zamorano,Maurizio Galderisi

• Publisher: Academic Press
• Year: 2016
• ISBN:
  9780128026472
• Topic: Medizin
• Subtopic: Toxikologie

Anticancer Treatments and Cardiotoxicity: Mechanisms, Diagnostic and Therapeutic Interventions presents cutting edge research on the adverse cardiac effects of both radiotherapy and chemotherapy, brought together by leaders in the field. Cancer treatment-related cardiotoxicity is the leading cause of treatment-associated mortality in cancer survivors and is one of the most common post-treatment issues among survivors of adult cancer. Early detection of the patients prone to developing cardiotoxicity, taking in to account the type of treatment, history and other risk factors, is essential in the fight to decrease cardiotoxic mortality.

This illustrated reference describes the most effective diagnostic and imaging tools to evaluate and predict the development of cardiac dysfunction for those patients undergoing cancer treatment. In addition, new guidelines on imaging for the screening and monitoring of these patients are also presented. Anticancer Treatments and Cardiotoxicity is an essential reference for those involved in the research and treatment of cardiovascular toxicity.

• Provides algorithms essential for the use of imaging, and biomarkers for the screening and monitoring of patients
• Written by world-leading experts in the field of cardiotoxicity
• Includes high-quality images, case studies, and test questions
• Describes the most effective diagnostic and imaging tools to evaluate and predict the development of cardiac dysfunction for those patients undergoing cancer treatment

Section IV

Imaging Evaluation of Cardiac Structure and Function in Cancer Patients

Outline

Chapter 20 The Role of Echocardiography

Chapter 21 The Role of Cardiovascular Magnetic Resonance (CMR)

Chapter 22 Nuclear Medicine Imaging and Cardiotoxicity

Chapter 20

The Role of Echocardiography

Abstract

The most commonly used parameter for monitoring LV function with echocardiography is LV ejection fraction (LVEF). LVEF itself and LVEF drop during and after cancer treatment are currently used to define the onset cardiotoxicity. New, normal cutoff points of LVEF (≥52% in men and ≥54 in women) have been recently established. Changes in LVEF indicative of LV damage can be more appropriately identified when comparisons are made between baseline and follow-up studies. ASE/EACVI recommendations on the use of cardiac imaging in cancer patients fix the drop of LVEF of at least 10 points to an LVEF <50% as indicative of cardiotoxicity. The sensitivity of 2D LVEF appears, however, to be poor for changes during time lower than 10% in cancer patients. Isolated diastolic abnormalities have been identified as early sign of anthracycline-induced LV dysfunction. Pulsed tissue Doppler and E/e′ ratio could be more sensitive than mitral inflow to detect LV diastolic dysfunction as a result of chemotherapy. Nevertheless, diastolic parameters have not shown any power in predicting subsequent cancer therapy-related cardiotoxicity. Right ventricular (RV) abnormalities may occur in oncologic patients for a number of reasons: preexisting RV dysfunction, neoplastic involvement (primary or metastatic), cardiotoxic effects of chemotherapy. However, frequency and prognostic values of RV involvement have not been investigated in the oncologic setting. Valvular heart disease may develop in oncologic patients for several reasons including primary or secondary (metastases) tumors affecting valve function, pancytopenia-related endocarditis, functional mitral and tricuspid regurgitation due to cardiac dysfunction, and pulmonary arterial hypertension, as a consequence of cancer-related cardiotoxicity. Although transthoracic echo is often sufficient to evaluate valve dysfunction and its hemodynamic consequences, transesophageal echocardiography may add incremental information.

Keywords

Cancer therapy; cardiotoxicity; echocardiography; left ventricle; ejection fraction; diastolic dysfunction; right ventricle; valvular heart disease

Chapter Outline

Standard Echo-Doppler Evaluation: LV Systolic and Diastolic Function, Right Ventricular Function, Valvular Heart Disease 143

LV Systolic Function 143

LV Diastolic Function 145

RV Function 147

Heart Valve Disease 147

References 147

Pericardial Disease in Oncologic Patients 151

Etiology 151

Diagnosis of Pericardial Disease in Oncologic Patients 152

References 158

The Role of Contrast Echocardiography 161

References 164

Stress Echocardiography 165

References 167

Advanced Echocardiography: Speckle Tracking Echocardiography and 3D Echocardiography 169

Three-Dimensional (3D) Echocardiography 169

Speckle Tracking Echocardiography 169

References 172

Chapter 20.1

Standard Echo-Doppler Evaluation: LV Systolic and Diastolic Function, Right Ventricular Function, Valvular Heart Disease

M. Galderisi and R. Sorrentino

Among the different cardiac imaging modalities, echocardiography has a key role in the evaluation of cancer patients because of its large availability and feasibility and also the lack of radiation exposure in comparison with other modalities. Echocardiography is therefore particularly suitable for serial assessment of left ventricular (LV) and right ventricular (RV) structure and function as well as for a comprehensive assessment of cardiac valves, aorta, and pericardium. The joint recommendations from the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) have recently described the role of echocardiography in the oncologic setting [1].

LV Systolic Function

The exposure to potentially cardiotoxic anticancer agents is a recognized indication for baseline and sequential evaluation of LV systolic function during and after cancer therapy treatment including radiotherapy [2,3]. Table 20.1 summarizes echo parameters of LV structure and systolic function (and their cutoff points of normalcy), which can also be used in the oncologic setting.

Table 20.1

Main Echo Doppler Parameters of LV and RV Function (and Relative Cutoff Points of Normalcy) to Be Evaluated in Cancer Patients During Time

Echo Doppler Parameter	Cutoff Point of Normalcy in Women	Cutoff Point of Normalcy in Men
LV end-diastolic diameter (mm)	<52.2 mm	<58.4 mm
LV end-systolic diameter (mm)	<34.8 mm	<39.8 mm
LV ejection fraction (%)	<54%	>52%
Septal e′ velocity (cm/s)^a	>7.6	>7.6
Lateral e′ velocity (cm/s)^a	>11.5	>11.5
E/e′ ratio (average e′)^a	<13	<13
RV basal diameter (mm)	<42	<42
TAPSE (mm)	<17	<17
Tricuspid annular s′ velocity (cm/s)^a	<9.5	<9.5

E, transmitral early velocity; e′, early diastolic velocity; LV, left ventricular; RV, right ventricular; s′, systolic velocity; TAPSE, tricuspid annular systolic excursion.

^aData referring to age range of 41–60 years.

The most commonly used parameter for monitoring LV function with echocardiography is LV ejection fraction (LVEF). Additional measurements of LV systolic function include stroke volume (mL, LV end-diastolic volume–LV end-systolic volume) and cardiac output (L/m, stroke volume × heart rate). Accurate assessment of EF by 2D echocardiography should be done at baseline, during, and after cancer treatment and is particularly useful in patients who present cardiac morbidities or clinical findings suggestive of LV systolic dysfunction [4,5]. According to the joint recommendations from The American Society of Echocardiography (ASE) and the European Association of Echocardiography (EAE), the method of choice for LV volume quantitation and LVEF determination (%, LVEDV–LVESV/LVEDV × 100, where EDV is end-diastolic volume and ESV is end-systolic volume) is the modified biplane Simpson’s (method of discs) in apical four-chamber and two-chamber views [6]. Fig. 20.1 shows a reduced LVEF (=45%) in a patient with lymphoma undergoing anthracycline treatment. The use of endocardial fractional shortening (%) by using linear measurements of LV internal diameters ((LV end-diastolic diameter–LV end-systolic diameter)/LV end-diastolic diameter × 100), used in the past and particularly in cancer childhood, should be discouraged because coronary artery disease may occur in patients with cancer and cancer therapy-related cardiac toxicity can even induce regional wall motion abnormalities in LV walls other than anterior septum and posterior wall which are taken into account when calculating endocardial fractional shortening. Since regional wall motion abnormalities often involve only few LV segments or walls without necessarily affecting global LV function, the visual assessment of the wall motion score index should be also reported [7].

Figure 20.1 Calculation of LVEF by 2D echocardiography in a patient with lymphoma undergoing anthracyclines. LVEF is 50% in apical four-chamber view (left panel) and 37% in apical two-chamber view (right panel). The final value of biplane LVEF is 45% (right panel). LVEDV, LV end-diastolic volume; LVEF, LV ejection fraction; LVESV, LV end-systolic volume; SV, stroke volume.

LVEF itself and LVEF drop during and after cancer treatment are currently used to define the onset of cardiotoxicity in cancer patients. Different cutoff values of LVEF (e.g., <50%, &l...