ReviewMonitoring chemotherapy-induced cardiotoxicity: Role of cardiac nuclear imaging
Section snippets
Anthracyclines
Anthracyclines (doxorubicin, daunorobucin, epirubicin, idarubicin, and so forth) are commonly used antineoplastic agents in a wide variety of hematologic and solid tumors.4, 5 Anthracyclines are highly potent anticancer agents. Cardiotoxicity is a well-known side effect of anthracyclines.6 As per recent estimates, by the year 2010, 1 in 200 adults in the United States will be a survivor of some form of childhood cancer.7 Because anthracyclines constitute the regimen for many of the common
Acute and early toxicity
Acute or subacute cardiotoxicity with anthracyclines occurs during or immediately after infusion and usually is self-limiting with discontinuation of therapy (eg, electrocardiographic abnormalities such as nonspecific ST-T changes and QT prolongation, pericarditis–myocarditis syndrome, and ventricular dysfunction with CHF).
Chronic and late-onset toxicity
Although late-onset cardiotoxic effects are noted after months to years, some of these chronic effects may start with early cardiac abnormalities that can progress over a period of time to overt cardiac dysfunction. Chronic effects persist after discontinuation of the anthracyclines and the clinical symptoms may include all signs of cardiomyopathy such as electrophysiologic changes, decrease of left ventricular function, changes in exercise capacity, and overt signs of CHF. Estimates based on
Risk factors
Cumulative dose,11 dose schedule,12, 13 female sex,14, 15 age, prior irradiation,16 concomitant administration of other chemotherapeutics,17, 18 and underlying heart disease have been associated with early and late-onset cardiotoxicity.19 Of these, the cumulative dose seems to be the most important factor. The usual dose of doxorubicin is 55 to 75 mg/m2 every 3 weeks. At a cumulative dose of more than 450 to 550 mg/m2 of doxorubicin, cardiomyopathy and CHF occur most frequently (Figure 1). Von
Mechanism
A number of mechanisms including free radical–mediated myocardial injury, myocyte death from calcium overload,22, 23, 24 alteration in adrenergic function, and inhibition of protein synthesis have been postulated as plausible mechanisms of doxorubicin cardiotoxicity. However, the exact mechanism of doxorubicin cardiotoxicity is not clear. Although the mechanism of anthracycline cardiotoxicity may be multifactorial, of all the hypotheses, oxidative injury from the production of oxygen free
Prevention
For more than 2 decades researchers have struggled to develop strategies to ameliorate or prevent doxorubicin cardiotoxicity. Reducing cumulative dose and frequent surveillance have been among the most effective strategies until now. A number of antioxidant and free radical scavengers have been developed for experimental and clinical studies, but without consistent benefit.29 These strategies have been devised based on the concept of free radical injury and relative weaker defense system of the
Monitoring and detection of cardiotoxicity
Along with attempts to reduce or prevent cardiotoxicity by developing newer forms of anthracyclines and other chemotherapeutic agents and other pharmacologic agents, the need arises for identifying patients at unusually higher risk for developing CHF. Detection of myocardial injury before irreversible functional impairment is the most logical approach for the prevention of doxorubicin-induced heart failure. This approach would allow maximum doses of doxorubicin to be administered without the
Endomyocardial biopsy examination
Endomyocardial biopsy examination is an invasive and expensive technique requiring interpretation by a skilled histopathologist. Endomyocardial biopsy examination requires a small sample of right ventricular myocardium to be obtained for histopathologic analysis. Although endomyocardial biopsy examination provides a histologic diagnosis along with grading of severity of disease (based on the Billingham score), it has multiple shortcomings.62, 63 The changes of doxorubicin cardiotoxicity are
Equilibrium radionuclide angiocardiography
Equilibrium radionuclide angiocardiography (ERNA) has been a reliable and reproducible test for monitoring and evaluation of left ventricular function in patients undergoing doxorubicin chemotherapy.66, 67 It is among the earliest and most widely used methods for this purpose. Change in left ventricular ejection fraction (LVEF) precedes overt heart failure in patients undergoing doxorubicin cardiotoxicity. Serial monitoring using ERNA allows the detection of a predetermined decrease in LVEF
Stress ERNA
Several investigators explored the role of exercise ERNA in detecting early cardiotoxicity.72, 73, 74 Studies suggested a failure to increase the LVEF by 5% or more during exercise RNA over the resting ejection fraction as an indication for risk of developing subsequent cardiomyopathy. Although initial studies showed exercise ERNA to be more sensitive than rest ERNA, specificity in the absence of serial testing was a concern. In addition, several healthy patients failed to increase the ejection
Diastolic dysfunction
Although resting ejection fraction as determined by ERNA has been standard practice, other variables have been tested for their use in predicting subsequent heart failure. Diastolic dysfunction has been examined by means of both echocardiographic and by radionuclide angiocardiography.75, 76, 77, 78 A reduction in peak filling rate was suggested as an early marker of anthracycline-induced cardiotoxicity.77 A decrease in peak filling rate was purported to occur earlier than reduction in ejection
Echocardiography
Echocardiography is another imaging modality commonly used for the evaluation of cardiac function and structure in patients, especially pediatric, undergoing anthracycline cardiotoxicity. Although it is used frequently, serial measurement of cardiac function is limited by a greater degree of variability that impairs its value in predicting heart failure. Echocardiographic studies based on ERNA guidelines have reported poor sensitivity of echo in detecting anthracycline-induced cardiac
Neuronal Imaging
Beyond the conventional methods, several newer agents have been evaluated in predicting heart failure caused by doxorubicin cardiotoxicity. Iodine-123–labeled metaiodobenzylguanidine (I-123 MIBG), an agent used for neuronal imaging in heart failure, has been proposed for understanding the contribution of abnormal adrenergic function in pathogenesis of doxorubicin cardiotoxicity (Figure 3).81, 82, 83, 84, 85 MIBG, a guanethidine analog, shares type I adrenergic neuroreceptor uptake storage and
Acknowledgment
The authors have indicated they have no financial conflicts of interest.
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2022, Presse MedicaleCitation Excerpt :Planar left anterior oblique (LAO) incidence permits an evaluation of LVEF by the normed ratio of LV activity between diastole and systole regions of interest (ROI) with a great inter and intra-observer reproducibility [121]. Its high reproducibility made it a preferred technique for the follow-up of patients under cardiotoxic chemotherapy [122,123]. LAO incidence is useful to realize phase analysis with Fourier transform to study intra and inter ventricular dyssynchronization.
Methods of screening, monitoring and management of cardiac toxicity induced by chemotherapeutics
2022, Chinese Chemical LettersCitation Excerpt :Currently established guideline for screening chemotherapy related cardiotoxicity includes assessment of left ventricular (LV) ejection fraction (EF), LV blood volume, diastolic function, MRI, computed tomography (CT), and positron emission tomography (PET) [99,100]. Other monitoring methods that are used in clinic includes endomyocardial biopsy, radionuclide angiocardiography (RNA), molecular imaging, and biochemical markers such as troponin T and B-natriuretic peptide (BNP) [101,102]. Here we will discuss the screening and monitoring methods in 4 different sections: (1) Screening based on clinical manifestation, (2) Analysis from cardiotoxic biomarker, (3) Imaging technologies, (4) Others.
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