Review of Tests for Monitoring Doxorubicin-lnduced Cardiomyopathy

Abstract

The objective of this review is to make physicians aware of new radionuclide methods to detect cardiac effects of chemotherapeutic drugs. This knowledge is important because of the limitations of the physical examination and the electrocardiogram for detecting early reversible cardiac damage. Presently left ventricular ejection fraction (LVEF) is routinely used to screen for cardiotoxicity. Since LVEF obtained by radionuclide angiocardiography is more accurate than the LVEF estimated by echocardiography, serial radionuclide LVEF monitoring is most commonly used to monitor cardiotoxicity. Diastolic measurements of left ventricular function (such as peak filling rate) are now being added to routine LVEF measurements to enhance standard radionuclide evaluation. This screening test should be done prior to beginning therapy and at appropriate points based on the baseline study, therapy scheme and the patient’s clinical status. At some centers, exercise LVEF methods are being used to determine if cardiac reserve is adequate for the patient to tolerate additional chemotherapy when cardiac injury may be present. Previously, endomyocardial biopsy was needed to detect and confirm early anthracycline cardiotoxicity. This invasive test may be replaced by a new noninvasive in vivo method using radioactive monoclonal antibodies against cardiac muscle (indium-lll-antimyosin). Because cardiac failure has been associated with adrenergic neuron injury, it has been proposed that radioactive methyliodo-benzylguanine may detect the adrenergic abnormality which may predict future development of congestive heart failure or sudden death months after therapy is discontinued. Advantages and disadvantages of these methods in evaluating cardiotoxicity, and an algorithm to optimally monitor antitumor therapy-induced cardiomyopathy are discussed.

Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients

“…The cycle was repeated every 3 weeks to a total of 10 cycles. Doxorubicin was discontinued if left ventricular ejection fraction (LVEF) decreased below 45% (Druck et al, 1984;Ganz et al, 1996). No radiotherapy was given during the study period.…”

“…Only endomyocardial biopsy has been considered to be sensitive and specific enough in predicting the development of CHF (Mason et al, 1978;Billingham and Bristow, 1984), but the invasiveness and potential complications of the procedure limit its clinical use. Radionuclide ventriculography (RVG) has been regarded as the best noninvasive method in identifying subclinical anthracycline cardiotoxicity in adult patients (Alexander et al, 1979;Schwartz et al, 1987;Ganz et al, 1996). Guidelines based on changes in systolic and diastolic left ventricular function have been given for monitoring patients receiving anthracycline therapy (Alexander et al, 1979;Schwartz et al, 1987;Ganz et al, 1996).…”

Doxorubicin Selectively Inhibits Brain Versus Atrial Natriuretic Peptide Gene Expression in Cultured Neonatal Rat Myocytes

“…This toxicity is characterized by progressive myocyte damage that can lead to dilated cardiomyopathy and refractory congestive heart failure. 2 The mechanisms that underlie the cardiotoxicity are only partially understood. Possible mechanisms include direct or indirect release of endogenous toxins (eg, histamine), 3 alterations in intracellular calcium homeostasis, 4 generation of free radicals that damage cellular membranes, 5,6 and intercalation of drug in the nuclear and mitochondrial genome, resulting in diminished RNA and protein synthesis.…”

The feasibility of high-dose chemotherapy in breast cancer patients with impaired left ventricular function

“…Quantitative radionuclide angiocardiography has been established as the preferred method of monitoring patients treated with anthracyclines [25][26][27] and can identify patients at a high risk of developing significant cardiac toxicity. In a retrospective study, Schwartz et al 26 found that in patients treated with doxorubicin, a decline of 10% or more in absolute LVEF to a value of 50% or less, as determined by ERNA, identified patients who subsequently developed clinical congestive heart failure if therapy with doxorubicin was continued.…”