Severe ventricular dysrhythmias and silent ischemia during infusion of the antimetabolite 5-fluorouracil and cis-platin

Hrovatin, Enzo; Viel, Elda; Lestuzzi, Chiara; Tartuferi, Lucia; Zardo, F.; Brieda, Marco; Dametto, Ermanno; Piazza, Rita; Antonini‐Canterin, Francesco; Vaccher, E.; Meneguzzo, Nereo; Nicolosi, Gian Luigi

doi:10.2459/01.jcm.0000237914.12915.dd

Cited by 29 publications

(21 citation statements)

References 22 publications

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“…Chronic anthracycline cardiotoxicity (even many years after the completion of therapy) manifests often as life-threatening arrhythmias [34]. 5-Fluorouracil has been demonstrated to be associated with EKG signs of myocardial ischemia while less frequent alterations include arrhythmias [35]. High dose of cyclophosphamide may cause malignant arrhythmias inducing sometimes fatal outcomes [36].…”

Section: Ekg and Cardiotoxicity Of Ctmentioning

confidence: 99%

Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography

Galderisi

Marra

Esposito

et al. 2007

Cardiovasc Ultrasound

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Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic) dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation.

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Section: Ekg and Cardiotoxicity Of Ctmentioning

confidence: 99%

Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography

Galderisi

Marra

Esposito

et al. 2007

Cardiovasc Ultrasound

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“…A major factor limiting cisplatin treatment is concern regarding its acute and cumulative cardiotoxicity 7,8 . Clinical reports regarding acute cisplatin treatment have identified myocardial infarction and severe ventricular arrhythmias in young patients 9,10 . Those studies suggested that the use of cisplatin can be a risk factor for coronary heart disease.…”

Section: Introductionmentioning

confidence: 99%

Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: Role of endoplasmic reticulum stress

Jones²,

Guo³

et al. 2010

Clin Exp Pharma Physio

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1. Cisplatin is a potent chemotherapeutic agent with broad-spectrum antineoplastic activity against various types of tumours. However, a major factor limiting treatment with cisplatin is its acute and cumulative cardiotoxicity. The aim of the present study was to explore the effect of cisplatin on myocardial contractile function and the possible underlying cellular mechanisms. 2. C57 mice were treated with cisplatin (10 mg/kg per day, i.v.) or vehicle (0.9% NaCl) for 1 week and myocardial function was assessed using the Langendorff and cardiomyocyte edge-detection systems. Transmission electron microscopy, mitochondrial membrane potential, indices of endoplasmic reticulum (ER) stress and caspase 3 activity were evaluated. 3. Cisplatin-treated mice developed myocardial contractile dysfunction, as evidenced by a reduction in left ventricular developed pressure (LVDP) and the first derivative of LVDP (+/-dP/dt). Cisplatin treatment significantly prolonged time to 90% relengthening, depressed peak shortening, maximal velocity of shortening/relengthening (+/-dL/dt) and augmented the frequency-elicited depression in peak shortening. The JC-1 fluorescent assay demonstrated that cispatin-induced cardiac dysfunction was associated with mitochondrial membrane depolarization. Transmission electron microscopy revealed that cisplatin induces ultrastructural abnormalities of the mitochondria. Following cisplatin treatment, cardiomyocytes show activation of the ER stress response, increased caspase 3 activity and increased terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) staining. 4. The data indicate that cisplatin is cardiotoxic and may lead to left ventricular dysfunction and depressed cardiomyocyte contraction associated with mitochondrial abnormalities, enhanced ER stress and apoptosis. This work should shed some light on the management of cisplatin-induced cardiac injury.

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“…In addition to increasing the frequency of cardiotoxicity, the presence of preexisting heart disease increases the severity of cardiotoxic reactions to 5-FU [3]. Accordingly, a careful pre-administration cardiac evaluation is essential [46].…”

Section: Risk Stratificationmentioning

confidence: 99%

“…Thus, in conjunction with a thorough pre-treatment clinical assessment, frequent symptom, blood pressure, and ECG monitoring are essential components of any treatment protocol [46].…”

Section: Risk Stratificationmentioning

confidence: 99%