Early Detection of Cardiomyopathy by Speckle Echo, High Sensitive Troponin and Cardiac Ryanodine Receptors

Overview

Early detection of cardiomyopathy in patients receiving Anthracycline chemotherapy and determine if speckle tracking echo and Troponin gene will add benefit for early detection of cardiomyopathy. Improve economic impact of oncologic patients from whom high sensitive troponin negative and normal speckle tracking patients can be safely excluded from long-term cardiac monitoring programs. To correlate between the molecular gene expression of troponin genes and ryanodine receptor in cardiomyopathy

Anthracycline chemotherapy has saved the lives of many cancer victims during the 50 years after their discovery.These patients are prone to higher risk of cardiovascular death than the risk of tumor recurrence, particularly in childhood cancer survivors in whom the cardiac mortality rate is seven fold higher. Cardiac toxicity remains an important side effect of anticancer therapies, leading to increased mortality due to mainly heart failure, but also arrhythmias, hypertension, thromboembolism. The time from early development of cardiac dysfunction to the modification or end of chemotherapy and beginning of heart failure therapy, is an important determinant of the extent of recovery. The Cardiotoxicity of anthracyclines may be acute, early or late. A recent study involving 2625 patients (mean follow-up 5 years); showed a 9% overall incidence of Cardiotoxicity after anthracycline treatment, 98% of cases occurred within the first year and were asymptomatic. Cardiotoxicity has been defined using various classifications. Recent guidelines suggest that Cancer therapeutics-related cardiac dysfunction (CTRCD) is defined as a decrease in the LVEF (by echocardiography) of \>10 percentage points to a value below the lower limit of normal. Echocardiography should be repeated before every next administration of anthracycline, after 3, 6, and 12 months from the end of therapy with anthracycline but...Not all patients treated with chemotherapy require such frequently repeated LVEF monitoring as suggested by the guidelines because of the negative impact on patient management and cost-effectiveness ratio for the national health system. Speckle-tracking echocardiography is a noninvasive ultrasound imaging technique that allows for early an objective and quantitative evaluation of global and regional myocardial function. New elevation of serum troponin detected with high sensitivity Troponin assays in patients receiving anthracyclines also predicts subsequent LV dysfunction. Ryanodine receptors (RyRs) are a class of intracellular calcium channels in various forms of excitable tissues like muscles and neurons. In heart failure the RyR2 channels become abnormally active or "leaky" and are unable to remain closed during diastole. This leads to an increase in spontaneous Ca+2 spark frequency and dysregulated Ca+2 handling within the cardiomyocyte, resulting in decreased systolic contraction and irregular contractile activity.

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