Correlation of Anthracycline Induced Early Onset Chronic Cardio Toxicity With Pro BNP and Echocardiography

Abstract

During the last few decades, overall survival of cancer patients has improved. Now more cancer survivors reach old age, in which cardiovascular diseases remain the leading cause of mortality. [1] Cardio toxicity secondary to chemotherapy also puts cancer survivors at high risk of death secondary to cardiovascular events. [2] Anthracyclines (Doxorubicin, Daunorubicin, Idarubicin, Epirubicin and Mitoxantrone) are the class of chemotherapeutic agents that are potentially cardio toxic. [3] Cardio toxicity caused by anthracyclines can present as acute and chronic cardiotoxicity. Acute cardiotoxicity is seen in <1% of the patients which is usually reversible and self-limiting. [4] Chronic toxicity however can have two presentations, either as early onset chronic toxicity and or late onset chronic toxicity. [5] Early onset chronic cardio toxicity happens within first 12 months of chemotherapy, with peak incidence documented in the initial three months. [6] Late onset cardio toxicity develops after 12 months of chemotherapy and can manifest as late as 1-2 decades after chemotherapy. The late onset cardio toxicities are not reversible. [4] Anthracycline are assumed to cause cardiomyocyte impairment by forming free radicles and reactive oxygen species which contribute to oxidative stress resulting in mitochondrial damage and cell death [7]. Moreover, calcium and iron hemostasis is also affected by anthracycline which contribute to cardiomyocyte damage. Topoisomerase 2 ß is another mechanism of causing injury to non-proliferative cells like cardiomyocyte. [7][8] These different mechanisms are thought to be causing the cardiac cell death. Early detection of cardio toxicity in patients treated with anthracyclines remains an important topic for research. Different biomarkers like troponins, brain natriuretic peptide (BNP), C reactive protein (CRP), myeloperoxidase (MPO), galectin-3 and nitrous oxide have been studied for detecting cardiotoxicity caused by anthracyclines. [3][6][9][10] Azher et al reported high levels of Troponin I in patients who developed cardiotoxicity after Anthracycline based chemotherapy. [6] Lipshultz et al found high CRP values in pediatric cancer survivors. In addition to these studied biomarkers certain other markers are also under evaluation and have been evaluated in a couple of studies. Myeloperoxidase is pro inflammatory enzyme. Ky et al found that high MPO levels were related to risk of cardiotoxicity after anthracycline based chemo therapeutic agents at 15 months follow up. Nitrous oxide is another marker that plays a vital role in cardiomyocyte contractility. Guler at al noticed high nitrous oxide values in pediatric patients who received with doxorubicin with post chemotherapy low left ventricular ejection fraction (LVEF) and fractional shortening. [9] A correlational analysis by Annop et al noticed that high pro b-type natriuretic peptide (ProBNP) levels were associated with fractional shortening. [3]