HH

1. ADRIAMYCIN INDUCED
CARDIOTOXICITY

2. Introduction
Mechanisms
Risk factors
Clinical manifestations
Diagnosis
Management
Prevention

3. INTRODUCTION
• DOXORUBICIN is an Anthracycline derivative anticancer drug.
• Effective and more frequently used agent .
• Its major adverse effect is cardiotoxicity ---> which limits its use.
• Incidence of acute cardiotoxicity is approximately 11%.
• Chronic cardiotocxicity is around 1.7% .
• Doxorubicin cardiomyopathy once developed carries a poor prognosis and is
frequently fatal.

4. • ~50% mortality in 1year who develop congestive heart failure
• Many preventive measures have been proposed.
• Presently available treatment of established cardiomyopathy does not
appear to improve prognosis.

5. MECHANISMS
MOA
• Topoisomerase II inhibitor
• Intercalates between DNA base pairs
• Inhibits Replication and Transcription
• Reactive Oxygen Species Formation
• DNA damage through
Topoisomerase II
• induction of APOPTOSIS
• Protein synthesis inhibition

6. RISK FACTORS
• Age < 4 Yr, > 65 yr
• Females
• Raised Cardiac biomarkers
• Previous HF/ Cardiomyopathy/
CTRCD
• Severe VHD
• MI/ PCI / CABG
• Stable Angina
• LVEF < 50%
• HTN
• DM
• Smoking
• Hyperlipidemia
• Obesity

7. CLINICAL MANIFESTATIONS
Acute
• Occurs during and within 2-3
days of administration
• Incidence is 11%
• Chest pain
• Sinus tachycardia
• Paroxysmal non sustained SVT
• Premature atrial and
ventricular beats
Chronic
• Incidence 1.7%
• Dose related Incidence
4% 500-550mg/m2
18% 551-600mg/m2
36% >600 mg/m2
• Usually seen within 30 days of
administration of its last dose
• Can occur even after 6-10 years
after its administration

8. • History
• CVS Examination : signs of overt heart failure
• ECG: non specific ST-T waves changes
• Chest X-ray : cardiomegaly and signs of pulmonary venous congestion
• ECHO with doppler study
• Radionucleotide ventriculography : assess LV systolic and diastolic function
• MIBG nuclear imaging to assess cardiac adrenergic denervations
• Antimyosin antibody study`
• B-natriuretic peptide, Troponin T or I levels
• Endomyocardial biopsy: loss of myofibrils, distension of sarcoplasmic reticulum, vacuolization of the
cytoplasm

9. DIAGNOSIS
• New CV symptoms
• New abnormalities in Cardiac functionon CV imaging
• New increase in Cardiac bio-markers

19. The rationale of baseline risk assessment , monitoring and early
detection of cardiotoxicity in patients, who are treated with
anthracyclines is that early detection of subclinical cardiotoxicity and
intervention may decrease the risk of progression to heart failure and
thus improve the quality of life and outcomes.

20. THANK YOU