Cardiac
Anthracycline related toxicity
Mortality from anthracycline induced cardiac failure is high (in the range of 20% - 50%)
Anthracycline related cardiomyopathy:
- Does not respond well to diuretics or inotropic therapy
- Patients often have subclinical (asymptomatic disease)
In anthracycline related cardiomyopathy, echocardiography or radionuclide angiocardiography show:
- Abnormal systolic function with reduced left ventricular contractility
- Increased afterload
- Afterload depends on:
- blood pressure (normal)
- size of the ventricular cavity (normal)
- left ventricular thickness (reduced)
Reduced fractional shortening. Left-ventricular fractional shortening (FS) and left-ventricular ejection fraction (EF) are the most commonly used parameters
Mechanism:
- Myocyte injury secondary to generation of free radical oxygen species (ROS) and lipid peroxidation of the cell membrane to cardiomyocyte injury acquired during anthracycline exposure 9
- Anthracyclines can induce ROS generation both enzymatically and through the formation of anthracycline-iron complexes20
- Superoxide anions can be generated from these anthracycline complexes which can cause subcellular damage directly or be converted to hydroxyl radicals that are toxic and react causing lipid perioxidation and damage to the DNA.9
- Cardiac myocytes are more susceptible to damage by free radicals because of their highly oxidative metabolism and relatively poor antioxidant defenses such as catalase and glutathione peroxidase20
- Anthracyclines have a high affinity for cardiolipin, a mitochondrial membrane phospholipid, resulting in anthracycline accumulation in cardiac cells.9
- Ongoing disruption of mitochondria by anthracyclines causes a decrease ATP production in cardiac cells as well as affects multiple structural gene products which eventually reduces cardiac myocytes to contract effectively.9
- Histologically, there is loss of myofibrils and cytoplasmic vacuolation secondary to dilated sarcoplasmic reticulum in the myocardial cells2.
Presentation:
The presentation varies and can be:
1. Acute/subacute
- Happens within hours or days after administration of anthracycline
- Characterized by:
- transient arrhythmia
- pericarditis/myocarditis
- left-ventricular failure
- Unusual
- Generally reversible with supportive care
2. Early onset chronic
- Gradually increasing symptoms of heart failure
- Usually within a year of therapy
- Increased risk with increased cumulative anthracycline dose.
3. Late onset chronic
- Left ventricular dysfunction and arrhythmias in a previously asymptomatic patient
- Late onset anthracycline cardiac dysfunction is a result of damaged caused during therapy that is not serious enough to cause symptoms immediately15
- Develops after 1 year to decades after end of therapy with anthracyclines (can occur as long as 20 years later)
- Increased risk with increased cumulative anthracycline dose
NB
- Anthracycline cardiomyopathy may be asymptomatic (subclinical)
- Onset can be early or late
- Pregnancy, general anesthetic or severe exertion can precipitate congestive failure
