Lecture 9 - cardio-oncology Flashcards
who does cardio-oncology occur in?
Occurs in up to one quarter of cancer patients*
Most serious
Cardiac dysfunction
Heart failure (HF)
what is cardio-oncology?
Cardio-oncology is an emerging subspecialty within internal medicine, and particularly cardiology, which involves the prevention and management of cardiovascular injury from cancer therapies
CVD remains a leading cause of death in cancer survivors (second only to cancer recurrence)
There are also overlapping risks for CVD and cancer which confounds the problem
common overlapping risks between CVD and cancer are age, sex, tobacco, diabetes, obesity, htn etc
what are the main categories of cardiovascular complications of cancer therapy?
- Myocardial dysfunction and heart failure (HF)
- Coronary artery disease (CAD)
- Valvular disease
- Arrhythmias
- Arterial hypertension
- Thromboembolic disease
- Peripheral vascular disease and stroke
- Pulmonary hypertension
- Pericardial complications
what are cardiotoxic effects of associated chemotherapies?
HER2 targeted therapies (trastuzumab, pertuzumab), proteosome inhibitors (bortezomib, carfilzomib), anthracyclines (doxorubicin, epirubicin, idarubicin), tyrosine and VEGF inhibitors (bevacizumab, sunitinib and sorafenib), platinum based therapies (cisplatin), meicotjubules inhibitors (paclitaxel, docetaxel and vincristine), and radiation
may lead to cardiomyopathy and heart failure, hypertension, coronary artery does ease,a arrhythmias or pericardial disease.
what are the stages of development of cardio toxicity?
- asymptomatic - chemotherapy and risk factors such as anthracycline, inflammation, free radicals
- symptomatic heart failure. epigenetic changes such as DNA methylation, histone acetylation and microRNA targeting.
- severe/refractory heart failure. abnormal cell signalling
- cardiac death. cardiovascular disfunction
describe the anthracyclein cardiotoxity effect.
Anthracyclines belong to Type I agents and cause irreversible and dose-dependent damage, which consist of cellular death, either via necrosis or apoptosis.
molecular mechanism for cardiotoxic effects of doxorubicin
1. generation of reactive oxygen species and membrane damage
2. inhibition of topoisomerase ii-b and topoisomerase I mitochondrial
3. modulation of intracellular calcium release
diagnosis with cardiac biomarker abnormalities, myocardial strain imaging
how is doxorubicin-induced cardiotoxicty treated in paediatrics?
Around 1 in 10 childhood cancer survivors develop a symptomatic cardiac event over time.
Childhood exposure leads to late, irreversible cardiomyopathy.
Current gold standard for monitoring cardiac function:
left ventricular ejection fraction (LVEF)
measured via echocardiogram
Dexrazoxane is the only FDA- approved drug for preventing anthracycline-induced cardiotoxicity
what is used to treat paediatric cardio toxicity?
peadiatric cancer cardiotoxicty when using a DOXORUBICIN can be treated with DEXRAZOXANE.
Dexrazoxane is a cardioprotective agent that works by binding to iron and chelating it, which prevents the iron from participating in chemical reactions that generate free radicals
Doxorubicin, as a chemotherapy agent, functions in part by binding to the Top2β-DNA complex, thereby preventing the resealing of the DNA strands that the enzyme has cut, leading to the formation of DNA breaks. These breaks can result in cell damage
what is Herceptin associated with?
Trastuzumabis highly effective for humanepidermal growth factor receptortype 2 (HER2)–positive breast cancer but is associated with a decline inleft ventricular ejection fraction
highest risk of cardiotoxciity when
1. trastuzumab + doxorubin
2. trastuzumba + paclitaxel
3. trastuzumba monotherpay
4. trastuzumb + minimal port anthracyclein exposure
how does trastuzumab
(herceptin) lead to cardiac toxicity?
In the heart, neuroregulin (NRG-1) triggers HER-4/HER-4 homo-dimerisation and HER-4/HER-2
Heterodimerisation on cardiomyocytes to induce protective pathways in response to stress
Blockade of cardiac HER-2 by Herceptin results in disruption of NRG signalling and results is
Cardiomyocyte dysfunction and death
what is the effect of chemotherapy agent vs HER2 targeted agents?
chemotherapy agents eg anthracycline can cause type 1 irreversible cardiac damage. cumulative dose-relate cardiomycoyte injury leading to cell death. may present acutely in 1 week with ECG abnormalities, or chronically in 1 year with cardiac dysfunction
HER2 trageted agents such sas tratuzumab causes type 2 reversible cardiac damage. there is cellars dysfunction during therapy, and symptomatic changes in LVEF
what are other medications to reduce cardio toxicity ?
Carvedilol isa beta blocker.
Lisinopril is a medication of the angiotensin-converting enzyme inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks
what are prophylactic strategies for all chemotherapy drugs?
all chemotherapy drugs; identify and treat cardiovascular risk factors. treat comorbidities eg CAD. avoid QT prolonging drugs and among electrolyte abnormalities. minimise cardiac irradiation.
what are prophylactic strategies for anthracyclines and analogues?
limit cumulative dose;
*daunorubicin <800 mg/m2
*doxorubicin <360
*epirubicin<720
*mitoxantrone <160
*idarubicin <150
altered delivery system or continuous IV
dextrazoxane as an alternative
ACE-1 or ARB, beta blockers, station, aerobic exercise
what are prophylactic strategies for trastuzumab?
ace inhibitors, beta blockers - carvedilol
