Download Eds: Kimmick, Lenihan, Sawyer, Mayer, Hershman Ronald J. Krone

Chapter 8: Interactions between
Cancer, cancer treatment, and
myocardial ischemia
- Ronald J. Krone
- Preet Paul Singh
- Chiara Melloni
Cardio-Oncology
Eds: Kimmick, Lenihan, Sawyer, Mayer, Hershman
Chapter 8: Interactions between
Cancer, cancer treatment, and
myocardial ischemia
- Ronald J. Krone
- Preet Paul Singh
- Chiara Melloni
Cardio-Oncology
Eds: Kimmick, Lenihan, Sawyer, Mayer, Hershman
The age groups where cancer is more common are also the age
groups where CAD is common.
After age 25, cardiac disease, primarily CAD, and malignancy
are the two most common causes of death in adults.1,2
Age Specific Death Rate
4500
deaths per 100,000 persons
4000
3500
3000
2500
2000
1500
1000
500
0
25-34
35-44
45-54
55-64
65-74
75-84
85 and
older
Malignancy
8.8
28.8
111.6
300.1
666.1
1202.3
1729.5
Heart Disease
7.6
25.8
61.6
186.6
409.2
1172.0
4285.2
Age Groups
Driver JA, et aI Incidence of cardiovascular disease and cancer in advanced age: prospective cohort study.
BMJ 20 08;337:a2467.
Share risk factors
Coronary Disease and Cancer
• Shared risk factors
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–
–
–
–
Age
Smoking
Obesity
Diabetes
Lack of physical activity
• Mechanisms in Common
– Inflammation (found in obesity, smoking, diabetes,
hypertension)
– Oxidative stress (lipid peroxidation, toxins, smoking)
Koene RJ, et al. Shared Risk Factors in Cardiovascular Disease and Cancer.
Circulation 2016;133:1104-14
Risk Factors
Risk Factors for coronary disease
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Age
Smoking history (any smoking)
Family history of coronary disease (coronary interventions, coronary bypass,
myocardial infarctions in relatives < 55 years of age
Diabetes-especially insulin requiring
Lipid Profile (need not be fasting-2 hours after a meal)
Peripheral vascular disease (carotid and/or femoral bruits)
Coronary calcifications (can be seen on non-contrast CT examinations of the
chest)
Risk can be evaluated at http://my.americanheart.org/cvriskcalculator and
http://www.cardiosource.org/scienceand-quality/practice-guidelines-and-qualitystandards/2013-prevention-guideline-tools.aspx
Risk factors for cancer also are in Red
Koene RJ, et al. Shared Risk Factors in Cardiovascular Disease and Cancer. Circulation 2016;133:1104-14.
Interactions between therapies
Cancer therapy can affect coronary arteries
• 5-FU,capecitabine, paxitaxil and docetaxel cause
endothelial injury and vasospasm
• Cisplatin especially with bleomycin and vinblastine
causes endothelial damage and can cause coronary
vasospasm
• Sunitinib and sorafanib plus other TKIs can cause
progression of coronary disease
• Bevacizumab associated with increased coronary events
• Hormonal therapy associated with myocardial infarctions
and angina
• Radiation causes endothelial injury and ultimately
coronary stenosis
Coronary calcifications are often
visible on standard CTs
CT of chest showing calcium
in RCA and LAD
coronary arteries
CT of chest showing calcium
in Left Main and proximal LAD
coronary arteries
Drugs commonly used in cancer patients that
are CYP3A4 substrates
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Chemotherapeutic Agents
etoposide
doxorubicin
ifosfamide
Antibiotics
vincristine
busulfan
everolimus
Anti-Inflammatory agents
cyclosporine
tacrolimus
sirolimus
Other Medications
alprazolam
carbamazepine
Macrolide
tamoxifen
imidazoles
Targeted anti-neoplastic agents
imatinib
ibrutinib:
olaparib:
ruxolitinib:
sunitinib
bosutinib
The commonly used statins, simvastatin and atorvastatin
are CYP3A4 inhibitors and interact with the cancer drugs
above. Pravastatin and rosuvastatin are not CYP3A4
inhibitors and do not interact.
The Coronary Vessels
• The left main divides into the
Anterior descending and
circumflex arteries which supply
most of the heart.
• The Anterior Descending usually
supplies the septum, the apex
and much of the anterolateral
wall
• The circumflex supplies the
lateral wall and a variable amount
of the inferior wall
• The Right coronary supplies the
right ventricle and the inferior
septum and a variable amount of
the inferior-posterior and
occasionally lateral wall
ACS in the Cancer Patient
A different risk/benefit ratio
• the algorithms that guide ACS management may not apply in the setting
of ongoing cancer management..
• Decision-making needs to consider multiple CONSIDER acuity/severity of
the cardiac condition
• the stage, treatment plan, and goals of care for the cancer.
• This requires active communication between the oncologist and the
cardiologist,
• Issues: for the oncologist and cardiologist:
– The severity and acuity of the coronary disease,
– the severity and stage of the cancer,
– the renal function which may be damaged with repeated PCI procedures, the
anticipated long term toxicity of the cancer therapy,
– the likelihood of developing severe thrombocytopenia on treatment,
– the need for cancer surgery within 6 months of the cardiac
•
In a patient actively receiving cancer therapy, the primary indication for
urgent revascularization is acute coronary syndrome (ACS), where the risks
of inaction are high.
Criteria for high risk NSTE-ACS with
indication for invasive management
Primary
• Relevant rise or fall in troponin
• Dynamic ST- or T-wave changes (symptomatic or silent)
• Continuing or recurrent pain
Secondary
• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73 m²)
• Reduced LV function (ejection fraction <40%)
• Early post infarction angina
• Recent Percutaneous coronary intervention (PCI)
• Prior Coronary artery bypass graft surgery (CABG)
• Intermediate to high GRACE risk score68 http://www.outomes.org/grace.
MACE after surgery after Percutaneous Coronary
Interventions with stentsthe importance of time from procedure
<30 Days
30 to 90
3
3-6
6-12
>12
days
months
months
Months
months
50%
14%
4%
35%
13%
15%
6%
9%
Time from PCI
MACE after Bare
Metal Stent
MACE after Drug
Eluting Stent
van Kuijk JP et al. Timing of noncardiac surgery after coronary artery stenting with bare
metal or drug-eluting stents. Am J Cardiol 2009;104:1229-34.
Recommendations for timing of surgery after previous
Percutaneous Coronary Intervention (PCI)
Type of PCI
2014 ESC/ESA Guidelines103
2014 ACC/AHA
Guidelines108
Bare Metal
4 weeks to 3 months (I,B)
≥30 days (I, B)
≥12 months (IIa, B)
≥12 months (I, B)
Stent
Drug Eluting
Stent First
≥6 months (IIb, B)
Generation
2nd and 3rd
≥6 months (IIa, B)
generation
DES
Balloon
≥2 weeks (IIa, B)
≥2 weeks (I, C)
angioplasty
Kristensen SD,, et al. 2014 ESC/ESA Guidelines on non-cardiac surgery: Eur Heart J 2014;35:2383-431.
Fleisher LA, et al. 2014 ACC/AHA Evaluation and Management of Noncardiac Surgery JACC 2014;64:e77-e137.
Revascularization for
Chronic Stable Angina
in a patient with Cancer
Revascularization could be considered in a
patient with chronic stable coronary disease
where complex cancer surgery is needed and
the patient would be unable to tolerate the
procedure unless some revascularization was
done in advance (usually limited to severe left
main disease or very proximal anterior
descending involving the left main).
This will of course delay the cancer surgery
Modified from ESC/ESA Guidelines on non-cardiac
surgery in patients with coronary stenosis
Low-Risk
Surgery <1%
Superficial surgery
Intermediate –
Risk
1-5%
High-risk
> 5%
Breast Surgery
Intraperitoneal
splenectomy, Hiatal hernia
repair, cholecystectomy
Head and neck surgery
Major abdominal
surgery involving
pancreas, liver etc
Esophagectomy
Endocrine Thyroid
Hip and spine surgery
Repair of perforated
bowel
Pulmonary or liver
transplant
Pneumonectomy
Major urological surgery
Non-Major intra thoracic
Total Cystectomy
Adrenal resection
Cardiac toxicities associated with 5FU and capecitabine
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Vasospasm
Angina Pectoris
Acute coronary syndrome
Myocardial infarction
Acute myocarditis
Takotsubo stress cardiomyopathy
Global cardiomyopathy.
Sinus Bradycardia
Ectopic ventricular beats
Prolonged QT with torsade de Point
Ventricular tachycardia
Cardiogenic shock
Sudden death
Acute pericarditis
Most Common cardiac responses
to 5-FU
• Vasospasm with angina
• Angina without clear vasospasm
• Myocardial infarction
• Management is empirical and uncertain.
Pretreatment with calcium channel blockers and
nitrates have been advised but patients should be
monitored in hospital and infusion stopped at
first sign of vasospasm. Protection unpredictable
and often unsuccessful.
Radiation and Cardiac disease
• Toxicities seen in cardiac structures in the radiation
beam
– Carotid Arteries
– Coronary Arteries (Stenosis-accelerated atherosclerosis)
• Left main
• proximal Right
• left anterior descending
– Mitral Valve (calcification and stenosis)
– Aortic Valve (calcification and stenosis)
– Pericardial (calcification and fibrosis-constriction or
effusion/tamponade)
– Ventricular myocardium (usually right ventricle)
Long Latency after Radiation
• Prolonged follow-up is needed
• Those at greatest risk-treated as children and
those with Hodgins lymphoma (HL) treated
with “mantle radiation.”
• 111 survivors treated for HL followed with
Coronary CTA
– At 5 years 15% had lesions
– At 10 years 34% had lesions
Girinsky T et al. Prospective coronary heart disease screening in asymptomatic Hodgkin
lymphoma patients Int J Rad Onc, Biol Phys 2014;89:59-66
Summary
• We have described areas where collaboration
between the cardiologist and oncologist are
essential
– Acute coronary syndrome
– Chronic stable coronary disease –evaluation for
cancer surgery
– 5-FU and Capecitabine--vasospasm, angina
– Radiation-long term surveillance