modern cardiology supportmodern cardiology supportfor the acute oncology patientfor the acute oncology patient

Chris PlummerCardiology, Freeman Hospital.

Chris PlummerCardiology, Freeman Hospital.

cardiology in acute oncologycardiology in acute oncology

what can go wrong ?what can go wrong ? acute coronary syndromesacute coronary syndromes

5FU5FU

arrhythmiasarrhythmias LQTLQT

heart failureheart failure anthracyclinesanthracyclines trastuzumabtrastuzumab et al.et al.

chest painchest pain

acute coronary syndromesacute coronary syndromes

2006 2008

ACS - organisationACS - organisation

ACS - complicationsACS - complications

death

ACS - ppci in oncology patientsACS - ppci in oncology patients

anti-platelet agentsanti-platelet agents bleeding risk if thrombocytopenicbleeding risk if thrombocytopenic

heparinheparin bleeding risk if liver dysfunctionbleeding risk if liver dysfunction

post-MI drugspost-MI drugs aspirin, clopidogrelaspirin, clopidogrel statinstatin ACE inhibitorACE inhibitor -blocker.-blocker.

essential after stenting

chest pain 5-FU/capecitabinechest pain 5-FU/capecitabine

riskrisk case reports of chest pain, MI, death case reports of chest pain, MI, death 1960s 1960s higher risk (x 4) in patients with CADhigher risk (x 4) in patients with CAD Kosmas Kosmas et al. et al. J Cancer Res Clin OncolJ Cancer Res Clin Oncol 2008; 2008;134134:75-82:75-82

n=644, no known CAD,n=644, no known CAD,26 developed symptoms & ECG changes:26 developed symptoms & ECG changes: 99//381381 = 2.4% si-5FU= 2.4% si-5FU

33//5454 = 5.6% capecitabine= 5.6% capecitabine

1414//209209 = 6.7% ci-5FU (p=0.012).= 6.7% ci-5FU (p=0.012).

chest pain 5-FU/capecitabinechest pain 5-FU/capecitabine

eventsevents all 26 had ECG ST all 26 had ECG ST or or 77//2626 (27%) (27%) CK-MB x 2 (MI) CK-MB x 2 (MI)

17 S17 Sxx compatible with angina compatible with angina 6 6 CK-MB CK-MB 7 palpitations 7 palpitations 1 1 CK-MB, 2 AF, 1 AVB CK-MB, 2 AF, 1 AVB 2 syncope 2 syncope 2 CHB (1 death). 2 CHB (1 death).

chest pain 5-FU/capecitabinechest pain 5-FU/capecitabine

mechanismmechanism unknown !unknown ! in vitro evidence of coronary spasm relieved in vitro evidence of coronary spasm relieved

by nitratesby nitrates no clinical datano clinical data direct toxic effect on vascular endotheliumdirect toxic effect on vascular endothelium acute myocarditis.acute myocarditis.

chest pain 5-FU/capecitabinechest pain 5-FU/capecitabine

managementmanagement symptoms symptoms agent stopped agent stopped ECGECG CK-MB (if CK-MB (if x 2 x 2 CCU 72h, no further 5FU) CCU 72h, no further 5FU) sublingual nitrates, cardiac monitoringsublingual nitrates, cardiac monitoring patients without patients without CK-MB, CK-MB, 33//77 transdermal transdermal

nitrates, continuous ECG monitoring, nitrates, continuous ECG monitoring, rechallenged at reduced dose rechallenged at reduced dose 33//1515 recurrent toxicity. recurrent toxicity.more data !

arrhythmiasarrhythmias

arrhythmiasarrhythmias

emergency treatmentemergency treatment electricity!electricity!

pacing for bradycardiapacing for bradycardia cardioversion / defibrillation for unstable cardioversion / defibrillation for unstable

tachycardias.tachycardias.

arrhythmias - SVTarrhythmias - SVT

acute managementacute management

DiMarco et al. Circulation 1983;68:1263

arrhythmias - atrial fibrillationarrhythmias - atrial fibrillation

arrhythmias - atrial flutterarrhythmias - atrial flutter

arrhythmias - AF and flutterarrhythmias - AF and flutter

emergency treatmentemergency treatment DC cardioversion under GADC cardioversion under GA

urgent treatmenturgent treatment heart rate controlheart rate control

i.v. i.v. p.o. p.o. -blocker (or diltiazem)-blocker (or diltiazem)

anticoagulationanticoagulation for all if planning cardioversionfor all if planning cardioversion CHADS2 CHADS2 2 2 heparin heparin warfarin INR 2.5 warfarin INR 2.5 [dabigitran].[dabigitran].

arrhythmias -TdParrhythmias -TdP

characteristicscharacteristics LQTs (multiple)LQTs (multiple) drug-induced LQT (multiple - drug-induced LQT (multiple - http://www.qtdrugs.org))

short – long – shortshort – long – short twisting of the points twisting of the points syncope / pre-syncope syncope / pre-syncope warm up / downwarm up / down spontaneous terminationspontaneous termination degeneration to VF degeneration to VF death. death.

arrhythmias -TdParrhythmias -TdP

risk factorsrisk factors QT (QTc > 500ms QT (QTc > 500ms x 2-3 risk) – check ! x 2-3 risk) – check ! drugsdrugs bradycardia, pausesbradycardia, pauses KK++, Mg, Mg2+2+, Ca, Ca2+2+

PVCsPVCs ageage female sexfemale sex structural heart disease.structural heart disease.

arrhythmias -TdParrhythmias -TdP

managementmanagement continuous ECG monitoringcontinuous ECG monitoring stop drug(s)stop drug(s) magnesium sulphate i.v.magnesium sulphate i.v. replace Kreplace K++ to 4.5 – 5.0mM to 4.5 – 5.0mM pacing for bradycardia.pacing for bradycardia.

Drew et al. JACC 2010;55:934-947

heart failureheart failure

cardiac toxicity – the problemcardiac toxicity – the problem

myocardium function symptoms

cytotoxics(anthracycline)

pathway block(HER2)

heart failure

little mitosis0.45 to 1% / year

requirement for adaptation

+XX

trastuzumabtrastuzumab

FinHerFinHerpivotal pivotal

metastaticmetastatic NOAHNOAHNSABP NSABP

B-31B-31

BCIRG BCIRG 006006 HERAHERA

timing of timing of trastuzumabtrastuzumab

before concurrent concurrentafter mean

21 days

after mean

21 days

after mean

89 days

LVEF LVEF ≥ 10%≥ 10% 6.8% 28% 23% 14% 18% 7%

NYHA III/IVNYHA III/IV 0.9% 16% 2% 4% 2% 0.6%

substantial substantial recovery recovery reportedreported

N/A N/A Yes Yes N/A Yes

B-31B-31 HERAHERA

trastuzumab - time coursetrastuzumab - time course

CREC – 79% symptomatic pts improved on RCREC – 79% symptomatic pts improved on Rxx

recovery: trastuzumab + Pac recovery: trastuzumab + Pac ((55//55)) >> trastuzumab + AC >> trastuzumab + AC ((1414//2121))

B-31, n=31 NYHA III/IVB-31, n=31 NYHA III/IV 1 had S1 had Sxx at at 66//1212

29% complete recovery of EF29% complete recovery of EF 75% had EF >50%75% had EF >50%

HERA HERA (Suter (Suter et al. JCOet al. JCO 2007; 2007;2525:3859-3865):3859-3865)

trastuzumab - reversibilitytrastuzumab - reversibility

nn asymptomaticasymptomatic recovery (EF >55%)recovery (EF >55%)

EF + asymptomaticEF + asymptomatic 2525 25 25 (100%)(100%) 17 17 (68%)(68%)

EF + NYHA IIEF + NYHA II 3636 36 36 (100%)(100%) 24 24 (67%)(67%)

EF + NYHA III-IVEF + NYHA III-IV 1010 8 8 (80%)(80%) 6 6 (60%)(60%)

management – NICE 2006management – NICE 2006

treatment - ACEi ± -blockertreatment - ACEi ± -blocker

ACEACEii e.g. perindopril 2mg ode.g. perindopril 2mg od c.i. c.i. knownknown renal artery stenosis, (renal failure) renal artery stenosis, (renal failure) GP will check C&Es and titrate to 4mg odGP will check C&Es and titrate to 4mg od

-blocker-blocker e.g. bisoprolol 1.25mg ode.g. bisoprolol 1.25mg od c.i. symptomatic bradycardia, c.i. symptomatic bradycardia, severesevere asthma asthma GP check HR/symptoms and titrate to 10mg odGP check HR/symptoms and titrate to 10mg od

continue unless there is a reason to stop.continue unless there is a reason to stop.

conclusionsconclusions

oncology cardiologyoncology cardiology

increasing interactionincreasing interaction new drugsnew drugs increasing awareness of the risks of old drugsincreasing awareness of the risks of old drugs

new management for MI (acute & chronic)new management for MI (acute & chronic) capecitabine > si 5-FUcapecitabine > si 5-FU watch QT watch QT (don’t believe the ECG machine!)(don’t believe the ECG machine!)

heart failureheart failure acuteacute chronic - chronic - ACEi, ACEi, -blockers, aldosterone antagonists, devices-blockers, aldosterone antagonists, devices

need more good trial data. need more good trial data.