CASE I

C.C. : chest pain

D. : 6 months

P. I. : 본 74세 여환은 20 년 전부터 HTN 있어 local

에서 medication 중으로 내원 6 개월 전부터

exertional chest pain 있어 further evaluation 및

proper management 위해 내원함.

F/74 이 O 인 #4615763

Chest pain profile

Onset : 6개월전

Duration : 10 mins

Frequency : 1~2회/주

Character : squeezing

Location : substernum

Radiation : Lt. arm and neck

Associative Sx : none

Relieving Fx : rest

Aggravating Fx : exertion

Risk Fx : HTN, age

NTG response : no response

P.Hx DM/ HTN/ Hepatitis/ Pul Tbc ( - / + / - / - )

Smoking : none

Alcohol : social

ROS Dyspnea / D.O.E ( - / - )

Chest pain / Palpitation( + / - )

Diziness ( - )

F/74 이 O 인 #4615763

P/Ex

BP 180 / 100 mmHg PR 72 bpm

RR 12 /min BT 36.7 oC

Not so ill-looking appearance

Clear breath sound without rales

RHB without murmur

F/74 이 O 인 #4615763

ECG at admission

HR 69 bpm

Chest PA at admission

Laboratory

CBC : 7610/14.6/221k

BUN/Cr : 24/0.8

T.chol/TG/HDL/LDL: 179/459/39/79

Random glucose : 111

Echocardiography

Normal global LV systolic function

(EF=60 %)

Borderline enlarged LA

(volume index : 28.2 ml/m2)

No RWMA

Coronary angiography

LCA

Coronary angiography

RCA

Treatment options for this patient

• Medical treatment

• PCI: but where?

• CABG: Poor anatomy and patient refusal

Optimal medical treatment is still a viable option

Grading of Angina Pectoris

Canadian Cardiovascular Society (CCS)

Functional Classification:

modification of the New York Heart Association (NYHA)

Functional Classification

I. Ordinary physical activity does not cause

II. Ordinary physical activity results in

III. Less than ordinary physical activity causes

IV. anginal syndrome may be present at rest

# Ordinary physical activity (undue fatigue) :

Walking one to two blocks or

climbing more than one flight

Risk Stratification

• The severity of angina:

also an important predictor of

outcome

• Normal resting ECG in stable angina

pectoris: well-preserved LV Fx. and

a favorable long-term prognosis.

• peak exercise capacity measured in metabolic

equivalents is among the strongest predictors

of mortality among men with cardiovascular

disease

Myers J, Prakash M, Froelicher V, et al: Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002; 346:793-801.

Risk Stratification Based on

Noninvasive Testing

High Risk (>3% annual mortality rate)

• Severe resting LV dysFx. (EF < 0.35)

• RWMA (involving > two segments)

• High-risk TMT result

• large perfusion defect

• multiple perfusion defect

• increased lung uptake (in thallium-201 scan)

Committee to update the 1999 guidelines for the management of patients with chronic stable angina). 2002 American College of Cardiology and American Heart Association

Meaning of These Feature

• Regardless of the severity of symptoms

• high likelihood of CAD

• risk for left main or triple-vessel CAD

impaired left ventricular function

• high risk for experiencing coronary events

↓

should undergo coronary arteriography

Comprehensive management of

Chronic Coronary Artery Disease

(1) Lifestyle modification for

reduction of coronary risk factors

(2) Treatment of associated diseases

that can precipitate or worsen angina

(3) Pharmacological management

(4) Revascularization (PCI or CABG)

PCI vs Medical

• Over 20,000 cases/year in Korea

Over 1,000,000 cases/year in US

Over 2,000,000 cases/year worldwide

• Superior control of angina

• Improved exercise capacity

• Improved quality of life

• No randomized trial has demonstrated a reduction

in death or MI with PCI compared to medical Tx.

for chronic stable angina

Class I indication

• Disabling chronic stable angina(CCS III or IV)

despite medical therapy

• High risk criteria on clinical assessment or

non invasive testing regardless of symptom

• Angina patients who survived sudden cardiac

death or serious ventricular arrhythmia

• Angina patients with CHF symptom and sign

Gibbons et al. 2002 ACC/AHA Practice Guidelines

• Randomized controlled trial:

Clinical Outcomes Utilizing Revascularization and

Aggressive druG Evaulation (COURAGE trial)

• 50 U.S. and Canadian Centers

• 2287 patients, 1999~2004

• Inclusion

CCS I~III stable angina stable post MI asymptomatic patients:angiographically documented CAD with at least 1 vessel

• Exclusion

persistent CCS IV refractory to medical Tx.Unstable anginaunstable post MILt.main > 50%LVEF < 30%markedly positive stress test

• Initial treatment Strategy randomization1138: optimal medical Tx.1149: PCI + optimal medical Tx.

• Optimal medical Tx:aspirin, clopidogrel, simvastatin, metoprolol and/or amlodipine, lisinopril or losartan, long-acting nitrates, as well as lifestyle change

• PCI:performed within 105 days of diagnostic angio

• Primary end point: Death / non fatal MI

Event rate at 4.6 years of FU

Weber et al. AJC 2002;89:suppl:27A

1. Aspirin in the absence of contraindication

2. Beta-blockers as initial therapy in the absence of contraindications

3. ACE inhibitor in patients with CAD

who also have diabetes and/or

left ventricular systolic dysfunction.

4. Calcium antagonists and/or long acting nitrates

as initial therapy or reduction of symptoms

when beta blockers are contraindicated

or not successful or unacceptable side effects

5. Sublingual or spray of NTG

for immediate relief of angina

6. target LDL of less than 100 mg/dL.

Gibbons et al. ACC/AHA practice guideline 2002

Class I

1. Clopidogrel when aspirin is absolutely contraindicated

2. Calcium antagonists instead of beta blockers as initial

therapy

3. ACE inhibitor in all patients with CAD or other vascular

disease.

Gibbons et al. ACC/AHA practice guideline 2002

Class IIa

Beta-blockers

Increased

diastolic

perfusion

Less exercise

vasoconstriction

More spasm?

Heart rate

After load

Heart size

Contractility

O2 wastage

Anti-arrhythmic

DEMAND SUPPLY

Subendocardial

ischemia

O2 vs O2

demand supply

Wall

stress

Equivalent doses

• Propranolol (pranol® )

• Metoprolol (betaloc® )

• Atenolol (tenormin® )

• Carvedilol (dilatrend® )

• Bisoprolol (concor® )

80mg

100mg

50mg

12.5mg

10mg

Beta 1 selectivity: Bisoprolol > atenolol > metoprolol

M.Gabriel Khan. Cardiac drug therapy. 6th ed.

Supply

Anti-ischemic Effect of Calcium Antagonists

Collateral flow

Vasodilation

Demand

O2

demand

Wall

stress

pre-load

or contractility

or afterload

or heart rate

O2 deficit

O2

supply

• Non- Dihydropyridine: HR↓, Contractility↓

Verapamil (Isoptin® ), Diltiazem (Herben® )

• Dihydropyridine: vasodilation↑

Nifedipine (Adalat® ), amlodipine(Norvasc® ),

felodipine (Splendil® ), Nicardipine (Perdipine® )

Reduced

venous

return

Arterioles

Reduced

Afterload

Reduced Preload

Nitrates

Action of Nitrates on Circulation

DilateDilate

Tolerance

Renin

A II

Dilate

Tolerance

Blood volume ↑

Coronary

dilation

Increased

coronary

perfusion

Preparation of agent Dose Schedule

Nitroglycerin

Ointment 0.5-2 inches 2-3 times/d

Buccal or transdermal 1-3 mg 3 times/d

Trandermal patch 0.4-1.2 mg/h for 12-14hrs

Oral sustained release 9.0-13.5mg 2-3 times/d

Isosorbid dinitrate (isoket® )

Oral 10-60mg 2-3 times/d

Oral sustained release 80-120mg Once daily

Isosorbid-5-mononitrate (imdur® )

Oral 20-30mg 2 times/d

Oral sustained release 60-240mg Once daily

Other Anti-angina drug

• Potassium channel opener

- Nicorandil : Sigmart®

• Direct NO donor

- Molsidomine : Molsiton®

Nicorandil :K+ATP Channel Opening Action

1. Microvascular Dilation

2. Ischemic preconditioning (Cardioprotective Effects)

KATP Channel Opening

K+

Hyperpolarization

Ca++ channel closing

Ca++

Stored in SR

Ca++ sensitivity

decrease

Ther Res 1996;17:1155-60

...CH=CH-CO-SCoA

3-ketoacyl-CoA

thiolase

...CH-CH2-CO-SCoA

Oll

...CH-CH2-CO-SCoA

OHl

H2O

NAD

SCoAFAD

Mitochondria

-oxidation

Spiral

CH3-CO-SCoA

Enoyl -CoA

Hydratase

Acyl-CoA

dehydrogenase

...CH2-CH2-CO-SCoA

3-OH-Acyl-CoA

dehydrogenase

-

Trimetazidine

mitochondria

cytoplasm

FATTY ACID

OXIDATION

GLUCOSE

OXIDATION

GLYCOLYSI

S

Acetyl CoA

ATPContractile Function

Basal Metabolism

Pyruvate

Fatty Acids Glucose

Trimetazidine Inhibits Fatty Acid Oxidation

Lactate

+ H+’s

Trimetazidine

O2

H2O

Mechanism of action of anti-platelet agents

Aspirin

Awtry EH & loscalzo J, Circulation, 2000

2nd Prevention- CV death 17% ↓

- AMI 34% ↓

- CVA 35% ↓

- All CV disease 35% ↓

AHA ecommendation

Anyone with atherosclerosis

Initial Tx: 160-325mg at 1st day

Subsequent Tx: 75-160 mg/day

Discharge medications

Aspirin 100mg #1

Trimetazidine 60mg #3

fenofibrate 160mg #1

Sigmart 15mg #3

Amlodipine 5mg #1

Tenormin 50mg #2

Tritace 5mg #1

Dichlozid 12.5mg #1

CASE II

C.C. : chest pain

D. : 1 month

P. I. : 본 65세 남환은 2006년 본원에서 colon

polypectomy 시행 받은 Hx 외에는 특이 과거력 없는

분으로 내원 1 개월 동안의 chest pain 주소로

further evaluation and proper management 위해

내원함.

M/65 김 O 영 #5171606

Chest pain profile

Onset : 3개월전

Duration : several mins

Frequency : 2~3회/day

Character : 뜨금한 느낌

Location : substernum

Radiation : none

Associative Sx : sweating

Relieving Fx : resting

Aggravating Fx : exertion(Canadian class II)

Risk Fx : age

NTG response : not trial

P.Hx DM/ HTN/ Hepatitis/ Pul Tbc ( - / - / - / - )

Smoking : none

Alcohol : social

ROS Dyspnea / D.O.E ( - / - )

Chest pain / Palpitation( + / - )

Diziness / Headache ( - / - )

M/65 김 O 영 #5171606

P/Ex

BP 120 / 60 mmHg PR 88 bpm

RR 12 /min BT 36.7 oC

Not so ill-looking appearance

Clear breath sound without rales

RHB without murmur

M/65 김 O 영 #5171606

ECG at admission

HR 77 bpm

Treadmill test

Bruce protocol, Stage II with symptoms

Echocardiography

Normal global LV systolic function

(EF=76 %)

No RWMA

Coronary angiography

LCA

Coronary angiography

RCA

• left main coronary artery or its “equivalent” “severe pLAD and pLCx (both >70%)”are particularly life threatening.Mortality among medically treated patients:29% at 18 months and 43% at 5 years.

Caracciolo EA et al. Circulation 1995; 91:2325-2334.

CABG• Around 2500 cases/year in Korea (in 2002)

Around 350,000 cases/year in US

20% of CABG is off pump

• excellent short- and intermediate-term results

in the management of stable CAD

• 80% free of angina at 5 years

63% at 10 years, but only 15% after 15years

• long-term results are affected by failure of

venous grafts

Abu-Omar Y, Taggart DP: Off-pump coronary artery bypass grafting. Lancet 2002; 360:327-330

• CABG for Lt. main

• CABG for 3VD

• CABG for 2VD with significant pLAD with abnormal LV Fx.

• PCI for 2 or 3VD with significant pLADwith suitable anatomy and normal LV Fx and no DM

- recurrent angina, repeat revascularization due to

incomplete revascularization and restenosis of PCI

- survival benefit from CABG in left ventricular dysfunction,

proximal LAD stenosis, DM

PCI vs CABG

MACCE

Death

TVR

Coronary angiography

Pre-intervention CYPHER 3.5 x 18

MLA on IVUS : 4.7 mm2

Discharge medications

Aspirin 100mg #1

Plavix 75mg #1

Pletaal 200mg #2

Lipitor 40mg #1

Sigmart 10mg #2

Tenormin 50mg #1

Capril 18.75mg #3

CASE III

C.C. : chest pain

D. : 1 month

P. I. : 본 40세 남환은 8개월 전 HTN 진단받고 3개월간 PO

medication 하다 자의로 투약 중단한 분으로 6개월 전부터 산

악 자전거 탈 때 가슴이 따끔거리는 증상이 있었으나 수초 내로

완화되어 별다른 치료 없이 지냈으며, 1개월 전 싸이클 대회에

참가했을 때 턱 쪽으로 방사되는 흉통이 30분간 지속되어 NTG

복용하였으나 증상 완화되지 않고 힘겹게 회복한 후 본원 외래

내원하여 시행한 CAOD CT상 LAD에 90% LN 소견 보여 입원

하였다.

(입원 당일 아침 운전 시 30초간 resting chest pain 있었다 함)

M/40 배 O 성 #3197646

Chest pain profile

Onset : 6개월 전

Duration : 5~10초

Frequency : 1~2회/월

Character : squeezing pain

Location : substernum

Radiation : Lt arm and chin

Associated Sx : dizziness

Aggrevating Fx : exertion(Canadian class II) but not always

Risk Fx : HTN, smoking

NTG : no response

P.Hx DM/ HTN/ Hepatitis/ Pul Tbc ( - / + / - / )

Smoking : 40PYRs, current smoker

Alcohol : social

Hyperthyroidism

ROS Dyspnea / DOE ( - / - )

Chest pain / Palpitation ( + / - )

Diziness/ Headache ( - / - )

Nausea/ Vomiting ( - / - )

M/40 배 O 성 #3197646

P/Ex

BP 145 / 90 mmHg PR 70 bpm

RR 16 /min BT 36.7 oC

Clear breath sound without rales

RHB without murmur

M/40 배 O 성 #3197646

Initial ECG(2007/3)HR 70 bpm

Initial TMT stage IV negative, echo: not remarkable

--> NTG trial

1 month later…..

• 4/30 싸이클 대회에 참여하여 턱쪽으로방사되는 흉 통이 30분간 지속되어 NTG

복용하였으나 증상 완화되지 않고 갑자기 심장이 덜컥하는 느낌이 들면서 의식이 흐려지다 회복됨 OPD로 내원

What would be the diagnostic

evaluation of choice in this patient

• Repeat TMT and echo

• Take the patient directly to cath lab

• Refer the patient for Head up tilt test to rule out

vasovagal syncope

• How about a Coronary CT angiography?

CT angiography

Coronary angiography

Pre-intervention ENDEAVOR 4.0 x 24

Discharge medications

Aspirin 100mg #1

Plavix 75mg #1

Lipitor 10mg #1

Sigmart 10mg #2

Pranol 60mg #3

Complications of coronary

angiography and interventions

• Patients clinical

characteristics

associated with higher

mortality during

coronary angiography

– Cardiogenic Shock

– Left main stenosis

– LV ejection < 30%

– Diabetes mellitus

– Renal failure

Complication Percent (%)

Death 0.08-0.1

CVA 0.08-0.1

Arrhythmia 0.3-0.5

Vascular 0.2-1.6

Anaphylaxis 0.1

Cholesterol

emboli0.15

Accuracy of 64-MDCT for stenosis

>1.5mm9395482Ropers

All95861270Raff

All9699-35Pugliese

All9599252Mollet

>1.5mm9794-67Leschka

All9773-88-59Leber

>1.5mm9695666Fine

All9490869Ehara

Analyzed segment

s

Specificity (%)

Sensitivity (%)

Exclusion (%)

patientnumber

First author