ISCHEMIC HEART DISEASE

(IHD)
Ischemic Heart Disease (IHD)
Three main coronary arteries:
1. Left anterior descending artery
2. Circumflex artery
3. Right coronary artery

Coronary arteries are blood vessels

that carry blood, oxygen and
other nutrients to the heart
tissue to help it work effectively.
Getting older – hardened coronary
arteries & build up fatty deposits
on the inner lining of the vessel
(atherosclerosis) - narrowing of
the coronary arteries- blood
supply to heart muscle is
reduced  symptoms of
coronary artery disease

http://intensivecare.hsnet.nsw.gov.au/five/htm/cabg.php
 Jenis IHD/PJK

1. Chronic stable exertional angina pectoris

2. Unstable angina,
3. Non–ST-segment-elevation myocardial
infarction (NSTEMI),
4. ST-segment-elevation myocardial infarction
(STEMI)
5. Tipe lain  Ischemia without clinical symptoms
or owing to coronary artery vasospasm (variant
or Prinzmetal’s angina)
 Epidemiology
- CVD claimed 949,619 lives, or 1 of every 2.5
deaths.

- More than 2600 Americans die of CVD each day,

or on average of 1 death every 33 seconds.

- Coronary Artery Disease (CAD) was responsible

for 459,841 deaths (or 48%) from CVD.
 Etiology

1. Atheroscheloris
Faktor risiko a.l. kolesterol, dislipidemia, DM, riwayat keluarga, obat-obatan
(kokain)
2. Spasm
Spasme arteri koroner pd semua ras (Jepang)
Spasme krn mediator a.l. SE, endotelin, dsb ; terjadi setiap saat , sering tdk terkait
dg latihan fisik
3. Embolism
Jarang terjadi krn arteri koroner pendek; dpt terjadi pd pasien dengan riwayat
endokarditis
4. Congenital
Prevalensi kecil (1-2%)
 Etiology
Endothelial dysfunction is characterized by
1. Imbalance between vasodilating & vasoconstricting  vascular
reactivity  imbalance between procoagulant and anticoagulant
substances  promoting platelet aggregation & thrombus formation.
2. Increase in the expression of leukocyte adhesion molecules  promotes
the migration of inflammatory cells in the subintimal vessel wall.
3. Increases the permeability of the endothelium to low density lipoprotein
(LDL) cholesterol and inflammatory cells that promote their migration and
infiltration in the subintimal vessel wall.

The evolution of endothelial dysfunction to the formation of fatty streaks

in the coronary arteries and eventually to atherosclerotic plaques.
Pathophysiology
 Atherosclerosis*

A lesion begins as a fatty streak (a) and can develop into an

intermediate lesion (b), and then into a lesion that is vulnerable to
rupture (c) and, finally, into an advanced obstructive lesion (d)

*Rader DJ & Daugherty A. Nature. Vol. 451, February 2008

 Atherosclerosis*

a. Atherogenic lipoproteins such as low-density lipoproteins (LDLs) enter the intima, where
they are modified by oxidation or enzymatic activity and aggregate within the extracellular
intimal space, thereby increasing their phagocytosis by macrophages. Unregulated uptake
of atherogenic lipoproteins by macrophages leads to the generation of foam cells, which are
laden with lipid. The accumulation of foam cells leads to the formation of fatty streaks, which
are often present in the aorta of children, the coronary arteries of adolescents, and other
peripheral vessels of young adults. Although they cause no clinical pathology, fatty streaks
are widely considered to be the initial lesion leading to the development of complex
atherosclerotic lesions.

*Rader DJ & Daugherty A. Nature. Vol. 451, February 2008

 Atherosclerosis*

b. Vascular smooth muscle cells — either recruited from the media into the intima or
proliferating within the intima — contribute to this process by secreting large amounts of
extracellular-matrix components, such as collagen. The presence of these increases the
retention and aggregation of atherogenic lipoproteins. In addition to monocytes, other types
of leukocyte, particularly T cells, are recruited to atherosclerotic lesions and help to
perpetuate a state of chronic inflammation. As the plaque grows, compensatory remodelling
takes place, such that the size of the lumen is preserved while its overall diameter increases.

*Rader DJ & Daugherty A. Nature. Vol. 451, February 2008

 Atherosclerosis*

c. Foam cells eventually die, resulting in the release of cellular debris and crystalline
cholesterol. In addition, smooth muscle cells form a fibrous cap beneath the endothelium,
and this walls off the plaque from the blood. This process contributes to the formation of a
necrotic core within the plaque and further promotes the recruitment of inflammatory cells.
This nonobstructive plaque can rupture or the endothelium can erode, resulting in the
exposure of thrombogenic material, including tissue factor, and the formation of a thrombus
in the lumen. If the thrombus is large enough, it blocks the artery, which causes an acute
coronary syndrome or myocardial infarction (heart attack).

*Rader DJ & Daugherty A. Nature. Vol. 451, February 2008

 Atherosclerosis*

d. Ultimately, if the plaque does not rupture and the lesion continues to grow, the lesion can
encroach on the lumen and result in clinically obstructive disease.

Plaque Rupture (Animasi 1, Animasi 2, Animasi 3)

*Rader DJ & Daugherty A. Nature. Vol. 451, February 2008

 Pathophysiology

• Ischemia may be defined as

lack of oxygen and decreased
or no blood flow in the
myocardium.
 Clinical Presentation & Diagnosis
Gejala
• Chest pain; may be painless or “silent”
• Typical pain radiation  anterior chest pain (96%), left upper arm
pain (83.7%), left lower arm pain (29.3%), neck pain (22%).

Hal-hal yang membantu menegakkan diagnosa

• Family history MI, stroke, and peripheral vascular disease,
hypertension, smoking, familial lipid disorders, and diabetes
mellitus.
• Lab test: hemoglobin, fasting glucose, fasting lipoprotein panel,
resting ECG, and chest x-ray
 Diagnostic Tests
1. Electrocardiogram (ECG)
2. Exercise Tolerance Testing
Test toleransi/treadmill
Dapat dikombinasi dengan test perfusi miokardial dg Thallium
(201Tl) utk reversible/ireversible aliran darah jantung
3. Cardiac Imaging
Test radionukleid angiografi (techtenium-99m) mengukur EF (ejection fraction)
4. Echocardiography
Pharmacologic stress echocardiography (dobutamine, dipyridamole or
adenosine) or pacing may be done to identify abnormalities during stress
5. Cardiac Catheterization & Coronary Arteriography
 Treatments

- Desired Outcome
- Short term: reduce & prevent anginal
symptoms that limit excecise capability &
impair QOL
- Long term: prevent CHD events (MI,
arrhytmias, HF, life)
 Treatments

- Risk Factor Modification

- Unalterable: gender, age, family history
or genetic composition, environmental
influences
- Alterable: smoking, HTN, hyperlipidemia,
obesity, sedentary life style,
hyperuricemia, type A behavior pattern,
drugs (progestin, corticosteroid and
cyclosporine)
 Treatments

Non Pharmacology Therapy

Revascularization
- Percutaneous Coronary Intervension (PCI) –
Percutaneous Transluminal Coronary Angioplasty
(PTCA)
- Coronary Artery Bypass Grafting (CABG)
 Treatments
PCI - PTCA (Animasi)
 Treatments
CABG
- Ilustrasi http://www.columbiasurgery.org/pat/cardiac/cabg.html#
 Treatments

Pharmacology Therapy

1. Beta Adrenergic Blocking Agents

2. Nitrates
3. Calcium Channel Antagonists
4. Investigational Agents
 Treatments
1. Beta Adrenergic Blocking Agents
- Decreased HR, Contractility, BP  reduce MVO2
- Benefit in pt with
- limited physical activity due anginal attack,
- HTN,
- supraventicular arrhytmias or post-MI angina, and
- anxiety associated w/ angina
- ISA, Cardioselective
- Side Effects
- hypotension, heart failure, bradycardia, heart block, bronchospasm,
peripheral vasoconstriction & intermittent claudication, altered glucose
metabolism, lipid abnormalities
 Treatments

1. Beta Adrenergic Blocking Agents

- Discontinuation: due to CNS adverse effect of fatigue,
malaise & depression
- Abrupt withdrawal – tapering down for 2 days
- Drug of choice for chronic exertional angina, chronic
angina due to reduce silent ischemia, early morning peak
of ischemic activity & improving mortality after MI
- CCB as substitute – monotherapy or combination
- Prototype drug: metoprolol, propanolol, atenolol
 Treatments

2. Nitrates
- Reduction of MVO2 secondary to venodilation & arterial-
arteriolar dilation leading to reduction wall stress from
reduce ventricular volume & pressure
- Large first pass effect, short to very short t1/2, large Vd,
high CL, large interindividual variability
- Nitroglycerin concentration – route of administration
- Used for acute anginal attack, prevent effort or stress
induced attacks, or for long-term prophylaxis (combine
w/ beta blocker or CCB)
 Treatments

2. Nitrates
- Side effects:
- postural hypotension, headache, flushing, nausea, tachycardia, rash
- Keep in tighly closed glass container – avoid mixing w/
other meds – reduce nitro adsorption & vaporization
- Repeated use is not harmful or addicting
- Nitrate tolerance – reduction of tissue cyclic GMP due to
decreace production & increase breakdown of guanylate
cyclase, and increase superoxide level
- Lack of cGMP – depletion of intracellular sulfhydryl
cofactor (cystein)
Nitrate Products

Product Onset (min) Duration Initial Dose

Nitroglycerin
IV 1–2 3–5 min 5 µg/min
Sublingual/lingual 1–3 30–60 min 0.3 mg
PO 40 3–6 h 2.5–9 mg tid
Ointment 20–60 2–8 h 1/2–1 in
Patch 40–60 >8h 1 patch
Erythritol tetranitrate 5–30 4–6 h 5–10 mg tid
Penterythritol 30 4–8 h 10–20 mg tid
tetranitrate
Isosorbide dinitrate
Sublingual/chewable 2–5 1–2 h 2.5–5 mg tid
PO 20–40 4–6 h 5–20 mg tid
Isosorbide mononitrate 30–60 6–8 h 20 mg qd, bida

aProduct-dependent.
 Treatments

3. Calcium Channel Antagonist

- Modulation of calcium entry into vascular smooth muslce
and myocardium, as well as variety of other tissue
- Reduce MVO2
- Pt w/ contraindication or intolerance to beta blockers,
Prinzmetal’s angina, PVD, severe ventricular
dysfunction, HTN
- HOPE study – suggest ACEI for preventing long-term
consequenses of IHD
 Treatments

4. Investigational Agents
- Ranolazine – reduction in fatty acid oxidation – swift in
myocardial energy production of glucose which is less
oxygen
- Therapeutic angiogenesis – stimulate blood vessel
growth ex. Ad5FGF-4
- Selective 5-HT3 antagonists – reduce pain following MI
ex. MCI 9042
- 5-HT2A antagonists, Tedisamil
- Markers: CRP, IL-6, MMP-9
 Treatments
Effect of Drug Therapy on Myocardial Oxygen Demanda
LV Wall Tension
Heart Rate Myocardial Systolic LV
Contractility Pressure Volume
Nitrates ⇑ 0 ⇓ ⇓⇓
β-Blockers ⇓⇓ ⇓ ⇓ ⇑
Nifedipine ⇑ 0or ⇓ ⇓⇓ 0or ⇓
Verapamil ⇓ ⇓ ⇓ 0or ⇓
Diltiazem ⇓⇓ 0or ⇓ ⇓
0or ⇓
aCalcium channel antagonists and nitrates also may increase myocardial oxygen
supply through coronary vasodilation. Diastolic function also may be improved
with verapamil, nifedipine, and perhaps, diltiazem. These effects may vary
from those indicated in the table depending on individual patient baseline
hemodynamics.
Abbreviation: LV = left ventricular.