Transcript Document

Chronic forms of ischemic
heart disease
Taras V. Chendey, MD, PhD
Classification of chronic IHD
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Angina
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Cardiosclerosis (cardiofibrosis)
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Stable angina pectoris
Vasospastic angina
Coronary X-syndrome
Focal cardiosclerosis (post-MI)
 LV aneurysm
Diffuse cardiosclerosis (atherosclerotic c/s)
Silent myocardial ischemia (“painless
form if IHD”)
Physiology of coronary circulation
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Heart is supplied by two major coronary
arteries, originating from the aortic root
Major branches of coronary arteries lie on
the epicardial surface of the heart so the
direction of repfusion is from epicardium to
endocardium. Subendocardial layers of the
LV are most susceptible to ischemia
Coronary ostia are being blocked while
valve opens – no coronary blood flow during
systole
During diastole blood is forced into coronary
arteries. Driving force of coronary perfusion
is diastolic blood pressure. Heart rate
determines the duration of diastole: the
lower the HR the longer the duration of
coronary perfusion
Determinants of myocardial metabolic
needs and myocardial blood supply
Needs
Supply
 Systolic BP
 Diameter of
“double product”
coronary artery
 HR
 Blood O2 capacity
 Myocardial
– Hb concentration
contractility
 Myocardial stress
(Laplace equation
T=(p*R)/2*t)
ECG patterns of myocardial ischemia
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Fixed, stable obstructive coronary lesion
(>60% stenosis) – no ischemia at rest,
subendocardial ischemia on exertion
J point
Downsloping ST segment depression
J point
Horizontal ST segment depression
Measuring ST segment depression
Upsloping ST segment depression is not indicative for
myocardial ischemia and usually occurs with tachycardia
ECG patterns of myocardial ischemia
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Complete artery occlusion by spasm or clot (ACS)
– transmural myocardial ischemia regardless of
level of myocardial needs
Stable angina pectoris (I 20.8)
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The most common form of chronic
IHD
Prevalence: 20-40 cases per 1000
adults, 10-20% of men aged 65-74
yrs
Average annual mortality 0.9-1.4%,
annual MI rate is around 2.0%
Symptoms of Angina
Abrams J. N Engl J Med 2005;352:2524-2533.
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Classification and Severity of Angina
(Canadian classification)
Abrams,NEJM,2005;352:2524-2533
Abrams J. N Engl J Med
2005;352:2524-2533.
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Common Stress-Testing Procedures for the Evaluation of Chest Pain
Abrams J. N Engl J Med 2005;352:2524-2533.
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Typical result of positive stress test
Coronary angiography: gold standard for
diagnosis and risk stratification in chronic
IHD. Indications for coronary angiography:
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Class III-IV angina (disabling
angina), esp. despite treatment
Prior MI
Prior VF/resuscitated sudden cardiac
death
Exercise testing result compatible
with high risk
Recurrence of angina after
revascularization
From the angiography standpoint
coronary lesions can be classified into:
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Single-vessel
disease
Two-vessel
disease
Multi-vessel
disease
Left main disease
Stable angina management: general
measures
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Smoking cessation
Weight loss, diet and physical
activity
Control of blood pressure and
diabetes
Lipid management - statins. LDL-C
goal is <1.8 mmol/L or >50%
reduction from the baseline
Pharmacological treatment of stable angina:
drugs for prognosis improvement (prevention
of MI and death)
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Low-dose (75-100 mg) aspirin – on the
reglar basis
Clopidogrel if not tolerant to aspirin
Statins (simva, atorva, rosuva)
ACEis in patients with HTN, DM or heart
failure
Beta-blockers in patients with prior MI
Pharmacological treatment of stable angina:
drugs for symptom relief (antianginal drugs)
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Short-acting nitroglycerine (NG) –
sublingual tablets or spray
Mode of action: donator of NO (needs SHgroups for the reaction) → mostly
venodilatation → ↓ return of blood to the
heart → reduced preload and pressure in
ventricles → reduced myocardial oxygen
needs, enhanced subendocardial
perfusion.
Onset of action – up to 1 minute, duration
of action – up to 5 minutes. Daily multiple
doses are safe.
Long-acting nitrates & sydnonimines
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Extended-release NG (Sustac, Nitrong,
Nitrogranulong)
Isosorbide dinitrite: regular and
extended-release formulations (Isoket,
Isoket-ret., Cardiket)
Isosorbide-5-mononitrite: regular and
extended-release formulations (Olicard
retard, Monosan, Mononitrosid)
Pentaerythrytol tetranitrate (Erynit)
Sydnonimine derivate – molsidomine
(Sydnopharm)
Nitrates: PK features
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Low oral bioavailability due to first passage effect
(high inactivation in liver) – better with ER
formulations
Presence of nitrates in blood >24h leads to
exhaustion of SH-pool and development of
tolerance
In order to prevent tolerance allow at least 12-14
hours nitrate-free interval per day. Usually first
dose of long-acting nitrates is given in the
morning, second – at noon (if needed), then no
nitrates (except short-acting NG on demand)
Molsidomine doesn’t need SH-groups for releasing
NO – no tolerance.
Side effects: headaches (most common), hypotension.
Not indicated in valvular stenoses
Beta-blockers
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First-line antianginal therapy
Mode of action:
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negative chronotropic effect → ↓HR →
prolonged diastolic perfusion time (increased
supply)
negative inotropic effect → ↓contractility →
decreased myocardial metabolic needs
↓SBP → ↓afterload → decreased myocardial
metabolic needs
↑tone of intact coronary arteries → “reversed steal”
phenomenon (increased flow is affected artery)
All beta-blockers are equally effective in
preventing anginal episodes
Calcium channel blockres
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Verapamil & Diltiazem
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Negative chrono- and inotropic effects
Vasodilatation
Combination with beta-blockers prohibited!
(risk of profound bradycardia and complete
heart block)
Dihydropiridines (amlodipine, felodipine)
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Mostly vasodilatation, less negative inotropic
effect
Useful in vasospastic angina
Well combined with beta-blockers
Ivabradine (Coraxan)
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Selective If channel blocker
Selective negative chronotropic
effect
No effect on BP, LV contractility and
conduction
May be first-line antianginal if betablocker is contraindicated
Can be combined with any other
antianginal
Trimetazidine (Preductal MR)
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Oral 3-ketoacylthiolaze (3-KAT) inhibitor
3-KAT activity is responsible for fatty acid
oxidation in muscles
Inhibition of 3-KAT switches metabolism from
aerobic fatty acid oxidation to anaerobic glycolisis,
thus favorably influencing myocardial O2
demands and ATP balance in cell.
No effect on BP, HR, contractility and conduction
Well tolerated, few side effects
Usually added to haemodynamic antianginals as a
second-line therapy
Revascularization in angina
-Single or two-vessel
disease
-Multi-vessel or left
main stem disease
-Preserved LV EF
-Depressed LV EF
-technical suitability
-technical inability to
perform PCI