Atherosclerotic and Ischemic Heart Disease

Howard L. Sacher, D.O.Long Island Cardiology and Internal Medicine

Teaching Objectives

A. To understand the pathogenesis of atherosclerosis and assess coronary flow reserve

B. To properly diagnose and manage stunned and hiberhating myocardium

C. To make appropriate decisions in non-invasive testing processes and medical management of chronic ischemic heart disease, including the use of coronary angioplasty and coronary artery bypass grafts (CABG).

Teaching Objectives (cont)

D. To manage secondary prevention of coronary artery disease

E. To manage unstable angina, variant angina , something and silent myocardial ischemia

F. To something with considerations for the woman patient

Coronary Heart Disease

• One million deaths among Americans are the result of CAD

• More than two out of every five deaths are result of CAD

• Of current US populations 1 in 4 suffer from some form of CVD

• Prevalence increases markedly with age

Reduction in mortality of CAD Deaths

• Reduction of risk factors– Hypertension– Diabetes– Hyperlipidemia

• Inprovement of socioeconomic circumstances

• New methods of diagnosis and treatment• Enhanced access to care

Vascular Injury

• Vascular endothelial injury is a critical initiating event in atherogenesis. It leads to– Lipid accumulation– Release of various growth factors– Migration and proliferation or smooth muscle

cells

Pathophysiology

• Classification of vascular injury is divided into 3 types:– Type I functional alteration– Type II Endothelial and Intimal damage,

the internal elastic lamina is preserved– Type III Deep injury involving the intima

and media. The lamina is not preserved

After Type I injury the endothelium’s ability to release intrinsic relaxing substances

Proposed scenario of EDRF and Endothelin during ischemic syndromes

ACh decreases as risk factors increase, decreasing the smooth muscles’ ability to relax

Endothelium

• Decrease vasodilitory substances such as EDRF (nitric oxide) with associated anti-proliferative properties

• Releasing vasoconstriction substances such as endothelin, with associated migration properties

• Critical balance between nitric oxide and endothelin maybe major determinant in regulatory system and regional hemodynamic function and cellular proliferation

CAD Risk Factors

• Age• Male / Female• Obesity• Smoking• Hypertension• Diabetes• Family History• Hyperlipidemia

Approach to Patients with CAD

• History

• Physical Exam

• Treatment

• EKG

• Cardiac enzymes – CPK-MB, Troponin

• Admit to hospital

Approach to Patients with CAD (cont)

• Stress test– Gradual exercise stress test

– Regular stress test, exercise or pharmacological

– Stress echo or pharmacological

• Coronary and cardiac catheterization – angioplasty• Percutaneous transluminal coronary angioplasty

with stenting• Coronary artery bypass surgery

Smooth Coronary artery segment that shows EDRF dependent dilation to ACh will also dilate with exercise

But when evaluating coronary segments that where irregular and stenosed, they did not show EDRF dependent dilation to ACH. These

did not dilate with exercise

Adenosine

• Thought to act on the coronary vasculature by stimulating the Adenosine A2 receptors on the smooth muscles.

• Adenosine crosses the endothelial barriers to stimulate the Endothelial Independent Pathway for vasodilatation

Adenosine• Is thought to act on the coronary vasculature via

stimulation of the adenosine A2 receptors on smooth muscle cells which activates adenylate cyclase to produce cyclic adenosine monophosphate (cAMP) and smooth muscle relaxation. At pharmacological doses , adenosine can cross the endothelium something and stimulate the receptors on the smooth muscle directly in an endothelium independent mechanism. Adenosine also acts predominantly on vessel less than 150 micrometers in diameter and therefore mainly assesses it’s changes in the coronary resistance vessels

Nitroglycerine

• A vasodilator that acts directly on smooth muscle through a cGMP mechanism – non endothelial dependant vascular response. Because coronary microvessels contain the enzyme needed to convert nitroglycerine into nitric oxide, nitroglycerine creates a dose related dilation of coronary vessles > 200 microns in diameter

Coronary Stenosis

• As coronary stenosis, the microvascular dilates to compensate

• During increased myocardial demand, the capacity of the microvascular to dilate further is limited , (vessels already maximally dilated) resulting in myocardial ischemia.

Treatment

A. Nitrates – a) Dilates vessels and improves flowb) Reduces afterload and preload

a) Preload = volume – end diastolic volumeb) Afterload = amount of pressure generated to push blood out of

the heartc) Contractility can be improved by decreasing preload and

afterload but if too vigorous will decrease contractilityd) In La Places Law, Tension = pressure X resistancee) As the preload pressure decreases and radius goes down so wall

tension is less, therefore heart does not need to push as hard

Treatment (cont)

B. Beta Blockersa) Decrease contractility therefore decrease

myocardial oxygen demand by decreasing wall tension

C. ACE- I

D. Lipid Lowering

E. Aspirin

Stunned and Hibernating Myocardium

A. Hibernating Myocardium1. Areas of myocardium supplied by severely stenosed

coronary arteries that over time develop impaired left ventricular contractility despite the presence of viable myocardium

2. Clinical importance is that if blood flow is improved to these areas, there is improvement in contractility, which is associated with something of heart failure symptoms, and improved survival

Stunned and Hibernating Myocardium (cont)

B. Stunned Myocardium1. Areas of myocardium that develop post

ischemic dysfunction in the absence of, or with minimal necrosis

2. Stunned is seen following acute myocardial infarction or repeat episodes of angina

Stunned and Hibernating Myocardium (cont)

C. Both stunned and hibernating are characterized by sever wall motion abnormalities in the presence of living or viable myocardium

D. Dysfunctional stunned myocardium is more acute and will regain function over time without intervention

E. Hibernating myocardium is more chronic and rigorous restoration of blood flow by revascularlization (CABG / PCTA with stenting) in order to restore contractility

Stunned and Hibernating Myocardium (cont)

F. Sunning can follow hibernation if the residual stenosis is sufficiently severe. If the area is necrotic, revascularization will not improve ventricular function.

The hypokinetic inferior and akinetic apical wall is shown to improve several months after revascularization

Bayes Theorum- Non-invasive Testing

• Predictability of a given test depends on the prevalence of the disease in the study population. Low likelihood, low probability, high likelihood, high probability. Therefore, routine testing on asymptomatic individuals without significant cardiac risk factors should be avoided, because such tests will result in more false positive than true positive. Diagnostic invasive testing is best applied to the group with an intermediate probability of coronary artery disease such as patients with multiple risk factors and atypical chest pain or patients with typical chest pain but no risk factors.

Who benefits from Diagnostic testing from this last graph?

• A Pt with a low pre-test probablity of disease will continue to have a low likelihood of disease regardless of a (-) test

• A Pt with a high pre-test probability of disease will continue to have a high likelihood of disease regardless of a (-) test

• Diagnostic testing is most beneficial for those Pt’s with intermediate probability for disease

Normal MIBI – uniform tracer uptake globally on SA slices

Normal VLA slices

Normal HLA slices of the same patient

Patient with Basilar Septal ischemia evidenced by decreased tracer uptake at STR with increased uptake at RST

Pt also has some apical thinning

With a completely reversible Septal wall toward the Anterior segments of the ventricle on HLA

Ischemia that is a result of Stress is dynamic with cascade of events, pain and ECG changes are seen late in the game

The Role of Diagnostic Testing

• Once the diagnosis of CAD has been made, or the patient has stable anginal symptoms, non-invasive testing remains useful in stratifying patients into high risk and low risk groups, monitoring changes in patient status and drug management.

Nuclear Imaging

• The value of nuclear perfusion imaging using Thallium or Sestamibi (Technetium), has been established for over 20 years. In comparison to exercise treadmill testing, perfusion imaging is more sensitive and provides better localization and identification of multi-vessel disease. Technically adequate studies are obtained in nearly all patients.

Sudden Cardiac Death in Ischemic HD

• A. Between 300,000-400,00 deaths per year.• B. Accounts for 50% of all US cardiac deaths and

approximately 25% of natural deaths.• C. Cardiac arrest may be first manifestation in many

patients with CAD and ½ of all sudden deaths occur in patients without a prior history of ischemic heart disease.

• D. Other causes of sudden death– 1.Dilated or hypertrophic cardiomyopathy-10-15%– 2. Valvular heart disease-5%– 3. WPW, long QT syndrome, and idiopathic V-fib

Sudden Cardiac Death-Treatment

• A. Beta-blockers

• B. ACE-Inhibitors

• C. Anti-arrhythmics- Amiodarone

• D. Implantable Cardioverter Defibrillator- most effective tool at reducing incidence of sudden death (MADIT trial)

• E. Revascularization to decrease ischemia

Moral of story is to revascular for the greatest

reduction in long term mortality

Patient has significant multivessel disease – MIBI reveals a inferior wall infarction with septal and anterior wall ischemia. Areas of the inferoseptal walls may also reveal some peri-infarct ischemia

Medical Management of Chronic Ischemic Heart Disease

• In the U.S., more than 6 million Americans have a history of CAD and an estimated 11 million are affected in some degree with coronary plaque formation.

• Most important factor in Myocardial Oxygen demand is Heart Rate

• 2nd Most important factor is Left Ventricular Wall Tension– LVWT is related to mean pressure during systole, LV volume and contractility

– Inc. LVWT = Inc resistance to coronary flow with concomitant Inc. in O2 demand

Silent Ischemia

• A. 30-40% of patients with myocardial ischemia due to CAD are asymptomatic, they do not experience ischemic cardiac symptoms.

• B. Risk of MI and sudden death as great as those experiencing symptoms (angina).

• C. Evaluation includes– 1. Exercise testing– 2. Ambulatory ST segment monitoring– 3. Other non-invasive studies

Cont’d

• D. Incidence post infarction approximately 30%.

• E. Treatment similar to patients with symptoms.

Hint: know thisTrinitrogylcerin and Isosorbide are directly active as -ONO2. -ONO2 is then converted to nitric oxide which acts both pre and post synaptically to vasodilate

Treatment of Ischemic HD

• A. Nitrates• B. B-blockers• C. Ca-channel blockers• D. Platelet inhibitors

– 1.ASA-50-500mg– 2. Clopidogrel- ASA intolerant– 3. High dose ASA greater than 1000mg may

not result in platelet inhibition

Cont’d

• E. Lipid lowering agents– 1.reduce LDL to less than 100– 2.HDL should be more than 40– 3.TG should be less than 150– 4.Agents (Statins, Fibrates, Resins and Niacin)– 5. Particle size and density important, large

particles and decreased density more favorable

Cont’d

• F. ACE inhibition• G. Questionable ARB• H. Folic Acid- protective against CAD in

patients whose homocysteine levels are elevated– 1.For high homocysteine levels, 1mg folic acid,

if can not reduce, then add pyridoxine 200mg daily plus Vit B12 500mg IM for 5 days then 500mg monthly thereafter.

Cont’d

• I. Reduction of body weight• J. Control diabetes• K. Stop smoking• L. Diet low in saturated fats with addition of

antioxidants Vit C and E and flavinoids is recommended, add fiber to diet (25g)

• M. Control BP• N. Red wine should be considered non alcohol grape

juice products may be beneficial as well• O. Exercise