Angina Pectoris

CAD Coronary Artery Disease / Coronary Atherosclerotic Heart Disease

Yang HaiBo MD Department of cardiology, 1st affiliated hospital of ZZU

types of CAD asymptomatic ischemia angina pectoris myocardial infarction ischemic cardiomyopathy sudden cardiac death

Stable angina pectoris

Angina Pectoris (AP)

Myocardial Infarction (MI)

Unstable angina pectoris (UAP) ST segment Elevation Myocardial Infarction (STEMI) Non-ST segment Elevation Myocardial Infarction (NSTEMI)

Acute Coronary Syndrome( ACS)

stable AP

epidemiology

of ischemic heart disease

*6,750,000 Americans with angina pectoris

*350,000 new cases occur each year *prevalence of angina pectoris in elderly men : 21.1% (65 ~ 69 yrs) to 27.3% (80 ~ 84 yrs) women : 13.7% (65 ~ 69 yrs) and 24.7%(≥85 yrs).

Etiology of ischemic heart disease *Atherosclerosis :the most common cause *Coronary spasm *Coronary thrombi *Coronary emboli *Ventricular hypertrophy *Aortic stenosis *Oxygen-carrying capacity ↓:carboxyhemoglobin 、 anemia

*…….

Pathophysiology

of ischemic heart disease

Could relax correspond to the demand↑ of oxygen oxygen supply / demand balance maintained

Fixed when the oxygen demand increased→ imbalance between myocardium oxygen supply/demand→ symptoms and signs of ischemia

Pathophysiology

of ischemic heart disease

cardiac ischemic pain arise from sensory afferents located in the coronary vessels and myocardium sensitive to stretch and irritation by local noxious chemical stimuli

Pathophysiology

of ischemic heart disease

provoking factors

alleviating factors

mental stress physical stress cold air

↑ preload ↓ constriction periferal artery relax ↑ myocardium contractivity ↓

lying down

↑ heart rate ↓ ↑ BP ↓

↓

supply

↑ demand

angina

Angina relief

Oxygen demand=BPs×HR

supply ↑ demand ↓

Symptom angina pectoris

angina pectoris(AP) Definition

a syndrome due to transient myocardial ischemia, characterized by chest discomfort, radiate to the back, neck, jaw,teeth& epigastrium, usually caused by exertion & emotion , last several minutes and relieved by rest or nitrates, mostly the etiology is CAD

◆ character ◆ location and duration ◆ provoking or exacerbating factors ◆ alleviating factors

First Description of Angina Those who are afflicted with it are seized while they are walking (more especially if it be uphill, and soon after eating), with a painful and most disagreeable sensation in the breast, which seems as if it would extinguish life, if it were to increase or to continue; but the moment they stand still, all this uneasiness vanishes.This elegant description by William Heberden first published 225 years ago eloquently captures the symptomatic characteristics of angina pectoris. It is a common and important symptom affecting many patients with coronary artery disease. Heberden W. Classics of Cardiology. Dover Publications, 1941; I:221.

Angina is unpleasant sensation, usually not pain The unpleasant sensation is more typically characterized as a pressure or tightness, a heaviness 、 squeezing or burning Most patients with true angina do not use this term to describe their sensation. The pressure is not perceived by the patient as pain such that the interviewer who specifically asks about pain may be misled

CHARACTERISTICS OF TYPICAL AND ATYPICAL ANGINA PECTORIS

Typical • Substernal ,Characterized by a heavy, squeezing or burning feeling • Precipitated by exertion or emotion • Promptly relieved by rest or nitroglycerin Atypical • Located in the left chest, abdomen, back, or arm in the absence of mid-chest pain • Sharp or fleeting • Repeated, very prolonged • Unrelated to exercise • Not relieved by rest or nitroglycerin • Relieved by antacids • Characterized by palpitations without chest pain.

The usual distribution is referral to all or part of the sternal region, the left side of the chest, and the neck and down the ulnar side of the left forearm and hand. With severe ischemic pain, the right chest and right arm are often involved as well, although isolated involvement of these areas is rare. Other sites sometimes involved, either alone or together with other sites, are the jaw, epigastrium, and back.

Provoking &Exacerbating

Factors Classic Precipitation:

exercise & emotional stress Other Precipitants: high pressure meeting stressful emotional incident cold weather activity heavy meals lying down (at times )←venous return↑

Alleviating Factors *Cessation of activity *Sublingual nitroglycerin--nonspecific *Getting out of the cold *Completing the uphill walk In Summary :cessation a factor that increase cardiacofoxygen demand

Signs during Angina *Softening of the S1- result of ischemic left ventricular dysfunction

*Paradoxical splitting of the S2-related to asynergy and prolongation of left ventricular contraction results in delayed closure of the aortic valve

*S3 & S4-result of ischemic left ventricular dysfunction *Transient apical systolic murmursattributed to reversible papillary muscle dysfunction secondary to transient myocardial ischemia

Diagnostic Tests X-ray ECG Echocardiography Nuclear imaging techniques Coronary angiography(CAG)

Diagnostic Tests:X-ray Usually normal ……

Diagnostic Tests:ECG Rest ECG Captured during an episode Exercise ECG Ambulatory Holter monitoring

Diagnostic Tests: Rest ECG ECG at rest may commonly be normal in pts with AP. In the Rochester, Minnesota, area, 59% of the 1154 individuals presenting with chest pain were found to have normal resting ECGs (Mayo Clin Proc 1984; 59:247)

Useful to seek evidence of prior MI and persisting ST↓, which portending an unfavourable prognosis T-wave change, intraventricular conduction defects, and atrial abnormalities may also be evident

Diagnostic Tests :

ECG captured during an episode Transient ischemic ST segment depression T wave inversion T wave pseudonormalization ST segment elevation: Variant angina

Diagnostic Tests:Exercise ECG

TREADMILL

STATIONARY BIKE

Diagnostic Tests:Exercise ECG Cornerstone of diagnostic testing for SAP It should be performed prior to moving toward more detailed, costly or invasive procedures

There are at least four important potential objectives that may be achieved by conducting this test: Correlation of patient symptoms with the presence of ischemia Definition of risk of future events To provide the patient with an exercise prescription To evaluate the efficacy of pharmacologic & revascularization therapy

Diagnostic Tests:Exercise ECG Indications: To determine the likelihood of coronary disease To assess the likelihood of anatomic or functionally severe disease that may be of prognostic importance To determine functional capacity To assess the effects of therapy

Diagnostic Tests:Exercise ECG Clinical Contraindications:(to be continued) Acute myocardial infarction Unstable angina prior to a period of stabilization Uncompensated severe CHF Advanced AVB or life threatening arrhythmias Acute myocarditis or pericarditis Severe aortic stenosis Severe resting hypertension& any medical condition that precludes the patient from being able to walk safely on the treadmill

Diagnostic Tests:Exercise ECG Clinical contraindications:(continued) Left bundle branch block Left ventricular hypertrophy with strain Ventricular preexcitation (WPW syndrome) Permanent ventricular pacing on the ECG (due to the uncertain diagnostic value of additional ST segment changes in these settings, but do not preclude use of the ETT to assess exercise performance or evaluate the risk of arrhythmia when indicated)

Diagnostic Tests:Exercise ECG Criteria: Point : 60ms after J point

Criteria : >0.1mV ST depression

ST

Slowly upsloping

ST

Downsloping

specific ST

Horizontal

STSegment Depression

Diagnostic Tests:Echocardiography Left ventricular (LV) evaluation is probably the single most important *overall systolic function *regional wall motion *ventricular mass *geometry

Diagnostic Tests:Exercise ECT Nuclear imaging techniques

transverse

sagittal

coronal

TL201 SPECT stress & delayed images

Exercise perfusion imaging incorporates all the components of the exercise ECG with images of myocardial blood flow by using either thallium-201 or a technetium-99m (99m Tc)-based perfusion tracer. The radionuclide is injected intravenously at peak exercise or at a symptom-limited endpoint, patient is encouraged to exercise for another 30 to 45 seconds to ensure that initial myocardial uptake of the tracer reflects the perfusion pattern at peak stress. Acquisition of the stress images is performed several minutes later when the patient is at rest. A separate image acquisition is obtained at rest to compare the stress images with images of resting perfusion. Reversible perfusion defects between stress and rest indicate exercise-induced ischemia, whereas irreversible defects usually represent regions of myocardial fibrosis

Diagnostic Tests: CAG coronary angiography : gold criteria

Differential Diagnosis

Causes of chest discomfort and pain

Cardiac

Noncardiac

Angina Acute myocardial infarction Aortic dissection Pericarditis

Esophagitis, esophageal spasm, or reflex Peptic ulcer

Myocarditis Mitral valve prolapse

Gall bladder disease Musculoskeletal including osteochondritis cervical disc, thoracic outlet syndrome Hyperventilation Anxiety Psychogenic Pneumonia Pulmonary embolus Pneumothorax Pulmonary hypertension

The key to determining whether the discomfort is cardiac is to review its: ◆ character ◆ location and duration ◆ provoking or exacerbating factors, and ◆ alleviating factors

Diagnosis

Angina Grades Canadian Cardiovascular Society grading scale Class I

experience angina only with strenuous or

protracted physical activity Class II experience only slight limitation with vigorous physical activity such as walking up a hill briskly Class III have marked limitation, with symptoms during the activities of everyday living Class IV have the inability to perform the activities of daily living because of symptoms as well as angina that may occur at rest Although this classification has some virtue it also has limitations, as recently highlighted; hence, it does not address changes in the pattern or frequency of angina or take into account the warm-up effect or the self-imposed alteration in activities of daily living that may subtly modify symptomatic status

angina pectoris stable ischemia syndrome

stable AP: symptom charactors fixed 1~3m silent ischemia syndrome X

unstable AP

initial onset AP : history<1m or… accelerated AP :worsen in 3 m angina decubitus Prinzmetal variant angina post infarction AP : in 1 m post AMI

Treatment of Stable Angina Pectoris

Principle of Management relief of symptom reduction of risk to future untoward events known to develop, i.e., UAP, MI & Death retarding or halting the progression of underlying atherosclerosis

Medical Therapy--aspirin enteric-coated aspirin, 75 to 325 mg per day produces a sustained functional defect in the platelet associated with prolongation of the bleeding time

arachidonic acid cyclo-oxygenase← inhibition (aspirin)

thromboxane A2(TXA2) (the key modulator of irreversible platelet aggregation)

Medical Therapy:Nitrates Reduce preload Reduce afterload Dilate epicardial coronary Nitric oxide (NO)

Frishman WH: Pharmacology of the nitrates in angina pectoris. Am J Cardiol 56:8I, 1985.

Medical Therapy :Nitrates Nitrate dosing*

Formulation?

Dose

Frequency

Onset/duration action

Sublingual tablet GTN

0.3~.6 mg

As required

2 min/20~30 min

Sublingual tablet ISDN

2.5~10 mg

As required

5~10 min/1?~2h

Oral spray GTN

0.4-mg metered dose

As required

2 min/20~30 min

Oral GTN SR

2.6 mg 2.6.5.2

Three times a day

2~5 min/3~5h

Buccal tablet GTN

1, 2, 3, and 5 mg

Two or three times a day

2~5 h/3~5 h

Oral ISDN

10~30mg

Two or three times a day

15 min/4~6h

Oral ISDN SR

80~120 mg

Daily

60 min/10~12 h

Oral IS-5-MN

20 mg

Twice a day

30 min/5~7h

Oral IS-5-MN SR

60~240 mg

Daily

60 min/10~14 h

GTN ointment 2%

0.5~2”

Twice a day

15 min/8 h

Transdermal GTN patch

0.2~.8 mg/h*

Daily

30 min/12~24h

* Adapted from Abrams J. Therapy of angina pectoris with long acting nitrates: Which agent and when. Can J Cardiol 1996; 12C:9C-16C. GTN indicates nitroglycerin;

ISDN, isosorbide Dinitrate;

IS-5-MN, isosorbide-5-mononitrate;

* A nitrate-free interval of at least 8 h per 24-h period should be provided to avoid tolerance.

and SR, sustained release.

Medical Therapy :Nitrates Principle side effects headache flushing lightheadness Occasionally side effects nitrates syncope Because: a rapid decline in systolic blood pressure in the upright position, associated with arterial dilatation and venous pooling.

Medical Therapy :ß-blocker Mechanism

Medical Therapy:

ß-blocker Pharmacology

classes of ß-receptors :ß -1 and ß -2

Cardioslectivity: nonselective: affect the heart, peripheral vasculature, bronchial tree, and modulation of hepatic and skeletal muscle glyconeogenesis ß -1 selective: (metoprolol and atenolol) tends to circumvent the undesirable consequences (constriction of the bronchial tree and arterial smooth muscle ) of nonselective b-blockade Selective b-1 blocker effects, however, are only relatively selective, and at increased doses these agents produce ß -2 blockade

Medical Therapy :ß-blocker Name (proprietary)

Property

Frequency

Propranolol (Inderal)

Nonselective

Twice a day

80-320

Daily

60-320

(Inderal LA)

Daily dose, mg

Nadolol (Corgard)

Nonselective

Daily

80-240

Timolol (Blocadren)

Nonselective

Twice a day

15-45

Metoprolol (Lopresor)

B1 selective

Twice a day

100-400

Daily

100-400

(Lopresor SR) Atenolol (Tenormin)

B1 selective

Daily

50-200

Acebutolol (Sectral)

B1 selective partial ISA

Twice a day

200-600

Pindolol (Visken)

Nonselective ISA

Twice a day

15-45

Three times a day (>30 mg total) Sotalol (Sotacor)*

Nonselective with type 3 Twice a day

160-480

antiarrhythmic effect * Sotalol is not approved for angina pectoris use.

ISA indicates intrinsic sympathomimetic activity.

Medical Therapy :ß-blocker Untoward effects of nonselective ß-blockade Coronary vasoconstriction : Prinzmetal variant angina× Peripheral circulatory vasoconstriction : Raynaud’s disease× Bronchial constriction: Asthma, COPD × ↓Response to hypoglycemia Impaired hepatic gluconeogenesis Impaired general awareness ↓Triglycerides/↓high-density lipoprotein cholesterol

Medical Therapy :Calcium-blocker When symptoms persist or side effects limit treatment with ß-blockers and/or nitrates, the use of calcium antagonists may provide significant additional relief. It has been suggested that a special niche for calcium antagonists resides with Prinzmetal’s variant angina patients .

Medical Therapy :Calcium-blocker Classification of calcium-blocker *Dihydropyridines nifedipine SR nifedipine longer-acting: felodipine amlodipine

*Diltilzem *Verapamil

Medical Therapy: Calcium-blocker provoking factors

alleviating factors

mental stress physical stress cold air

↑ preload ↓ constriction periferal artery relax ↑ myocardium contractivity ↓

lying down

↑ heart rate ↓ ↑ BP ↓

↓

supply

↑ demand

angina

angina relief

supply ↑ demand ↓

Medical Therapy :Calcium-blocker Calcium channel blockers: dosing and properties

Blockers*

Dose, mg/frequency

Nifedipine

30~120/three times a day

↑

→

↓↓

Nifedipine GITS

30~80/daily

→

→

↓↓

Diltiazem

30~90/three or four times a day

↓↓

↓

↓

Diltiazem SR

60~120/twice a day

↓↓

↓

↓

Verapamil

80~120/three or four times a day

↓

↓↓

↓

Verapamil SR

120~240/daily or twice a day

↓

↓↓

↓

Amlodipine

2.5~10/daily

↑

→

↓↓

Felodipine

5~20/daily

↑

→

↓↓

Nicardipine

10~20/three times a day

↑

→

↓↓

Isradipine

2.5~10

↑

→

↓↓

Bepridil

200~400/daily

↓

→↓

↓

* GITS indicates gastrointestinal system; SR, sustained release.

Heart rate

Atrioventricular

Blood pressure

Risk Assessment & Reduction Fundamental component of management

@dietary modification @ideal body weight (obesity) @reduces cholesterol and saturated fat @cessation of smoking @controlling elevated blood pressure and blood sugar @regular physical activity into a patient’s daily @HMG-Co A (hydroxy-methylglutaryl co-enzyme A ) reductase

big five risk factors atherosclerosis hypertension smoking diabetes hypercholesterolemia and family history

Risk Assessment & Reduction HMG-Co A reductase inhibitor

HMG-Co A (hydroxy-methylglutaryl co-enzyme A )reductase HMG-Co A reductase inhibitor (statin)

CH ↓25% LDL↓35% mortality ↓ ↓myocardial infarction ↓ ↓

Revascularization Catheter intervention PTCA STENTING …

CABG:coronary artery bypass graft

intracoronary

STENT

stent_webvsn.avi

Coronary artery bypass graft (CABG)

Approach to Patients with Chronic Stable Angina

1.Identify and treat precipitating factors, such as anemia, uncontrolled hypertension, thyrotoxicosis, tachyarrhythmias, uncontrolled congestive heart failure, and concomitant valvular heart disease. 2.Initiate risk factor modification, physical exercise, diet, and life style counseling. Initiate therapy with an HMG-CoA reductase inhibitor, as needed, to reduce LDL cholesterol below 100 mg/dl. 3.Initiate pharmacotherapy with aspirin and a beta blocker. Strongly consider an ACE inhibitor as first-line therapy in all patients with chronic CAD.

4.Use sublingual nitroglycerin for alleviation of symptoms and prophylactically.

5.If episodes occur more than two or three times per week, the next step is addition of a calcium antagonist or a long-acting nitrate via eccentric dosing schedules to prevent nitrate tolerance. The decision to add a calcium antagonist or a long-acting nitrate is not based entirely on the frequency and severity of symptoms. The need to treat concomitant hypertension or the presence of left ventricular dysfunction and symptoms of heart failure may be an indication for the use of one of these agents, even in patients in whom episodes of symptomatic angina are infrequent.

6.If angina persists despite two antianginal agents (a beta blocker with either a long-acting nitrate preparation or a calcium antagonist), add the third antianginal agent. 7.Coronary angiography, with a view to considering coronary revascularization, is indicated in patients with refractory symptoms or ischemia despite optimal medical therapy; it should also be carried out in patients with "high-risk" noninvasive test results and in those with occupations or life styles that require a more aggressive approach.