Acute coronary syndrome : Pathophysiology

 ACS – is a continuum disease process. Patients with acute coronary syndromes have some degree of coronary artery occlusion. The degree of occlusion defines whether the acute coronary syndrome is: -Unstable angina -non-Q-wave /non-ST segment elevation MI -only the inner layer of myocardium is damaged.  -Q-wave / ST segment elevation MI -all layers of myocardium is damaged.

 Angina - is a subjective experience of chest discomfort resulting from an imbalance oxygen supply and demand.

4 Classifications of Angina:  1.) Stable – predictablepan, in frequency and duration, which can be relieved with nitrates and rest.  2.) Unstable – increased pain, which s easily induced. Occurs even at rest, relieved by rest and /or nitroglycerin.  3.) Prinzmetal or variant – pain from unpredictable coronary artery spasm.  4.) Microvascular or x sndrome – angina-like chest pain due to imparement of vasodilator reserve in a patient with normal coronary arteries.

ACS Pathophysiology

Pathophysiology  The development of any acute coronary syndromes begins with a rupture or erosion of plaque – an unstable and lipid rich substance. The rupture results in platelet adhesions, fibrin clot formation, and activation of thrombin.  ACS most commonly results when a thrombus partially occludes the blood flow.

Distal embolisation of a platelet-rich thrombus causing occlusion of intramyocardial arteriole (arrow). Such an event may result in micro-infarction and elevation of markers of myocardial necrosis.

What Causes It:  Family history of heart disease  Obesity  Smoking  High-fat, high-carbohydrate diet  Sedentary lifestyle  Menopause  Stress  Diabetes  Hypertension  Hyperlipoproteinemia

Risk Factors  Most common in men, specially those older than 50 years  Also in postmenoposal women – due to lack of estrogen that made them prone to atherosclerotic disease, whereby the coronary arteries lose their ability to dilate and to increase blood flow.

What to look for:  Burning  Squeezing  Crushing tightness in the substernal or precordial chest that may radiate to the left arm neck, jaw, or shoulder blade.

Goal of Treatment in Angina  To reduce myocardial oxygen demand or increase oxygen supply. MEDS: Nitrates – reduce myocardial oxygen consumption. Anti Platelet drugs – to minimized platelet aggregation. Antilipemic drugs – can reduce elevated serum cholesterol. Obstruction lesions – CABG and PTCA

Electrocardiogram of a 48 year old woman with unstable angina (top). Note the acute ischaemic changes in leads V1 to V5 (arrows). Coronary angiography revealed a severe mid-left anterior descending coronary artery stenosis (arrow, bottom left), which was successfully stented (bottom right)

Right coronary artery angiogram in patient with non-ST segment elevation myocardial infarction (top left), showing hazy appearance of intraluminal thrombus overlying a severe stenosis (arrow). Abciximab was given before direct stenting (top right), with good angiographic outcome (bottom)

Myocardial Infarction (MI):  Is a sever, persistent chest pain that isn’t relieved by rest or nitroglycerin.  Pain is describe as crushing or squeezing  Usually substernal, but may radiate to the left arm, jaw, neck, or shoulder blade.

Goal of Treatment in MI  To relieve pain, stabilized heart rhythm, revascularized the coronary artery, preserve myocardial tissue, and reduce cardiac workload. MEDS: Thrombolytic theraphy – which should be given 6 hours or less before the onset of pain otherwise it will be useless. To be able to dissolve clots it should be a new clot not a clot that is already formed. It is contra indicated to if the pain started more than 6 hours ago because there is no benefit at all in giving the medication and it can only increase bleeding.

 PTCA – is an option for opening blocked or narrowed arteries.  Oxygen – to increase oxygenation of the blood.  Nitroglycerin – administered sublingually to relieve chest pain,  Morphine – administered as analgesia.  Aspirin – administered to inhibit platelet agregation.  Lidocaine – may be used if arrhythmias are present.  Physical activity is limited for the first 12 hours – to reduce cardiac work load. A patient with acute MI is permitted to perform activities that require minimal effort such as bathroom privileges and self care routines. Unsupervised ambulation in the hall is not promoted instead, strict supervision is necessary. Not all activities are allowed to be performed by the patient even if it is supervised since they may not be appropriate given the condition of the patient.

 Provide a clear liquid diet – anticipate order for low-cholesterol, low sodium diet without caffeine.  Provide stool softener – to prevent straining during defecation.

The TIMI risk score Used in Identifying higher risk patients By: Antman and colleagues Rates of death from all causes and non-fatal myocardial infarction at 14 days, by TIMI risk score. Note sharp rate increase when score ≥ 3

Simplified management pathway for patients with unstable angina or non-ST segment elevation myocardial infarction

TIMI risk score 1 point each for presence of :  Age > 65 years  Documented prior coronary artery stenosis > 50%  Three or more conventional cardiac risk factors (e.g. age, sex, family history, hyperlipidemia, diabetes, smoking, obesity)  Use of aspirin in the preceding 7 days  Two or more anginal events in the preceding 24h  ST-segment deviation (transient elevation or persistent depression)  Increased cardiac biomarkers Score 5 – 7 : high risk Score 3 – 4 : intermediate risk Score 0 – 2 : low risk (Pollack et al, 2003)

The perfect marker  Marker for myocardial necrosis, and also for cardiac ischemia  Linear relationship between blood levels and extent of myocardial injury (and prognosis)  100% sensitive  100% specific  Immediate increase (+ constant blood level for hours to days)  Test kits : reliable, rapid, universally available and inexpensive

What about troponin T and I ?  Very high sensitivity for myocardial necrosis  Related to prognosis  Not 100% specific for atherosclerotic coronary artery disease myocarditis, cardiomyopathy, myocardial contusion,... renal failure, auto-immune diseases,...)  Up to 6 hours before raised blood levels no early MI diagnosis possible  Raised blood levels for many days troublesome diagnosis of re-infarction BUT

Role for myoglobin ?  Initial elevation : 1 to 4h after onset better early marker than troponins BUT : early myoglobin is less sensitive and less specific (due to skeletal muscle trauma) than late troponin decisions mainly based on clinical skills, ECG and late troponin (except rarely for reperfusion therapy)  Duration of elevation : 24 – 48h useful for re-infarction diagnosis

Role for CK-MB ?  Initial elevation comparable with troponins  Less sensitive than troponins  High specificity (comparable with troponins)  Rapid rise and fall (instead of gradual fall for troponins) allowing more accurate estimation of MI extent