Ischemic heart disease
Imbalance between the myocardial blood flow and the metabolic demand of the myocardium Reduction in coronary blood flow is related to : Progressive atherosclerosis with increasing occlusion of coronary arteries. Vasospasm Thrombosis, or circulatory changes leading to hypoperfusion.
Clinical manifestations of IHD
Myocardial infarction: The duration and severity of ischemia is enough to cause necrosis of heart muscle Non infarct effects of myocardial ischemia: Angina pectoris Chronic IHD with heart failure Sudden cardiac death
ROLE OF CORONARY ATHEROSCLEROIS : Coronary atherosclerosis Chronic fixed obstruction Coronary AS with superadded changes “Acute plaque change” • Hemorrhage into atheroma • Rupture / fissuring – Exposing thrombogenic plaque • Erosion / ulceration – Exposing thrombogenic subendothelial basement membrane
Factors triggering acute plaque change…….
1. Adrenergic stimulation Physical stress Hypertension Local spasm 2. Structure and composition of plaque Dynamic Eccentric configuration Large core of necrotic debris macrophages Thin fibrous cap BREAKDOWN OF PLAQUE Metalloproteinases in macrophages High stress by flowing blood at junction of plaque and normal vessel wall
ROLE OF INFLAMMATION Important role in all stages, inception to complication Endothelial cells Secretion of ICAM1, VCAM1, E & P selectin Accumuln of T cells & macrophages in arterial wall Secretion of TNF, IL-6, IFN Activate endothelial cell and macrophage Metalloproteinases by macrophage Digest collagen in fibrous cap
Rupture of plaque Hence levels of CRP predict risk of AS dvlpt.
ROLE OF CORONARY THROMBUS NO thrombus --- STABLE Angina Non occlusive thrombus with thromboemboli ---- UNSTABLE Angina Occlusive thrombi ----TRANSMURAL MI Variable thrombi ----SUBENDOCARDIAL MI Thromboemboli ---- SUDDEN Death
ROLE OF VASOCONSTRICTION Compromises lumen size local mechanical forces Potentiates plaque disruption VASOCONSTRICTION STIMULATED BY Circulating adrenergic agonists Locally released platelet contents Endothelial dysfunction Impaired secretion of NO ( relaxing factor) Increased endothelin ( contracting factor)
Angina pectoris - a symptom complex of IHD characterized by paroxysmal attacks of chest pain, usually substernal or precordial, caused by myocardial ischemia that falls short of inducing infarction. There are several patterns: Stable angina Variant / Prinzmetal angina Unstable angina Sudden death
Stable angina :(typical) – Paroxysms of pain related to exertion Relieved by rest or vasodilators. Chronic stenosing AS Subendocardial ischemia ST-segment depression Variant or Prinzmetal's angina – Classically occurs at rest Reversible spasm in normal to severely atherosclerotic coronary arteries. Transmural ischemia ST-segment elevation
Unstable angina – (crescendo angina) Prolonged pain, at rest in stable angina patient, Or, worsening of pain in stable angina. Called “preinfarction angina”. Harbinger of MI Due to disrupted plaque + Thrombus + Embolisation +/- vasospasm Sudden cardiac death – Unexp death from cardiac causes usually within 1 hour after a cardiac event or without the onset of symptoms. Usually high-grade stenosis with acute coronary changes.
Incidence and risk factors
Incidence: with age. 45% : < 65yrs. Risk factors : Same predisposition as to atherosclerosis Hypertension Cigarette smoking Diabetes mellitus Genetic (hypercholesterolemia) Women : Protected during reproductive years. Postmenopausal Estrogen : Coronary artery disease.
The acute coronary syndromes
Myocardial infarction Unstable angina Sudden cardiac death
MYOCARDIAL INFARCTION (heart attack)
Leading cause of death in industrialized nations Death of cardiac muscle due to Irreversible ischemic injury. 2 types ; SUBENDOCARDIAL : Subendocardial myocytes most susceptible TRANSMURAL : A “ wave front” of cell death extends through the myocardium. More common.
Differences between subendocardial and transmural infarcts
SUBENDOCARDIAL Multifocal, patchy Circumferential; inner 1/3 or ½ of ventricular wall Coronary AS +/thrombus Often caused by shock
TRANSMURAL Unifocal, solid Follows arterial supply, usually full thickness Diffuse stenosing AS + BP Causes shock Global hypotension
Pathogenesis ( transmural MI)
CORONARY ARTERY OCCLUSION: Severe coronary atherosclerosis diffuse (involving more than one major arterial branch) segmental, typically involves proximal 2 cm of arteries (epicardial) C/S : Area of coronary artery lumen must be < 25% to significantly affect perfusion.
2. ACUTE PLAQUE CHANGE Hemorrhage Erosion Rupture Ulceration Fissure 3. SUPERIMPOSED PLATELET ACTIVATION 4. THROMBOSIS 5. VASOSPASM : Isolated Intense Prolonged
SEQUENCE OF EVENTS Initiating event Sudden change in the morphology of an atheromatous plaque:
Disruption of plaque
Platelets exposed to subendothelial collagen and necrotic plaque contents
Platelets : adhesion, aggregation, activation, release (TXA2, serotonin, platelet factors 3 ,4)
THROMBUS evolves, occludes lumen in mins….
Which plaques are vulnerable ?
Plaques with Large number of foam cells and extra cellular lipid Thin fibrous cap Few smooth muscle cells Clusters of inflammatory cells. These usually rupture at the junction of the fibrous cap with normal artery (maximum mechanical stress)
When are plaques vulnerable?
Adrenergic stimulation Causes systemic hypertension / vasospasm, puts stress on the plaque Causes circadian periodicity , of MI (6 am to 12 noon), when there is max platelet aggregation and rise in BP Intense emotional stress
of cases are due to atherosclerotic plaque disruption 10% of cases are due to Vasospasm Isolated, intense, prolonged. Emboli From LA in atrial fibrillation Left sided mural thrombus Paradoxical embolism from Rt side into systemic circulation) Unexplained
Arterial obstruction causes loss of blood supply to myocardium. Ischemia results in changes at 3 levels o Biochemical o Functional o Morphological
GLYCOLYSIS : Aerobic ceases : Anaerobic starts
high energy phosphates (Creatine phosphate, ATP)
Breakdown products ( Lactic acid )
Upto 20 mins: Reversible. After 20-40 mts : Irrevers. necrosis Prolonged ischemia : injury of microvasculature Coagulation necrosis is the main mechanism of cell death Myocardial contractility is lost in 60 seconds following ischemia
Onset of ATP depletion
Loss of contractility ATP reduced to 50% ATP reduced to 10% Irreversible cell injury Microvascular injury
Less than 2 mt 10 mt
20-40 mts More than 1 hr
Factors influencing development of infarction
Location, severity, rate of development of coronary atherosclerotic obstruction Size of vascular bed compromised Duration of occlusion Metabolic needs of myocardium at risk Extent of collateral vessels Presence, site, severity of vasospasm Other factors : Altern in BP, heart rate, cardiac rhythm
TRANSMURAL INFARCTS: Due to occlusion of
Involves ant wall of LV near apex Ant part of IV septum Apex (circumferentially)
LAD artery (40-50%)
RCA (30-40%) Inferior post wall of LV Post part of IV septum Inferior posterior wall of RV Left circumflex: Lateral wall of LV except apex
Figure 12-12, paage 574 robbins
“Area at risk”: Area supplied by occlud. artery Ischemia more pronounced in Subendocardium Diffusion of nutrients from lumen : Thin rim of subendocardial myocardium preserved SEQUENCE OF EVENTS ISCHEMIC COAGULATIVE NECROSIS
MORPHOLOGY OF A MYOCARDIAL INFARCT : GROSS
Infarct <12 hours : Not apparent grossly Visualised in 2-3 hours if triphenyl tetrazolium chloride used (TTC solution) Thin slice of myocardium dipped in TTC soln.
Non infarcted : Brick red Infarcted : pale, unstained (preserved dehydrogenase) ( depleted dehydrogenase)
GROSS…… 12 – 24 HOURS Red blue hue UPTO 10 DAYS Yellow tan soft 10 – 15 DAYS Rim of hyperemia IN WEEKS Fibrous scar MICROSCOPY Wavy fibres at periphery Coagulative necrosis Myocytolysis ( vacuolar degeneration of myocytes ) Inflammatory repsonse Granulation tissue Scarring
Evolution of morphological changes in MI
O-1/2 hrs ½ to 4 hr None none None
None, variable waviness at border Occasional dark Coagulation mottling necrosis, edema Dark mottling Coag necrosis, pyknosis, cbn
Contraction band necrosis
Mottling yellow tan centre
Coagulation necrosis, neutrophil infiltrate in interstitium
Myofibre disintegration, dying neutrophils, early phagocytosis at border Brisk phagocytosis of dead cells, early granulation at margins
Hyperemic border, central yellow tan softening 7-10 days Depressed red tan margins, max Yellow tan soft centre
3-4 days: dense polymorph infiltrate
7-10d, most myocytes removed by phagocytosis
Red grey depressed borders
More than 2 months
Well established granulation tissue Grey white scar. Increased Progresses collagen from border to deposition center Scarring Dense complete collagenous scar
Granulation tissue with loose collagen and abundant capillaries
Well healed infarct with replacement of necrotic fibres by scar.
Why does the infarct extend?
Thrombus (retrograde progression) Platelet –fibrin microemboli Impaired contractility (compromises blood flow) Arrhythmia: impairs contractility Vasospasm
Infarct and reperfusion
Restoration of coronary flow (reperfusion) is achieved rapidly by thrombolysis, balloon angioplasty, coronary arterial bypass graft This can cause: • Reperfusion induced arrhythmia • Myocardial hemorrhage • Irreversible injury (reperfusion injury) • Myocardial stunning (microvascular injury and prolonged ischemic dysfunction)
Complications of myocardial infarction
Depend on infarct size and extent Contractile dysfunction: LVF Pulmonary edema or “pump failure”
Cardiogenic shock Arrhythmias: Sinus bradycardia, tachycardia, ventricular fibrillation, heart block
Pericarditis: 2nd to 3rd day. Fibrinous / fibrinohemorrhagic RV infarction: Associated with LV infarct Infarct extension Infarct expansion: Weakened necrotic muscle
Stretching , thinning and dilatation of infarct. Predisposes to mural thrombus Mural thrombus Can cause thromboembolism
Ventricular aneurysm: False aneurysms Rupture
Hematoma ( Communicating with ventr. cavity Limited by a pericardial adhesion ) True aneurysm: Bound by ventricular wall. Can cause thrombosis, arrhythmia, heart failure.
Myocardial rupture : Cardiac rupture syndromes Rupture of ventricular wall In 3-7 days hemopericardium, cardiac tamponade Rupture of IV septum: Leads to left to right shunt Papillary muscle rupture : (least common) Leads to acute mitral regurgitation Papillary muscle dysfunction due to ischemia Progressive late heart failure
Ventricular wall rupture and hemopericardium
Typical symptom Precordial pain, Rapid weak pulse, Profuse sweating, Dyspnea. May be asymptomatic. “silent MI” characteristic of diabetics
1. Leucocytosis: neutrophilia, 2. High ESR (1st week) 3. ECG changes: ST elevation, Q waves in transmural infarct. 4. Serum CRP : Predictor of risk of MI.. > 3 mg/l : high risk -3 mg/l: moderate risk
5. SERUM ENZYMES
A. SGOT (AST): : few hours, peaks : 24 hours, : 48-72 hours. Nonspecific: present in RBC, Liver, Skl. muscle B. LDH (lactate dehydrogenase) : first day peaks : 3-4days :14-15 days LDH1 : Cardiac iso-enzyme , more specific. LDH1/LDH2 ratio reversed
C. Creatine kinase: composed of dimers M and B CK-MM : Skeletal muscle & heart CK-MB : Myocardium rises : 2-4 hr peaks : 24 hours declines : 48-72 hours
CK-BB : Brain and lung Total CK : 2-4 hr, peak in 24 hours, :72 hours. Non specific. Increases in skeletal muscle injury also
6. TROPONINS Proteins that regulate calcium mediated contraction of skeletal and cardiac muscle. Cardiac specific proteins : complete specificity & high sensitivity After MI, increased levels of : Troponin I (TnI) Troponin T (TnT) …….(Same as CK-MB) Levels elevated : up to 10 days , Hence, diagnosis possible even after CK-MB levels return to normal. Following chest pain, Unchanged levels of : CK and CK-MB : first 2 days Troponin : following days