ISCHEMIC HEART DISEASE

ISCHEMIC HEART DISEASE

1. Ischemic Heart Disease

2. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

3. INTRODUCTION TO IHD Ischemic heart disease (IHD) represents a group of pathophysiologically related syndromes resulting from myocardial ischemia — an imbalance between myocardial perfusion and cardiac demand for oxygenated blood. Ischemia limits tissue oxygenation (and therefore ATP generation) as well as availability of nutrients and removal of metabolic wastes . >90% myocardial ischemia results from reduced blood flow due to obstructive atherosclerotic lesions in the EPICARDIAL CORONARY ARTERY. IHD usually is synonymous with coronary artery disease (CAD).

4. Causes of IHD The syndromes of IHD are the late manifestations of coronary atherosclerosis (beginning even in childhood or adolescence). 90% 10% Coronary emboli , Myocardial vessel inflammation , Vascular spasm , Conditions where otherwise modest vascular occlusions may become consequential Myocardial hypertrophy , Tachycardia Hypoxem ia, and Systemic hypotension (e.g., shock).

5. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

6. Atherosclerosis of Epicardial coronary artery Progressive narrowing of lumen Stenosis “FIXED OBSTRUCTION” Acute plaque erosion or rupture THROMBOSIS Compromises blood flow >70% occlusion Significant CAD (precipitated by exercise) -90% occlusion Significant CAD even at rest. STABLE ATHEROSCLEROTIC PLAQUE

7. STABLE ATHEROSCLEROTIC PLAQUE Unpredictable and abrupt conversion to Rupture, or Superficial erosion, or Ulceration, or Fissuring, or Deep Hemorrhage Partially life threatening ATHEROTHROMBOTIC plaque SUPERIMPOSED THROMBUS Partially or Completely occludes the artery IHD

8. Ischemic Heart Disease No plaque disruption STABLE ANGINA Plaque disruption Thrombosis +/- Vasoconstriction +/- Emboli UNSTABLE ANGINA Acute Plaque Changes Abrupt Thrombotic Occlusion Myocardial Necrosis MI Regional myocardial ischemia Fatal Ventricular Arrhythmia SUDDEN CARDIAC DEATH

9. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

10. ANGINA PECTORIS (Chest Pain) Angina pectoris is characterized by paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort caused by transient ( 15 seconds to 15 minutes ) myocardial ischemia that is insufficient to induce myocyte necrosis. The pain is described as constricting , squeezing , choking , or knifelike . - probably is a consequence of the ischemia-induced release of adenosine , bradykinin , and other molecules that stimulate the vagal and afferent nerves .

11. STABLE ANGINA ‘ Typical Angina Pectoris ’. MC form. It is caused by an imbalance in coronary perfusion (due to chronic stenosing coronary atherosclerosis) relative to myocardial demand , such as that produced by physical activity , emotional excitement , or any other cause of increased cardiac workload . Usually relieved by rest (which decreases demand) or administering nitroglycerin , a strong vasodilator (which increases perfusion).

12. PRINZMETAL VARIANT ANGINA uncommon from of episodic myocardial ischemia - caused by coronary artery spasm . May have significant coronary atherosclerosis, but the anginal attacks are unrelated to physical activity, heart rate, or blood pressure. Can be triggered by alcohol , iced drinks , atrial pacing , cocaine , nicotine and hyperventilation . Responds promptly to vasodilators , such as nitroglycerin and calcium channel blockers .

13. UNSTABLE ANGINA “ Crescendo Angina ”. Pattern of increasingly frequent pain , often of prolonged duration, that is precipitated by progressively lower levels of physical activity or that even occurs at rest . Caused by the disruption of an atherosclerotic plaque with superimposed partial (mural) thrombosis and possibly embolization or vasospasm (or both). Unstable angina serves for imminent MI – “ Preinfarction Angina ” .

14. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

15. MYOCARDIAL INFARCTION “ heart attack ,” Due to necrosis of heart muscle resulting from ischemia . It is a diseased condition which is caused by reduced blood flow in a coronary artery due to atherosclerosis and occlusion of an artery by an embolus or thrombus . It is one of the major causes of emergency medical conditions worldwide.

16. EPIDEMIOLOGY Women tend to be remarkably protected against MI during their reproductive years. Menopause — with declining estrogen production — is associated with exacerbation of coronary artery disease. Therefore, IHD is the most common cause of death in elderly women .

17. ETIOLOGY AND RISK FACTORS Smoking Lack of Exercise Job Stress Dietary Saturated Fat Diet Family h/o IHD DM HTN LDL HDL TG Obesity

18. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

19. PATHOGENESIS Biochemical changes Ultrastructural Changes

20. CORONARY ARTERY OCCLUSION :

21. BIOCHEMICAL CHANGES Cessation of aerobic metabolism (within seconds). Onset of ATP depletion (within seconds) To 50% of N in 10 minutes. To 10% of N in 40 minutes. Accumulation of noxious metabolites ( eg. Lactic Acid). Myocardial contractility ceases within a minute. ULTRASTRUCTURAL CHANGES Myofibrillar relaxation. Glycogen depletion. Cell & Mitochondrial swelling Develop within a few minutes (Reversible) Irreversible Severe Ischemia (Blood flow is 10% of N) >20-40 mins. Myocyte Necrosis MYOCARDIAL RESPONSE TO ISCHEMIA:

22. ULTRASTRUCTURAL CHANGES Capillary Irreversible injured myocyte Mitochondrial swelling

23. location, size, and morphologic features of an acute MI Extent of collateral supply The presence, site, and severity of coronary arterial spasm

24. LAD – Left Anterior Descending Artery ~ 40-50% cases ARTERY ZONE OF PERFUSION RCA – Right Coronary Artery ~ 30-40% cases LCX – Left Circumflex Artery ~ 15-20% cases

25. Inner 1/3 rd gets affected first (farthest) If blood supply is restored – Outer 2/3 rd gets reperfused . “ SUBENDOCARDIAL INFARCT ” Other causes: Severe Atherosclerosis Hypotension Shock superimposed on coronary stenosis. After 3-6 hours Zone of necrosis extends through the entire wall thickness. “ TRANSMURAL INFARCT ”

26. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

27. MORPHOLOGICAL CHANGES Nearly all transmural infarcts affect at least a portion of the left ventricle and/or interventricular septum. 15% to 30% of MIs that involve the posterior or posteroseptal wall also extend into the right ventricle. Isolated right ventricle infarcts occur in only 1% to 3% of cases. Myocardial infarcts less than 12 hours old usually are not grossly apparent. Infarcts more than 3 hours old can be visualized by exposing myocardium to vital stains, such as triphenyltetrazolium chloride , a substrate for lactate dehydrogenase. By 12 to 24 hours after MI, an infarct usually can be grossly identified by a red-blue discoloration caused by stagnated, trapped blood. Thereafter, infarcts become progressively better delineated as soft, yellow-tan areas; by 10 to 14 days , infarcts are rimmed by hyperemic (highly vascularized) granulation tissue. Over the succeeding weeks, the infarcted tissue evolves to a fibrous scar .

28. Acute myocardial infarct , predominantly of the posterolateral left ventricle, demonstrated histochemically by a lack of staining by triphenyltetrazolium chloride in areas of necrosis (arrow) . Note the myocardial hemorrhage at one edge of the infarct that was associated with cardiac rupture, and the anterior scar (arrowhead) , indicative of old infarct .

29. The microscopic appearance also undergoes a characteristic sequence of changes: Typical features of coagulative necrosis become detectable within 4 to 12 hours of infarction. “Wavy fibers ” also can be present at the edges of an infarct reflecting the stretching and buckling of noncontractile dead fibers . Sublethal ischemia can also induce intracellular myocyte vacuolization . Necrotic myocardium elicits acute inflammation (typically most prominent 1 to 3 days after MI), followed by a wave of macrophages that remove necrotic myocytes and neutrophil fragments (most pronounced by 5 to 10 days after MI). The infarcted zone is progressively replaced by granulation tissue (most prominent 1 to 2 weeks after MI), which in turn forms the provisional scaffolding upon which dense collagenous scar forms. In most instances, scarring is well advanced by the end of the sixth week . Healing requires the migration of inflammatory cells and ingrowth of new vessels from the infarct margins. Thus, an MI heals from its borders toward the centre , and a large infarct may not heal as fast or as completely as a small one .

30. Microscopic features of myocardial infarction and its repair A , One-day-old infarct showing coagulative necrosis and wavy fibers (elongated and narrow, as compared with adjacent normal fibers at right ). Widened spaces between the dead fibers contain edema fluid and scattered neutrophils . B , Dense polymorphonuclear leukocytic infiltrate in area of acute myocardial infarction of 3 to 4 days ' duration. C , Nearly complete removal of necrotic myocytes by phagocytosis (approximately 7 to 10 days ). D , Granulation tissue characterized by loose collagen and abundant capillaries. E , Well-healed myocardial infarct with replacement of the necrotic fibers by dense collagenous scar. A few residual cardiac muscle cells are present.

31. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

32. SYMPTOMS Light-headedness Palpitation Anxiety Insomnia Hyper/hypertension Arrhythmias Chest pain Dyspnoea Fatigue Increased sweating Weakness Nausea Vomiting

33. COMPLICATIONS Contractile dysfunction. Papillary muscle dysfunction Right ventricular infarction. Myocardial rupture. Congestive heart failure Cardiogenic shock Arrhythmias Pericarditis Rupture Chamber dilation. Mural thrombus Thromboembolism Ventricular aneurysm Cardiac(Ventricular)Aneurysm

34. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

35. CHRONIC ISCHEMIC HEART DISEASE Chronic IHD, also called ischemic cardiomyopathy , is essentially progressive heart failure secondary to ischemic myocardial damage. In most instances, there is a history of previous MI . In this setting, chronic IHD appears when the compensatory mechanisms (e.g., hypertrophy) of residual viable myocardium begin to fail . In other cases , severe obstructive CAD can cause diffuse myocardial dysfunction without frank infarction. Clinical Features : Severe, progressive heart failure characterizes chronic IHD Occasionally punctuated by new episodes of angina or infarction. Arrhythmias, CHF, and intercurrent MI account for most of the associated morbidity and mortality.

36. MORPHOLOGY: Patients with chronic IHD typically exhibit left ventricular dilation and hypertrophy , often with discrete areas of gray -white scarring from previous healed infarcts. There is moderate to severe atherosclerosis of the coronary arteries, sometimes with total occlusion. The endocardium generally shows patchy, fibrous thickening and mural thrombi may be present. Microscopic findings include myocardial hypertrophy , diffuse sub-endocardial myocyte vacuolization , and fibrosis from previous infarction.

37. ISCHEMIC HEART DISEASE Introduction Pathogenesis ANGINA PECTORIS MYOCARDIAL INFARCTION Introduction Epidemiology Etiologies and Risk factors Pathogenesis Morphological changes Symptoms Complications CHRONIC IHD DIAGNOSIS

38. DIAGNOSIS

39. Cardiac Biomarkers The laboratory evaluation of MI is based on measuring blood levels of macromolecules that leak out of injured myocardial cells through damaged cell membranes Myoglobin Cardiac troponins T and I ( TnT , TnI ) Creatine kinase (CK) (specifically the myocardial isoform, CK-MB) Lactate dehydrogenase

40. Troponins and CK-MB have high specificity and sensitivity for myocardial damage. Total CK activity is not a reliable marker of cardiac injury since various isoforms of CK are also found in brain , myocardium , and skeletal muscle . CK-MB isoform —principally derived from myocardium , but also present at low levels in skeletal muscle—is the more specific indicator of heart damage . TnI and TnT normally are not found in the circulation; however, detectable after acute MI. Cardiac troponin and CK-MB are equally sensitive markers of the early stages of an MI , persistence of elevated troponin levels for approximately 10 days allows the diagnosis of an acute MI long after CK-MB levels have returned to normal. With reperfusion , both troponin and CK-MB levels may peak earlier owing to more rapid washout of the enzyme from the necrotic tissue.

41. Protein elevation in serum after MI Serum Protein 1st elevation (hours) Peak elevation (hours) Duration of elevation (days) AST/SGOT 2-4 2-4 3 (2-3x normal only) LDH 2-4 6-9 1 CK 4-6 18-36 3 (2-3xnormal only) CKMB 2-4 24 3 (2-3xnormal only) Myoglobin 2-3 6-9 1 Troponin I and T 4-6 24-36 Trop I 7-10 Trop T 10-14

42. Other markers

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