The Heart -1 Updated for Spring 2008 Dr. Amitabha Basu MD

Topic Heart failure Ischemic heart disease

Congestive heart failure Def: reduced cardiac output to meet the demand. In many pathologic states, the onset of heart failure is preceded by cardiac hypertrophy. Pathogenesis: flow chart next slide.

+ Flow chat Increased work load, MI, pressure/ volume overload ↓ re-expression of embryonic/fetal type of protein (β-myosin heavy chain) + Reduced capillary density → reduced oxygen supply Heart failure These re-expression of embryonic/fetal type are associated with myocardial hypertrophy.

Congestive heart failure So, it is long term process. Clinical: similar to RHF Often progress from the underling diseases like Hypertension Cor-pulmonale Valvular disease Multiple MI

Morphology of congestive heart failure Concentric hypertrophy Pressure over load Caused By: hypertension Narrow chamber and thick wall Eccentric hypertrophy Volume over load. Caused by valve regurgitations Dilated chamber/thick wall END

Left Heart failure Left heart failure: etiology Ischemic heart disease Hypertension Aortic / Mitral valve disease Presentation: acute onset of dyspnea, pulmonary edema, rales, S3 gallop. Complication: Cardiogenic shock

Pulmonary congestion and edema. Intraalveolar pale pink, low protein, few lymphocytes fluid: Transudate)

Right heart failure Etiology: Clinical: Complication: Left heart failure and Cor-pulmonale Clinical: jugular venous distension, hepatoslemegaly, dependent edema, ascites, pleural effusion. Complication: Chronic passive congestion of liver (nutmeg liver) Cardiac cirrhosis and centrilobular necrosis.

A classic case of progression of heart failure Next slide

LVF ↓ Dyspnea ← Pul. Edema (T) + heart failure cells ← ↑Hydrostatic pr. ←PHT reduced lung edema ← ↓ Flow of blood in the lung ←RHF Increased (central) venous pressure ↑ Hydrostatic pressure in peripheral blood vessels in the soft tissue = Pitting (dependent edema) + Ascitis Develop Passive venous congestion of various organs Liver: hepatomegaly (Nutmeg liver)/cardiac cirrhosis Spleen: congestive splenomegaly Kidney : Hypoxia (Sec. hypertension) PHT- pulmonary hypertension

Ischemic Heart Disease (IHD) Dr. Basu MD

Do you know Propels over 6000 liters of blood through the body daily. Beats more than 40 million times a year. Yearly economic burden of ischemic heart disease is estimated to be in excess of $100 billion.

Topic Definition Types of IHD Pathogenesis of Ischemic Heart Disease Myocardial infarction

Ischemic Heart Disease There is an imbalance between the myocardial demand and the blood supply. Age: Male: middle age Female : post menopausal Epidemiology: leading cause of death for both males and females in the United States.

Types of ischemic heart disease Angina ( with > 75% narrowing) Angina pectoris (classical, stable angina) Prinzmetal variant Unstable angina Myocardial infarction (100% occlusion) Sudden cardiac death Chronic ischemic heart disease Acute Coronary Syndrome

Pathogenesis of IHD Narrowing (stenosis) of coronary artery: Mostly fixed arthrosclerosis. Complete obstruction (occlusion) of the lumen of coronary artery: Thrombus developed on an atheroma / embolism**. 75% or more narrowing: Ischemic symptoms (angina). Complete occlusion (100% ): Infarction

Morphology- Angina Fixed Atherosclerotic narrowing of the coronary artery. This partial occlusion may produce angina.

Coronary artery showing: >75% narrowing, which would be associated with angina.

Nearly complete luminal occlusion Nearly complete luminal occlusion. Following acute plaque change This produce myocardial infarction

Angina Pectoris Angina pectoris is characterized by: Type: Intermittent chest pain caused by transient, reversible myocardial ischemia. Type: Typical or stable angina pectoris. Fixed atherosclerotic narrowing (75% or greater). Prinzmetal, or variant , angina. Unstable angina pectoris (crescendo angina). Preinfarction angina.

Typical or stable angina pectoris Episodic chest pain associated with exertion or stress. Pathogenesis: Fixed coronary atherosclerotic narrowing without plaque change ( > 75% but not full) Pain is relived by rest or vasodilators (nitroglycerine) that reduce the venous return.

Prinzmetal Angina Is a form of angina pectoris which occurs at rest and presumably stems from a coronary artery spasm with or without an obstructive lesion in the artery.

Unstable Angina (crescendo angina) Pathogenesis: acute plaques change but without 100% occlusion. Clinical: Increased frequency of anginal pain. Pain precipitated by less exertion. Pain is more intense and last longer. High risk for Myocardial infarction.

Biochemical of angina C-reactive protein (CRP) may serve as a marker to predict the risk of MI in patients with angina. Also serve as a marker to predict the risk of new infarcts in patients who recover from infarcts.

Myocardial Infarction

Myocardial infarction Sudden (> 30 min.) pain May be in shock due acute LVF : Pulmonary edema. Statistics: In U.S. 1.5 million/yr. 25% die in acute phase within 1 hr. At age 45 –55 : M:F::4:1 At age 80 equal incidence among sexes

Pathogenesis of Myocardial Infarction – 100% Occlusive intracoronary thrombus By:- 1. Provoked by complications of Atheroma: E.g. : Rupture of plaque. 2. Coronary artery spasm: ? Smoking 3. Emboli (Source is the proximal part of same blood vessels).

Types of Myocardial Infarction Subendocardial MI: < 50% of the wall thickness Any MI typically begins in this area (most poorly perfused area of the myocardium). EKG: ST segment depression. Transmural MI: Necrosis extend externally and involve entire myocardium. Most common type, take about 24 hrs to develop.

M.I: Sites of occlusion:infarction LAD = Lt. Ant. Desc. A (40 –50%):- Lt.Ventricle : anterior and apical Ant.2/3 of Inter Ventricular Septum (IVS) RCA= Rr. Coronary A (30 40%) Lt.Ventricle : post. wall I.V.S.post.1/3 LCX= Lt. Circumflex A(15-20%):- Lt.Ventricle -- lateral wall

LAD occlusion Right Coronary occlusion Left Circumflex occlusion

Morphology Time Gross Features Light Microscope Electron Microscope Reversible Injury Time Gross Features Light Microscope Electron Microscope 0-½ hr None Relaxation of myofibrils; glycogen loss; mitochondrial swelling.

Morphology of Myocardial Infarction Time from Onset Gross Morphologic Finding 18 - 24 Hours Pallor of myocardium 3 - 7 Days Hyperemic border with central yellowing 10 - 21 Days Maximally yellow and soft with vascular margins 7 weeks White fibrosis

Acute myocardial infarct, predominantly of the posterolateral left ventricle SCAR

Irreversible cell death Time from Onset Microscopic Finding 0-30 min. No change (E.M- Mitochondrial swelling) Irreversible cell death ↓ 1-3 hours Few wavy fibers at the margin of MI. 4-12 hours Loss of cross striations and edema. 12-24 hours Coagulative necrosis, Marginal contraction bands necrosis, ( and PMNs infiltrate).

Plenty of PMNs and coagulation necrosis Time from Onset Microscopic Finding 24 - 72 Hours Plenty of PMNs and coagulation necrosis 4-7 days Macrophage & mononuclear infiltration 10-21 Days prominent granulation tissue 7-8 Wk Fibrosis: Healing

1 to 3 hours wavy fibers (elongated and narrow), compared with adjacent normal fibers (at right).

12 -24 hrs. Contraction band necrosis : Note the many irregular darker pink wavy contraction bands extending across the fibers. CONTRACTION BANDS

Remote infarction ( left Trichrome stain: showing blue collagen).

MECHANISM of reperfusion injury Generation of oxygen free radicals from infiltrating leukocytes And apoptosis.

Effect of reperfusion injury

In MI the ratio of 1: 2 is >1.5 Biochemistry of MI Elevated by Peak Return to normal MYOGLOBIN may rise immediately CK- MB 4-8 hr 18-20hr 2-3 days CK-MB Isoform 1 & 2 Normal ratio of 1 : 2 = 1.2 In MI the ratio of 1: 2 is >1.5

Biochemistry of MI Elevated by Peak Return to normal Cardiac specific Troponin I and T 3-6 hr 16-20hr 7-10 days LDH ( level depends on the amount of cell death) 24hr 3-6 days 8-14 days In MI, LDH “Flip” occur. Normally LDH2 > LDH1, After MI : LDH1 > LDH2

Enzymes

Complications of MI Arrhythmias with possible "sudden death” (ventricular fibrillation) Occur immediately [ MOST COMMON cause of sudden death in MI] Acute fibrinous pericarditis Typical onset: Second or third day Late: Dressler syndrome Rupture of the wall and tamponade or VSD 3-7 days after the MI Papillary muscle rupture and mitral incompetence

Cardiac tamponade Occur due to hemopericardium. ↑ pericardial pressure = ↓ diastolic filling of the ventricles, and hence in stroke volume Signs: Sudden drop in systolic and well as diastolic blood pressure. Distended jugular vein. Right ventricular and right atrial collapse.

OTHERS complications Mural thrombi and thrombo-embolism: Infarct of Brain, kidney, Intestine 1wk or > Carcinogenic shock (10% cases) MI is the most common cause of Cardiogenic shock. Multi-organ failure Extension of infarct or repeat 2nd infarction- ? diagnosis Any time and the most common cause of sudden death weeks after an MI Ventricular aneurysms Late complication

Myocardial rupture in an acute infarct in the wall : ? consequence Hemopericardium Cardiac tamponade:- Acute chest pain/ sudden drop of BP

Rupture of the ventricular septum (L) and papillary muscle (R) Left-to-right shunt and right heart failure. Pan systolic murmur Produce sudden mitral insufficiency. Holosystolic murmur (laterally at the apex of the heart with the patient in the left lateral decubitus position) radiated to axilla .

left ventricular aneurysm: does not contract , so the ejection fraction and stroke volume of the heart are reduced- patient feels week!.

Clinical Features of Myocardial Infarction Severe, crushing substernal chest pain. Pain radiate to either: Neck ,Epigastrium,Shoulder. Or left arm. In up to 50% of cases, pain is preceded by episodes of angina pectoris.

Diagnosis of Myocardial Infarction EKG – ST elevation changes, T wave inversion and Q wave- transmural infarct. Echo cardiogram Myocardial enzyme markers Creatinine Kinase Troponins Lactate dehydrogenase, Myoglobin

Sudden Cardiac Death (SCD) Mechanism of SCD is most often a lethal arrhythmia . Commonest cause = I.H.D Other causes:- Aortic stenosis 2nd Myocardial infarct M.V. prolapse Cardiomyopathy Myocarditis

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