Cardiac Pathology PDF

CARDIAC PATHOLOGY DR MBAYAH ETABALE LECTURER AND ANATOMICAL PATHOLOGIST 1 COURSE OUTLINE  General Principles of Cardiac Disease  Cardiac Failure  Congenital Heart Diseases  Endocardial Diseases  Myocardial Diseases  Pericardial Diseases...

CARDIAC PATHOLOGY DR MBAYAH ETABALE LECTURER AND ANATOMICAL PATHOLOGIST 1 COURSE OUTLINE  General Principles of Cardiac Disease  Cardiac Failure  Congenital Heart Diseases  Endocardial Diseases  Myocardial Diseases  Pericardial Diseases 2 OBJECTIVES  Discuss heart failure  Write short notes on the 5 most common congenital cardiac anomalies: TOF, VSD, ASD, PDA and Coarctation of the Aorta  Describe the aetiology, pathogenesis, clinical features and morphological characteristics of rheumatic fever  Describe the aetiology, pathogenesis, clinical features and morphological characteristics of infectious endocarditis  Contrast systemic hypertensive heart disease and pulmonary hypertensive heart disease  Describe the aetiology, pathogenesis, morphological features and clinical features of myocardial infarction  Write short notes on cardiomyopathies  Discuss pericarditis 3 GENERAL PRINCIPLES OF CARDIAC DISEASE 4 GENERAL PRINCIPLES OF CARDIAC DISEASE 1. Abnormal cardiac conduction leading to 4. Shunts that allow abnormal blood flow either right- uncoordinated myocardial contractions to-left (bypassing the lungs) or left-to-right (causing  Heart block volume overload  Arrhythmias 5. Pump Failure 2. Blood flow obstruction  Systolic Failure  Atherosclerosis  Diastolic Failure  Thrombosis 6. Rupture of the heart or a major vessel  Valvular stenosis 3. Regurgitant flow causing output from each contraction to be directed backward 5 MAJOR CLASSES OF DISEASES  Congenital  VSD, ASD, PDA, Coarctation of the aorta, tetralogy of Fallot, bicuspid aortic valve, etc.  Inflammatory  Endocarditides, myocarditides, pericarditides  Ischaemic  Ischaemic heart disease  Degenerative  Myxomatous valves, calcific valves  Neoplastic  Myxoma, fibroma, lipoma, papillary fibroelastoma, rhabdomyoma, angiosarcoma 6 CARDIAC FAILURE HEART FAILURE  Aka congestive heart/cardiac failure, CHF/CCF  Heart cannot maintain an adequate cardiac output (CO) for the metabolic requirements of the body or can only do so with elevated filling pressures  Characterised by:  Diminished CO (forward failure);  Accumulation of blood in the venous system (backward failure) or  Both of the above 8 CHF Cause Examples Reduced ventricular contractility Myocarditis, dilated cardiomyopathy (DCM) MI Pressure Overload/Ventricular Outflow HTN, aortic stenosis (AS) [Left HF] Obstruction (VOO) Pulm HTN, pulm valve stenosis [Right HF] Impaired Ventricular Filling Mitral Stenosis (MS), tricuspid stenosis Myocardial fibrosis, restrictive cardiomyopathy (RCM), massive left ventricular hypertrophy, amyloidosis Constrictive pericarditis Volume Overload LV volume overload (mitral/aortic regurgitation) [MR/AR] RV volume overload (ASD) VSD Increased metabolic demand (high output) 9 Arrhythmia AF, Tachyarrhythmia, Complete Heart Block COMPENSATORY MECHANISMS 1. Activation of neurohumoral systems  Blood volume expansion by salt and water retention  Tachycardia 2. Ventricular dilatation  Improves myocardial contractility by myofibre stretching (Frank-Sterling Law) 3. Cardiac hypertrophy  Improves myocardial contractility by increasing the myofibre bulk 10 1. NEUROHUMORAL COMPLENSATION Heart Failure Reduced contractility Neurohumoral A0 Fluid Overload Sympathetic NS A0 RAAS A0 ANP Secretion + Chronotropism Vasoconstriction Natriuresis + Ionotropism Na+ and Fluid Retention Diuresis Vasoconstriction Vasodilatation 11 ↑BP Alleviation of fluid overload 2. FRANK STARLING MECHANISM  CO is a function of:  Preload: volume and pressure of blood in the ventricle during diastole  Afterload: arterial resistance  Myocardial contractility  Ventricular performance related to the degree of myocardial stretching  Increased preload increases contractility (but up to a limit) – compensation  Beyond the limit, further increase in preload causes deterioration of myocardial function – decompensation 12 3. CARDIAC HYPERTROPHY  Cardiomyocytes adapt to increasing workload by increasing the number of sarcomeres which in turn increases the size of the cardiomyocytes – hypertrophy  Two main types of cardiac hypertrophy:  Concentric hypertrophy  In response to pressure overload e.g. systemic hypertension  New sarcomeres added in parallel to existing sarcomeres in the myocyte  Results in thicker myocytes (and thicker ventricular wall)  Dilated hypertrophy  In response to volume overload e.g. valvular regurgitation  New sarcomeres added in series to existing sarcomeres in the myocyte  Results in longer myocytes  The ventricle is dilated; the ventricular thickness may be normal, increased or reduced 13  14 Source: Robbins Basic Pathology, 10th Edition COMPENSATION OCCURS AT A COST  Increased heart rate, increased contractility both increase metabolic demands of the myocardium  Supply of these requirements does not increase in tandem with the demand predisposing to ischaemic injury 15 TYPES OF HEART FAILURE  Acute Heart Failure  Left-sided Heart Failure (LHF)  Chronic Heart Failure  Right-sided Heart Failure  Biventricular Heart Failure  Low-Output Heart Failure  High-Output Heart Failure 16 1. LOW-OUTPUT HEART FAILURE VS HIGH-OUTPUT HEART FAILURE Low-Output Heart Failure High-Output Heart Failure  Occurs when cardiac output is insufficient to meet  Occurs when cardiac output is higher than normal normal body requirements i.e. < 5 L/min i.e. > 5 L/min but still insufficient to meet body requirements  Causes:  Causes:  Ischaemic heart disease  Anaemia (severe or chronic)  Hypertensive heart disease  Thyrotoxicosis  Valvular heart diseases  Beriberi  Myocarditis  Pregnancy  Cardiomyopathies  Large arteriovenous shunt 17 2. ACUTE VS CHRONIC HEART FAILURE Acute Heart Failure Chronic Heart Failure  Develops suddenly, over hours or over a few days  Develops over weeks and months  Causes:  Causes:  Acute coronary arterial occlusion  Ischaemic heart disease  Pulmonary embolism  Benign systemic hypertension  Acute valve rupture  Chronic valvular disease  Acute myocarditis  Chronic lung disease  Malignant systemic hypertension  Chronic severe anaemia  Effects  Effects  Sudden death  Sudden death  Acute pulmonary oedema  Acute pulmonary oedema  End-organ acute ischaemia  End-organ acute ischaemia 18 2. ACUTE VS CHRONIC HEART FAILURE Left Heart Failure Right Heart Failure Ischaemic Heart Disease Left Heart Failure Systemic Hypertension Cor Pulmonale Mitral / Aortic Valve Disease Multiple / Large Pulmonary Emboli Myocardial Diseases: Myocarditis, Cardiomyopathies Pulmonic / Tricuspid Valve Disease Congenital Heart Disease: Left – Right Shunts 19 3.1. LEFT HEART FAILURE  There is reduction in the left ventricular output and an increase in left atrial or pulmonary venous pressure  Manifestations of LHF include:  Pulmonary congestion and oedema  Reduced renal perfusion causing:  Salt and water retention to expand blood volume  Ischaemic acute tubular necrosis  Impaired waste excretion leading to azotaemia  Reduced CNS perfusion causing hypoxic encephalopathy 20 MORPHOLOGICAL CHANGES IN LEFT HEART FAILURE  Heart  Lungs  Gross  Gross  LV hypertrophy  Heavy and boggy  LV dilatation  Micro  LA dilatation  Oedema of the alveolar septae  Micro  Oedema in the alveolar space  Myocyte hypertrophy  RBCs in the alveolar space (vascular leakiness)  Areas of fibrosis  Haemosiderin-laden macrophages 21 22 CHRONIC PASSIVE CONGESTION OF THE LUNG 23 LEFT HEART FAILURE CLINICAL FEATURES  Cough  Oliguria  Dyspnoea  Azotaemia  Exertional  CNS manifestations  At rest  Irritability  Orthopnoea  Reduced cognition  Paroxysmal nocturnal dyspnoea  Restlessness  Stupor  Blood-tinged sputum  Coma  Cyanosis  Renal manifestations 24 3.2. RIGHT HEART FAILURE  Reduction in RV output  Clinical features are due to systemic venous and portal venous congestion  Key organs:  Liver – hepatomegaly  Spleen – splenomegaly  GIT – impaired nutrient absorption  Serous cavities – pleural effusion, pericardial effusion, ascites  Soft tissues – oedema  Renal – congested, hypoxic injury, ATN 25 26 CONGENITAL HEART DISEASES INTRODUCTION  Anomalies of the heart and great vessels that are  Anatomical Classification of CHD: present at birth 1. Shunts  Most are sporadic  L-R Shunt Malformations  Approx. 1% of live births  R-L Shunt Malformations  Higher incidence in premature and still born infants 2. Obstructions  The aetiology is unknown in approx. 90%  Clinical Classification of CHD: 1. Cyanotic CHD  Multifactorial e.g.: 2. Acyanotic CHD  Trisomy 21 (10% of cases)  Congenital rubella infection (10 – 20% of cases) 28 CYANOTIC CONGENITAL HEART DISEASES  These conditions are caused by shunting of venous blood from the right side of the heart / great vessels to the left side of the heart / great vessels bypassing the lungs  Results in reduced oxygenation of blood entering systemic  Clinically manifests as cyanosis (bluish-tinge of skin and mucosae) very early on  5 Ts: 1. Tetralogy of Fallot (commonest) 2. Transposition of great vessels 3. Truncus arteriosus communis 4. Tricuspid valve atresia 5. Total anomalous pulmonary venous return 29 1. TETRALOGY OF FALLOT  Caused by anterosuperior displacement of the infundibular (conal) septum  A tetrad  Right ventricular outflow tract obstruction (pulmonic valve stenosis)  Right ventricular hypertrophy  Large VSD  Overriding aorta (aortic opening just above the VSD) 30 Source: Mad About Medicine 1. TETRALOGY OF FALLOT  Disease severity depends on size of pulmonic aperture  Mild stenosis: L – R shunting, pink tetralogy  Become cyanotic later in childhood or adulthood  Murmur  Severe stenosis: R – L shunting → cyanosis (classic tetralogy)  Cyanotic at birth  Difficulty in breathing  Failure to thrive  “Tet” spells  Murmur 31 1. TETRALOGY OF FALLOT 32 ACYANOTIC CONGENITAL HEART DISEASES  Consists of shunt malformations (L – R) and obstructions  Cyanosis is not the key defining feature  Cyanosis may occur in the complication Eisenmenger complex  Examples:  Ventricular Septal Defect (VSD)  Atrial Septal Defect (ASD)  Persistent Ductus Arteriosus (PDA)  Coarctation of the Aorta 33 Source: Robbins Basic Pathology, 10th Edition 1.VENTRICULAR SEPTAL DEFECT (VSD)  Most common CHD (30% of cases)  Maternal alcohol consumption is a risk factor  30% isolated, 70% associated with TOF  May involve:  The membranous portion  Most common (90%)  The muscular portion  Less common  Tend to be multiple  Tend to close spontaneously Source: Robbins Basic Pathology, 10th Edition 34 1.VENTRICULAR SEPTAL DEFECT (VSD)  Clinical features  Management of cardiac failure  Small VSDs asymptomatic  Caloric support  Close spontaneously in about 2 years  Prophylaxis / treatment of endocarditis  Large VSDs symptomatic  Surgery  Failure to thrive  Difficulty breathing  Fast breathing  Frequent respiratory infections  Large VSDs may complicate with Eisenmenger complex  Treatment 35 2. ATRIAL SEPTAL DEFECTS (ASD)  Account for approximately 8% of all CHD  Most common congenital anomaly seen in adult life  3 types:  Ostium primum ASD  Ostium secundum ASD  Sinus venosus ASD  L-R shunt but less problematic  Pulmonary HTN and HF occur in approximately 10% of cases  ASD is usually diagnosed in early adult life  Paradoxical emboli are an important complication 36 Source: Robbins Basic Pathology, 10th Edition 3. PERSISTENT DUCTUS ARTERIOSUS  Failure of closure of ductus arteriosus  90% isolated  Delayed closure is common in premature infants  Also associated with congenital rubella  Asymptomatic at birth with continuous machinery murmur  May complicate with Eisenmenger complex – lower extremity cyanosis  Indomethacin used in treatment 37 Source: Robbins Basic Pathology, 10th Edition 4. COARCTATION OF THE AORTA  Narrowing of the aorta  M:F = 2:1  Infantile form – associated with PDA  Coarctation is distal to arch but proximal to PDA  Lower extremity cyanosis in infants  XO  Adult form – no PDA  Hypertension in upper extremities; hypotension in lower extremities  Typically discovered in adulthood  Collateral circulations develop across the intercostal arteries; engorged arteries cause notching of the ribs (seen on radiographs)  Associated with bicuspid aortic valve  Other cardiovascular associations  ASD  VSD  MR 38 Source: Robbins Basic Pathology, 10th Edition ✓ Cerebral aneurysms 4. COARCTATION OF THE AORTA 39 ENDOCARDIAL DISEASES OUTLINE A. Introduction B. Degenerative Valve Diseases C. Inflammatory Diseases D. Carcinoid Heart Disease E. References 41 B. INTRODUCTION ▪ The main causes of valvular heart disease are: ▪ Rheumatic fever ▪ Endocarditis ▪ Congenital heart diseases ▪ Degenerative changes (Calcification, Myxomatous Degeneration) ▪ Left valves more susceptible to injury due to higher haemodynamic pressures ▪ Principles of valvular dysfunction 1. Failure to sufficiently open: stenosis 2. Failure to sufficiently close: regurgitation/incompetence/insufficiency 3. Failure to both open and close sufficiently 42 C. DEGENERATIVE VALVULAR DISEASES 1. Calcification: 1. Calcific Aortic Stenosis 2. Mitral Valve Calcification 2. Altered Valvular ECM 1. Myxomatous Mitral Valve 43 1. CALCIFIC AORTIC STENOSIS  Degenerative valvular change due to repetitive mechanical stresses; also includes fibrosis  Two types:  Congenital type  Due to congenital bicuspid aortic valves  Commonest congenital valvular anomaly  ~ 2% of the population  Develops premature fibrosis and calcification (age 40 – 50)  Senile type  Typically involves patients ≥ 70 years of age  Calcification manifests as nodular masses on the outflow aspect of the cusps 44 1. CALCIFIC AORTIC STENOSIS Source: Robbins Basic Pathology, 10th Edition 45 Source: Pathology Illustrated, 7th Edition 2. MITRAL VALVE CALCIFICATION  Usually in the elderly  Degenerative, non-inflammatory calcific nodular deposits within the mitral annulus  Clinical consequences include: 1. Regurgitation can occur from inadequate systolic contraction of the mitral valve ring 2. Stenosis can occur because leaflets are unable to open over bulky deposits 3. Nodular calcific deposits can impinge on conduction pathways causing arrhythmias ▪ Potentially sudden cardiac death 4. Ulcerated nodules may lead to thrombus formation which may lead to embolism 5. Rarely, these deposits can become a focus for infective endocarditis 46 2. MITRAL VALVE CALCIFICATION Source: Robbins Basic Pathology, 10th Edition 47 DEGENERATIVE VALVULAR DISEASES 1. Calcification: ✓ 1. Calcific Aortic Stenosis ✓ 2. Mitral Valve Calcification ✓ 2. Altered Valvular ECM 1. Myxomatous Mitral Valve 48 1. MYXOMATOUS MITRAL VALVE  Aka mitral valve prolapse  Complications  Due to accumulation of ground substance in the valve  Mitral valve regurgitation → → → CCF  One or both mitral valve leaflets are enlarged,  Infective endocarditis myxomatous and floppy  Arrhythmias  They balloon back into the left atrium during systole  Atrial thrombi and thromboembolism causing the characteristic “mid-systolic click”  Sudden cardiac death  F >>>>> M  Associated with connective tissue disorders e.g. Marfan syndrome  97% asymptomatic 49 1. MYXOMATOUS MITRAL VALVE 50 Source: Robbins Pathologic Basis of Disease, 10th Edition DEGENERATIVE VALVULAR DISEASES 1. Calcification: ✓ 1. Calcific Aortic Stenosis ✓ 2. Mitral Valve Calcification ✓ 2. Altered Valvular ECM 1. Myxomatous Mitral Valve ✓ 51 D. INFLAMMATORY DISEASES I. Acute Rheumatic Fever i. Rheumatic Heart Disease II. Endocarditis i. Infectious endocarditis a. Acute infectious endocarditis b. Sub-acute infectious endocarditis ii. Non-infectious endocarditis a. Non-bacterial thrombotic endocarditis b. Libman-Sacks endocarditis 52 I. ACUTE RHEUMATIC FEVER  An immunologically mediated systemic inflammatory condition caused by an abnormal response to infection by strains of group A β- streptococci (pharyngitis, skin infection, etc.)  Cross reaction of Abs against bacterial M-protein with host glycoprotein Ags  Manifests as acute rheumatic heart disease  Endocarditis  Myocarditis  Pericarditis 53 I. ACUTE RHEUMATIC FEVER  Gross  Serofibrinous pericardial exudate  Valves – vegetations: 1 – 2 mm on the commissural aspect  Micro  Inflammatory lesions in any of the heart layers – Aschoff bodies  Lø  Plasma cells  A0 Mø (Anitschkow cells) Source: Robbins Pathologic Basis of Disease, 10th Edition 54 I. ACUTE RHEUMATIC FEVER – MANIFESTATIONS MAJOR JONES CRITERIA 1. Carditis  3 weeks after other signs  Pericardial friction rub  Best felt over bones and tendons  Arrhythmias 4. Erythema marginatum  Cardiac dilatation with failure (few extreme cases)  Red rings 2. Arthritis  Bathing suit distribution  Pain, swelling 5. Syndenham chorea  Migratory involving big joints, one after the other  Late neurological sign (about 3 months after ARF)  Last for about a week then resolve  1/3 of cases  Responds to aspirin  Emotional lability; involuntary choreiform movements; explosive and halting speech 3. Subcutaneous nodules 55 I. ACUTE RHEUMATIC FEVER – MANIFESTATIONS MAJOR JONES CRITERIA 56 I. ACUTE RHEUMATIC FEVER – MANIFESTATIONS MAJOR JONES CRITERIA AND MINOR JONES CRITERIA 57 CHRONIC RHEUMATIC HEART DISEASE  Organisation of the ARF lesions with subsequent healing by fibrosis Gross ARHD CRHD Valve Vegetations 1-2 mm, commissural aspect Valve leaflet scarring and thickening Commissural fusion and shortening Thickening and fusion of chordae tendinae Microscopy ARHD CRHD Valve, Myocardium Aschoff nodules Fibrotic areas Valves Fibrin thrombi on valves Scarring with areas of neovascularisation; +/- calcifications 58 CHRONIC RHEUMATIC HEART DISEASE 59 Source: Robbins Pathologic Basis of Disease, 10th Edition D. INFLAMMATORY DISEASES I. Acute Rheumatic Fever ✓ i. Rheumatic Heart Disease ✓ II. Endocarditis i. Infectious endocarditis a. Acute infectious endocarditis b. Sub-acute infectious endocarditis ii. Non-infectious endocarditis a. Non-bacterial thrombotic endocarditis b. Libman-Sacks endocarditis 60 II. ENDOCARDITIS  Refers to inflammation of the inner lining of a heart valve, a cardiac chamber or great blood vessel with formation of vegetations  May be due to:  An infectious process – infective endocarditis  Acute endocarditis  Subacute endocarditis  A noninfectious process – noninfectious endocarditis  Nonbacterial thrombotic endocarditis  Libmann-Sacks endocarditis 61 II. INFECTIOUS ENDOCARDITIS  Microbial invasion of heart valves or mural  Most common cause in IV drug abusers endocardium or lining of great blood vessels with  High-virulence organism that infects normal valves destruction of underlying tissues  Results in large vegetations that destroy the valve (acute endocarditis)  Invasion is by circulating microbes  Staphylococcus epidermidis associated with endocarditis of  Streptococcus viridans prosthetic valves  Most common overall cause  Streptococcus bovis is associated with endocarditis in  Low-virulence organism that infects previously damaged valves patients with underlying colorectal carcinoma e.g. chronic rheumatic heart disease, mitral valve prolapse  HACEK organisms (Haemophilus, Actinobacillus,  Results in small vegetations that do not destroy the valve (subacute endocarditis) Cardiobacterium, Eikenella, Kingella) are associated with endocarditis with negative blood cultures  Staphylococcus aureus  Fungi 62 II. INFECTIOUS ENDOCARDITIS  Vegetations contain  Necrotic debris  Fibrin/thrombus  Inflammatory cells  Microbes  Predominantly affects aortic and mitral valves  Tricuspid valve in IV drug abusers  Fungal organisms tend to cause larger vegetations  Due to their friable nature, septic systemic emboli may develop leading to distant abscesses (septic infarcts) 63 II. INFECTIOUS ENDOCARDITIS – ACUTE VS SUBACUTE Acute Endocarditis Subacute Endocarditis  Aggressive infection by a highly virulent organism  Low virulence organisms  S. aureus  Viridans streptococci  HACEK group  Can occur in normal valves  Usually affect an abnormal native valve (e.g. RHD),  A lot of destruction prosthetic valve, congenital heart anomaly, etc.  Runs a course of days  Amount of valvular destruction is comparatively less  High mortality rates even with treatment  Runs a course of weeks to months  Most patients recover with appropriate antibiotic therapy 64 II. INFECTIOUS ENDOCARDITIS – MORPHOLOGY 65 Source: Robbins Pathologic Basis of Disease, 10th Edition II. INFECTIOUS ENDOCARDITIS – CLINICAL FEATURES  Fever  Due to bacteraemia  Most consistent feature  Murmur  Due to vegetations on heart valves  Janeway lesions  Non-tender erythematous macules on palms and soles  Osler’s nodes  Tender nodules on pulps of digits  Subungual splinter haemorrhages  Due to septic emboli  Roth spots 66  Retinal haemorrhages II. INFECTIOUS ENDOCARDITIS – DIAGNOSIS 67 NON-INFECTIOUS ENDOCARDITIS NON-BACTERIAL THROMBOTIC ENDOCARDITIS (NBTE)  Loose deposition of small (≤ 5 mm) sterile thrombi on the leaflets of cardiac valves  Encountered in debilitated patients aka marantic endocarditis  Due to hypercoagulability  Endocardial injury is also a cause  Valvular abnormality is not a prerequisite  Gross – loosely adherent valvular commissure vegetations  Micro – thrombi loosely adherent to valve, devoid of inflammation or destruction of underlying valve tissue 68 Source: Robbins Pathologic Basis of Disease, 10th Edition NON-INFECTIOUS ENDOCARDITIS LIBMANN-SACKS ENDOCARDITIS  Aka Endocarditis of Systemic Lupus Erythematosus  Deposition of small (≤ 4 mm) sterile thrombi on the leaflets, chordae of cardiac valves or mural endocardium  Encountered in SLE, antiphospholipid syndrome  Due to deposition of immune complexes leading to localised inflammation, necrosis and thrombosis  Subsequent fibrosis leads to valvular deformation  Valvular abnormality is not a prerequisite 69 D. INFLAMMATORY DISEASES I. Acute Rheumatic Fever ✓ i. Rheumatic Heart Disease ✓ II. Endocarditis ✓ i. Infectious endocarditis ✓ a. Acute infectious endocarditis ✓ b. Sub-acute infectious endocarditis ✓ ii. Non-infectious endocarditis ✓ a. Non-bacterial thrombotic endocarditis ✓ b. Libman-Sacks endocarditis ✓ 70 E. CARCINOID HEART DISEASE  Due to carcinoid tumours that  Bradykinin  Cardiac features cause carcinoid syndrome  Prostaglandins  White plaque-like endocardial  Carcinoid syndrome  Tachykinins thickenings  Multisystemic manifestations caused  Systemic manifestations  Valvular thickening by bioactive substances that are  Flushing  Valvular stenosis produced by carcinoid  Diarrhoea  Valvular insufficiency (neuroendocrine) tumours  Dermatitis  Bioactive substances  Bronchoconstriction  Serotonin (5-HT)  Cardiac manifestation – carcinoid  Histamine heart disease  Kallikrein 71 E. CARCINOID HEART DISEASE 72 Source: Robbins Pathologic Basis of Disease, 10th Edition DEGENERATIVE VALVULAR DISEASES 1. Calcification: ✓ 1. Calcific Aortic Stenosis ✓ 2. Mitral Valve Calcification ✓ 2. Altered Valvular ECM ✓ 1. Myxomatous Mitral Valve ✓ 73 MYOCARDIAL DISEASES OUTLINE ▪ Objectives ▪ Hypertensive Heart Disease ▪ Ischaemic Heart Disease ▪ Myocarditis ▪ Cardiomyopathies ▪ References 75 OBJECTIVES 1. Contrast systemic hypertensive heart disease and pulmonary hypertensive heart disease 2. Define ischaemic heart disease 3. List the 4 clinical syndromes associated with ischaemic heart disease 4. Describe the aetiology, pathogenesis, morphological features and clinical features of myocardial infarction 5. Classify the causative agents of myocarditis 6. Write short notes on cardiomyopathies 76 A. HYPERTENSIVE HEART DISEASE  Hypertrophic adaptive response of the heart to chronic arterial resistance  Can be left-sided (systemic HHD) or right-sided (pulmonary HHD) aka cor pulmonale 77  SYSTEMIC HYPERTENSIVE HEART DISEASE 1. Chronic elevation of systemic peripheral vascular resistance (pressure load) 2. Concentric myocardial hypertrophy 3. Myocardial dysfunction: i. Increased end diastolic pressures ii. Myocyte degeneration (exhaustion) iii. Ischaemic injury 4. Cardiac complications: i. Ischaemic heart disease Source: Muir’s Textbook of Pathology ii. Dysrhythmias iii. Congestive cardiac failure 78 iv. Sudden cardiac death Source: Robbins Pathologic Basis of Disease PULMONARY HYPERTENSIVE HEART DISEASE  RV hypertrophy and dilatation due to pulmonary HTN  May be acute (e.g. PTE) or chronic  Acute cor pulmonale  Dilated RV, RA; normal wall thicknesses  Usually after massive pulmonary embolisation  Chronic cor pulmonale  RV hypertrophy. May be equal to or exceed LV thickness  RV dilatation  Due to chronic right ventricular pressure overload 79 Source: Robbins Basic Pathology, 10e B. ISCHAEMIC HEART DISEASE  A group of cardiac conditions characterised by inadequate  Severe anaemia cardiac perfusion relative to cardiac demand  Advanced lung disease 1. Angina  Cyanotic CHD 2. Acute Myocardial Infarction  CO poisoning  Cigarette smoking 3. Sudden Cardiac Death 4. Chronic Myocardial Infarction 3. Reduced coronary blood flow  Coronary artery disease  Causes include:  Arteritis 1. Increased myocardial demand  Emboli  Tachycardia  Cocaine-induced vasospasm  Hypertrophy  Shock 2. Hypoxia 80 SYNDROME I – ANGINA  Ischaemia causes pain but is not enough to cause  Presents as chest pain (< 20 minutes); radiates to the left arm or jaw; sweating and shortness of breath myocyte death (reversible injury)  Relieved by rest or nitroglycerine  Recurrent II. Unstable angina  < 20 min  Occurs with progressively lowering exertions or at rest  Types  Attributed to acute plaque change I. Stable angina  High risk of progression to myocardial infarction  Occurs during exertion or some stress III. Variant (Prinzmetal) angina  Decreased blood flow is not able to meet the metabolic  Episodic chest pain unrelated to exertion demands of the myocardium during exertion  Due to a coronary artery spasm  Typically associated with coronary stenosis of at least 70%  Relieved by nitroglycerin and calcium-channel blockers 81  SYNDROME 2 – MYOCARDIAL INFARCTION  Severity and duration of the ischaemia causes death of  Difficulty in breathing cardiac muscle  Infarction involves the left ventricle  > 90% of MIs are related to coronary atherosclerosis  LAD obstruction (45%)  Rupture of an atherosclerotic plaque, thrombosis and  Commonest complete coronary artery occlusion  → anterior wall and anterior septum infarction  Clinical features include:  RCA obstruction  Severe crushing chest pain > 20 minutes that radiates to  → posterior wall and posterior septum infarction the left arm or jaw  LCX obstruction  Not relieved by nitroglycerin  → lateral wall infarction  Sweating  Infarction is subendocardial or transmural 82 Source: Robbins Basic Pathology, 10e SYNDROME 2 – MYOCARDIAL INFARCTION: TOPOGRAPHY Source: Muir’s Textbook of Pathology 83 Source: Robbins Pathologic Basis of Disease  SYNDROME 2 – MYOCARDIAL INFARCTION: MORPHOLOGY Time from Gross Changes Microscopic Changes Complications Infarction myocardial irritability and dysfunction > arrhythmia 86 SYNDROME 4 – CHRONIC ISCHAEMIC HEART DISEASE  Poor myocardial function due to chronic ischaemia with or without infarction  Progresses to CCF  Typically seen in elderly patients with multi-vessel coronary atherosclerosis  May follow an MI  Infarction > cardiac hypertrophy of residual myocardium > myocardial exhaustion > pump failure  This is termed post-infarction cardiac decompensation  An MI may be absent  Chronic ischaemia > myocardial dysfunction >  Pump failure  Arrhythmias 87  C. MYOCARDITIS  A diverse group of conditions in which  Immunological  Myocyte necrosis/damage infectious agents and inflammatory  ARF  Inflammatory cells processes target the myocardium  SLE  Fibrosis  Aetiology  Polymyositis  Parasites  Viruses:  Sarcoidosis  Clinical features  SARS-Cov-2  Hypersensitivity myocarditis (to drugs)  Asymptomatic  Coxsackieviruses  Idiopathic CMV  Arrhythmias   Pathogenesis  HIV  CCF  Viral cytopathic effect  Influenza virus  Cell mediated immunity against infected  Parasitic cells  Trichinella spiralis  Cross-reaction of viral antigen with  Trypanosoma cruzi myocardial protein  Toxoplasma gondii  Microscopic features 88  Bacterial  Oedema  Borrelia burgdorferi  D. CARDIOMYOPATHIES  Intrinsic abnormality in function of the myocardium  Acquired forms:  Peripartum dilated cardiomyopathy  Myocardial dysfunction must be unrelated to coronary artery disease, valvular heart disease, hypertension or II. Secondary CMs shunts  The myocardium is involved as part of a generalised multi-organ disorder  Can be Primary or Secondary  Infiltrative diseases: amyloidosis I. Primary CMs  Metabolic diseases: glycogen storage disorders, haemochromatosis  Disease is solely/predominantly confined to the myocardium  Toxicity: drugs, alcohol  Congenital or acquired  Inflammatory: sarcoidosis  Neuromuscular dystrophies  Congenital types:  Nutritional 1. Dilated cardiomyopathy – dilated, poorly-contracting ventricle (systolic dysfunction)  Autoimmune 2. Hypertrophic cardiomyopathy – thick-walled left ventricle(diastolic  Endocrine dysfunction) 89 3. Restrictive cardiomyopathy – failure of left ventricle to relax (diastolic dysfunction) Source: Robbins Basic Pathology, 10e  1. DILATED CARDIOMYOPATHY (DCM)  Most common type of CM  90% of cases  Dilatation of all 4 chambers of the heart  Force transmission disorder  Results in systolic dysfunction (ventricles cannot pump)  50% mortality within 5 years of Dx:  CCF  Regurgitation of atrioventricular valves  Thromboembolic stroke  Conduction defects  Treatment is heart transplant Source: Robbins Basic Pathology, 10e 90 PERIPARTUM CARDIOMYOPATHY  Recognised pregnancy complication since the 1800s  LV systolic failure onset towards the end of pregnancy of within a few months after delivery  Cause is unknown  Risk factors:  African ancestry  Obesity  HTN  Multiparity  Increased age  Unpredictable course: recovery or end-stage heart disease  High risk of recurrence 91 2. HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM)  50% are familial (AD) with defect in myosin heavy chain – force generation disorder  Heavy, muscular, hypercontractile myocardium with impaired relaxation and cardiac filling (diastolic dysfunction)  Clinical features:  Asymptomatic (majority)  Sudden death (ventricular arrhythmias)  Syncope, with exercise (LVOO)  Exertional dyspnoea (CCF)  Angina (ischaemic heart disease)  Atrial fibrillation  Systemic embolism particularly strokes  Highly arrhthymogenic microscopic features  Myocyte disarray  Myocardial ischaemia Source: Robbins Basic Pathology 92  Myocardial fibrosis 3. RESTRICTIVE CARDIOMYOPATHY  Normal systolic function with diminished cardiac output  Decreased compliance of the ventricular endomyocardium that restricts filling during diastole  Causes include:  Amyloidosis  Sarcoidosis  Endomyocardial fibrosis  Loeffler syndrome (endomyocardial fibrosis ± eosinophilia)  Presents as congestive heart failure  Mural thrombus overlying fibrosis is common 93 Source: Robbins Basic Pathology, 10e PERICARDIAL DISEASES OUTLINE  Objectives  Introduction  Fluid Accumulations  Pericarditis 95 INTRODUCTION  Normally 30 – 50 mL of clear serous fluid  Visceral pericardium  Parietal pericardium 96 PERICARDIAL FLUID ACCUMULATIONS  Volume > 50 mL = pericardial effusion:  Ruptured MI  Ruptured aortic dissection 1. Serous  Malignant neoplasms  Starling forces  CCF 3. Chylous  Hypoproteinaemia  Mediastinal lymphatic obstruction with rupture into the pericardial space 2. Serosanguinous  Rarely of clinical significance  Trauma  Surgery  Bleeding disorders  Malignancy 97 PERICARDITIS  Infectious  Acute – viral infections (uncommon)  Chronic – tuberculosis  Immunologic  RF  SLE  Post-infarctional  Uraemic  Radiation-induced  Cardiac surgery  Inflammation of neighbouring structures: pneumonia, pleurisy  Metastases 98 CHRONIC PERICARDITIS 1. Adhesive pericarditis  Healed serous pericarditis  Focal adhesions of pericardium on epicardium 2. Fibrotic pericarditis  End-result of severe exudative pericarditis  Extensive scarring/fibrosis 3. Fibrocalcific pericarditis  Superimposition of calcification on fibrotic pericarditis  Rare nowadays 99 COMPLICATIONS OF PERICARDIAL DISEASES  Significant pericardial effusion may cause a cardiac tamponade  Compression of the heart by pericardial fluid  Prevents dilatation of the atria and ventricles  Fibrotic pericarditis may lead to constrictive pericarditis  Prevents dilatation of the heart during diastole 100 REFERENCES  Robbins Basic Pathology, 10th Edition  Pathology Illustrated, 7th Edition  Fundamentals of Pathology, 2018 Edition  Muir’s Textbook of Pathology, 15th Edition  Robbins and Cotran Pathologic Basis of Disease, 10th 101