Valvular heart disease and Infective endocarditis By Dr. Ashraf Abdelfatah Deyab Assistant Professor of Pathology Majmaah University- Collage of Medicine Heart valvular disease objectives Causes of valvular heart disease. Pathophysiology &clinical features of rheumatic heart diseases. Pathogenesis of infective endocarditis and list its predisposing factors and causes. Heart Valvular Disease -HVD Introduction: Normal Valves Unidirectional blood flow, operate to direct a one-way flow of blood from the atria to the ventricles to the arteries. Normal Valves Unidirectional blood flow, operate to direct a one-way flow of blood from the atria to the ventricles to the arteries. Valve competency depends on : Leaflets, Annulus, Cords, Papillary muscles, Ventricular wall. Types of valves Atrioventricular (AV) bicuspid (mitral) valve (4PV- LV). Aortic semilunar valve (RV- Aorta) Atrioventricular (AV) tricuspid valve (SVC+IVC- RV). Pulmonary semilunar valve(RV-PT)- (LPA&RPA). The mitral valve bicuspid valve with thin delicate& leaflets Mitral stenosis show diffuse fibrous thickening &distortion commissural fusion Mechanical Valve Why HVD draw the clinical attention? HVD come to Clinical attention because - Impose hemodynamic burden by causing - Impose hemodynamic burden by causing Obstruction (stenosis) Obstruction (stenosis) Regurgitation (incompetence) Regurgitation (incompetence) - Increase susceptibility to infective endocarditis. - Increase susceptibility to infective endocarditis. Whats the types of HVD?? Valvular stenosis ? Valvular stenosis ? Stenosis is the failure of a valve to open completely, which impedes forward flow. - VS Lead to heart failure - Definition of Valvular Regurgitation ? Insufficiency results from failure of a valve to close completely, thereby allowing reversed flow. (other names: leaky, insufficiency,.) - VR due to 1) intrinsic disease of the valve cusps or 2) Damage to or distortion Valvular Heart Disease -VHD Commonest affected sites: 1) Isolated disease. 1) Isolated disease. 2) Combined disease. 2) Combined disease. Lesions of Mitral &Aortic > more common than lesion affected Tricuspid & Pulmonic valves. What are the causes of VHD-? I. Acquired HVD: II. Congenital HVD: aortic and pulomonic valves are more affected, e.g sizes, numbers and malformed leaflet, attachment( commonest Bicuspid aortic valve disease) Unknown Acquired stenoses of the aortic and mitral valves account for approximately two thirds of all cases of valve disease. Valvular Heart Disease- Etiology Post-inflammatory healed scar (RHD of untreated bacterial infection). Endocarditis ( haemtogical spread of infective agents, surgery ?,oral?,IV drugs ect- scar affecting all sites of the valves) Mitral valve Prolapse (MVP), Floppy MV into LA tissue of valve abnormal mild Degenerative & senile calcification (aorta) Valvular Heart Disease- Etiology Abnormalities of Leaflets and Commissures Abnormalities of Left Ventricular Cavity and/or Annulus- Abnormalities of Tensor Apparatus. Cardiomyopathy (heart muscles disease). Connective tissue disease Aortic aneurysms & HTN Syphilis VHD- Etiology+ excepted outcome Post-inflammatory healed scar (RF)- MS+MR & AS+MR. Endocarditis- MR & AR. Degenerative disease (aorta) - AR. Senile calcific disease- AS. Mitral Prolapse- MR Mitral Prolapse- MR Abnormalities of Tensor Apparatus- (rupture papillary muscle or chordae or dysfunction) MS. Abnormalities of Tensor Apparatus- (rupture papillary muscle or chordae or dysfunction) MS. Abnormalities of Left Ventricular Cavity and/or Annulus- (cardiomyopathy or myocarditis) MR & AR Key: (MS+MR: Mitral stenosis + Regurgitation \ AS+AR: Aortic stenosis + Regurgitation ) AS+AR: Aortic stenosis + Regurgitation ) Valvular heart disease-clinical consequences Depending on: 1) The valve involved. 2) The degree of impairment. 3) How fast it develops. 4) The rate and quality of compensatory mechanisms. Valvular heart disease-clinical consequences 1) Valvular stenosis leads to pressure overload of the heart. 2) Valvular insufficiency leads to volume overload of the heart. 3) Sudden destruction of an aortic valve cusp -cause massive regurgitation- fatal. 4) Pregnancy can exacerbate valve disease and lead to poor maternal or fetal outcome. 5) Ejection of blood through the stenotic valves lead to injury of the endocardium. HVD What are the symptoms? Shortness of breathing- daily activities Weakness or dizzness Discomfort in the chest Palpitation Swelling of ankles Complication of valvular disease (1) infective endocarditis. (2) Insufficiency, Stenosis- if massive-Fatal. (2) Insufficiency, Stenosis- if massive-Fatal. (3) Chordal rupture. (3) Stroke or other systemic infarct, resulting from embolism of leaflet thrombi. (4) Arrhythmias, both ventricular and atrial (5) Heart failure (6) Pulmonary edema venous congestion. (7) Hypertrophy and dilatation of atrium. Heart valvular disease objectives Causes of valvular heart disease. Pathophysiology &clinical features of rheumatic heart diseases. Pathogenesis of infective endocarditis and list its predisposing factors and causes. Rheumatic heart disease Rheumatic heart disease RHD RHD: important public health problem, affecting an estimated 15 million people. RHD? RHD? characterized by repeated inflammation of heart valve with fibrinous resolution, deforming fibrotic valvular disease, include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords Rheumatic fever (RF) Rheumatic fever (RF) is an acute, immunologically mediated, multisystem inflammatory disease. Causative agent: Occurs a few weeks after an episode of group A streptococcal pharyngitis. 10 days to 6 weeks RF is clinically divided into 2 phases: I- Acute rheumatic carditis I- Acute rheumatic carditis II- Chronic rheumatic carditis- valvular lesion e.g mitral stenosis II- Chronic rheumatic carditis- valvular lesion e.g mitral stenosis EPIDEMIOLOGY Identical to group A streptococcal upper respiratory tract infections. MOST OFTEN IN CHILDREN, 5-15 yrs. ? LOWER STANDARDS OF LIVING ? OVERCROWDING RF\RHD- pathogenesis RF results from immune responses to Group A -hemolytic streptococci, which happen to cross-react with host tissues. RF results from immune responses to Group A -hemolytic streptococci, which happen to cross-react with host tissues. Antibodies +CD4 lymphocytes directed against the M proteins of streptococci have been shown to cross-react with self antigens in the heart. Antibodies +CD4 lymphocytes directed against the M proteins of streptococci have been shown to cross-react with self antigens in the heart. Produced cytokines that activate macrophages (such as those found in Aschoff bodies)- Damage heart tissue. RF morphology Acute Rheumatic Carditis: - Focal sub-endocardial inflammatory lesions, forming distinctive lesions occur in the heart, called Aschoff bodies ( fibrinoid necrosis+ mononuclear inflammatory infiltrate+ lymphocytes +occasional plasma cells). - Anitschkow cells ( Large plump histiocytes). - Pancarditis: affecting 3 layers causing pericarditis, Fibrinous pericarditis myocarditis can lead CHF or endocarditis - Inflammation of the endocardium &valves - results in fibrinoid necrosis within the cusps or along the tendinous cords. Overlying by small vegetations (1- to 2-mm), called Verrucous endocarditis, along the lines of closure- may resolved or under go fibrosis. RF morphology Acute Rheumatic Carditis (Pancraditis) : - Focal sub-endocardial inflammatory lesions, forming distinctive lesions occur in the heart, called Aschoff bodies ( fibrinoid necrosis+ mononuclear inflammatory infiltrate+ lymphocytes +occasional plasma cells), may be overlying by small vegtataion. - Anitschkow cells ( Large plump histiocytes). - Pancarditis: affecting 3 layers causing pericarditis, Fibrinous pericarditis myocarditis can lead CHF or endocarditis Acute rheumatic carditis: marked by intestitial granulomatous inflammation with so-called "Aschoff nodules". Fibrinous pericarditis gross& microscopy ( strands of pink fibrin extending outward) RHD morphology Chronic RHD: No Aschoff bodies noted-organization, fibrosis are the features. Inflammation of the endocardium &valves -. Fibrotic valve along the lines of closure. Leaflet thickening, commissural fusion and shortening, and thickening and fusion of the tendinous cords. Chronic rheumatic heart disease. The mitral valve demonstrates the typical "fish mouth" shape with commissural fusion Chronic rheumatic heart disease. The mitral valve demonstrates the typical "fish mouth" shape with commissural fusion RF clinical features (major criteria) 1) Migratory polyarthritis of the large joints. (2) Pancarditis. (3) Subcutaneous nodules. Painless, firm collections of collagen fibers over bones or tendon (4) Erythema marginatum of the skin: trunk or arms as muscl (5) Sydenham chorea, a neurologic disorder with involuntary rapid, purposeless movements. Erythema marginatum Subcutaenous nodule RF clinical features (minor criteria) Minor manifestations are (nonspecific): 1) Fever. 2) Arthralgia.(synovial+ joint) 3) Elevated CRP& ESR 4) Leukocytosis 5) ECG changes 6) Previous episode of rheumatic fever or inactive heart disease RF- Diagnosis The diagnosis is established by the so- called Jones criteria: 1) Evidence of a preceding group A streptococcal infection. 2) Presence of two of the major manifestations listed above or one major and two minor manifestations (nonspecific: fever, arthralgia, elevated CRP). Heart valvular disease objectives Causes of valvular heart disease. Pathophysiology &clinical features of rheumatic heart diseases. Pathogenesis of infective endocarditis and list its predisposing factors and causes. Infective endocarditis Infective Endocarditis = IE Definition: Infection of the cardiac& endocardium valves, with formation of adherent colonization or invasive mass of thrombotic debris and organisms, termed a vegetation. Any microorganism may be present, but most cases are bacterial Infective endocarditis (IE) Vegetations: composed of thrombotic debris and organisms, often associated with destruction of the underlying cardiac tissues. Vegetations Very dangerous and virulence, difficult to cure, required surgery. Death days to weeks if not treated. Infective endocarditis (IE) Classification according Infective agents: 1) Bacterial infection (Bacterial endocarditis) 2) Fungal infection 3) Non- infective endocarditis (sterile) Infective endocarditis (IE) Clinical classification: 1) Acute infective endocarditis necrotizing, ulcerative, destructive lesions. necrotizing, ulcerative, destructive lesions. 1) Sub-acute endocarditis the organisms are of lower virulence, forming insidious infections of deformed valves that are less destructive. the organisms are of lower virulence, forming insidious infections of deformed valves that are less destructive. IE-risk group Predisposing factors Valve abnormalities. * preexisting cardiac abnormalities. * preexisting cardiac abnormalities. * prosthetic heart valves. * prosthetic heart valves. * Congenital HD or repaired * Congenital HD or repaired Dental or surgical procedure. Contaminated needle shared by IV drug Breaks in the epithelial barriers of the gut, oral cavity, or skin. Infective endocarditis (IE) pathogenesis IE: around 30% occur on normal valves. Predisposition factor such as: Predisposition factor such as: Cardiac abnormality (congenital, autoimmune, surgery, elderly).which creates turbulence, and endothelial injury, such as valve stenosis/regurgitation, prosthesis, septal defect. Infective endocarditis (IE) pathogenesis Microorganisms agent: Microorganisms agent: Streptococcus viridans (oral cavity normal flora) can infect either healthy or deformed valves. can infect either healthy or deformed valves. Virulent S. aureus - found on the skin can infect either healthy or deformed valves. Infective endocarditis (IE) pathogenesis HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella), all commensals in the oral cavity. Prosthetic valve endocarditis is caused by coagulase-negative staphylococci (e.g., S. epidermidis). Others cause of IE is fungal infection (non- bacterial). IE Morphological changes common site Aortic valve left heart Mitral valve left heart Right heart involved mainly in drugs abuser. Single or multiple lesion > one valve. IE morphology (Acute) Vegetations: presence of friable, bulky, potentially destructive ( made up of fibrin, inflammatory cells, and bacteria or other organisms) on heart valves. Ring abscess: erosion into the underlying myocardium and produce an abscess. Emboli shed from vegetations; leading to sequelae such as septic infarcts or mycotic aneurysms. Acute endocarditis of congenital bicuspid aortic valve Extensive cuspal destruction and ring abscess Histologic appearance of vegetation abscess formation IE morphology (sub-acute) Sub-acute endocarditis: - Less valvular destruction. - Less valvular destruction. - Vegetations with granulation tissue, - Vegetations with granulation tissue, indicative of healing process in the base. indicative of healing process in the base. - fibrosis, calcification, and a chronic inflammatory infiltrate can develop. - fibrosis, calcification, and a chronic inflammatory infiltrate can develop. IE clinical features Acute Symptoms: Explosive rapidly developing fever, chills, weakness, and lassitude, Weight loss. Signs: Cardiac Murmurs, Splenomegaly Clubbing of Fingers. Systemic embolization- effects: 1) Mycotic aneurysm(weak vessel, hemorrhage) 2) 2) Renal Lesions, Infarcts, GN ( trapping of immune complexes ) 3) Brain. Sub-ungual finger - small splinter hemorrhages in a patient with infective endocarditis Diagnostic Criteria for Infective Endocarditis I) - Pathological criteria: - Histologic findings (+ve vegetation or abscess). - Histologic findings (+ve vegetation or abscess). - Positive +ve for Microorganisms, or by culture). - Positive +ve for Microorganisms, or by culture). - Embolus - Embolus II) - Clinical criteria: (a) Major - Blood culture(s) positive multiple. (a) Major - Blood culture(s) positive multiple. Echocardiographic identification trans-eosph Echocardiographic identification trans-eosph New valvular regurgitation. New valvular regurgitation. (b) Minor- fever, not diagnostic Echo, (b) Minor- fever, not diagnostic Echo, Other not-significant bacteria, vascular lesion Other not-significant bacteria, vascular lesion Immunological phenomena e.g GN Immunological phenomena e.g GN Duke Diagnostic criteria: (physical, lab, echo, blood cultutre) Duke Diagnostic criteria: (physical, lab, echo, blood cultutre) NON-INFECTED (Sterile) VEGETATIONS Caused by: 1) Nonbacterial thrombotic endocarditis: - Non-invasive vegetation (small sterile thrombi). - Non-invasive vegetation (small sterile thrombi). - No inflammation detected. - No inflammation detected. - Single or multiple along the line of closure of the leaflets or cusps. - Single or multiple along the line of closure of the leaflets or cusps. 2) The endocarditis of (SLE), called Libman- Sacks endocarditis. Nonbacterial thrombotic endocarditis (NBTE). Thrombotic vegetations along the line of closure of the mitral valve Nonbacterial thrombotic endocarditis (NBTE Bland thrombus, no inflammation in the valve cusp IE Complications Myocarditis & valvular defect > 90% Renal: Infarction& Glomerulonephritis. Brain: Infarction& retinal emboli. Splenomegaly & infarct +\-. Hematuria. Splinter hemorrhages & clubbing. VHD Frequent causes VHD Frequent causes VALVULAR DEGENERATION ASSOCIATED WITH CALCIFICATION - Aortic stenosis ( RF, degenerative) - Aortic stenosis ( RF, degenerative) - Mitral annular calcification - Mitral annular calcification - Mitral stenosis - Mitral stenosis MITRAL VALVE PROLAPSE (MYXOMATOUS DEGENERATION OF THE MITRAL VALVE) Aortic stenosis-Morphology Macroscopic of nonrheumatic, calcific aortic stenosis (either tricuspid or bicuspid valves): 1) H eaped-up protruded calcified masses. 2) The free edges of the cusps are not involved. 3) In rheumatic (and congenital) aortic stenosis commissural fusion is not seen. Microscopic: 1) large nodular calcific deposits Calcified aortic valve stenosis of old age Congenitally Bicuspid Aortic Valve BAV Most frequent congenital CVS malformation. BAVs are predisposed to progressive degenerative calcification. Responsible for 50% of cases of aortic stenosis BAVs 2 functional cusps, unequal size, incomplete commissural separation. BAVs 2 functional cusps, unequal size, incomplete commissural separation. complications of BAV include: Aortic stenosis or regurgitation, Infective endocarditis, Aortic dilation OR dissection. Mitral annular calcification Defined as degenerative calcific deposits Site: in fibrous ring (annulus) of mitral valve. Common in women over > age 60. Grossly, irregular, stony hard, occasionally ulcerated nodules (25 mm in thickness). NOT affect valvular function GENERALLY. NOT affect valvular function GENERALLY. May lead to: MR, MS, Arrhythmias, thrombosis, embolism, Infective endocarditis. May lead to: MR, MS, Arrhythmias, thrombosis, embolism, Infective endocarditis. Mitral Stenosis Overview Definition: Obstruction of LV inflow that prevents proper filling during diastole Normal MV Area: 4-6 cm 2 Rheumatic carditis is the predominant cause Prevalence and incidence: decreasing due to a reduction of rheumatic heart disease. Etiology: RF, Infective endocarditis, annular calcification. Macroscopic: Thickened rigid leaflets & chordae tendineae- fish-mouth deformity Macroscopic: Thickened rigid leaflets & chordae tendineae- fish-mouth deformity Hypertrophied and dilated left atrium, thrombi Hypertrophied and dilated left atrium, thrombi Mitral stenosis show diffuse fibrous thickening &distortion commissural fusion MITRAL VALVE PROLAPSE (MYXOMATOUS DEGENERATION )(MPV) Definition: Mitral valve leaflets (one or both) are floppy and prolapse, or balloon back, into the left atrium during systole. - The histologic change in the tissue is called myxomatous degeneration. myxomatous degeneration. - MVP affects approximately 3% of adults in USA. - Pathogenesis of MVP: Unknown, Uncommonly, MVP is associated with heritable disorders of CT diseases. Mitral valve Pronounced hooding of MV with thrombotic plaques Myxoid degeneration, heart valve Complication of valvular disease (1) infective endocarditis. (2) Insufficiency, Stenosis- if massive-Fatal. (2) Insufficiency, Stenosis- if massive-Fatal. (3) Chordal rupture. (3) Stroke or other systemic infarct, resulting from embolism of leaflet thrombi. (4) Arrhythmias, both ventricular and atrial (5) Heart failure (6) Pulmonary edema venous congestion. (7) Hypertrophy and dilatation of atrium. Heart valvular disease objectives Causes of valvular heart disease. Pathophysiology &clinical features of rheumatic heart diseases. Pathogenesis of infective endocarditis and list its predisposing factors and causes.