Cardiac Valve Pathology Lecture PDF

Cardiac Valve Pathology Eugen Petcu, MD, PhD Associate Professor, Department of Biomedical Sciences [email protected] All the images and information included in this presentation are from Robbins and Cotran, Pathologic Basis of Disease, 10th edition  Session Objectives At the...

Cardiac Valve Pathology Eugen Petcu, MD, PhD Associate Professor, Department of Biomedical Sciences [email protected] All the images and information included in this presentation are from Robbins and Cotran, Pathologic Basis of Disease, 10th edition  Session Objectives At the conclusion of the session, you will be able to: Describe and explain the most important features defining cardiac valvular disease Compare and contrast the causes and consequences of aortic valve stenosis Define mitral valve prolapse and mitral annular calcification Demonstrate an understanding of the etiopathogenesis of acute rheumatic fever and rheumatic heart disease Summarize the pathology of acute and subacute infective endocarditis, as well as their associated macroscopic, microscopic, and clinical consequences Differentiate between nonbacterial endocarditis and Libman-Sacks endocarditis Valvular disease Valvular disease may result in stenosis, or both. Stenosis: it is caused by a primary cuspal abnormality determined by a chronic process: calcification or valve scarring. Insufficiency: is caused by an intrinsic disease of the valve cusps (e.g., The Outcome: depends on: endocarditis) or disruption of the supporting structures (tendinous the valve involved cords, papillary muscles). the degree of impairment the tempo of its development It can appear abruptly, as with chordal rupture, or insidiously as a the compensatory mechanisms. consequence of leaflet scarring and retraction Rapid destruction of an aortic valve cusp by infection can cause massive Valvular disease can involve only one valve (the mitral valve being the regurgitation and the abrupt onset of most common target), or more than one valve. cardiac failure. Rheumatic mitral stenosis usually Turbulent flow through diseased valves murmurs progresses over years, and its clinical effects are well tolerated until late in the Severe stenosis thrills (may be palpated) course. Etiology Valvular abnormalities can be congenital or acquired The most common congenital valvulopathy is a bicuspid aortic valve, containing only two functional cusps instead of the normal three Acquired valvulopathies: stenoses of the aortic and mitral valves account for approximately two thirds of all valve disease. Calcific Aortic Stenosis Most cases asymptomatic calcifications on a CXR In some patients, it can be severe enough to require surgical intervention. The incidence parallels longevity. In normal valves: when patients reach their 70s and 80s; A) Calcific aortic stenosis of a previously normal. Nodular masses of calcium are heaped up within the sinuses of Valsalva (arrow). In bicuspid valves: when patients reach their 40s and 50s B) Calcific aortic stenosis occurring on a congenitally bicuspid valve. One cusp has a partial fusion at its center, called a raphe (arrow) Pathogenesis Simple progressive age-associated “wear and tear” Cuspal fibrosis and calcification Equivalent of atherosclerosis It is associated with hyperlipidemia, hypertension, inflammation, and other factors implicated in atherosclerosis C) Fused commisures in rheumatic aortic valve stenosis Congenital Bicuspid Aortic Valve thrombus calcifications In ~1% of the population; ~50% of cases of aortic stenosis in adults Familial clustering  associated with mutation in NOTCH1 Morphology: two functional cusps, usually unequal in size Larger valve  has midline raphe (from incomplete commissural separation during development) Raphe = major site where calcific deposits occur Calcific Aortic Stenosis Histology The calcified masses generally start at the base. Calcium deposition leads to a reduction of the valve functional area which determines outflow obstruction and pressure overload. nodular calcific deposits Calcific Aortic Stenosis Physiopathology Obstruction Left ↑ Pressure and Ventricle Hypertrophy Heart Failure Gradient Narrowing Pressure ↑ Ischemia, Angina, Syncope Exhaustion of compensatory cardiac function Mitral Valve Prolapse (MVP) One or both mitral leaflets are “floppy” and prolapse—they balloon back into the left atrium during systole. Associated conditions Marfan syndrome Ehlers-Danlos syndrome Pathogenesis polycystic kidney disease myxomatous degeneration of the mitral valve fragile X syndrome -valvular leaflets become abnormal secondary to excessive degradation of collagen and elastin by Etiology proteolytic enzymes Myxomatous degeneration accumulation of proteoglycans -the chordae tendinae become weakened and -Primary spontaneous elongated -Secondary to a connective tissue -annular dilation of the mitral valve disorder. connective tissue disorders Rheumatic fever deficiency in collagen and elastin cause leaflets to Myocardial infarction be mostly thin and translucent Mitral Valve Prolapse Morphology -prominent hooding with prolapse of the posterior mitral leaflet (arrow) into the left atrium; -the atrium also is dilated suggesting long-standing valvular insufficiency and volume overload Normal heart valve (D) and myxomatous mitral valve (E). E: collagen in the fibrosa layer is loose and disorganized, proteoglycan deposition in the central spongiosa layer is markedly expanded  Mitral Annular Calcification (MAC) MAC is most commonly an incidental finding requiring no specific treatment other than assessment and modification of cardiovascular risk factors. See in women > 60 years old; especially in those with myxomatous mitral valve or elevated left ventricle pressure Pathogenesis: degenerative calcific deposits that develop in the fibrous annulus. MAC may be associated with atherosclerosis. The most important intervention for most Irregular, stony hard, occasionally patients with MAC is evaluation and treatment ulcerated nodules at the base of the of standard cardiovascular risk factors. leaflets  Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) Acute rheumatic fever RF is immunologically mediated, multisystem inflammatory disease that occurs after group A β-hemolytic streptococcal infections (pharyngitis, and occasionally infections at other sites, such as skin). Rheumatic heart disease RHD is the cardiac manifestation of acute rheumatic fever. It is associated with inflammation of all parts of the heart, but valvular inflammation and scarring produce the most important clinical features. CDC Rheumatic heart disease is essentially the only cause of acquired mitral stenosis. Pathogenesis RHD is an immunological reaction: streptococci are completely absent from the lesions. A genetic susceptibility is likely to influence the development of the cross-reactive immune ARF is a host immune responses to group A responses. streptococcal antigens that cross-react with host proteins. 1. Ab-Ag binding can activate Complement 2. Cytokine production by the stimulated T cells leads to macrophage activation https://labpedia.net/elementary-immunology/chapter-25- autoimmune-diseases-rheumatic-fever/ ARF Clinical Features 3% of patients: typically appears 10 days to 6 weeks after a group A streptococcal infection. It occurs most often in children between 5 and 15 years of age Acute carditis: Pericardial friction rubs Tachycardia Arrhythmias. Myocarditis Mitral valve insufficiency Heart failure. 1% of affected individuals die of fulminant RF involvement of the heart. Arthritis typically begins with migratory polyarthritis (accompanied by fever) in which one large joint after another becomes painful and swollen for a period of days and then subsides spontaneously, leaving no residual disability Acute Rheumatic Fever Subcutaneous nodules present on extensor surfaces Erythema marginatum : irregular skin rash areas Semantic Scholar Sydenham chorea : neurologic disorder with involuntary rapid movement (dance -like movements) Dermatology Advisory Sydenham’s Chorea  ARF Morphology Myocarditis Distinctive lesions in the heart—called Aschoff bodies —are composed of foci of T lymphocytes, occasional plasma cells, and plump activated macrophages called Anitschkow cells. Diffuse inflammation and Aschoff bodies may be found in any of the three layers of the heart, resulting in pericarditis, myocarditis, or endocarditis (pancarditis). Aschoff body in a patient with acute carditis. The myocardium exhibits a circumscribed nodule of mixed mononuclear inflammatory cells with associated necrosis. Within the inflammation, large activated macrophages show prominent nucleoli, as well as chromatin condensed into long, wavey ribbons (caterpillar cells) represented by the arrows. These are also known as Anitschkow cells. Endocarditis – Irregular, warty projects/vegetations along the lines of closure Pericarditis – “bread and butter”  fibrinous pericardial exudate RHD Clinical Features It is diagnosed years or even decades after the initial episode of RF Cardiac murmurs Cardiac hypertrophy and dilation Heart failure Arrhythmias Thromboembolic complications Endocarditis Variable prognosis Surgical repair of diseased valves Replacement of diseased valves Chronic Rheumatic Heart Disease Morphology The mitral valve is virtually always involved in chronic RHD; It is affected in isolation in roughly two-thirds of cases. It is affected along with the aortic valve in another 25%. Tricuspid valve and pulmonary valve are only rarely affected In rheumatic mitral stenosis, calcification and fibrous bridging across the valvular commissures create “fish mouth” stenoses. If severe, the left atrium progressively dilates and may harbor mural thrombi that can embolize. Congestive changes in the lungs may induce pulmonary vascular and parenchymal changes; over time, these can lead to right ventricular hypertrophy. Infective Endocarditis (IE) =microbial infection of the heart valves or the mural endocardium that leads to the formation of vegetations composed of thrombotic debris and organisms, often associated with destruction of the underlying cardiac tissues.. Acute and subacute forms Acute IE : infection of a previously normal heart valve by a highly virulent organism (e.g., Staphylococcus aureus ) that rapidly produces destructive lesions. Difficult to cure with antibiotics alone and often require surgery Substantial morbidity and even mortality. Subacute IE: infection of a deformed valve by organisms with lower virulence (e.g., viridans streptococci) that cause insidious infections; Overall less destruction. Protracted course of weeks to months Cures can often be achieved with antibiotics alone Infective Endocarditis Risk Factors Rheumatic Heart Disease Mitral Valve Prolapse Degenerative Calcific Valvular Stenosis Prosthetic Valves Congenital Defects Immunocompromised patients (i.e., drug abuse disorder, neutropenia, immunodeficiency, malignancy, diabetes) Infective Endocarditis Clinical Features Acute endocarditis has a stormy onset with rapid onset of Fever Chills Weakness Fever is the most consistent sign of IE; it can be slight or absent, in older adults. Murmurs are present in the majority of patients, either from a new valvular defect or from a preexisting abnormality.  Infective Endocarditis Etiology 60% of cases : Streptococcus viridans (a commensal in the oral cavity) Virulent S. aureus found on the skin can infect either healthy or deformed valves -20% to 30% of cases overall Other bacterial causes :-Enterococci -HACEK group : -Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella -Commensals in the oral cavity. Gram-negative bacilli and fungi : rarely Prosthetic valve endocarditis occurring in the 1 to 2 months after surgical implantation is typically caused by skin flora , S. aureus and S. epidermidis ; prosthetic valve infections 1 year or more after surgery tend to be caused by streptococci.  Infective Endocarditis Morphology: Vegetations The aortic and mitral valves are the most common sites of infection (A) Subacute IE of mitral valve : large, friable vegetations caused by S. viridans are indicated by arrows. (B) Acute IE of congenitally bicuspid aortic valve caused by Staphylococcus aureus : extensive cuspal destruction and ring abscess (arrow). Infective Endocarditis Histology Vegetation: fibrin platelets inflammatory cells bacteria Infective Endocarditis Simple Cardiology Merck Manual A. Janeway lesions B. Roth spots D. Osler nodes https://medpics.ucsd.edu/index.cfm?c urpage=image&course=clinImg&mode C. Splinter hemorrhages =browse&lesson=118&img=2172  Nonbacterial Thrombotic Endocarditis Valvular damage is not a prerequisite for NBTE; this condition usually occurs on previously normal valves. NBTE is often seen in those with cancer-particularly mucinous adenocarcinomas, sepsis or associated with hypercoagulable states Disseminated intravascular coagulation Hyperestrogenic states Endocardial trauma, as from an indwelling catheter, is a well-recognized predisposing condition. A. Nearly complete row of thrombotic vegetations along the line of closure of the mitral valve leaflets (arrows) B. Histology of bland vegetation, with virtually no inflammation in the valve cusp (c) or the thrombotic deposit (t). The thrombotic material (fibrin, platelets, blood components) is only loosely attached to the cusp (arrow) Libman-Sacks Endocarditis Small (1-4 mm), sterile vegetations in patients who have systemic lupus Vegetations erythematosus. Vegetations are due to immune complex deposition with activation of complement. Vegetations can occur on any valve surface, chordae, or on the atrial and ventricular endocardium Can lead to fibrosis, scaring and fusion of leaflets Histology: intense valvulitis and fibrinoid necrosis: fine, granular, pink-tan, fibrinous eosinophilic material https://www.an nalsthoracicsurg ery.org/article/S 0003- 4975(17)30185- 6/fulltext Photomicrograph shows section of mitral valve leaflet vegetation with deposition of fibrin and small collections of neutrophils and monocytes, Vegetations but no bacterial colonies Summary General features defining cardiac valvular disease Aortic Stenosis - Congenital bicuspid valve - Acquired - Equivalent of the age-related atherosclerosis - ”wear and tear” mechanism Infective Endocarditis -acute vs subcaute Mitral Valve Prolapse -etiology, morphology, clinico-pathological consequences. -floppy leaflets, myxomatous degeneration -Streptococcus viridans vs Staphiloccocus aureus -Janeway lesions, Roth spots, Nail bed or Splinter Mitral Annular Calcification hemorrhages, Oser nodules - most of the time no therapy, associated with coronary and atherosclerotic disease. Nonbacterial thrombotic endocarditis -mucinous adenocarcinoma, hypercoagulable states, sterile Acute Rheumatic Fever vs Rheumatic Heart Disease vegetations/thrombi, infarcts - group A beta hemolytic streptococci -Aschoff bodies, Anitschikow cells Libman-Sacks endocarditis -ARF JONES major criteria -SLE, immune complex depositions, valvulitis, fibrinois -RHD-the only cause of acquired mitral stenosis “fish- necrosis. mouth” pattern (please also see table on slide 4) Lecture Feedback Form: https://comresearchdata.nyit.edu/redcap/surveys/?s=HRCY448 FWYXREL4R