Hypertensive Heart DiseaseSYSTEMIC (LEFT-SIDED) HYPERTENSIVE HEARTDISEASE: Criteria for diagnosis :(1) left ventricular hypertrophy ( concentric)(2) history or pathologic evidence of hypertension. Asymptomatic and suspected only by ECG orEchocardiographic indications of left ventricularenlargement.
Atrial fibrillation (owing to left atrial enlargement),or C.H.F with cardiac dilation, or both. Effective control of hypertension can prevent orlead to regression of cardiac hypertrophy andits associated risks.Morphology: Left ventricular hypertrophy . Left ventricular wall thickness may exceed 2 cmand heart weight may exceed 500 gm.
Microscopically:o The earliest change is increase in transversediameter of myocytes.o At more advanced stage cellular and nuclearenlargement becomes more irregular withvariation in cell size , and interstitial fibrosis.
PULMONARY (RIGHT-SIDED) HYPERTENSIVE HEARTDISEASE (COR PULMONALE): Right ventricular ( hypertrophy, dilation, and failure )secondary to pulmonary hypertension caused bydisorders of lungs or pulmonary vasculature . Those caused by diseases of left side of heart, orcongenital heart diseases are excluded.
Cor pulmonale may be acute or chronic,depending on suddenness of developmentof pulmonary hypertension:- Acute cor pulmonale: can follow massivepulmonary embolism. Chronic cor pulmonale: usually secondary toprolonged pressure overload caused byobstruction of pulmonary arteries or arterioles.
Morphology: Acute cor pulmonale: marked dilation of rightventricle without hypertrophy. Chronic cor pulmonale: right ventricular wallthickens up to 1.0 cm or more, and may evenapproximate that of left ventricle.
Cardiomyopathies: Heart disease resulting from a primaryabnormality in myocardium. Three patterns:o Dilated cardiomyopathy.o Hypertrophic cardiomyopathy.o Restrictive cardiomyopathy. The dilated form is most common (90% of cases),and the restrictive is least prevalent.
DILATED CARDIOMYOPATHY:Also called congestive cardiomyopathy.Causes: Familial (genetic) : autosomal dominant. Toxicities: chronic alcoholism. Myocarditis. pregnancy-associated nutritional deficiency. Immunologic reaction. In some patients: unknown ( idiopathic ).
Morphology: Heart is large and flabby, with dilation of allchambers. Mural thrombi are common and may be a sourceof thromboemboli. Mitral or tricuspid regurgitation results fromventricular chambers dilation (functionalregurgitation). Muscle cells are attenuated, stretched, and irregular. Interstitial and endocardial fibrosis of variabledegree is present
Clinical Features: Occur at any age, but usually between 20 and 50 y’s. Slowly progressive signs and symptoms of CHFsuch as shortness of breath, and easy fatigability. Secondary mitral regurgitation and abnormalcardiac rhythms are common. Death is due to progressive cardiac failure orarrhythmia and can occur suddenly. Embolism from dislodgment of an intracardiacthrombus may occur. Cardiac transplantation is only hope.
HYPERTROPHIC CARDIOMYOPATHY : characterized by: myocardial hypertrophy,abnormal diastolic filling, and in one third of casesintermittent ventricular outflow obstruction.Morphology: Massive myocardial hypertrophy withoutventricular dilation. disproportionate thickening of ventricular septumas compared with free wall of left ventricle (ratiogreater than 3:1) termed asymmetrical septalhypertrophy.
On cross-section: ventricular cavity has"banana-like" configuration by bulging ofventricular septum into lumen. Microscopically:(1) Extensive myocyte hypertrophy withtransverse myocyte diameters greater than 40 µm(normal 15 µm).(2) Haphazard disarray of myocytes.(3) Interstitial and replacement fibrosis.
Pathogenesis: H.C.M caused by a mutation in any one ofseveral genes that encode proteins that arepart of sarcomere. Sarcomere is the contractile unit of cardiac andskeletal muscle. Most cases are familial and pattern of transmissionis autosomal dominant with variable expression. Remaining cases appear to be sporadic.
Mutations are found in at least 12 sarcomeric genes. Including: β-myosin heavy chain (β-MHC),cardiac troponinT, α-tropomyosin, andmyosin-binding protein C (MYBP-C). Of these, mutation in β-MHC gene is most common .
Clinical Features: Impaired diastolic filling of massivelyhypertrophied left ventricle. 25% of patients have dynamic obstruction toleft ventricular outflow. Limitation of cardiac output and secondaryincrease in pulmonary venous pressure causeexertional dyspnea. Harsh systolic ejection murmur, caused byventricular outflow obstruction .
Owing to massive hypertrophy: myocardial ischemiacommonly results, even in absence of concomitantCAD, and thus anginal pain is frequent. The major clinical problems in H.C.M are:o atrial fibrillation with mural thrombus formation ,and possibly embolization.
o infective endocarditis of mitral valve.o intractable cardiac failure.o ventricular arrhythmias , and sudden death. Hypertrophic cardiomyopathy is one of the mostcommon causes of sudden, otherwise unexplained,death in young athletes.
RESTRICTIVE CARDIOMYOPATHY : Decrease in ventricular compliance, resulting inimpaired ventricular filling during diastole. The contractile (systolic) function of left ventricleis usually unaffected. Idiopathic ; or associated with distinct diseasesthat affect myocardium: radiation fibrosis,amyloidosis, sarcoidosis, or metastatic tumor.
Morphology: Ventricles are of normal size or slightly enlarged. Cavities are not dilated, and myocardium is firm. Microscopically: patchy or diffuse interstitial fibrosis,which can vary from minimal to extensive.amorphous deposits of pale pink material between myocardial fibers.This is characteristic for amyloid. Amyloidosis is a cause for restrictive cardiomyopathy.
Valvular Heart Disease: Valvular involvement by disease causes stenosis,insufficiency (regurgitation or incompetence), or both. Stenosis is failure of a valve to open completely,thereby impeding forward flow. Insufficiency, in contrast, results from failure of a valveto close completely, thereby allowing reversed flow. Valvular abnormalities may be caused by congenitaldisorders , or by a variety of acquired diseases. The most important causes of acquired heart valvediseases are:
VALVULAR DEGENERATION CAUSED BY CALCIFICATION : due to calcific deposits (composed of calcium phosphatemineral). The most frequent calcific valvular diseases are:-Calcific Aortic Stenosis:It is the consequence of calcification owing to progressiveand advanced age-associated "wear and tear“ injuryMorphology:The morphologic hallmark of calcific aortic stenosis isheaped-up calcified masses within the aortic cusps.( a heavily calcified aortic valve removed at the time of surgical valve replacement )
Clinical Features: obstruction to left ventricular outflow leads togradually increasing pressure gradient across thecalcified valve. cardiac output is maintained by development ofconcentric left ventricular (pressure overload)hypertrophy. The hypertrophied myocardium tends to be ischemicand angina pectoris may appear. There may be impairment of both systolic and diastolicmyocardial function, with symptoms of CHF. such patients require prompt relief of obstruction bysurgical valve replacement.
Mitral Annular Calcification: Degenerative calcific deposits can develop in fibrousring (annulus) of mitral valve. The process generally does not affect valvular function. however, it may lead either to:o regurgitation by interfering with systolic contraction ofmitral valve ring.o stenosis by impairing opening of mitral leaflets.o arrhythmias and occasionally sudden death by calciumdeposits penetrating sufficiently deeply to impinge onatrioventricular conduction system.
Mitral annulus calcification: pathology specimenThis autopsy specimen demonstrates thickened mitral valve leafelts, with marked stenosis.The mitral annulus calcification is seen as pale white lumps under the endothelium aroundthe margins of the valve
MYXOMATOUS DEGENERATION OF MITRAL VALVE(MITRAL VALVE PROLAPSE): one or both mitral leaflets are "floppy" and prolapse, orballoon back into left atrium during systole. most often in young women. Usually an incidental finding on physical examination. may lead to serious complications in minority of cases.Morphology: ballooning (hooding) of mitral leaflets. leaflets are often enlarged, redundant, thick, andrubbery. Chordae tendineae are elongated, thinned, andoccasionally ruptured.
Slide Description: This is floppy mitral valve seen from above (left).Note also the thickened, distorted tricuspid valve, probablyrheumatic in origin.
Pathogenesis: there is developmental defect of connective tissue,possibly systemic. So it is a common feature of Marfan syndrome (causedby mutations in gene encoding fibrillin-1 )Clinical Features: Most patients are asymptomatic, discovered on routineexamination by presence of a midsystolic click . when mitral regurgitation occurs, there is a late systolicor sometimes holosystolic murmur. A minority of patients have chest pain mimickingangina, dyspnea, and fatigue.
RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE : Rheumatic fever ( RF ) is an acute, immunologicallymediated, multisystem inflammatory disease thatoccurs a few weeks following an episode of group Astreptococcal pharyngitis. Acute rheumatic carditis during active phase of RF mayprogress to chronic rheumatic heart disease (RHD). The most important consequence of RV is chronicvalvular deformities, characterized principally bydeforming fibrotic valvular disease (particularly mitralstenosis)
Morphology: During acute RF, focal inflammatory lesions are foundwithin heart called Aschoff bodies ( rheumaticgranuloma ). Aschoff bodies consist of foci of degenerated collagensurrounded by lymphocytes (primarily T cells),occasional plasma cells, and plump macrophages calledAnitschkow cells (pathognomonic for RF). Anitschkow cells have abundant cytoplasm and centralround-to-ovoid nuclei in which the chromatin isdisposed as a central, slender, wavy ribbon (hence thedesignation "caterpillar cells"). Some of larger macrophages become multinucleated toform Aschoff giant cells.
Aschoff bodies may be found in any of three layers ofheart ( pericardium, myocardium, or endocardium )hence the lesion is called pancarditis. involvement of endocardium and left-sided valvesresults in fibrinoid necrosis within cusps or alongchordae tendineae . on which sit small (1- to 2-mm) vegetations (verrucae)along lines of closure. These irregular, warty projections (verrucae ) arise fromprecipitation of fibrin at sites of erosion, related tounderlying inflammation and collagen degeneration.
Chronic RHD is characterized by organization of acuteinflammation and subsequent fibrosis. valvular leaflets become thickened and retracted,causing permanent deformity. Microscopically there is diffuse fibrosis and oftenneovascularization that obliterate the originallyavascular leaflet architecture.In chronic rheumatic mitral valvulitis the valve leaflets and chordae tendineae arethick, rigid, and interadherent.
Pathogenesis: acute rheumatic fever is a hypersensitivity reactioninduced by group A streptococci. antibodies directed against M proteins of certain strainsof streptococci cross-react with glycoprotein antigensin heart, joints, and other tissues. The onset of symptoms 2 to 3 weeks after infection andthe absence of streptococci from the lesions supportthe concept that RF results from an immune responseagainst the offending bacteria.
Clinical Features: RF is characterized by major manifestations:(1) migratory polyarthritis of large joints,(2) carditis.(3) subcutaneous nodules.(4) erythema marginatum of skin.(5) Sydenham chorea ( neurologic disorder withinvoluntary purposeless, rapid movements ). The diagnosis is established by so-called Jones criteria:the presence of two of major manifestations, or onemajor and two minor manifestations ( fever, arthralgia,or elevated blood levels of acute phase reactants-CRP).
Acute RF appears most often in children betweenages 5 and 15, but about 20% of first attacks occurin middle to later life. Although pharyngeal cultures for streptococci arenegative by the time the illness begins, antibodiesto one or more streptococcal enzymes, such asstreptolysin O and DNAse B are present and can bedetected in sera of most patients.
INFECTIVE ENDOCARDITIS (IE ): is characterized by colonization or invasion of heartvalves or endocardium by a microbe, leading toformation of bulky friable vegetations composed ofthrombotic debris and organisms, often associated withdestruction of underlying cardiac tissues. Although fungi, rickettsiae (Q fever), and chlamydiaehave been responsible for these infections, most casesare bacterial (bacterial endocarditis).
Etiology and Pathogenesis: classified on clinical grounds into acute and subacuteforms. Acute endocarditis: destructive infection of a previouslynormal heart valve with a highly virulent organism(S. aureus ) as in intravenous drug abusers. Subacute endocarditis: organisms of low virulence(Streptococcus viridans )can cause infection ina previously deformed valves. Prosthetic valve endocarditis is caused most commonlyby coagulase-negative staphylococci ( S. epidermidis).
Morphology: In both subacute and acute forms friable, bulky, anddestructive vegetations containing fibrin, inflammatorycells, and bacteria or other organisms are present onheart valves . The aortic and mitral valves are most common sites ofinfection The vegetations may be single or multiple and mayinvolve more than one valve. Vegetations sometimes erode into underlyingmyocardium to produce an abscess cavity (ring abscess). Fungal endocarditis tends to cause large vegetationsthan does bacterial infection.
Systemic emboli may occur because of friable nature ofvegetations, and may cause infarcts in brain, kidneys,myocardium, and other tissues. Because the embolic fragments contain large numbers ofvirulent organisms, abscesses often develop at sites ofsuch infarcts (septic infarcts). With passage of time, fibrosis, calcification, and chronicinflammatory infiltrate may develop.
Mitral vegetation in a 78-year-old man with infective endocarditis.Intraoperative photograph shows a large vegetation (arrow) adhering to posteriormitral leaflet (arrowhead).
Diagnostic Criteria for Infective EndocarditisPathologic Criteria:Microorganisms, demonstrated by culture or histologic examination, in a vegetation, embolus from avegetation, or intracardiac abscess.Clinical Criteria:Major:-Positive blood culture(s) indicating characteristic organism.Echocardiographic findings ; including valve-related or implant-related mass or abscess, or partialseparation of artificial valve.New valvular regurgitation.Minor:-Predisposing heart lesion or intravenous drug use.Fever.Vascular lesions ; including arterial petechiae, subungual/splinter hemorrhages , emboli, septic infarcts,mycotic aneurysm, intracranial hemorrhage, Janeway lesions.Immunologic phenomena ; including glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor.Microbiologic evidence ; including single culture showing uncharacteristic organism.Echocardiographic findings consistent with but not diagnostic of endocarditis ; including new valvularregurgitation, pericarditis.
Diagnosis by Duke Criteria, requires either pathologic orclinical criteria; if clinical criteria are used, 2 major, or 1major + 3 minor, or 5 minor criteria are required fordiagnosis. Janeway lesions are small erythematous lesions onpalms and soles. Osler nodes are small subcutaneous nodules in pulp ofdigits. Roth spots are oval retinal hemorrhages with palecenters. Prevention of IE is done by prophylactic use ofantibiotics in patient with cardiac anomaly or artificialvalve who is about to have a dental, surgical, or otherinvasive procedure.
Nonbacterial Thrombotic Endocarditis (NBTE): NBTE is characterized by deposition of small masses(1 to 5 mm) of fibrin, platelets, and other bloodcomponents on leaflets of cardiac valves. In contrast to vegetations of IE, the valvular lesions ofNBTE are nondestructive , sterile and do not containmicroorganisms. NBTE is often encountered in debilitated patients,such as those with cancer or sepsis ( hence previouslytermed marantic endocarditis). NBTE may producing emboli and resultant infarcts inbrain, heart, or elsewhere.