Sakchai Chitpakdee, M.D.

ContentsArteriosclerosisTumors of blood vesselsHeart failureIschemic heart diseaseValvular heart diseasesRheumatic heart diseaseInfective endocarditisMyocarditisPericardial diseases

Arteriosclerosis

= hardening of the arteriesAtherosclerosis ○ Large & medium size vesselsMonckeberg medial calcific sclerosis○ Medium size vessels with tunica media

calcificationArteriolosclerosis○ Small arteries/arterioles

Atherosclerosis

“intimal lesion”: atheromas or fibrofatty plaques or atheromatous plaques”Large and medium size arteries

Raised focal plaque within the intimaCore lipid (cholesterol/cholesterol esters) and a covering fibrous capCells: foamy cells (macrophage/SMC), lymphocytes

Atherosclerosis

Complicated lesion:CalcificationRupture/ulceration -> atheroemboli, thrombusHemorrhage ThrombosisAneurysmal dilation

AtherosclerosisEpidemiology & risk factors:

Age: middle or later ageSex: pre-menopause -> M > F

60s to 70s -> M = FGenetics: familialHyperlipidemia: high cholesterol/TG & ↓ HDLHypertensionCigarette smokingDiabetes mellitus

Atherosclerosis

Epidemiology & risk factors:Elevated plasma homocysteineOther factors:○ Competitive stressful lifestyle: type A

personality○ Lack of exercise○ ObesityModerate intake of alcohol -> protective factor

Clinical features & prevention

Clinical features:Ischemic/infarction of organsAtherosclerotic aneurysm

Prevention:Primary prevention: risk factor modificationSecondary prevention: prevent recurrence of events or complications (antiplatlet drugs etc)

Tumors

Benign neoplasms:Hemangioma: capillary, cavernous, pyogenic granulomaLymphangioma: simple (capillary), cavernous lymphangioma (cystic hygroma)Glomus tumor, myopericytomaVascular ectasia: nevus flammeus, spider telangiectasia, hereditary hemorrhagic telangiectasia (osler-Weber-Rendu dis.)Bacillary angiomatosis: B. henselae infection

Tumors

Intermediate-grade neoplasms:Kaposi sarcomaHemangioendothelioma

Malignant neoplasms:AngiosarcomaHemangiopericytoma (benign & malignant)

Hemangioma

Capillary hemangioma:Skin, subcutaneous tissue, oral cavities of head and neck, lung, liver, kidneyStrawberry type (juvenile hemangioma): 1:200 newborns: fade 1-3 yr, regress by 7 yr

Cavernous hemangioma:Older age, less circumscribed, deeperNo regress

Hemangioma

Pyogenic granuloma (lobular capillary)Polypoid nodules of skin, gingiva, oral mucosaBleeding, ulceratedGranuloma gravidarum: 1% pregnant women, pyogenic granuloma at gingiva, regress after delivery

Lymphangioma

Lymphangioma circumscriptum (capillary ymphangioma)

Subcutaneous mass of head and neckCavernous lymphangioma

Cystic hygromaNeck and axilla of childrenTurner syndrome: neck region

Vascular ectasia

Nevus flammeus:Birthmark of head and neck, flatPink to purple regress

Port-wine stain: no regressTrigeminal nerve Sturge-Weber syndrome (ecephalotrigemina angiomatosis), venous mass of leptimeninges seizure, hemiplegia, mental retardation

Kaposi sarcoma

Chronic, classic european KSLymphadenopathy, African, endemic KSTransplant-associated (immunosuppression-associated) KSAIDS-associated KSClinical: patches plaques nodulesCause: HSV-8, HIV?

Angiosarcoma

Malignant endothelial neoplasmsSkin, soft tissue, breast, liverCause:

Breast: radiation, lymphedemaLiver: polyvinyl chloride (PVC), throrotrastSkin: arsenic (pesticide)

Heart failure

CHF = congestive heart failure Common end result of many forms of HDUnable to pump blood at rate of body requirementProgressive deterioration of myocardial contraction

Systolic dysfunctionDiastolic dysfunction

Left-side heart failure

Cause: IHD, HT, aortic & mitral valve disease, cardiomyopathyClinical:

Forward effect: poor organ perfusion (prerenal azotemia, hypoxic encephalopathy)Backward effect: pulmonary edema (dyspnea, orthopnea, PND)

Right-side heart failure

Cause: pulmonary HT (cor pulmonale)Hypertrophy of right ventricle, atrium, septum left-side HFClinical:

Forward effect: poor oxygenationBackward effect: organ edema, effusion

What is Ischemic Heart Disease?

Myocardial ischemiaImbalance btw supply (perfusion) & demand of oxygenated bloodIschemia ↓Oxygen

↓ Nutrient substrates↓ Metabolites removal

Ischemia Dysfunction of pumpingAbnormal heart rhythmsMyocardial infarction (Necrosis)

Etiology of IHD

90 % coronary artery atherosclerosis

Atherosclerosis narrow lumenthrombus formationcoronary vasospasm

Others: hypertrophy, hypovolemia, hypoxemia,↑ heart rate

Clinical manifestation

Four syndromes:1. Myocardial infarction2. Angina pectoris: variants

1. Stable angina2. Prinzmetal angina3. Unstable angina

3. Chronic ischemic heart disease 4. Sudden cardiac death

Role of fixed coronary obstruction

At least 75 % reduction of cross-sectional area (insufficient compensatory vasolidation)At least 90 % reduction ischemia at restAtherosclerosis type IV-VIAffected location: proximal (LAD, LCX), entire (RCA)

Clinical manifestation

Stable plaque Unstable plaqueStable angina Acute coronary syndromes

Acute coronary syndromes:unstable angina, acute MI, and sudden death

Role of acute plaque change

Acute plaque change/disruption:Hemorrhage into atheroma ↑ volume Rupture or fissuring ThrombosisErosion or ulceration Thrombosis

A = Plaque ruptureB = Thrombus over plaque ruptureC = Massive plaque rupture with thrombus

Angina pectoris

Paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort caused by transient (15 sec to 15 min) myocardial ischemia that falls short of inducing cellular necrosis (infarct)Three patterns:

Stable or typical anginaPrinzmetal or variant anginaUnstable or crescendo or accelerating or preinfarction angina

Angina pectoris

Stable angina:Most common, and predictableReduction of coronary perfusion by chronic stenosing coronary atherosclerosisPain brought by physical excertion, emotional stress, heat or cold fever, anemia etcPain relieved by rest (decreased demand) or nitroglycerin (vasodilator)Monitoring ECG: ST segment depression or elevation or T-wave inversion

Angina pectoris

Prinzmetal variant angina:Uncommon, and unpredictableOccur at rest not related to physical and emotional exertionCoronary artery vasospasmAtherosclerosis-induced hypercontractility, vasospastic chemicals secretion by mast cells and abnormal calcium influxResponse well to calcium-channel blockers and nitroglycerinECG: elevation of ST-segment

Angina pectorisUnstable angina:

Angina occurring with increasing frequency, precipitated with less effort, often occurs at rest and tends to be prolonged durationMost induced by disruption of atherosclerotic plaque with partial thrombosis and possibly embolization or vasospasmHarbinger of subsequent acute MIThrombus labile and lasts 20 to 30 minutes10 to 15% total occlusion collateral vessel

Myocardial infarction

Necrosis of myocardiumProlonged period of ischemia at rest lasting > 20 min, unresponsive to NTGIschemic ECG change and positive cardiac enzymes25 % silent: old age, diabeticsSubendocardial VS Transmural infarction

Non-Q-wave VS Q-wave infarction

Myocardial infarction

Transmural (Q-wave) infarctionFull or nearly full thickness necrosisAcute plaque change + completely obstructive thrombosis (fixed and persist > 1 hour)ECG: ST segment elevation Q wave

Subendocardial (Non-Q-wave) infarction1/3 to ½ inner ventricle thickness necrosisIncomplete obstructive thrombosis (>30-40 min)¼ complete obstruction + collateral supplyECG: ST segment elevation Non-Q-wave

Morphological change

Almost all transmural MI involve at least a portion of left ventricleCoronary arteries and MI site:

LAD (40-50%) -> ant wall of LV, apex, ant portion of ventricular septumRCA (30-40%) -> inf-post wall of LV, post portion of ventricular septum, RV (inf-post)LCX (10-20%) -> lateral wall LV except apex

1 day 3 to 4 days

7 to 10 days 3 weeks

Evolution of morphology change

Time Morphology change0 - ½ hours Ultrastructural change (EM)

2 – 3 hours Triphenyltetrazolium chloride dye:noninfarct area brick-red, infarcted unstained

4 – 24 hours Gross: dark mottling area, Histology: hemorrhage and necrosis

1 – 7 days Gross: yellow-tan mottling, reddish borderHistology: neutrophils and macrophages

7 – 14 days Gross: red-tan marginHistology: macrophages and granulation tissue

2 – 8 weeks Gross: gray-white scarHistology: collagen deposition

> 2 months Scarring complete

Cardiac enzymes

Released enzymes after myocardial cell dead:

MyoglobinTroponin (TnI and TnT)Creatine kinase (total CK and CK-MB)LDH (LDH1, LDH2)

Cardiac enzymes

0 20 40 60 80 100 120 140 160Hours from onset of infarction

7x

6x

5x

4x

3x

2x

1x

Upp

er li

mit

of n

orm

al s

erum

leve

l

LDH

Troponin I

MyoglobinTotal CK

CK-MB

Consequences and complications

50 % AMI deadHalf of dead occur within 1 hour (VF)In-hospital death rate 30% 10-13 %75 % develop one or more complications

Contractile dysfunction cardiogenic shock10 – 15 % of AMI and 70 % mortality rateArrhythmias sudden deathbradycardia, tachycardia, VPC, VT, VF asystole

Consequences and complications

Myocardial rupture:Ventricular free wall cardiac temponadeVentricular septum left-to-right shuntPapillary muscle acute MR

PericarditisInfarct extension and expansionMural thrombus thromboembolism

Consequences and complications

Ventricular aneurysm thrombus, arrhythmias, heart failure, rupturePapillary muscle dysfunction MRProgressive late heart failure

Cardiac rupture

Rupture ventricular septum

Rupture papillary muscle

Fibrinous Pericarditis

Apical left ventricular aneurysm

Wall thinning and mural thrombus

Prognosis

Extent and location of infarctionQuality of left ventricular functionPrevious cardiovascular healthAge, female gender & other diseasesTotal mortality for 1st year = 30 %3 – 4 % mortality with each passing year

Treatment

Decrease myocardial oxygen demandIncrease myocardial oxygen supplyMonitoring and treat complicationDecrease myocardial oxygen demand:

Preload & afterload reductionHR control, pain relief, activity restriction

Increase oxygen supply:Oxygen administrationAntiplatelet therapy (aspirin), thrombolytic drugAngioplasty(PTCA), atherectomy, CABG

Infarct modification after reperfusion

Early reperfusion:Salvage ischemic myocardium (15-20 min)Limit infarct size (after longer interval)

Critical period: first 3 – 4 hoursThrombolytic Rx: streptokinase, and tissue type plasminogen activator (tPA), reteplase (rPA)PTCA: eliminate thrombus and relieve some underlying atherosclerotic plaque

Thrombolysis:Enzymatic digestion of thrombus to open lumen

Percutaneous transluminal coronary angioplasty (PTCA):Physical disruption of plaque to open lumen

Coronary artery bypass grafting (CABG):Surgical placement of a new conduit to bypass occlusion

Chronic ischemic heart disease

Progressively develop heart failure as a consequence of ischemic myocardial damageIschemic cardiomyopathy

After MI cardiac decompensation of hypertrophic noninfarcted myocytesNo MI severe obstructive coronary disease

diffuse myocardial dysfunction

Sudden cardiac death

Unexpected death from cardiac causes early (usually within 1 hour)Causes:

Majority IHDOthers: congenital structural or coronary arterial abnormalities○ Aortic valve stenosis, mitral valve prolapse○ Myocarditis○ Dilated and hypertrophic cardiomyopathy

Mechanism: arrhythmia (Asystole, VF)

Endocardial and valvular diseases

Stenosis = failure of a valve to open completely

Regurgitation/Insufficiency = Inability of a valve to close completely

Major causes

Mitral valve stenosis:Postinflammatory scarring (RHD)

Mitral valve regurgitation:Abnormalities of leaflets and commissures○ Postinflammatory scarring○ Infective endocarditis○ Floppy mitral valve (Prolapse)Abnormalities of tensor apparatus○ Rupture of papillary muscle/cordae tendinae

Major causes

Aortic stenosis:Postinflammatory scarring (RHD)Senile calcific aortic stenosisCalcification of a congenitally deformed valve

Aortic regurgitationPostinflammatory scarringInfective endocarditisAortic diseases: Syphilitic aortitis, Marfan syndrome, Rheumatoid arthritis

Disorders of Mitral valve

Mitral stenosis:Abnormal Lt. atrial-Lt. ventricular pressure gradient during diastoleAtrial enlargement and hypertrophySevere PHT, Rt. Ventricular hypertrophy, Rt. HFClinical: Dyspnea, orthopnea, weakness, Dysarrhythmia (AF) emboli

Disorders of Mitral valve

Mitral regurgitation:Elevation of Lt. atrial volume and pressureLt. atrial and ventricle dilate and hypertrophySevere: Lt. HF, pulmonary congestion

Disorders of Aortic valve

Aortic stenosis:Lt. ventricular-aortic pressure gradientLt. ventricular hypertrophySevere: myocardial ischemia, Lt. HFClinical: Anginal pain, syncope, fatigue and low systolic blood pressure

Disorders of Aortic valve

Aortic regurgitation:Lt. Ventricle volume overloadLt. Ventricular hypertrophy and dilationSevere: Lt. HFClinical: palpations, trobbing heart (large stroke volume)

Rheumatic fever and Rheumatic heart disease

Rheumatic fever:acute, immunologically mediated multisystem inflammatory diseaseoccurs a few weeks after an episode of group A (beta-hemolytic) streptococcal pharyngitisacute rheumatic carditis may progress to chronic valvular deformities

Rheumatic fever- Diagnosis

Jones criteria:2 major criteria or1 major and 2 minor criteria

plusevident of antecedent group A streptococcal infection○ positive throat culture○ positive group A strep. antigen test○ elevated serum anti-strep. antibody titer

Jones criteria

Major criteria:CarditisPolyarthritis (Migratory)Chorea (Sydenham)Erythema marginatum of skinSubcutaneous nodules

Jones criteria

Minor criteria:Clinical findings:○ Arthralgia○ FeverLaboratory findings:○ Elevated acute phase reactant (ESR,CRP)○ Prolonged PR interval on ECG

Rheumatic heart disease

Acute rheumatic fever: CarditisEndocarditis, myocarditis, pericarditisPancarditisAschoff bodies, Antischkow cells (Pathognomonic), Aschoff giant cells

Chronic rheumatic heart disease:deformed fibrotic valves (MV>AV>TV>PV)Frequent cause of MS (99% of cases)

Pathogenesis

hypersensitivity reaction induced by group A streptococcalStreptococcal antigens (M protein) that cross-react with human tissue through molecular mimicryMost ARF-associated strains: M type 3, 1, 18, 5 and 6M protein: antiphagocytic surface antigens

Clinical Features

ARF occurs 10 days to 6 weeks (usu. within 3 wks) after pharyngitismost often in children age of 5 to 15 years old1/3 of ARF patients has no history of previous pharyngitisSerologic study: antistreptolysis-O (ASO) or antideoxyRNase B (anti-DNase B) titer

Treatment

anti-streptococcal therapy:IM benzathine penicillin10 days oral penicilin or erythromycin

anti-inflammatory therapy:oral salicylatescorticosteroid (prednisolone) with severe cases of carditis

Prophylaxis: antibiotics given 5 yrs to lifetime prophylaxis

Infective endocarditis

caused by invasion and colonization of endocardial structures by microorganisms which resulting in inflammation

bacteria (most common): bacterial endocarditisfungi, rickettsiae (Q fever) and clamydiae: uncommon

Infective endocarditis

Acute endocarditis:destructive infection, frequently in normal heart valve, with highly virulent organismsleads to death within days or weeks of > 50% of patients

Subacute endocarditis:infection with low virulent organisms in abnormal heartdisease appears insidious and protracted course

Cause and Pathogenesis

Cardiac and vascular abnormalities:rheumatic heart diseasemyxomatous mitral valve (MVP)degenerative calcified valvular stenosisbicuspid aortic valveartificial (prosthesis) valvesvascular grafts

Cause and Pathogenesis

Host factors:neutropeniaimmunodeficiencytherapeutic immunosuppressiondiabetic mellitusalcoholintravenous drug abuse

Cause and Pathogenesis

Causative organisms:○ alpha-hemolytic (viridans) streptococci (50-

60%)○ S. aureus (10-20%)○ HACEK group: Haemophilus, Actinobacillus,

Cardiobacterium, Eikenella and Kingella)○ S. epidermidis in prosthetic valve○ 10% culture negative endocarditis

previous antibiotic therapydifficult to culture or deep enbedded organism

Cause and Pathogenesis

Portal of entry:dental or surgical procedureinfection at other site injection eg. IVDUsoccult sources from gut, oral cavity, or trivial injuries

antibiotic prophylaxis

Clinical features

Subacute endocarditisFever (Prolonged)non-specific symptoms: fatigue, weight loss flulike syndromeMurmurs (90% in left-side disease)Others: petechiae, subungual hemorrhage, Roth spots in the eyes (microemboli)

Acute endocarditis: fever, chills, weakness, murmur, CHF

Complications

Cardiac complications:valvular insufficiency or stenosiscardiac failuremyocardial ring abscess with perforationsuppurative pericarditisprothesis valve leakage or dehiscence

Embolic complications:Left-side: brain, MI, spleen, kidneysRight-side: lung infection

Myocarditis

Inflammatory process of the myocardium resulting in injury of cardiac myocytesCauses:

infectionsImmune-mediatedothers: sarcoidosis, giant cell myocarditis

Causes of myocarditis

Infections:Viruses: Coxsackies virus, ECHO, influenza, HIV, CMVClamydiae: C. psittaciRickettsiae: R. typhi typhus feverBacteria: Diphtheria, N. Meningitidis, Borrelia Lyme diseaseFungi: CandidaProtozoa: Trypanosoma chagas disease, toxoplamosisHelminths: trichinosis

Causes of myocarditis

Imune-mediated reactions:PostviralPoststreptococcal (rheumatic)SLEDrugs: Methydopa, sulfonamidesTransplant rejection

Unknown causes:sarcoidosisGiant cell myocarditis

Clinical features

Asymptomatic complete recoveryArrhythmiasCardiomegaly functional valvular regurgitationHeart failure deathDevelop DCM years laterDiagnosis: endomyocardial biopsy

Pericardial effusion

Accumulation of noninflammatory fluid in the pericardial sac (normal 30 – 50 mL of fluid)Cardiac tamponade = external compression of the heart chambers resulting in filling impair

↓ stroke volume, HR ↑Rx: pericardiocentesis

Pericarditis

Inflammation of the pericardiumAcute pericarditis:

Serous/ fibrinous/ purulent/ hemorrhagic/ caseousFever, tachycardia, chest pain, pericardial friction rub

Chronic pericarditis:Constrictive pericarditis/ adhesive mediastinopericarditis

References1. Ramzi S. Cotran: Robbins’ Pathologic Basis of

disease, 6th ed. Philadelphia, WB Sauders, 19992. Copstead Banasik: Pathophysiology biological

and behavioral perspective, 2nd ed3. Baunwald: Heart disease: A textbook of

Cardiovascular Medicine, 6th ed. Philadelphia, WB Sauders, 2001

4. Eugene Braunwald: Cardiovascular diseases: Harrison’s Manual of Medicine, 15th ed. McGraw-Hill, 2002