1. Acquired valve diseases Prof. S. Smiyan

2. EPIDEMOLOGY ARF is mainly a disease of children aged 5–14 years. ARF is mainly a disease of children aged 5–14 years. Initial episodes become less common in older adolescents and young adults and are rare in persons aged >30 years. Initial episodes become less common in older adolescents and young adults and are rare in persons aged >30 years. There is no clear gender association for ARF, but RHD more commonly affects females, sometimes up to twice as frequently as males. There is no clear gender association for ARF, but RHD more commonly affects females, sometimes up to twice as frequently as males.

3. ORGANISM Caused by group A streptococcus. Caused by group A streptococcus. There is a latent period of ~3 weeks (1–5 weeks) between the precipitating group A streptococcal infection and the appearance of the clinical features of ARF. There is a latent period of ~3 weeks (1–5 weeks) between the precipitating group A streptococcal infection and the appearance of the clinical features of ARF.

4. PATHOGENESIS Rheumatic fever affect the peri-arteriolar connective tissue and can occur after an untreated Group A streptococcal pharyngeal infection. Rheumatic fever affect the peri-arteriolar connective tissue and can occur after an untreated Group A streptococcal pharyngeal infection. It is believed to be caused by antibody cross-reactivity. This cross- reactivity is a Type II hypersensitivityreaction and is termed molecular mimicry It is believed to be caused by antibody cross-reactivity. This cross- reactivity is a Type II hypersensitivityreaction and is termed molecular mimicrycross-reactivityType II hypersensitivitycross-reactivityType II hypersensitivity

5. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy.Aschoff bodiesAschoff bodies

6. In acute RF, these lesions can be found in any layer of the heart and is hence called pancarditis. In acute RF, these lesions can be found in any layer of the heart and is hence called pancarditis. The inflammation may cause a serofibrinous pericardial exudates described as “bread- andbutter” pericarditis, which usually resolves without sequelae The inflammation may cause a serofibrinous pericardial exudates described as “bread- andbutter” pericarditis, which usually resolves without sequelaepericarditis

7. CLINICAL FEATURES

8. Nimishikavi S, Stead L Streptococcal Pharyngitis – Images in Clinical Medicine. NEJM 2005: 352:e10.

9. Arthritis: This is usually polyarthritis, sometimes flitting from joint to joint (migratory), affecting the larger joints more than the smaller ones. Arthritis: This is usually polyarthritis, sometimes flitting from joint to joint (migratory), affecting the larger joints more than the smaller ones. Swelling, redness and tenderness are the common findings and occasionally joint effusions. Swelling, redness and tenderness are the common findings and occasionally joint effusions.

10. Skin lesions : The classical erythema marginatum—large erythematous lesions with prominent margins slightly raised. Skin lesions : The classical erythema marginatum—large erythematous lesions with prominent margins slightly raised. The red margins take longer to fade and so the lesions sometimes look like red rings The red margins take longer to fade and so the lesions sometimes look like red rings

11. Subcutaneous nodules : These are painless, roundish, firm lumps overlaid by normal looking skin Subcutaneous nodules : These are painless, roundish, firm lumps overlaid by normal looking skin They range from a few millimeters to 1.5 cm in diameter, and are localised over bony prominences like the elbow, shin and spine. They sometimes last longer than a month. They range from a few millimeters to 1.5 cm in diameter, and are localised over bony prominences like the elbow, shin and spine. They sometimes last longer than a month.

12. Up to 60% of patients with ARF progress to RHD. Up to 60% of patients with ARF progress to RHD. The endocardium, pericardium, or myocardium may be affected. The endocardium, pericardium, or myocardium may be affected. Valvular damage is the hallmark of rheumatic carditis. The mitral valve is almost always affected. Valvular damage is the hallmark of rheumatic carditis. The mitral valve is almost always affected.

13. 13 Rheumatic heart disease. Abnormal mitral valve. Thick, fused chordae

14. 14 Another view of thick and fused mitral valves in Rheumatic heart disease

15. It presents with breathlessness, chest pain of pericardial type, and palpitations due to tachycardia. It presents with breathlessness, chest pain of pericardial type, and palpitations due to tachycardia. a soft mid-diastolic murmur due to thickening of the mitral valve, the Carey-Coombs murmur, is the classical picture; a soft mid-diastolic murmur due to thickening of the mitral valve, the Carey-Coombs murmur, is the classical picture; Pericardial rub may be heard at some stage in the disease. Pericardial rub may be heard at some stage in the disease.

17. Sydenham's chorea commonly occurs in the absence of other manifestations, follows a prolonged latent period after group A streptococcal infection, Sydenham's chorea commonly occurs in the absence of other manifestations, follows a prolonged latent period after group A streptococcal infection, The choreiform movements affect particularly the head (causing characteristic darting movements of the tongue) and the upper limbs The choreiform movements affect particularly the head (causing characteristic darting movements of the tongue) and the upper limbs They may be generalized or restricted to one side of the body (hemi-chorea). They may be generalized or restricted to one side of the body (hemi-chorea). Chorea eventually resolves completely, usually within 6 weeks. Chorea eventually resolves completely, usually within 6 weeks.

19. Jones Criteria (1993) Major manifestations: Major manifestations: Arthritis (70%) – involves large joints simultaneously or in succession; responds dramatically to salicylates Carditis (50%) – includes some or all of the following in increasing order of severity:Tachycardia (out of proportion to the fever) – its absence makes the diagnosis of myocarditis unlikely Heart murmur of valvulitis – MR or AR Pericarditis – friction rub, pericardial effusion, chest pain, ECG changes Cardiomegaly – seen on chest X-ray Signs of CHF – gallop rhythm, distant heart sounds, cardiomegaly Valvulitis – murmurs Myocarditis – unexplained cardiomegaly or CHF or gallop Pericarditis – friction rub or pericardial effusion Miscellaneous findings – conduction disturbances in the ECG; 2D echo findings Erythema marginatum (<10%) – nonpruritic serpiginous or annular erythematous evanescent rashes most prominent on the trunk and inner proximal portions of the extremities; never on the face (disappear on exposure to cold and reappear after a hot shower or if covered with a blanket); blanches on pressure Erythema marginatum (<10%) – nonpruritic serpiginous or annular erythematous evanescent rashes most prominent on the trunk and inner proximal portions of the extremities; never on the face (disappear on exposure to cold and reappear after a hot shower or if covered with a blanket); blanches on pressure Subcutaneous nodules (2-10%) – particularly seen in recurrent cases; hard, painless, nonpruritic, freely movable swellings 0.2-2 cm in diameter; found symmetrically, singly or in clusters on the extensor surfaces of large & small joints, over the scalp or along the spine; last for weeks Sydenham’s chorea (15%) – occurs more often in prepubertal girls; consist of choreic movements (spontaneous purposeless movements followed by motor weakness),hypotonia, emotional lability, hyperactivity, separation anxiety, obsessions & compulsions; may be related to dysfunction of BG & cortical neurons; increased titers of “antineuronal antibodies” in >90% Sydenham’s chorea (15%) – occurs more often in prepubertal girls; consist of choreic movements (spontaneous purposeless movements followed by motor weakness),hypotonia, emotional lability, hyperactivity, separation anxiety, obsessions & compulsions; may be related to dysfunction of BG & cortical neurons; increased titers of “antineuronal antibodies” in >90%

20. Jones Criteria (1993) Minor manifestations: Minor manifestations: 1. Arthralgia – not considered a minor manifestation if arthritis is present 2. Fever – at least 38.8 C 3. Elevated acute phase reactants (CRP and ESR) 4. Prolonged PR interval on the ECG

21. EVIDENCE OF ANTECEDENT GROUP A STREPTOCOCCAL INFECTION 1. History of sore throat/scarlet fever unsubstantiated by lab. data is not adequate evidence of recent infection. 2. A negative rapid strep antigen detection test should be confirmed by a conventional throat culture. 3. Streptococcal antibody tests are the most reliable lab.evidence. The onset of the clinical manifestations coincide with the peak of the streptococcal antibody response.

22. 22 Recommendations of the American Heart Association

23. 23 Treatment Step I - primary prevention (eradication of streptococci) Step I - primary prevention (eradication of streptococci) Step II - anti inflammatory treatment (aspirin,steroids) Step II - anti inflammatory treatment (aspirin,steroids) Step III- supportive management & management of complications Step III- supportive management & management of complications Step IV- secondary prevention (prevention of recurrent attacks) Step IV- secondary prevention (prevention of recurrent attacks)

24. 24 STEP I: Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis) Agent Dose Mode Duration Benzathine penicillin G600 000 U for patients Intramuscular Once 27 kg (60 lb) 1 200 000 U for patients >27 kg or Penicillin VChildren: 250 mg 2-3 times daily Oral 10 d (phenoxymethyl penicillin) Adolescents and adults: 500 mg 2-3 times daily For individuals allergic to penicillin Erythromycin: 20-40 mg/kg/d 2-4 times daily Oral 10 d Estolate (maximum 1 g/d) or Ethylsuccinate40 mg/kg/d 2-4 times daily Oral 10 d (maximum 1 g/d) Recommendations of American Heart Association

25. Step II: Anti inflammatory treatment Clinical condition Drugs

26. Bed rest Bed rest Treatment of congestive cardiac failure: -digitalis,diuretics Treatment of congestive cardiac failure: -digitalis,diuretics Treatment of chorea: -diazepam or haloperidol Treatment of chorea: -diazepam or haloperidol Rest to joints & supportive splinting Rest to joints & supportive splinting 3.Step III: Supportive management & management of complications

27. STEP IV : Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks) Agent DoseMode Benzathine penicillin G1 200 000 U every 4 weeks*Intramuscular or Penicillin V250 mg twice daily Oral or Sulfadiazine 0.5 g once daily for patients 27 kg (60 lb Oral 1.0 g once daily for patients >27 kg (60 lb) For individuals allergic to penicillin and sulfadiazine Erythromycin250 mg twice daily Oral *In high-risk situations, administration every 3 weeks is justified and recommended Recommendations of American Heart Association

28. 0 Duration of Secondary Rheumatic Fever Prophylaxis CategoryDuration Rheumatic fever with carditis and At least 10 y since last residual heart disease episode and at least until (persistent valvar disease*) age 40 y, sometimes lifelong prophylaxis Rheumatic fever with carditis10 y or well into adulthood, but no residual heart disease whichever is longer (no valvar disease*) Rheumatic fever without carditis5 y or until age 21 y, whichever is longer *Clinical or echocardiographic evidence. Recommendations of American Heart Association

29. Overview of Valves

30. Mitral Stenosis Etiology: Etiology: predominant cause: rheumatic fever predominant cause: rheumatic fever rare cause rare cause Pathology: Pathology: thickening, shortening, adhering, calcium depositing, and scarring thickening, shortening, adhering, calcium depositing, and scarring four forms of fusion: (1) commissural, (2) cuspal, (3)chordal, (4)combined four forms of fusion: (1) commissural, (2) cuspal, (3)chordal, (4)combined two types of shape: fish-mouth shaped, funnel-shaped two types of shape: fish-mouth shaped, funnel-shaped

31. Mitral Stenosis Pathophysiology: Pathophysiology: normal cross-sectional area: 4-6 cm 2 normal cross-sectional area: 4-6 cm 2 mild MS: <2 cm 2, LAP ↑→ LAH mild MS: <2 cm 2, LAP ↑→ LAH ---compensated period ---compensated period moderate MS: <1.5 cm 2, PVP ↑, PCWP ↑, moderate MS: <1.5 cm 2, PVP ↑, PCWP ↑, → interstitial edema → interstitial edema severe MS: <1.0 cm 2,PAP ↑→ RVoverload severe MS: <1.0 cm 2,PAP ↑→ RVoverload → RV failure → TR → PR → RV failure → TR → PR

33. Mitral Stenosis Clinical Manifestations (MVA <1.5cm 2 ) Clinical Manifestations (MVA <1.5cm 2 ) 1. Symptom: dyspnea, hemoptysis, cough, 1. Symptom: dyspnea, hemoptysis, cough, hoarseness (ortner ’ s syndrome) hoarseness (ortner ’ s syndrome) 2. Signs: 2. Signs: -Mitral faces -Mitral faces -Diastolic thrill at apex -Diastolic thrill at apex -S1 ↑ (flexible), OS(Opening snap), Diastolic rumbling murmur at apex, -S1 ↑ (flexible), OS(Opening snap), Diastolic rumbling murmur at apex, -P2 ↑, splitting, Graham-Steel murmur(PR),TR -P2 ↑, splitting, Graham-Steel murmur(PR),TR

34. Mitral Stenosis Laboratory Examination Laboratory Examination - ECG: - ECG: 1) left atrial enlargement: P wave (II,V 1 ) 1) left atrial enlargement: P wave (II,V 1 ) 2) Af; 2) Af; 3) right ventricular hypertrophy - X-film: change in cardiac silhouette, - X-film: change in cardiac silhouette, Kerley B lines Kerley B lines - Echocardiography: M- mode, Two- - Echocardiography: M- mode, Two- dimensional, Doppler dimensional, Doppler

35. 35 Physical exam the murmur "Tapping" sensation over area of expected PMI. "Tapping" sensation over area of expected PMI. Accentuated S1 Accentuated S1 Opening snap. Opening snap. Mid-diastolic murmur (rumble) low in pitch. Mid-diastolic murmur (rumble) low in pitch. S2-OS interval of 70 msec is seen in severe MS. S2-OS interval of 70 msec is seen in severe MS. Best heard after exercise, left lateral recumbency. Best heard after exercise, left lateral recumbency. Bell chest piece lightly applied. Bell chest piece lightly applied. Pulmonary HTN and RVF occur later in MS. Low sensitivity Pulmonary HTN and RVF occur later in MS. Low sensitivity P mitrale: P mitrale: Lead II broad and bifid > 0.12 sec Lead II broad and bifid > 0.12 sec Lead V1 broad and deep negative component of biphasic P wave, longer than 0.04 sec and 1 mm in depth. Lead V1 broad and deep negative component of biphasic P wave, longer than 0.04 sec and 1 mm in depth. If pulmonary hypertension is present, tall peaked P waves, right axis deviation, or right ventricular hypertrophy appears. If pulmonary hypertension is present, tall peaked P waves, right axis deviation, or right ventricular hypertrophy appears. Atrial fib. Atrial fib. Atrial flutter. Atrial flutter.

36. 36 CXR Straight left heart border. Straight left heart border. Large left atrium. Large left atrium. Sharply indenting esophagus. Sharply indenting esophagus. Elevation of left mainstem bronchus. Elevation of left mainstem bronchus. Large right ventricle and pulmonary artery if pulmonary hypertension is present. Large right ventricle and pulmonary artery if pulmonary hypertension is present. Calcification occasionally seen in mitral valve. Calcification occasionally seen in mitral valve.

37. 37 2D echocardiogram Estimates the severity of MS Estimates the severity of MS Measure the pressure gradient between LA to LV. Measure the pressure gradient between LA to LV. Define the etiology. Define the etiology.

38. 38 Surgery Indications for intervention focus on: Indications for intervention focus on: Episode of pulmonary edema, Episode of pulmonary edema, Decline in exercise capacity, Decline in exercise capacity, Evidence for pulmonary hypertension. Evidence for pulmonary hypertension. Percutaneous mitral balloon valvotomy: Percutaneous mitral balloon valvotomy: Mitral valve area <1.5 cm 2 Mitral valve area <1.5 cm 2 MVR: MVR: Mitral valve area <1.0 cm 2 Mitral valve area <1.0 cm 2

39. Rheumatic mitral stenosis

42. Mitral Stenosis Diagnosis & Differential diagnosis Diagnosis & Differential diagnosis - Diastolic rumbling murmur at apex - Diastolic rumbling murmur at apex + X-film + ECG + Echo + X-film + ECG + Echo - relative MS; Austin-Flint murmur; - relative MS; Austin-Flint murmur; left atrial myxoma ; Graham steell murmur left atrial myxoma ; Graham steell murmur Complication: Complication: Atrial fibrillation; acute pulmonary edema; Atrial fibrillation; acute pulmonary edema; congestive heart failure; thromboembolism; congestive heart failure; thromboembolism; infective endocarditis; pulmonary infective infective endocarditis; pulmonary infective

43. Mitral Stenosis Management: Management: - Medical treatment: - Medical treatment: Antibiotics, Diuretics and Digitalis, Antibiotics, Diuretics and Digitalis, Antiarrhythmic drugs, Anticoagulant Antiarrhythmic drugs, Anticoagulant - Percutaneous balloon mitral valvuloplasty - Percutaneous balloon mitral valvuloplasty ( PBMV) ( PBMV) - Surgical treatment: - Surgical treatment: Closed mitral valvotomy Closed mitral valvotomy Open valvotomy Open valvotomy Mitral valve replacement Mitral valve replacement

44. Balloon Mitral Commissurotomy

45. Mitral Regurgitation Etiology and Pathology Etiology and Pathology - Abnormalities of valve leaflets: - Abnormalities of valve leaflets: Rheumatic, infective Rheumatic, infective - Abnormalities of the mitral annulus: - Abnormalities of the mitral annulus: dilatation, calcification dilatation, calcification - Abnormalities of the chordae tendineae: - Abnormalities of the chordae tendineae: congenitally, infective, trauma, Rheumatic congenitally, infective, trauma, Rheumatic - Involvement of papillary muscle: CAD - Involvement of papillary muscle: CAD

46. Mitral Regurgitation Pathophysiology Pathophysiology In systolic period, blood flow from LV → LA, LA filling pressure ↑ ; In systolic period, blood flow from LV → LA, LA filling pressure ↑ ; in diastolic period, LV accepts more blood → LV dilation, hypertrophy → LVEDP ↑ → LAP ↑→ PCWP ↑→ PAP ↑→ RHF; CO ↓ in diastolic period, LV accepts more blood → LV dilation, hypertrophy → LVEDP ↑ → LAP ↑→ PCWP ↑→ PAP ↑→ RHF; CO ↓ Chronic Chronic Acute Acute

48. Mitral Regurgitation Clinical Manifestations Clinical Manifestations (1) Symptoms: asymptomatic( gradually,>20 years), (1) Symptoms: asymptomatic( gradually,>20 years), palpitation, fatigue, dyspnea, pulmonary edema palpitation, fatigue, dyspnea, pulmonary edema (2) Signs: (2) Signs: - apical pulse → left,lower - apical pulse → left,lower - apical beat heavy - apical beat heavy - cardiac dullness enlarged → left - cardiac dullness enlarged → left - pansystolic murmur at apex, radiate to left - pansystolic murmur at apex, radiate to left axilla, subscapular axilla, subscapular - S1 ↓,P2 ↑ - S1 ↓,P2 ↑

49. 49 ECG Left axis deviation. Left axis deviation. Left ventricular hypertrophy. Left ventricular hypertrophy. P waves broad, tall, or notched in standard leads. P waves broad, tall, or notched in standard leads. Broad negative phase of diphasic P in V1. Broad negative phase of diphasic P in V1.

50. 50 M Chadi Alraies

51. 51 2D echocardiogram Thickened mitral valve in rheumatic disease. Thickened mitral valve in rheumatic disease. Enlarged left ventricle with above-normal, normal, or decreased function. Enlarged left ventricle with above-normal, normal, or decreased function. Regurgitant flow mapped into left atrium. Regurgitant flow mapped into left atrium.

52. 52 Management Acute MR: Acute MR: Emergency surgery. Emergency surgery. Stabilization with vasodilators (nitroprusside) Stabilization with vasodilators (nitroprusside) Intra-aortic balloon counterpulsation. Intra-aortic balloon counterpulsation. Chronic MR: Chronic MR: Afterload reduction: ACEI Afterload reduction: ACEI Anticoagulation in case of atrial fibrillation. Anticoagulation in case of atrial fibrillation.

54. Mitral Regurgitation Diagnosis: Diagnosis: systolic murmur at apex + LA ↑, LV ↑ + Echo systolic murmur at apex + LA ↑, LV ↑ + Echo Differential Diagnosis: Differential Diagnosis: relative MR, ventricular septal defect, relative MR, ventricular septal defect, tricuspid regurgitation, aortic stenosis tricuspid regurgitation, aortic stenosis Management: Management: - Medical treatment - Medical treatment - Surgical treatment - Surgical treatment

55. 55 Aortic stenosis Etiology Bicuspid valve. Bicuspid valve. Degenerative Degenerative Congenital Congenital Rheumatic Rheumatic Infective endocarditis. Infective endocarditis.

56. 56 M Chadi Alraies

57. Aortic Stenosis Etiology & Pathology: Etiology & Pathology: - Rheumatic AS, Congenital AS, - Rheumatic AS, Congenital AS, Degenerative calcific AS Degenerative calcific AS Pathophysiology: Pathophysiology: - Obstruction to LVOT → LVH → LAH → PVP ↑→ - Obstruction to LVOT → LVH → LAH → PVP ↑→ Pulmonary edema; Pulmonary edema; - LVEF ↓→ ischemia of peripheral 、 brain 、 heart - LVEF ↓→ ischemia of peripheral 、 brain 、 heart

59. Aortic Stenosis Clinical Manifestations: Clinical Manifestations: - Symptoms: heart failure (fatigue, dyspnea), - Symptoms: heart failure (fatigue, dyspnea), angina pectoris, syncope, sudden death angina pectoris, syncope, sudden death - Signs: Apical impulse↑,to left - Signs: Apical impulse↑,to left Systolic thrill in AV area,pulse↓ Systolic thrill in AV area,pulse↓ Cardiac dullness→left Cardiac dullness→left Ejection sound & SM in AV area, radiate Ejection sound & SM in AV area, radiate to neck to neck A2↓ splitting paradoxically A2↓ splitting paradoxically

60. Rheumatic aortic stenosis and regurgitation

61. Aortic Stenosis Laboratory Examination: Laboratory Examination: ECG; X- film; ECG; X- film; Echocardiography; Angiography Echocardiography; Angiography Diagnosis & Differential Diagnosis: Diagnosis & Differential Diagnosis: - murmur + Echo - murmur + Echo - MI, TI, VSD - MI, TI, VSD - other murmurs of LVOT obstruction - other murmurs of LVOT obstruction

62. Rheumatic aortic stenosis and regurgitation

63. Aortic Stenosis Complications: Complications: Sudden death, heart failure, arrhythmia, Sudden death, heart failure, arrhythmia, infective endocarditis, systemic embolism infective endocarditis, systemic embolism Management: Management: - Medical treatment - Medical treatment - Surgical treatment - Surgical treatment

64. Rheumatic aortic stenosis and regurgitation

65. Aortic Regurgitation Etiology & Pathology Etiology & Pathology - Valvular Disease: - Valvular Disease: rheumatic, congenital, infective rheumatic, congenital, infective prolapse, ankylosing spondylitis, degenerative prolapse, ankylosing spondylitis, degenerative - Aortic Root Disease: - Aortic Root Disease: syphilitic aoritis, Marfan syndrome, syphilitic aoritis, Marfan syndrome, ankylosing spondylitis, degenerative ankylosing spondylitis, degenerative - Acute AR: infective, trauma, aortic dissection - Acute AR: infective, trauma, aortic dissection

66. Rheumatic aortic stenosis and regurgitation

68. Aortic Regurgitation Clinical Manifestations: Clinical Manifestations: - Symptom: palpitation, angina - Symptom: palpitation, angina - Sign: apical impulse→ left, inferior - Sign: apical impulse→ left, inferior cardiac dullness →left, inferior cardiac dullness →left, inferior Boot-shaped shadow—cardiac waist↓ Boot-shaped shadow—cardiac waist↓ DM in AV2 area →apex DM in AV2 area →apex S1↓,A2↓ S1↓,A2↓ relative MI—SM at apex relative MI—SM at apex relative MS—Austin Flint Sign: Peripheral vascular sign: relative MS—Austin Flint Sign: Peripheral vascular sign: - pulse pressure↑, carotid pulsation↑ - pulse pressure↑, carotid pulsation↑ - Musset sign, water hammer pulse, - Musset sign, water hammer pulse, Traube sign, Duroziez murmur, Traube sign, Duroziez murmur, Muller sign, Quincke sign, Muller sign, Quincke sign, Laboratory Examination: Laboratory Examination: ECG, X-Film, Echo, etc ECG, X-Film, Echo, etc