Assessment of CVS & Murmurs Rheumatic Fever Assessment of CVS & Murmurs

Rheumatic Fever Definition: Multisystem, Autoimmune, Inflammatory disorder of Skin, joint &heart. Following group A, ß-hemolytic streptococcal Pharyngitis * Acute: Fever, Inflammed Skin, joint &heart Chronic: scarring of heart valves (mitral) dysfunction. Rheumatoid Arthritis ? Pharyngitis only ? Other infections ? Why life long therapy ? 2

Introduction: “The most important consequence of rheumatic fever is recurrent autoimmune inflammation of heart valves due to ‘GABH Strep’ causing scarring of valves leading to severe cardiac dysfunction decades later” RHD – Mitral Stenosis. 3

Epidemiology Incidence more during - winter & early spring Ages 5-18 yrs are most susceptible Rare <3 yrs M:F equally except Sydenham’s chorea which is more common in girls Common in 3rd world countries Environmental factors-- over crowding, poor sanitation, poverty, Incidence more during - winter & early spring

Etiology Acute rheumatic fever is a systemic disease of childhood,often recurrent that follows group A beta hemolytic streptococcal infection It is a delayed non-suppurative sequelae to URTI with GABH streptococci. It is a diffuse inflammatory disease of connective tissue,primarily involving heart,blood vessels,joints, subcut.tissue and CNS

Etiology: Genetic Susceptibility – HLA DR 2 & 3 Environmental factor – GABH strep. Autoimmunity – Autoantibodies ? . Auto Ab to cardiac & brain stroma. Infl. mediators correlate with activity… But, level of Autoantibody does not correlate with clinical severity. ? Other Ab, other cause? 6

Etiology of Autoimmune disorders: 7

Pathogenesis Delayed immune response to infection with group.A beta hemolytic streptococci. After a latent period of 1-3 weeks, antibody induced immunological damage occur to heart valves,joints, subcutaneous tissue & basal ganglia of brain

Group A Beta Hemolytic Streptococcus Strains that produces rheumatic fever - M types l, 3, 5, 6,18 & 24 Different serotypes from strains causing impetigo or glomerulonephritis Pharyngitis- produced by GABHS can lead to- acute rheumatic fever , rheumatic heart disease & post strept. Glomerulonepritis Skin infection- produced by GABHS leads to post streptococcal glomerulo nephritis only. It will not result in Rh.Fever or carditis as skin lipid cholesterol inhibit antigenicity

Pathologic Lesions Fibrinoid degeneration of connective tissue, inflammatory edema, inflammatory cell infiltration & proliferation of specific cells resulting in formation of Ashcoff nodules , resulting in- -Pancarditis in the heart -Arthritis in the joints -Ashcoff nodules in the subcutaneous tissue -Basal gangliar lesions resulting in chorea

Summary: RHD Pathogenesis. Acute Rheumatic Fever

Clinical Features: Children 5-15 years common Fever 2-3 weeks following pharyngitis Migratory polyarthritis of large joints Pericardial friction rub Weak heart sounds Tachycardia, arrhythmias Increased vulnerability to reactivation with subsequent pharyngitis. Cumulative cardiac damage over decades 12

1.Arthritis Flitting & fleeting migratory polyarthritis, involving major joints Commonly involved joints-knee,ankle,elbow & wrist Occur in 80%,involved joints are exquisitely tender In children below 5 yrs arthritis usually mild but carditis more prominent Arthritis do not progress to chronic disease

2.Carditis Manifest as pancarditis(endocarditis, myocarditis and pericarditis),occur in 40-50% of cases Carditis is the only manifestation of rheumatic fever that leaves a sequelae & permanent damage to the organ Valvulitis occur in acute phase Chronic phase- fibrosis,calcification & stenosis of heart valves (fishmouth valves)

3.Sydenham Chorea Occur in 5-10% of cases Mainly in girls of 1-15 yrs age May appear even 6/12 after the attack of rheumatic fever Clinically manifest as-clumsiness, deterioration of handwriting,emotional lability or grimacing of face Clinical signs- pronator sign, jack in the box sign , milking sign of hands

4.Erythema Marginatum Occur in <5%. Unique,transient,serpiginous-looking lesions of 1-2 inches in size Pale center with red irregular margin More on trunks & limbs & non-itchy Worsens with application of heat Often associated with chronic carditis

5.Subcutaneous nodules Occur in 10% Painless,pea-sized,palpable nodules Mainly over extensor surfaces of joints,spine,scapulae & scalp Associated with strong seropositivity Always associated with severe carditis

Rheumatic Fever: Clinical Features Polyarthritis – w/ low grade fever, large joints, ( > 75%) migratory - affects 1 at a time, no permanent dysfx. Carditis - pericarditis, cardiomeagly, or valvulitis ( ~ 50%) (valvulitis is the most serious manifestation.) Chorea – late occurrence, 3 - 4 months after ( ~ 10%) infection, self-limiting, resolves in 1- 3 months. Erythema Marginatum – “classic” truncal rash, ( ~ 10%) migratory - appears & disappears within hours. (pink rash – irregular red edges – clear center) Subcutaneous Nodules – occurs late ( months (1 - 2%) after infection), painless small nodules over bony prominences - elbows, knees, spine.

Other features (Minor features) Fever-(upto 38.3 degree centigrade) Arthralgia Pallor Anorexia Loss of weight

Jones clinical Criteria of Diagnosis: Major Criteria Migratory Polyarthritis Carditis Subcutaneous nodules Erythema marginatum Sydenham Chorea Minor Criteria Nonspecific symptoms Fever Arthralgia High ESR / CRP Prolonged PR Interval Positive: 2 Major or 1 major + 2 minor Following Group-A strep. pharyngitis. 23

Heart Disease Rheumatic Heart Disease – usually occurs years after initial attack. Mitral valve is more commonly involved than aortic valve. Classically, pts have mitral stenosis as a result of calcification.

Laboratory Investigations: No specific laboratory investigations* Throat culture-GABH streptococci - Cultures are usually negative. High ESR Anemia, leucocytosis Elevated C-reactive protien ASO titre >200 Todd units. (Peak value attained at 3 weeks,then comes down to normal by 6 weeks) High Anti-DNAse B titres High Acute phase reactants – CRP, SAP, Complements, Coagulation Proteins. 25

Laboratory Findings (Contd) ECG- prolonged PR interval, 2nd or 3rd degree blocks,ST depression, T inversion 2D Echo cardiography- valve edema,mitral regurgitation, LA & LV dilatation,pericardial effusion,decreased contractility

Diagnosis Evidence of recent streptococcal infection can include: Increased antistreptolysin O or other streptococcal antibodies (anti-DNAse B) Positive throat culture for Group A beta-hemolytic streptococci Positive rapid direct Group A strep test Recent scarlet fever Rheumatic fever is mainly a clinical diagnosis No single diagnostic sign or specific laboratory test available for diagnosis Diagnosis based on MODIFIED JONES CRITERIA

Differential Diagnosis Juvenile rheumatiod arthritis Septic arthritis Sickle-cell arthropathy Kawasaki disease Myocarditis Scarlet fever Leukemia

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

Primary prophylaxis Timely diagnosis of GAS pharyngitis and appropriate treatment. Treatment of choice is still Penicillin as all GAS is susceptible. Treatment administered within 10 days of onset of illness has been shown to prevent ARF. Alternatives – amoxicillin, erythromycin, 1st generation cephalosporin

STEP I: Primary Prevention of Rheumatic Fever STEP I: Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis) Agent Dose Mode Duration Benzathine penicillin G 600 000 U for patients Intramuscular Once 27 kg (60 lb) 1 200 000 U for patients >27 kg or Penicillin V Children: 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 Ethylsuccinate 40 mg/kg/d 2-4 times daily Oral 10 d (maximum 1 g/d)

Step II: Anti inflammatory treatment Clinical condition Drugs

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

Secondary prophylaxis Pts diagnosed with ARF need to undergo secondary prophylaxis to prevent relapses. Prophylaxis regimens include oral Pen VK BID, Pen G IM qmonth, oral sulfisoxazole qday, or oral erythromycin BID.

STEP IV : Secondary Prevention of Rheumatic Fever STEP IV : Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks) Agent Dose Mode Benzathine penicillin G 1 200 000 U every 4 weeks* Intramuscular or Penicillin V 250 mg twice daily Oral Sulfadiazine 0.5 g once daily for patients 27 kg Oral 1.0 g once daily for patients >27 kg For individuals allergic to penicillin and sulfadiazine Erythromycin 250 mg twice daily Oral *In high-risk situations, administration every 3 weeks is justified and recommended

Duration of Secondary Rheumatic Fever Prophylaxis Category Duration 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 carditis 10 y or well into adulthood, but no residual heart disease whichever is longer (no valvar disease*) Rheumatic fever without carditis 5 y or until age 21 y, whichever is longer *Clinical or echocardiographic evidence.

Duration of treatment Rheumatic Fever without carditis 5yrs or until 21yo – whichever is longer Rheumatic Fever with carditis but no valvular disease 10yrs or “well into adulthood” – whichever is longer Rheumatic Fever with carditis and persistent valvular disease At least 10yrs since last episode and at least until 40yo; sometimes lifelong

Prognosis Rheumatic fever can recur whenever the individual experience new GABH streptococcal infection,if not on prophylactic medicines Good prognosis for older age group & if no carditis during the initial attack Bad prognosis for younger children & those with carditis with valvar lesions

Assessment of CVS & Murmurs

General Appearance Marfan Syndrome Acromegaly Turner Syndrome Tall, long extremities Associated with: aortic root dilitation, MV prolapse Acromegaly Large stature, coarse facial features, “spade” hands Associated with: Cardiac hypertrophy Turner Syndrome Web neck, hypertelorism, short stature Associated with: Aortic coarctation, pulmonary stenosis Pickwickian Syndrome Severe obesity, somnolence Associated with: Pulmonary hypertension Fredreich ataxia Lurching gait, hammertoe, pes cavus Associated with: hypertrophic cardiomyopathy Duchenne muscular dystrophy Pseudohypertrophy of the calves Cardiomyopathy Ankylosing spondylitis Straight back syndrome, stiff (“poker”) spine Associated with: AI, CHB (rare) Lentigines (LEOPARD syndrome) Brown skin macules that do not increase with sunlight Associated with: HOCM, PS

General Appearance- 2 Sarcoidosis Tuberous Sclerosis Myxedema Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu) Small capillary hemangiomas on the face or mouth Associated with: Pulmonary arteriovenous fistula Lupus Butterfly rash on face, Raynaud phenomenon- hands, Livedo reticularis Associated with: Verrucous endocarditis, Myocarditis, Pericarditis Pheochromocytoma Pale diaphoretic skin, neurofibromatosis- café-au-lait spots Associated with: Catecholamine-induced secondary dilated CM Sarcoidosis Cutaneous nodules, erythema nodosum Associated with: Secondary cardiomyopathy, heart block Tuberous Sclerosis Angiofibromas (face; adenoma sebaceum) Associated with: Rhabdomyoma Myxedema Coarse, dry skin, thinning of lateral eyebrows, hoarseness of voice Associated with: Pericardial effusion, LV dysfunction

Pathophysiology Stenosis- Regurgitation (insufficiency) narrowed valve, sloews forward blood flow increases afterload, dec. CO Regurgitation (insufficiency) increases preload heart pumps same blood again blood volume and pressures reduced in front of affected valve; increased behind affected valve results in heart failure

All valvular diseases have characteristic murmurs Damaged valve disrupts blood flow=turbulence & sound! Caused by Rheumatic Heart Disease Acute conditions (infective endocarditis) Acute MI Congenital Heart Defects Aging, etc

Auscultation Use the diaphragm for high pitched sounds and murmurs Use the bell for low pitched sounds and murmurs Sequence of auscultation upper right sternal border (URSB) upper left sternal border (ULSB) lower left sternal border (LLSB) apex apex - left lateral decubitus position lower left sternal border (LLSB)- sitting, leaning forward, held expiration

Grading the Intensity of Murmurs Grade 1 Murmur heard with stethoscope, but not at first Grade 2 Faint murmur heard with stethoscope on chest wall Grade 3 Murmur hears with stethoscope on chest wall, louder than grade 2 but without a thrill Grade 4 Murmur associated with a thrill Grade 5 Murmur heard with just the rim held against the chest Grade 6 Murmur heard with the stethoscope held away and in from the chest wall

Cardiac Murmurs Most mid systolic murmurs of grade 2/6 intensity or less are benign Associated with physiologic increases in blood velocity: Pregnancy Elderly In contrast, the following murmurs are usually pathologic: Systolic murmurs grade 3/6 or greater in intensity Continuous murmurs Any diastolic murmur

Maneuver Hemodynamic Effect Murmur Effect Normal respiration Transient ↑ in venous filling during inspiration ↑ right-sided murmurs Passive leg elevation ↑ venous return (transient ↑ in LV size and preload) ↑ right-sided murmurs, ↓murmur of HOCM and MVP Stand to squat ↑ right-sided murmurs, ↓murmur of HOCM and MVP Squat to stand ↓ venous return (transient ↓ in LV size and preload) ↑ murmur of HOCM, moves midsystolic click of MVP closer to S1 and ↑ MVP murmur, ↓ AS murmur Valsalva ↓ venous return (transient ↓ in LV size, preload, and relative systemic hypotension) ↑ murmur of HOCM, moves midsystolic click of MVP closer to S1, and ↓ murmur of MVP Isometric handgrip exercise ↑ afterload ↑ murmur of MR and VSD, ↓the murmur of HOCM, ↓AS murmur Inhaled amyl nitrate ↓ afterload ↓ murmur of MR and VSD, no change in AS murmur

Diagnostic Testing ECHOCARDIOGRAM Exercise testing To assess the clinical severity of valvular heart disease Those with inconsistent resting hemodynamics Equivocal history of symptoms Exercise testing in AS patients Should be ended promptly if: Cardiac symptoms provoked Decrease or minimal increase (<20 mmHg) in blood pressure Prior history of angina, congestive heart failure, or exertional syncope absolute contraindications to exercise testing Cardiac catheterization Usually not needed for primary evaluation

Innocent Murmurs Common in asymptomatic adults Characterized by Grade I – II @ LSB Systolic ejection pattern - no  with Valsalva Normal precordium, apex, S1 Normal intensity & splitting of second sound (S2) No other abnormal sounds or murmurs No evidence of LVH S1 S2

Characteristic of the NOT Innocent Murmur Diastolic murmur Loud murmur - grade IV or above Regurgitant murmur Murmurs associated with a click Murmurs associated with other signs or symptoms e.g. cyanosis Abnormal 2nd heart sound – fixed split, paradoxical split or single

Common Murmurs and Timing Systolic Murmurs Aortic stenosis Mitral insufficiency Mitral valve prolapse Tricuspid insufficiency Diastolic Murmurs Aortic insufficiency Mitral stenosis S1 S2 S1

Rheumatic Fever Prophylaxis Primary prophylaxis If living in an endemic area, with pharyngitis and a +test for group A strep or positive throat culture Given once, may be repeated as needed: PCN G 1.2 million U IM or PCN V 500 mg TID x 10d Azithromycin 500 mg on day 1, 250 mg daily for 4d Secondary prophylaxis PCN G 1.2 million units IM every 4 weeks or PCN V 250 mg PO BID or erythromycin 250 mg BID RHD without carditis- At least 5 years or until >21 y of age RHD with carditis, no valvular HD- At least 10 y or well into adulthood RHD with carditis and valvular HD- At least 10 years from last episode or until patient is older than 40 years