Valvular heart disease

I) Rheumatic fever and rheumatic heart disease (RHD): Rheumatic fever (RF) develops 2-4 weeks after Group A beta hemolytic streptococcal infection. Less than 3% of individuals suffering from streptococcal infections develop RF. It is most commonly seen in the 5 -15 years age group. Anti-streptococcal antibodies produced by an infected host cross react with identical epitopes on human myosin, laminin, vimentin, actin and N-acetylglucosamine, a mechanism known as “molecular mimicry”. These epitopes are normally present on cardiac valves, joint capsules, sarcolemmal membrane of smooth and cardiac muscle, neurons etc. Both Type I and type IV hypersensitivity reactions are seen. HLA DR7 and HLA DQ are associated with increased severity of RHD. Typically throat infections are followed by RHD while skin infections are followed by glomerulonephritis.

Valvular involvement in RHD presents as thickened valves with wart-like, firmly attached vegetations along the line of closure of leaflets and cusps. Mitral valve is most commonly involved, followed by aortic valve. Lesions get exacerbated in the event of recurrent streptococcal infections, this being the rationale for penicillin prophylaxis in all RF patients. In chronic mitral valve lesions, fibrosis leads to a “fish mouth” appearance. Both mitral stenosis and mitral regurgitation are seen in RHD, MS being more common. Adhesion of commissures, thickening, shortening and fusion of chordae tendineae and calcification are seen.

Other clinical features of RF: Rheumatic pericarditis is of the fibrinous type with a “bread and butter” appearance. A migratory polyarthritis occurs in RF. It involves mostly large joints like ankle and knee, presenting with moving pain and joint swelling. It does not cause permanent joint damage. Painless subcutaneous nodules are seen over extensor surfaces of the wrist, ankles, knees, elbows and are attached to deeper structures like tendons and periosteum. Erythema marginatum is a transient, migratory cutaneous lesion that presents as an erythematous rash with central clearing and raised edges, seen commonly on the trunk and extremities. Rheumatic chorea or Sydenham’s chorea presents with involuntary, jerky movements of the trunk and extremities.

II) Mitral stenosis: Most common cause of MS is RHD. It is seen more commonly in women. Normal mitral orifice is about 5cm2. Symptoms are seen when the valve opening narrows to 1 cm2. The left atrial pressure rises leading to left atrial hypertrophy and dilation, causing dysphagia. Pulmonary venous hypertension, pulmonary congestion, right heart failure and RVH follow. Right atrial thrombus may form. Atrial fibrillation may be present. On auscultation, a rumbling diastolic murmur is heard at the apex, with presystolic accentuation due to atrial kick. It begins with an opening snap which is caused as the stenotic valve suddenly tenses and halts its normal opening at the start of diastole. The murmur is best heard in the left lateral decubitus position. The intensity of the first heart sound is reduced if the valve is thickened and calcified. The presence of a loud S1 suggests that the patient may be a likely candidate for balloon mitral valvuloplasty. With the development of pulmonary hypertension, S2 may become a single sound. The OS occurs 40-120 milliseconds after A2. The A2-OS interval varies inversely with the severity of mitral stenosis. An A2-OS interval of less than 70 milliseconds usually suggests severe MS and an A2-OS interval of more than 100 milliseconds usually indicates mild MS.

III) Mitral regurgitation: It is seen in mitral valve prolapse (MVP), RHD, rupture of chordae tendineae or papillary muscle in AMI, infective endocarditis, dilation of the mitral valve ring and age-related calcification of the mitral valve annulus. The mitral valve doesn’t close properly leading to leaking of blood into the LA during LV systole. It causes LA dilation, LVH from volume overload, pulmonary congestion and RVH. The holosystolic murmur of MR is blowing, high-pitched and best audible at the apex with radiation to the left axillary and infrascapular area. There is weak correlation between the intensity of the murmur and the severity of MR. Murmurs of shorter duration usually correspond to mild MR. S3 and S4 may be heard. A low-pitched diastolic murmur may be heard at the apex following S3 in severe MR because of increased flow across the mitral valve.

IV) Mitral valve prolapse or MVP of floppy valve syndrome: It is the most common cause of MR. It is more common in women. It is more common in individuals with Marfan and Ehler Danlos syndrome. There is myxomatous degeneration of the valve leaflets, typically posterior leaflet of the mitral valve, which bulges abnormally into the left atrium during systole. A mid-systolic click is heard which may be followed by a mid or late systolic murmur. The duration of the murmur usually corresponds with the severity of MR.

The murmur gets longer and louder by standing, tachycardia and Valsalva maneuver; murmur gets shorter with squatting and hand grip. Amyl nitrate inhalation initially softens and then increases the murmur. Anything that decreases the left ventricular volume such as decreased venous return, tachycardia, increased myocardial contractility or reduced afterload will cause the mitral valve leaflets to prolapse earlier in systole, and systolic click and murmur will move towards the first sound and the murmur will become longer. On the other hand, when LV volume is increased because of increased venous return, increased afterload, decreased myocardial contractility and bradycardia, the onset of click and murmur will be delayed.

V) Aortic stenosis (AS): It may be calcific or non-calcific. Calcific AS is more common and is seen due to progressive fibrocalcific changes of a normal AV (from ageing and other risk factors), or congenitally abnormal AV as in bicuspid aortic valve. It begins as aortic sclerosis and slowly progresses to full blown AS. Aortic sclerosis is seen in over 50% individuals over the age of 85 years. Other causes of AS are RHD, congenital valvular stenosis and subaortic stenosis.

AS occurs as a result of inflammatory changes of the aortic valves. Infiltration with lipids including apoB, E and A1and oxidized LDL; oxidative damage, macrophage infiltration and calcification by modified valvular interstitial cells with osteoblastic activity is seen. The aortic valves show calcified nodules and valve damage. Obstruction to LV outflow causes concentric LVH.

It remains asymptomatic for many years. When symptoms appear, the disease is already at an advanced stage. It presents with angina, syncope and dyspnea which are exacerbated by exercise. Sudden death may occur. Auscultation shows an ejection systolic murmur which decreases with decreased preload (Valsalva, standing) and increases with increased preload (squatting, amyl nitrate). S4 is present. Transthoracic echo with doppler studies and cardiac catheterization are preferred investigations to diagnose AS. An effective valve orifice of <1 cm2 is the cutoff for severe AS.

VI) Aortic regurgitation: It is seen in RHD, infective endocarditis, aortic dissection, aortic root dilation , Marfan’s syndrome, chronic hypertension, bicuspid aortic valve etc. Patients present with exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, palpitations, and chest pain. Backflow of blood into the LV during systole across an improperly closing aortic valve causes increase in the LV end-diastolic volume and volume overload, causing LVH and LV dilation. The diastolic pressure decreases while pulse pressure increases. Stroke volume increases. Hyperdynamic circulation causes head nodding with systole (de Musset’s sign), bounding pulses (Corrigan’s water hammer pulse) and “pistol shot” sounds over the femoral artery. S3 and S4 may be present. AR murmur is diastolic, blowing, high-pitched and decrescendo, beginning soon after the aortic component of S2 (A2). It is loudest at the 3rd or 4th left parasternal intercostal area, best heard with the patient leaning forward, with breath held at end-expiration. It increases in response to maneuvers that increase afterload (e.g. squatting, handgrip). If AR is slight, the murmur may occur only in early diastole. If LV diastolic pressure is very high, the murmur is short. A mid-to-late diastolic rumble can be heard at the apex called Austin Flint murmur, which results from rapid regurgitant flow into the LV, causing mitral valve leaflet vibration.

VII) Pulmonic stenosis: Most commonly associated with congenital heart diseases. Acquired causes include carcinoid syndrome. It presents with systolic ejection murmur and RVH.

VIII) Pulmonary regurgitation: The most common cause is pulmonary hypertension. PR is usually asymptomatic. Can rarely occur in carcinoid syndrome and infective endocarditis. Signs include a decrescendo diastolic murmur (Graham Steell murmur) heard best at the left upper sternal border that radiates to mid-right sternal edge.

IX) Tricuspid stenosis: Most cases are due to RHD. Right atrial hypertrophy may occur. Giant “a ‘’ waves are seen on JVP tracing. Symptoms include fluttering discomfort in the neck , fatigue and cold skin and right upper quadrant abdominal discomfort (due to an enlarged liver). Kussmaul sign may be present. Auscultation shows soft opening snap and a mid-diastolic rumble with presystolic accentuation.

X) Tricuspid regurgitation: Common causes are RHD, infective endocarditis (intravenous drug users), carcinoid syndrome, dilated cardiomyopathy, pulmonary HT, Marfan’s syndrome, congenital lesions like Ebstein’s anomaly, endocardial cushion defects and drugs like ergotamine, fenfluramine and phentermine. It presents with elevated jugular venous pressures, hepatic congestion, fatigue and anorexia. AF and atrial flutter may occur. Prominent merged “c-v” waves are seen on JVP tracing. A holosystolic murmur is heard best at the left middle or lower sternal border. The murmur varies with respiration, becoming louder with inspiration (Carvallo sign).