Penyakit Jantung Rematik

01Pathophysiology

Rheumatic heart disease is the chronic cardiac consequence of acute rheumatic fever (ARF), which itself arises from an untreated or partially treated Group A beta-hemolytic Streptococcal pharyngitis (GAS, Streptococcus pyogenes). Understanding the chain of events from pharyngitis to permanent valve damage is essential for answering vignette-based questions correctly.

The central mechanism is molecular mimicry. The M protein on the surface of GAS shares structural homology with proteins found in human cardiac tissue, particularly cardiac myosin, laminin, and valve endothelial glycoproteins. When the immune system mounts a response against the streptococcal antigen, the resulting antibodies and T cells cross-react with self-antigens in the heart, joints, skin, and central nervous system. This is a combined Type II (antibody-mediated) and Type IV (T-cell-mediated) hypersensitivity reaction. This dual mechanism explains why the damage is both humoral and cellular.

In the heart, this autoimmune attack produces pancarditis, involving all three layers. Endocarditis targets the valve leaflets (especially the mitral valve), causing verrucous vegetations along the line of closure. Myocarditis results in Aschoff bodies, the pathognomonic granulomatous lesions composed of fibrinoid necrosis surrounded by Anitschkow cells (modified macrophages with characteristic "caterpillar" or "owl-eye" nuclei). Pericarditis may produce a fibrinous pericardial effusion.

The reason the mitral valve is most commonly and most severely affected relates to the hemodynamic stress it endures. The order of valve involvement is: Mitral > Aortic > Tricuspid > Pulmonary. In the acute phase, valvulitis produces mitral regurgitation (from inflammation and edema of the leaflets). Over years, repeated episodes of inflammation cause progressive fibrosis, thickening, commissural fusion, and calcification of the valve leaflets and chordae tendineae, leading to the classic mitral stenosis of chronic RHD. The valve orifice narrows to a characteristic "fish-mouth" or "buttonhole" appearance.

This is why the vignette shifts depending on the phase being tested. An acute presentation features a young patient with a new murmur and systemic inflammation. A chronic presentation features an older adolescent or young adult with exertional dyspnea, atrial fibrillation, and signs of left atrial enlargement and pulmonary hypertension from longstanding mitral stenosis.

02Classification and Clinical Manifestation

Modified Jones Criteria (2015 Revision) for Diagnosis of Initial Acute Rheumatic Fever

Diagnosis requires evidence of preceding GAS infection PLUS:

• 2 Major criteria, OR

• 1 Major + 2 Minor criteria

Note for moderate-to-high-risk populations (endemic regions): The criteria are relaxed. Monoarthritis and lower fever thresholds ($\ge \backslash geq$ 38.0 °C) can be accepted. Subclinical carditis detected only by echocardiography also qualifies as a major criterion in these populations.

Clinical Manifestations by System

Chronic RHD Classification by Valve Lesion

03Diagnostic Workup

The first priority when a vignette describes a child or adolescent with fever, joint pain, and a new murmur is to establish evidence of preceding GAS infection. The ASO (Antistreptolysin O) titer is the best initial serologic test and is elevated in approximately 80% of ARF cases. If the ASO is negative or borderline, the next step is to check the anti-DNase B titer, which improves sensitivity to over 90% when combined with ASO. It is important to recognize that a positive throat culture or rapid antigen test supports the diagnosis but is often negative because ARF develops 2 to 4 weeks after the pharyngitis, which may have already resolved.

Once GAS infection is confirmed, apply the Modified Jones Criteria as outlined above. The clinical findings in the vignette must meet the threshold of 2 major or 1 major plus 2 minor criteria.

Echocardiography is the cornerstone for evaluating cardiac involvement. It is the best initial test for detecting carditis, including subclinical carditis that has no audible murmur. The 2015 Jones Criteria revision recognized that Doppler echocardiographic evidence of valvular regurgitation (even without auscultatory findings) qualifies as carditis, which is a frequently tested concept. In chronic RHD, echocardiography is also the most accurate test for grading the severity of mitral stenosis, measuring the valve area (normal: 4 to 6 cm${}^2^2$; severe stenosis: 1.0 cm${}^2^2$), and assessing for complications such as left atrial thrombus.

ECG is a quick, inexpensive screening test. A prolonged PR interval is a minor criterion for ARF but is not diagnostic on its own. In chronic RHD with mitral stenosis, look for P mitrale (broad, notched P waves in lead II indicating left atrial enlargement) and atrial fibrillation.

Chest X-ray findings in chronic RHD include left atrial enlargement (which can cause esophageal compression on barium swallow and elevation of the left main bronchus), pulmonary venous congestion, and Kerley B lines from interstitial edema.

04Management and Treatment

Step 1: Eradicate GAS (Regardless of Throat Culture Result)

Even if the throat culture is negative at the time of ARF diagnosis, antibiotic treatment is given to eliminate any residual streptococcal carriage. The drug of choice is Benzathine penicillin G 1.2 million units IM as a single injection. This also serves as the first dose of secondary prophylaxis. For patients who cannot tolerate injections, oral Penicillin V for 10 days is an alternative. In patients with a confirmed penicillin allergy, azithromycin for 5 days is used.

Step 2: Control the Inflammatory Response

For arthritis and mild carditis without heart failure, high-dose aspirin (80 to 100 mg/kg/day in 4 divided doses) is the first-line anti-inflammatory agent. The dramatic and rapid response of joint symptoms to aspirin is so characteristic that failure to improve should prompt reconsideration of the diagnosis. Aspirin is maintained for 2 to 4 weeks, then tapered over 4 to 6 weeks while monitoring ESR and CRP for rebound.

For moderate to severe carditis with cardiomegaly or heart failure, prednisone (1 to 2 mg/kg/day, maximum 80 mg/day) is used for 2 to 3 weeks, then tapered gradually. As the prednisone taper begins, aspirin is started simultaneously to prevent inflammatory rebound after steroid withdrawal. Standard heart failure therapy (diuretics, fluid restriction, bed rest) is added as needed.

Step 3: Manage Sydenham Chorea

Chorea is usually self-limited, resolving over weeks to months. If movements are severe enough to interfere with daily function, carbamazepine or valproic acid can be used. Haloperidol was previously used but carries more side effects and is now less preferred.

Step 4: Institute Secondary Prophylaxis (This is the Most Tested Concept)

The single most important intervention in preventing recurrent ARF and progressive RHD is long-term secondary prophylaxis with benzathine penicillin G 1.2 million units IM every 3 to 4 weeks. The duration depends on the severity of the initial episode:

For patients with true penicillin allergy, oral erythromycin 250 mg BID can be used for prophylaxis, though adherence is inferior to monthly injections.

Step 5: Manage Chronic Valvular Disease

Patients with established mitral stenosis are managed medically until the stenosis becomes hemodynamically significant (valve area 1.5 cm${}^2^2$ with symptoms, or 1.0 cm${}^2^2$ regardless of symptoms). Medical management includes diuretics for congestion, heart rate control with beta-blockers (to prolong diastolic filling time across the stenotic valve), and anticoagulation with warfarin (target INR 2.0 to 3.0) if atrial fibrillation or left atrial thrombus develops. Note that direct oral anticoagulants (DOACs) are contraindicated in rheumatic mitral stenosis.

For surgical intervention, percutaneous balloon mitral valvotomy (PBMV) is the procedure of choice for symptomatic moderate-to-severe mitral stenosis with favorable valve morphology (pliable leaflets, no significant calcification, no left atrial thrombus, and no more than mild mitral regurgitation). When valve morphology is unfavorable, surgical mitral valve replacement with a mechanical prosthesis is indicated, which requires lifelong anticoagulation with warfarin.

Patients with RHD and valve abnormalities also require infective endocarditis prophylaxis before certain dental procedures.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on rheumatic heart disease questions is by confusing the acute valve lesion with the chronic valve lesion. In the acute setting, the valvulitis produces mitral regurgitation (a pansystolic murmur at the apex). In the chronic setting, after years of fibrosis and commissural fusion, the classic lesion is mitral stenosis (a low-pitched diastolic rumble with an opening snap). If the vignette describes a young patient with acute fever and a systolic murmur, that is mitral regurgitation from active carditis. If it describes an adult with dyspnea on exertion, atrial fibrillation, and a diastolic murmur, that is chronic mitral stenosis from old RHD.

Another frequent trap is Sydenham chorea presenting in isolation. Because chorea can appear weeks to months after the initial pharyngitis, by the time it manifests, the ASO titer may have already normalized and no other Jones criteria may be present. Despite this, chorea alone is sufficient to diagnose ARF without additional criteria, which is a point students often miss. The vignette may describe a child with involuntary movements and emotional lability but no fever, no arthritis, and a normal ASO titer, and the correct answer is still acute rheumatic fever.

A third trap involves post-streptococcal reactive arthritis (PSRA) as a distractor. PSRA occurs after GAS infection but the arthritis is non-migratory, persistent, and often involves small joints. It does not fulfill Jones Criteria. The key discriminator is the nature of the arthritis: migratory and large-joint for ARF versus persistent and potentially small-joint for PSRA.

Finally, students frequently forget the contraindication of DOACs in rheumatic mitral stenosis. If a vignette presents a patient with RHD-related atrial fibrillation and asks for the best anticoagulant, the answer is warfarin, not a DOAC. This was established after the RE-ALIGN trial demonstrated harm with dabigatran in mechanical heart valves, and current guidelines extend this caution to rheumatic valvular disease.

The core competency being tested across rheumatic heart disease questions is threefold: (1) the ability to trace the pathophysiologic chain from GAS pharyngitis through molecular mimicry to valve destruction, (2) correct application of Jones Criteria, and (3) commitment to long-term secondary prophylaxis as the most important management step in preventing disease progression.