What is the most likely diagnosis for a 29-year-old male presenting with intermittent fever, progressive exertional dyspnea, orthopnea, occasional palpitations, weight loss, and signs of right heart failure?

Most Likely Single Diagnosis: Chronic Constrictive Pericarditis (Tuberculous Etiology)

This 29-year-old male has chronic constrictive pericarditis, most likely secondary to tuberculosis, presenting with classic right heart failure and systemic inflammation. 1, 2

Pathophysiological Explanation Linking ALL Findings

The Core Mechanism

The thickened, fibrotic pericardium creates a rigid shell around the heart, preventing normal diastolic filling and causing equalization of diastolic pressures across all cardiac chambers. 3, 4

Right Heart Failure Dominance

• Elevated JVP with prominent v wave: The rigid pericardium prevents normal right atrial emptying, causing venous congestion with exaggerated v waves as blood attempts to enter the constricted right ventricle. 1, 2
• Hepatomegaly with tender liver: Chronic venous congestion from impaired right heart filling causes hepatic congestion and capsular stretch. 2
• Pedal edema: Systemic venous hypertension leads to peripheral fluid extravasation. 1

Cardiac Findings

• Pan-systolic murmur increasing with inspiration (Carvallo's sign): Severe tricuspid regurgitation develops secondary to right ventricular dilatation and annular dilatation from chronic constriction. 2
• Loud P2: Pulmonary arterial hypertension develops from chronic left atrial hypertension transmitted backward through the pulmonary circulation. 1
• Displaced, hyperdynamic apex: Despite constriction, the heart attempts compensatory mechanisms with preserved contractility but impaired filling. 3

Systemic Inflammatory Response

• Intermittent fever for 6 weeks: Active tuberculous pericarditis causes chronic inflammation with evening fever patterns typical of TB. 1, 2
• Weight loss (~4 kg): Systemic inflammation from tuberculosis combined with cardiac cachexia from chronic heart failure. 1
• Elevated ESR (68 mm/hr) and CRP: Markers of ongoing pericardial inflammation from active or chronic tuberculous infection. 2
• Neutrophil-predominant leukocytosis: Reflects active inflammatory process. 1

Hemodynamic Consequences

• Tachycardia (112/min): Compensatory response to reduced stroke volume from impaired ventricular filling. 2
• Low-normal blood pressure (108/68): Reduced cardiac output from constrictive physiology. 3
• Tachypnea and reduced SpO₂ (94%): Pulmonary venous congestion from elevated left atrial pressures causes interstitial edema. 1

ECG and Imaging Correlation

• Right axis deviation and RBBB: Chronic right ventricular strain and conduction system involvement from pericardial inflammation. 1
• Cardiomegaly on CXR: Dilated atria attempting to overcome constrictive physiology, though pericardial calcification may be absent in 60% of cases. 4
• Prominent pulmonary artery: Secondary pulmonary hypertension from chronic left-sided pressure elevation. 1

Anemia and Liver Dysfunction

• Anemia (Hb 10.4): Chronic disease anemia from prolonged inflammation plus possible bone marrow suppression from tuberculosis. 1
• Elevated AST/ALT and ALP: Hepatic congestion from right heart failure causes "cardiac cirrhosis" pattern. 2

Why Common Differentials Fail

Infective Endocarditis

• Three negative blood cultures definitively exclude this diagnosis. 5
• No vegetations on echo despite adequate imaging. 5
• While fever and elevated inflammatory markers are present, the absence of microbiological evidence and vegetation rules this out. 5

Primary Pulmonary Arterial Hypertension

• Age and presentation wrong: PAH typically affects younger women (20s-30s) with isolated dyspnea, not systemic inflammation. 5
• Fever and weight loss absent in primary PAH. 5
• Elevated inflammatory markers (ESR 68) not explained by PAH alone. 5
• Hepatomegaly pattern: PAH causes passive congestion, but the 6-week fever and constitutional symptoms point to inflammatory etiology. 2

Dilated Cardiomyopathy (Viral Myocarditis)

• Normal LV function on echo excludes this diagnosis—DCM requires reduced LVEF. 5
• Predominant right heart failure is atypical for viral myocarditis, which primarily affects the left ventricle. 5
• Six-week fever duration is too prolonged for acute viral myocarditis, which presents over days to 3 months. 5
• No troponin elevation mentioned (would be expected in active myocarditis). 5

Rheumatic Heart Disease

• Wrong valve involvement: Rheumatic disease primarily causes mitral stenosis with mid-diastolic murmur and loud S1, not isolated severe TR. 6
• No history of rheumatic fever or preceding streptococcal infection. 5
• Severe PAH with normal LV function doesn't fit rheumatic mitral disease pattern. 6

HIV-Related Cardiomyopathy

• HIV negative definitively excludes this. 5

Next ONE Investigation That Clinches Diagnosis

Cardiac CT or MRI with focus on pericardial thickness measurement is the single definitive next test. 3, 1

Why This Test

• Demonstrates pericardial thickening >4mm (normal <2mm), which is pathognomonic for constrictive pericarditis. 3, 1
• Identifies pericardial calcification (present in 40% of cases, may be missed on plain CXR). 4
• Shows characteristic septal bounce and ventricular interdependence on cine imaging. 1
• Reveals pericardial inflammation (enhancement on MRI) indicating active disease. 7

Critical Caveat

• Normal pericardial thickness does NOT exclude constriction—up to 18-28% of surgically proven cases have normal thickness on imaging. 1, 2
• If CT/MRI shows normal thickness but clinical suspicion remains high, proceed directly to cardiac catheterization showing equalization of diastolic pressures and square-root sign (present in 100% of cases). 2

Additional Diagnostic Maneuvers

• Pericardial fluid aspiration or biopsy (if effusion present) for TB culture, adenosine deaminase (ADA >40 U/L suggests TB), and PCR for Mycobacterium tuberculosis. 1, 2
• Interferon-gamma release assay (IGRA) may be negative in active TB pericarditis, so negative result doesn't exclude diagnosis. 1

Definitive Management

Immediate Medical Stabilization

• Diuretics with extreme caution: Gentle diuresis only to relieve severe congestion, as these patients are preload-dependent. 3, 2
• Avoid aggressive diuresis—can precipitate cardiovascular collapse by reducing the already compromised cardiac output. 3

Anti-Tuberculous Therapy (Start Immediately)

Initiate empiric 4-drug anti-TB therapy (rifampin, isoniazid, pyrazinamide, ethambutol) for 6-9 months while awaiting confirmatory tests. 1, 2

• Rationale: In developing regions and immigrants from TB-endemic areas (patient demographics not specified but clinical picture highly suggestive), tuberculosis is the leading cause of constrictive pericarditis. 1, 2
• Don't wait for microbiological confirmation—TB cultures are positive in only a minority of cases, and histopathology is often nonspecific. 2
• Add corticosteroids: Prednisone 1 mg/kg/day tapered over 6-8 weeks reduces inflammation and may prevent progression. 1

Definitive Surgical Treatment

Complete pericardiectomy (phrenic-to-phrenic) is the only curative treatment and should be performed once medically optimized. 3, 4, 2

Surgical Timing Algorithm

1. If NYHA Class III-IV with end-organ dysfunction: Optimize medically for 2-4 weeks with anti-TB therapy and gentle diuresis, then proceed to surgery. 2
2. If hemodynamically stable: Complete 2-3 months of anti-TB therapy to reduce pericardial inflammation before surgery. 1
3. If deteriorating despite medical therapy: Emergency pericardiectomy even in "end-stage" disease—mortality risk is high but is the only life-saving option. 1

Surgical Approach

• Subtotal pericardiectomy from phrenic nerve to phrenic nerve, removing both parietal and visceral pericardium. 4
• Operative mortality: 2-3% in experienced centers. 4
• Post-operative improvement: Nearly all survivors achieve NYHA Class I-II functional status. 4, 2

Critical Pitfall to Avoid

Do not delay surgery waiting for "optimal" medical management—chronic constriction causes irreversible myocardial atrophy and fibrosis if left untreated beyond 6-12 months. 3, 4

Prognosis If Untreated

Short-Term (6-12 Months)

• Progressive right heart failure with refractory ascites, anasarca, and cardiac cirrhosis. 4, 2
• Cardiac cachexia from chronic low cardiac output and systemic inflammation. 1
• Mortality rate 28-30% within first year without surgical intervention. 2

Mechanism of Death

• Sudden cardiac death from arrhythmias (atrial fibrillation common in chronic constriction). 3
• Progressive multi-organ failure from chronic venous congestion (hepatorenal syndrome, protein-losing enteropathy). 2
• Pulmonary embolism from chronic venous stasis. 4

Long-Term (>1 Year)

• Irreversible myocardial atrophy: Chronic constriction causes myocyte atrophy and fibrosis, making even successful pericardiectomy less effective. 3
• Permanent disability: Survivors without surgery remain NYHA Class III-IV with severely limited quality of life. 4
• 3-year survival without surgery: Approximately 50-60%. 4

Post-Surgical Prognosis (For Comparison)

• Operative mortality: 2-3%. 4
• 3-year survival post-pericardiectomy: 94%. 4
• 7-year survival: 87%. 4
• Functional status: >95% achieve NYHA Class I-II. 4, 2
• No recurrence if complete pericardiectomy performed. 4