What are the likely etiologies, diagnostic work‑up, and management for a 70‑year‑old patient with dyspnea, bilateral pedal edema, and an echocardiogram demonstrating restrictive cardiomyopathy?

Restrictive Cardiomyopathy in a 70-Year-Old: Etiologies, Diagnostic Work-Up, and Management

In a 70-year-old with dyspnea, pedal edema, and restrictive cardiomyopathy on echocardiogram, the most critical first step is to distinguish between constrictive pericarditis (which is surgically curable) and infiltrative/restrictive myocardial disease (which requires disease-specific therapy), as this distinction fundamentally alters both prognosis and treatment. 1

Most Likely Etiologies in This Age Group

The differential diagnosis in a 70-year-old includes:

• Cardiac amyloidosis (most common infiltrative cause at this age, particularly AL or TTR amyloidosis) 2, 3
• Constrictive pericarditis (mimics restrictive cardiomyopathy but is surgically curable) 1
• Sarcoidosis (can present with restrictive physiology and ventricular arrhythmias) 2
• Hemochromatosis (iron deposition in myocardium) 2
• Radiation-induced fibrosis (if prior chest radiation) 2
• Idiopathic restrictive cardiomyopathy (diagnosis of exclusion) 2, 3

Diagnostic Algorithm: Distinguishing the Cause

Step 1: Constrictive Pericarditis vs. Restrictive Cardiomyopathy

This is the most critical distinction because constrictive pericarditis is curable with pericardiectomy, while restrictive cardiomyopathy requires disease-specific medical therapy. 1

On the existing echocardiogram, look for:

• Septal bounce (ventricular interdependence) and respiratory variation of mitral E velocity >25% strongly favor constriction 1
• Tissue Doppler e' velocity >8.0 cm/s favors constriction (relatively preserved myocardial relaxation) 1
• Sparkling or granular myocardial texture, thickened interatrial septum, thickened AV valves, or small pericardial effusion suggest infiltrative disease (amyloidosis) 2
• Biatrial enlargement with normal or small ventricular size is seen in both conditions 2, 3

Order cardiac CT immediately:

• Pericardial thickness >3.0 mm or pericardial calcification confirms constrictive pericarditis 1

If CT shows normal pericardium, proceed to cardiac MRI:

• Late gadolinium enhancement patterns identify specific infiltrative causes (amyloidosis shows diffuse subendocardial or transmural enhancement; sarcoidosis shows patchy mid-wall enhancement) 1

Step 2: If Constrictive Pericarditis is Suspected

Measure CRP immediately to determine if there is active inflammation (potentially reversible with anti-inflammatory therapy) versus chronic fibrosis/calcification (requires pericardiectomy) 4

• If CRP is elevated and cardiac MRI shows pericardial enhancement, consider empiric anti-inflammatory therapy (colchicine, NSAIDs, or corticosteroids) 4
• If CRP is normal with severe symptoms, the patient has chronic constriction and should not have pericardiectomy delayed waiting for anti-inflammatory trials 4

Proceed to cardiac catheterization to confirm hemodynamics:

• RVEDP and LVEDP equal (within 5 mmHg) and RV systolic pressure <50 mmHg confirm constriction 1
• Refer for pericardiectomy if confirmed, with better outcomes when performed early 1

Step 3: If Restrictive Cardiomyopathy is Confirmed

Order the following tests to identify the specific etiology:

For amyloidosis (most common at age 70):

• Serum and urine protein electrophoresis with immunofixation to detect AL amyloidosis 3
• Serum free light chains (kappa/lambda ratio) 3
• Technetium-99m pyrophosphate (PYP) scan: Grade 2-3 cardiac uptake with absent monoclonal protein confirms TTR (transthyretin) amyloidosis without need for biopsy 3
• If PYP is positive, order TTR gene sequencing to distinguish hereditary from wild-type TTR amyloidosis 3
• If monoclonal protein is present or PYP is negative, endomyocardial biopsy with Congo red staining and mass spectrometry is required 3

For sarcoidosis:

• 18F-FDG PET scan shows patchy myocardial uptake 3
• Serum ACE level, chest CT for pulmonary involvement 3
• Endomyocardial biopsy may show non-caseating granulomas 3

For hemochromatosis:

• Serum ferritin, transferrin saturation, and iron studies 2
• Cardiac MRI with T2 imaging* quantifies myocardial iron deposition 3
• HFE gene testing for hereditary hemochromatosis 3

For familial restrictive cardiomyopathy:

• Detailed family history of cardiomyopathy or sudden death 2, 5
• Genetic testing for sarcomeric protein mutations (cTnI, cTnT, MyBP-C, MYH7, DES, FLNC) if family history is positive or patient is younger 5, 6

Step 4: Cardiac Catheterization if Diagnosis Remains Unclear

Hemodynamic findings that favor restrictive cardiomyopathy over constriction:

• LVEDP exceeds RVEDP by ≥5 mmHg at rest or with exercise 1
• RV systolic pressure >50 mmHg (pulmonary hypertension from chronic left-sided disease) 1

Management Based on Etiology

If Constrictive Pericarditis:

Pericardiectomy is curative and should be performed early before advanced disease develops (higher mortality with delayed surgery) 1

If Cardiac Amyloidosis:

• AL amyloidosis: Chemotherapy (bortezomib-based regimens) and autologous stem cell transplantation 1, 3
• TTR amyloidosis: Tafamidis (stabilizes TTR tetramers), patisiran or inotersen (gene silencers) 3
• Supportive care: Low-dose loop diuretics (avoid aggressive diuresis as these patients are preload-dependent), avoid digoxin and calcium channel blockers (bind to amyloid fibrils), consider anticoagulation for atrial fibrillation even without documented arrhythmia 3

If Hemochromatosis:

Phlebotomy or iron chelation therapy (deferoxamine, deferasirox) can reverse cardiomyopathy if started early 1

If Sarcoidosis:

Corticosteroids (prednisone 20-40 mg daily) with or without immunosuppressants (methotrexate, azathioprine) 3

If Idiopathic or Other Causes:

Supportive therapy only:

• Diuretics for volume management (use cautiously as these patients are preload-dependent) 1, 3
• Beta-blockers or calcium channel blockers for heart rate control to maximize diastolic filling time 3
• Anticoagulation if atrial fibrillation develops 3
• Consider heart transplantation in refractory cases, particularly in younger patients 6

Critical Pitfalls to Avoid

• Do not assume all restrictive physiology is myocardial disease—always rule out constrictive pericarditis first, as it is surgically curable 1
• Do not delay pericardiectomy in advanced constrictive pericarditis waiting for prolonged anti-inflammatory trials 4
• Do not use digoxin or calcium channel blockers in suspected amyloidosis—they bind to amyloid fibrils and cause toxicity 3
• Do not aggressively diurese—these patients are preload-dependent and can develop hypotension and renal failure 3
• Do not miss TTR amyloidosis—PYP scan is highly specific and can diagnose without biopsy if no monoclonal protein is present 3