What is the diagnosis and treatment for restrictive cardiomyopathy, potentially caused by underlying conditions such as amyloidosis or sarcoidosis?

Restrictive Cardiomyopathy: Diagnosis and Treatment

Diagnostic Approach

Restrictive cardiomyopathy (RCM) is diagnosed by demonstrating restrictive left ventricular pathophysiology—a rapid rise in ventricular pressure with minimal increases in filling volume due to increased myocardial stiffness—alongside non-dilated ventricles and atrial dilatation, which can be confirmed through echocardiography or cardiac catheterization. 1

Initial Clinical Assessment

• Look for dyspnea, fatigue, and prominent signs of right heart failure with fluid retention 2, 3
• Examine for Kussmaul sign (paradoxical rise in jugular venous pressure with inspiration), which is characteristic of restrictive physiology 3
• Note the absence of cardiomegaly on chest X-ray, which helps distinguish RCM from dilated cardiomyopathy 2
• Obtain detailed history focusing on potential underlying causes: family history (genetic forms), systemic symptoms suggesting amyloidosis/sarcoidosis, exposure to radiation or chemotherapy, or signs of iron overload 2

Essential Diagnostic Testing

Natriuretic peptides (BNP/NT-proBNP) should be measured as an initial screening test—elevated levels establish the need for further cardiac investigation, while normal values make significant cardiac dysfunction unlikely 2

Echocardiography is the most useful and widely available test to establish the diagnosis 2:

• Demonstrates diastolic dysfunction with preserved or reduced systolic function 1, 4
• Shows non-dilated ventricles with atrial enlargement 1
• Tissue Doppler with peak e' >8.0 cm/s suggests constrictive pericarditis rather than RCM 3
• Respiratory variation of mitral peak E velocity >25% also favors constriction over restriction 3

12-lead ECG should be obtained to assess for:

• Myocardial ischemia patterns (indicating higher sudden death risk, especially in pediatric patients) 5
• Low voltage (suggests amyloidosis) 6
• Conduction abnormalities (common in amyloidosis and sarcoidosis) 2, 6

Advanced Imaging for Etiology Determination

Cardiac MRI with late gadolinium enhancement identifies specific causes including amyloidosis (characteristic subendocardial or global enhancement) and sarcoidosis (patchy midwall enhancement) 3

CT imaging detects pericardial thickness >3.0 mm and calcification, which would indicate constrictive pericarditis rather than RCM 3

Hemodynamic Confirmation

Cardiac catheterization definitively demonstrates restrictive physiology and distinguishes RCM from constrictive pericarditis 3, 1:

• In RCM: LVEDP exceeds RVEDP by ≥5 mmHg, and RV systolic pressure is often >50 mmHg 3
• In constriction: RVEDP and LVEDP are equal (within 5 mmHg), and RV systolic pressure is typically <50 mmHg 3

Identifying Specific Etiologies

The three major treatable causes requiring specific diagnosis are cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis 6:

• For amyloidosis: Check serum and urine protein electrophoresis with immunofixation, serum free light chains, fat pad or rectal biopsy, and consider endomyocardial biopsy with Congo red staining 6
• For sarcoidosis: Obtain chest CT, serum ACE levels, and consider PET-CT or endomyocardial biopsy 6
• For hemochromatosis: Measure serum ferritin and transferrin saturation; cardiac MRI T2* imaging quantifies cardiac iron deposition 6

Endomyocardial biopsy may be necessary when non-invasive testing is inconclusive, particularly to diagnose infiltrative diseases 1, 4

Genetic testing should be considered when RCM presents in childhood without extracardiac abnormalities or when there is a family history, as mutations in cardiac troponin I, troponin T, desmin, and α-crystallin are associated with familial RCM 2

Treatment Strategy

Disease-Specific Therapies (When Available)

For cardiac amyloidosis, chemotherapy and autologous stem cell transplantation can control the disease in select cases 2, 7, 8

For cardiac hemochromatosis, iron chelation therapy with desferrioxamine can reverse cardiomyopathy if initiated early 2, 7, 8

For cardiac sarcoidosis, immunosuppressive therapy with corticosteroids is the mainstay of treatment 6

Symptomatic Heart Failure Management

The management of RCM is primarily palliative, focusing on treating heart failure symptoms with diuretics and heart rate control to optimize left ventricular filling 7:

• Use diuretics cautiously for pulmonary congestion and fluid retention, but avoid excessive diuresis as the fixed stroke volume makes patients highly susceptible to hypotension 5, 7, 8
• Optimize heart rate control to maximize left ventricular filling time, which is critical since cardiac output is entirely dependent on heart rate in RCM 5, 7
• Beta-blockers and calcium channel blockers should be used with extreme caution or avoided, as their negative chronotropic and inotropic effects are poorly tolerated due to RCM's unique physiology 5, 7, 8
• ACE inhibitors are generally ineffective in RCM 8
• Digoxin may be used to control heart rate in patients with atrial fibrillation 8

Arrhythmia and Thromboembolism Management

Anticoagulation should be used in all patients with atrial fibrillation regardless of CHA₂DS₂-VASc score due to high thromboembolism risk 5, 7

In cardiac amyloidosis, consider anticoagulation even in sinus rhythm due to amyloid infiltration causing diminished atrial contractility and increased thrombus formation risk 7

For hemodynamically unstable atrial fibrillation, use direct current cardioversion or amiodarone IV infusion 7

An ICD is recommended (Class I) in patients with sustained ventricular arrhythmias causing hemodynamic instability who are expected to survive >1 year with good functional status 7

Perioperative Considerations

Patients with RCM require a multidisciplinary approach for noncardiac surgery 2:

• Cardiac output is both preload and heart rate dependent—avoid significant volume reduction, bradycardia, tachycardia, and atrial arrhythmias 2
• Optimize volume status and heart failure medications before surgery 2
• Avoid overdiuresis and maintain adequate preload 2

Transplant Evaluation

Heart transplantation should be considered early, as RCM has the worst prognosis among all cardiomyopathy phenotypes 5, 7:

• Survival is 50% at 5 years after diagnosis 2
• Pediatric patients with RCM should be referred urgently to a transplant center, as heart transplantation is the only successful therapeutic option 5
• Most RCMs are progressive with poor prognosis despite medical management 2, 8

Monitoring Protocol

Regular assessment should include NYHA functional class, left atrial size, and ventricular function, as these predict mortality 5, 7

In pediatric patients, closer monitoring is warranted due to higher sudden death risk, particularly with ECG evidence of myocardial ischemia 7

Critical Pitfall

The most important pitfall is failing to distinguish constrictive pericarditis from RCM—constriction is curable with pericardiectomy, while RCM requires entirely different management 3, 8. Use the hemodynamic criteria (LVEDP-RVEDP gradient), imaging findings (pericardial thickness), and echocardiographic features (septal bounce, respiratory variation) to make this distinction definitively.