What causes restrictive heart disease?

Causes of Restrictive Cardiomyopathy

Restrictive cardiomyopathy is primarily caused by conditions that lead to myocardial stiffness through either pathological protein deposition or aggressive fibrotic processes, including amyloidosis, sarcoidosis, hemochromatosis, and various genetic mutations affecting sarcomeric proteins. 1

Primary Etiologies

Restrictive cardiomyopathy (RCM) can be classified into several categories based on underlying pathophysiology:

Infiltrative Disorders

• Amyloidosis - Characterized by extracellular deposition of amyloid protein fibrils in the myocardium 1, 2
• Sarcoidosis - Non-caseating granulomatous inflammation affecting the myocardium 1, 3
• Hemochromatosis - Iron overload in cardiac tissue leading to myocardial damage 1, 3
• Gaucher's disease - Accumulation of glucocerebroside in cardiac tissue 4
• Fabry's disease - Progressive accumulation of glycosphingolipids in cardiomyocytes 4, 5

Endomyocardial Disorders

• Endomyocardial fibrosis - Fibrosis of the endocardium and subendocardium 1, 5
• Eosinophilic myocarditis/hypereosinophilic syndrome - Eosinophilic infiltration of the myocardium 1, 4
• Radiation-induced fibrosis - Following therapeutic radiation exposure 1

Connective Tissue Disorders

• Scleroderma - Excessive collagen deposition in myocardial tissue 1, 4
• Pseudoxanthoma elasticum - Calcification and fragmentation of elastic fibers 4

Genetic/Familial Causes

• Sarcomeric protein mutations - Affecting cardiac troponin I (cTnI), cardiac troponin T, desmin, and α-crystallin 1, 5
• Hereditary hemochromatosis - Genetic disorder of iron metabolism 1
• Noonan's syndrome - Genetic disorder affecting multiple organ systems 4

Other Causes

• Idiopathic restrictive cardiomyopathy - No identifiable cause 1, 4
• Carcinoid heart disease - Valvular and endocardial fibrosis from carcinoid syndrome 4
• Lymphoma - Infiltration of cardiac tissue by lymphoma cells 4
• Churg-Strauss syndrome - Vasculitis with eosinophilic infiltration 4
• Cystinosis - Accumulation of cystine crystals in cardiac tissue 4

Pathophysiological Mechanisms

The common feature in restrictive cardiomyopathies is impaired ventricular filling due to increased myocardial stiffness. This occurs through several mechanisms:

1. Extracellular matrix remodeling - Pathological protein deposition or aggressive fibrotic processes resulting from diffuse myocyte cell death 1

2. Intracellular accumulation - Storage of abnormal substances within cardiomyocytes (as in Fabry's disease, glycogen storage disorders) 5

3. Myocardial infiltration - Infiltration of the myocardium by abnormal cells or substances 1, 5

4. Genetic mutations - Affecting sarcomeric proteins leading to defects in myocardial function and increased myofilament calcium sensitivity 1

Clinical Implications and Prognosis

Restrictive cardiomyopathy has significant implications for morbidity and mortality:

• Most forms are progressive with poor prognosis - 50% survival at 5 years after diagnosis 1
• Presents with symptoms of heart failure including dyspnea, fluid retention, fatigue, and weakness 1, 6
• Characteristic findings include normal or near-normal ventricular size and systolic function with biatrial enlargement 1, 6
• Atrial fibrillation is common across many etiologies 1
• Ventricular arrhythmias are particularly prevalent in sarcoidosis and some familial forms 1
• Cardiac conduction defects often accompany amyloidosis 1

Diagnostic Approach

Identifying the specific cause of restrictive cardiomyopathy is critical as some etiologies have disease-specific treatments:

• Echocardiography shows restrictive filling pattern with preserved ejection fraction 6
• Cardiac MRI or CT can assess for specific tissue characteristics 6
• Endomyocardial biopsy may be necessary when noninvasive testing is inconclusive 4, 5
• Genetic testing for familial forms, especially when presenting in childhood or adolescence 1, 7

Treatment Considerations

Treatment depends on the underlying cause:

• Disease-specific therapies exist for amyloidosis (stem cell transplantation and/or chemotherapy) and iron overload cardiomyopathy (iron chelation therapy) 1, 7
• Most other forms require management of heart failure symptoms with diuretics and rate control 6
• Heart transplantation may be considered for eligible patients with progressive disease 6

Early recognition and diagnosis are crucial to initiate appropriate therapy and potentially improve outcomes in this challenging group of cardiac disorders.