RESTRICTIVE CARDIOMYOPATHY

Restrictive cardiomyopathy (RCM) is a rare myocardial disease characterized by impaired ventricular compliance, with pathological stiffening of the heart walls that limits diastolic filling. Unlike dilated cardiomyopathy or hypertrophic cardiomyopathy, the ventricles have normal or only slightly increased wall thickness but exhibit severe impairment of their ability to expand, leading to increased filling pressures and progression to heart failure.

The main pathophysiological changes in RCM involve the loss of myocardial elasticity and an increase in cardiac tissue stiffness, often caused by infiltration of pathological substances (such as amyloid or iron) or progressive myocardial fibrosis. These changes result in a diastolic filling deficit, leading to increased atrial pressures and symptoms of congestive heart failure, predominantly affecting the right side of the heart.

Epidemiology

Restrictive cardiomyopathy is the least common primary cardiomyopathy, with an estimated prevalence of less than 1 case per 100,000 individuals. However, its true incidence may be underestimated due to diagnostic challenges and the variability in clinical presentation.

It primarily affects adults between the ages of 40 and 60 but can also be diagnosed in childhood, particularly in genetic forms or hereditary amyloidosis.

The causes can be either primary (idiopathic or genetic) or secondary, resulting from infiltrative or fibrotic diseases, such as:

• Cardiac amyloidosis: the leading cause of RCM in elderly patients, due to the accumulation of amyloid fibrils in the myocardium.
• Hemochromatosis: excessive iron accumulation in tissues, leading to myocardial damage.
• Cardiac sarcoidosis: a systemic granulomatous disease that can affect the heart.
• Endomyocardial fibrosis: a rare condition characterized by the deposition of fibrotic tissue that restricts ventricular compliance.
• Fabry disease: a lysosomal disorder leading to the accumulation of globotriaosylceramide in cardiomyocytes.
• Exposure to radiation or chemotherapeutic agents (anthracyclines): toxic factors that induce myocardial fibrosis.

In Western countries, the most frequent cause is cardiac amyloidosis, while in tropical regions, endomyocardial fibrosis is the predominant form of restrictive cardiomyopathy.

Pathophysiology

Restrictive cardiomyopathy is characterized by diastolic dysfunction with reduced ventricular filling capacity. Pathophysiologically, the heart becomes progressively stiffer due to infiltrative or fibrotic processes, which limit the expansion of the ventricular chambers during diastole.

The main pathophysiological mechanisms include:

• Increased myocardial stiffness: reduced ventricular compliance due to abnormal substance infiltration or diffuse interstitial fibrosis.
• Elevated filling pressures: impaired ventricular filling leads to increased atrial pressure, causing atrial dilation.
• Low-output heart failure: despite a relatively preserved ejection fraction, the reduced filling volume leads to decreased cardiac output.
• Systemic venous congestion: right ventricular dysfunction results in hepatic congestion, ascites, and peripheral edema.

Unlike other forms of heart failure, RCM is characterized by a relatively preserved or only mildly reduced ejection fraction but with marked systemic venous congestion and symptoms of right-sided heart failure.
In advanced amyloidosis cases, protein infiltration can also affect the conduction system, predisposing patients to arrhythmias and atrioventricular blocks.

Over time, disease progression leads to reduced cardiac output, which can result in hypotension, syncope, and severe functional impairment. In end-stage cases, RCM may evolve into refractory heart failure, requiring advanced support such as ventricular assist devices or heart transplantation.

Clinical Presentation

The clinical presentation of restrictive cardiomyopathy (RCM) varies depending on the underlying cause and disease stage.
In early stages, symptoms may be mild or absent, whereas as ventricular stiffness progresses, signs of right-sided heart failure and low cardiac output become apparent.

Key Signs and Symptoms

• Exertional dyspnea: due to elevated filling pressures and pulmonary congestion.
• Peripheral edema: a sign of right heart failure with fluid retention.
• Ascites and hepatomegaly: resulting from hepatic venous congestion.
• Fatigue and hypotension: secondary to reduced cardiac output.
• Palpitations: due to atrial fibrillation, which is common in patients with atrial dilation.
• Syncope: in advanced cases, caused by cerebral hypoperfusion or arrhythmias.

Unlike dilated cardiomyopathy, which is dominated by systolic dysfunction, RCM maintains a relatively preserved ejection fraction, but diastolic dysfunction results in a reduced filling volume and symptoms of systemic congestion.

Physical Examination

On physical examination, the most common findings in RCM include:

• Elevated jugular venous pressure: often with a prominent "y" descent, indicating diastolic dysfunction.
• Pulsus paradoxus: typical of cases with cardiac tamponade secondary to pericardial effusion.
• Mitral or tricuspid regurgitation murmur: due to atrial dilation with secondary valvular dysfunction.
• Kussmaul's sign: a paradoxical increase in jugular venous pressure during inspiration, characteristic of advanced cases.
• Normal or slightly reduced apical impulse: unlike dilated cardiomyopathy, the impulse is not hyperdynamic.

In many patients, RCM may be confused with constrictive pericarditis, a condition with similar hemodynamic features. Therefore, differentiating between the two is crucial for treatment.

Diagnosis

The diagnosis of restrictive cardiomyopathy is based on a combination of imaging and laboratory tests aimed at identifying diastolic dysfunction, atrial dilation, and potential underlying causes, such as amyloidosis or hemochromatosis.

Diagnostic Tests

• Electrocardiogram (ECG): often shows atrial fibrillation, low QRS voltages (especially in amyloidosis), and sometimes atrioventricular blocks.
• Transthoracic echocardiography: a first-line test, revealing dilated atria, non-dilated but stiff ventricles, and altered diastolic filling patterns.
• Tissue Doppler and strain imaging: useful for detecting subclinical myocardial dysfunction.
• Cardiac magnetic resonance (CMR): crucial for diagnosing amyloidosis (with diffuse late gadolinium enhancement) or hemochromatosis (with iron overload).
• Endomyocardial biopsy: reserved for uncertain cases, allowing definitive diagnosis of amyloidosis, sarcoidosis, or other infiltrative diseases.
• Genetic testing: indicated in patients with suspected hereditary forms, such as Fabry disease.

Differential Diagnosis

It is essential to distinguish RCM from other conditions with similar symptomatology, including:

• Constrictive pericarditis: often confused with RCM, it is distinguished by the presence of pericardial calcifications and responsiveness to pericardiectomy.
• Hypertrophic cardiomyopathy: characterized by asymmetric hypertrophy and outflow tract obstruction.
• Dilated cardiomyopathy: features ventricular dilation with reduced ejection fraction.

Treatment

The treatment of restrictive cardiomyopathy focuses on symptom control and managing complications, as there is often no curative therapy. Management depends on the underlying cause.

Pharmacological Management

• Diuretics: used to reduce venous congestion, with caution to avoid hypotension.
• Beta-blockers or calcium channel blockers: may help slow heart rate and improve diastolic filling.
• Anticoagulants: indicated in patients with atrial fibrillation to prevent thromboembolic events.

In patients with cardiac amyloidosis, specific treatments include the use of drugs like tafamidis, which stabilizes transthyretin and slows disease progression. In hemochromatosis, phlebotomy and iron chelation therapy can improve myocardial function.

Advanced Options

• Heart transplantation: considered for patients with refractory heart failure.
• Ventricular assist devices (VADs): in select cases, as a bridge to transplant.

Prognosis

The prognosis of restrictive cardiomyopathy depends on its etiology and disease progression rate. Patients with infiltrative forms, such as advanced amyloidosis, have a median survival of less than 5 years, whereas less aggressive forms may allow a good quality of life with appropriate therapeutic support.

Major Complications

• Refractory right-sided heart failure: the leading cause of hospitalizations.
• Ventricular arrhythmias and atrial fibrillation: increase the risk of stroke and sudden cardiac death.
• Pulmonary thromboembolism: due to venous stasis and atrial fibrillation.

Early identification and a multidisciplinary management approach can improve prognosis and quality of life for patients with RCM.

References
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