Can cystic fibrosis (CF) be associated with cardiomyopathy?

Cardiomyopathy in Cystic Fibrosis

Yes, cystic fibrosis can be associated with cardiomyopathy, both as a secondary consequence of pulmonary disease and potentially as a primary cardiac manifestation related to CFTR dysfunction. The cardiac involvement in cystic fibrosis is multifaceted and includes both right and left ventricular abnormalities.

Types of Cardiac Involvement in Cystic Fibrosis

Right Ventricular Dysfunction and Cor Pulmonale

• Cor pulmonale (right ventricular dysfunction) is the most common and serious cardiovascular complication in CF, primarily resulting from chronic hypoxemia due to progressive pulmonary disease 1
• Pulmonary hypertension develops in a significant proportion of CF patients with severe lung disease and is strongly correlated with oxygen status, independent of lung function 2
• Subclinical pulmonary hypertension in CF patients is associated with increased mortality 2

Left Ventricular Dysfunction

• Recent evidence suggests the existence of a specific CF-related cardiomyopathy affecting left ventricular function 3
• Both diastolic and systolic ventricular dysfunction have been documented in CF patients using advanced echocardiographic techniques 3
• Left ventricular cardiac abnormalities in CF may occur as both:
  • A secondary effect from pulmonary disease
  • A potential primary defect related to CFTR dysfunction in cardiac myocytes 4

Mechanisms of Cardiomyopathy in CF

• Hypoxemia is one of the most important factors contributing to heart involvement in CF, particularly for right ventricular dysfunction 3, 5
• Chronic inflammation associated with CF may contribute to myocardial dysfunction 3
• The Cystic Fibrosis Transmembrane Regulator (CFTR) has been found to be involved in the regulation of cardiomyocyte contraction, suggesting a potential direct role in myocardial function 3, 4
• Pulmonary vascular changes (Grade 3 Heath/Edwards) have been documented on autopsy in some CF patients with cardiac involvement 6

Clinical Presentation and Diagnosis

• Cardiac involvement in CF may be subclinical in many patients, especially in earlier stages 4
• Advanced echocardiographic techniques and magnetic resonance imaging are providing greater insight into cardiac function in CF patients 4
• Doppler echocardiography can detect elevated pulmonary artery systolic pressure (>35 mmHg) in CF patients without clinical evidence of cor pulmonale 2
• Left ventricular size, systolic function, and diastolic function are typically normal in most CF patients unless there are complicating factors 2

Management Considerations

• The primary approach to managing cor pulmonale in CF is treating the underlying hypoxemia 1, 5
• Regular cardiac evaluation should be considered in CF patients, particularly those with advanced lung disease 2
• The impact of pulmonary hypertension-specific therapies on outcomes in CF patients has not been well studied 5
• For patients with significant hypertrophic cardiomyopathy, treatment options may include β-blocker medications or surgical procedures such as myomectomy to decrease outflow obstruction, similar to management approaches for other forms of HCM 6

Prognostic Implications

• The presence of pulmonary hypertension in CF patients is associated with worse survival outcomes 2, 5
• Mortality is significantly higher in CF patients with pulmonary hypertension compared to those without pulmonary hypertension 2
• With advancing lifespans and activity levels in CF patients, understanding the risk of cardiac disease is becoming increasingly important for minimizing morbidity in adults with CF 4

As CF patients live longer due to improved treatments, cardiac complications may become more prevalent and clinically significant, warranting careful cardiac monitoring and appropriate management strategies.