Why do carcinoid tumors cause right-sided heart disease?

From the Guidelines

Carcinoid tumors cause right-sided heart disease primarily through the release of vasoactive substances, especially serotonin, into the bloodstream, which triggers the formation of fibrous plaques on the tricuspid and pulmonary valves, leading to valve thickening, retraction, and dysfunction. This occurs when carcinoid tumors metastasize to the liver, allowing these substances to bypass hepatic metabolism and enter the systemic circulation 1. The right side of the heart is predominantly affected because the lungs filter out these substances before they can reach the left heart chambers.

Key Pathophysiological Mechanisms

• The release of serotonin and other bioactive compounds from carcinoid tumors into the bloodstream leads to the formation of fibrous plaques on the heart valves.
• The tricuspid valve is more often affected than the pulmonary valve, resulting in tricuspid regurgitation and pulmonary stenosis.
• The severity of cardiac involvement often correlates with elevated levels of 5-HIAA (5-hydroxyindoleacetic acid), a serotonin metabolite, in the urine.

Clinical Manifestations and Treatment

• Carcinoid heart syndrome typically manifests as right heart failure symptoms such as peripheral edema, ascites, and fatigue.
• Treatment focuses on managing the underlying carcinoid tumor with somatostatin analogs like octreotide to reduce hormone production, while severe valvular disease may require surgical valve replacement 1.
• The development of carcinoid heart disease leads to a dramatic worsening of prognosis in patients with neuroendocrine tumors, with a 3-year survival rate of 31% compared to 68% in patients without carcinoid heart disease 1.

From the Research

Pathophysiology of Carcinoid Tumors and Right-Sided Heart Disease

• Carcinoid tumors cause right-sided heart disease due to the release of vasoactive substances, particularly serotonin, which stimulates fibroblast growth and fibrogenesis, leading to cardiac valvular fibrosis 2, 3.
• The pathophysiology of carcinoid heart disease is still not completely understood, but it is believed to be multifactorial, involving various vasoactive substances secreted by the tumor 2, 4.
• The fibrotic process caused by serotonin and other tumor-secreted factors leads to the development of fibrotic endocardial plaques, resulting in valve dysfunction and right-sided heart failure 2, 3.

Clinical Manifestations and Diagnosis

• Carcinoid heart disease primarily affects right heart valves, causing tricuspid and pulmonic regurgitation, and less frequently, stenosis of these valves 3.
• Left heart valves are usually spared due to the enzymatic inactivation of vasoactive substances, such as serotonin, in the lung vasculature 3.
• Diagnosis of carcinoid heart disease is typically made using transthoracic echocardiography, which demonstrates thickened right heart valves with limited mobility and regurgitation 2, 5.

Treatment and Management

• Treatment of carcinoid heart disease focuses on controlling the underlying carcinoid syndrome, targeting subsequent valvular heart disease, and managing consequent heart failure 3, 6.
• Surgical valve replacement and catheter-directed valve procedures may be effective for selected patients with carcinoid heart disease 3, 6.
• Timely diagnosis and early surgical treatment are crucial, as carcinoid heart disease is associated with increased morbidity and mortality 6, 4.