What is carcinoid heart disease?

From the Guidelines

Carcinoid heart disease is a serious cardiac complication that affects approximately 50-60% of patients with carcinoid syndrome, primarily impacting the right side of the heart and leading to significant morbidity and mortality if left untreated. This condition is characterized by the thickening and stiffening of the tricuspid and pulmonary valves due to fibrous plaques formed from serotonin and other vasoactive substances released by carcinoid tumors 1. The valve changes result in regurgitation (leaking) and stenosis (narrowing), impairing proper blood flow through the heart. Symptoms of carcinoid heart disease include fatigue, shortness of breath, swelling in the legs and abdomen, and signs of right heart failure.

Diagnosis and Treatment

Diagnosis involves echocardiography, blood tests for elevated NT-proBNP levels, and measurement of 5-HIAA (a serotonin metabolite) in urine 1. Treatment typically includes somatostatin analogs like octreotide (100-500 mcg subcutaneously three times daily or 20-30 mg long-acting formulation monthly) to control hormone secretion, diuretics for fluid retention, and ultimately valve replacement surgery for severe cases. The use of octreotide is recommended based on the results of the PROMID study, which showed median times to tumor progression of 14.3 and 6.0 months in the octreotide LAR and placebo groups, respectively (P=.000072) 1. The left heart is usually spared because the lungs metabolize the harmful substances before they reach the left side, unless the patient has a patent foramen ovale or the tumor has metastasized to the lungs, allowing these substances to bypass pulmonary filtration.

Risk Factors and Prevention

A recent study involving 250 patients with carcinoid syndrome showed that those with 5-HIAA levels of 300 mcmol or greater (57 mg) over 24 hours and with 3 or more flushing episodes per day were more likely to have carcinoid heart disease 1. A cardiology consultation and echocardiogram are recommended to assess whether the patient has carcinoid heart disease, especially in patients with carcinoid syndrome and signs and symptoms of heart disease or with planned major surgery. Early detection and treatment of carcinoid heart disease are crucial to prevent significant morbidity and mortality.

Management and Follow-up

In patients who have clinically significant tumor burden or progressive disease, initiation of either octreotide or lanreotide is recommended to potentially control tumor growth if they are not already receiving it 1. No clear consensus exists on the timing of octreotide or lanreotide initiation in asymptomatic patients with metastatic NETs and low tumor burden. Although initiation of octreotide or lanreotide can be considered in these patients, deferring initiation until evidence of tumor progression is seen may also be appropriate in selected patients. Regular follow-up with echocardiography and monitoring of 5-HIAA levels are essential to assess the effectiveness of treatment and detect any potential progression of carcinoid heart disease.

From the Research

Definition and Pathophysiology

• Carcinoid heart disease (CHD) is a rare and potentially lethal manifestation of an advanced carcinoid (neuroendocrine) tumor 2, 3.
• The pathophysiology of CHD is related to vasoactive substances secreted by the tumor, of which serotonin is most prominent in the pathophysiology of CHD 3.
• Serotonin stimulates fibroblast growth and fibrogenesis, which can lead to cardiac valvular fibrosis 3.

Clinical Manifestations

• CHD primarily affects right heart valves, causing tricuspid and pulmonic regurgitation and less frequently stenosis of these valves 2, 3.
• Left heart valves are usually spared because vasoactive substances such as serotonin are enzymatically inactivated in the lung vasculature 3.
• Symptomatic CHD usually presents between 50 and 70 years of age, initially as dyspnea and fatigue 3.
• Echocardiography is the mainstay of imaging and demonstrates thickened right heart valves with limited mobility and regurgitation 2, 3.

Diagnosis and Management

• A combination of biomarkers and cardiac imaging is used in screening and diagnosis of carcinoid heart disease in patients with carcinoid syndrome 4.
• The management of carcinoid heart disease involves medical and surgical treatment and requires a multidisciplinary approach for optimized care 4.
• Surgical valve replacement and catheter-directed valve procedures may be effective for selected patients with CHD 2, 3, 5.
• Somatostatin analogs form the therapeutic cornerstone in the medical management of these patients 6.

Prognosis

• The development and progression of carcinoid heart disease are associated with an unfavorable outcome 6.
• A recent analysis of 200 cases demonstrated an increase in median survival from 1.5 years to 4.4 years in the last two decades 2.
• Valve replacement surgery has been found to be an effective treatment that can both relieve intractable symptoms and contribute to improved clinical outcomes 2, 6.