Survival trends in the management of carcinoid heart disease among patients with neuroendocrine tumors

Background: Nearly 20% of patients diagnosed with neuroendocrine tumors (NET) will develop carcinoid syndrome (CS), with 20-25% of CS patients developing carcinoid heart disease (CHD). The risk factors for developing CHD and prognostic variables in the current day of NET management are lacking. Objectives: The main objectives of this study were to describe the clinical, laboratory, and imaging risk factors for developing CHD in CS patients, and to identify predictors of survival in NET patients. Methods: A single-institution, retrospective analysis of patients with well-differentiated NET from January 2010 to December 2024 was conducted. Cox proportional hazard regression assessed the association between baseline covariates and CHD development (primary endpoint), and overall survival (OS; secondary endpoint). CHD was defined as moderate or severe tricuspid regurgitation on echocardiogram, consistent with prior studies. Survival curves for OS and CHD development were estimated using the Kaplan-Meier method. A p-value of 0.05 was considered statistically significant. Results: We identified and included 270 patients with NET in the study. Median age was 64.5 years, 52% were male and 5.6% were diagnosed with CHD. CS was present in 10% of patients (n=27), and 41% of those with CS developed CHD. The most common primary tumor sites were lung (26%), pancreas (17.4%), and small intestine (16.2%). On multivariable analysis, right ventricular (RV) dilation was also associated with shorter time to CHD diagnosis (hazard ratio [HR] 7.65, 95% CI: 1.03-56.78, p=0.047). The diagnosis of CHD was associated with a higher number of hospitalizations overall and the use of systemic or multimodal therapies.For the secondary endpoint of OS, median OS for patients with CHD was 90.8 months, while median OS was not reached for the full NET cohort. CHD development was independently associated with worse OS in extended Cox models (HR 7.09; 95% CI 1.84-27.40, p=0.004), highlighting its strong prognostic impact beyond baseline tumor factors. The use of systemic therapy (HR 8.97; 95% CI: 1.78-45.25, p=0.0101) and high-grade (G3) tumors were associated with worse OS (HR 6.92; 95% CI: 2.40-19.92, p<0.001). Conclusion: Among patients with NET, the diagnosis of CHD, use of systemic/multimodal therapy, and high-grade tumors were associated with worse overall survival. Although the incidence of CHD is low, close monitoring for early diagnosis and intervention remain critical in the management of these patients.