CardioNETPOL National Registry of Carcinoid Heart Disease (CardioNETPOL)

Carcinoid Heart Disease National Registry of Poland

Carcinoid tumors are neuroendocrine tumors (NETs), most commonly originating from the gastrointestinal tract, that may secrete bioactive substances such as serotonin. Persistent exposure to these mediators can lead to carcinoid syndrome and, in up to 50% of patients, carcinoid heart disease (CHD). CHD is characterized by fibrotic degeneration of cardiac valves, predominantly right-sided, resulting in progressive valvular dysfunction and a significant increase in mortality.

The mechanisms underlying selective cardiac involvement and predictors of disease progression remain incompletely understood. In addition, optimal timing and selection of surgical versus transcatheter valve interventions, particularly in high-risk patients, require further clarification.

This multicenter, retrospective observational registry aims to identify and characterize patients with carcinoid heart disease and at least moderate valvular involvement. CHD is defined by confirmed neuroendocrine tumor, echocardiographic evidence of ≥ moderate valvular disease with features of fibrosis, elevated NT-proBNP (>260 ng/L), and histopathological confirmation when available.

Approximately 100-120 consecutive patients will be enrolled over 12 months. Standardized data collection will include detailed echocardiographic assessment, demographic and clinical characteristics, cardiovascular risk factors, comorbidities, tumor features, oncological treatment history, and cardiac management strategies.

The primary objective is to describe the clinical profile and management of patients with CHD in a real-world multicenter setting. Secondary objectives include identifying factors associated with advanced valvular dysfunction and evaluating eligibility and outcomes of transcatheter valve therapies. The registry is expected to improve risk stratification and support clinical decision-making in carcinoid heart disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Neuroendocrine Tumors; Carcinoid Syndrome; Carcinoid Heart Disease; Valvular Heart Disease Patients
• Intervention / Treatment: Other: Observational Registry of Carcinoid Heart Disease

Detailed Description

Carcinoid tumors are well-differentiated neuroendocrine neoplasms (NETs) capable of secreting vasoactive and fibrogenic substances, including serotonin, tachykinins, histamine, and prostaglandins. Persistent exposure to these mediators, particularly in the presence of hepatic metastases bypassing first-pass metabolism, may lead to the development of carcinoid syndrome and, in a substantial proportion of patients, carcinoid heart disease (CHD). Cardiac involvement is characterized by plaque-like fibrotic thickening of the endocardium, predominantly affecting right-sided heart valves, leading to leaflet retraction, reduced mobility, and progressive valvular regurgitation and/or stenosis. Over time, this process results in right ventricular volume overload, chamber dilation, heart failure symptoms, and reduced survival.

Although CHD represents a major determinant of prognosis in patients with carcinoid syndrome, important gaps remain in understanding its natural history, predictors of progression, and optimal management strategies. The incidence and severity of cardiac involvement vary considerably between individuals with similar oncologic profiles. Biomarkers such as NT-proBNP are widely used for screening and monitoring, but their integration with imaging findings and clinical variables in risk stratification requires further refinement. In addition, advances in oncological therapy have improved overall survival in NET patients, thereby increasing the clinical relevance of long-term cardiovascular complications.

Surgical valve replacement has traditionally been the standard treatment for advanced valvular dysfunction in CHD. However, many patients are at elevated operative risk due to metastatic disease burden, hepatic dysfunction, malnutrition, or other comorbidities. Emerging transcatheter valve therapies, including bicaval valve implantation and transcatheter tricuspid valve replacement or repair, offer potential alternatives for selected high-risk patients. Data regarding patient selection, anatomical suitability, procedural feasibility, and outcomes in the specific context of CHD remain limited.

This multicenter, retrospective, observational registry is designed to provide a comprehensive characterization of patients with carcinoid heart disease and at least moderate valvular involvement. Participating centers will identify consecutive eligible patients treated within predefined study periods to minimize selection bias. The registry reflects real-world clinical practice and does not mandate any additional diagnostic or therapeutic interventions beyond standard of care.

The study population consists of adult patients with a confirmed diagnosis of neuroendocrine tumor consistent with carcinoid tumor and evidence of carcinoid-related cardiac involvement. Cardiac involvement is established by echocardiographic documentation of at least moderate valvular dysfunction in conjunction with morphological features typical of fibrotic degeneration. Elevated NT-proBNP levels are required to support the presence of hemodynamic significance. In patients undergoing cardiac surgery, histopathological confirmation of carcinoid-related fibrosis will be recorded when available.

A standardized data collection framework will be applied across centers. Baseline demographic data include age, sex, body mass index, and relevant cardiovascular risk factors. Comorbid conditions such as hypertension, diabetes mellitus, chronic kidney disease, chronic liver disease, and prior cardiovascular events will be documented. Functional status will be assessed using available clinical classifications, including New York Heart Association (NYHA) class where recorded.

Comprehensive echocardiographic data will form a core component of the registry. Parameters to be collected include qualitative and quantitative assessment of tricuspid and pulmonary valve morphology and function, evaluation of left-sided valves when involved, right and left ventricular dimensions and systolic function, atrial size, inferior vena cava dimensions, and estimation of pulmonary artery pressures. When available, advanced imaging modalities (e.g., three-dimensional echocardiography or cardiac magnetic resonance imaging) will be documented, but their use is not mandated by the protocol.

Oncological variables will include primary tumor location, histopathological grade (if available), presence and distribution of metastases (hepatic, lymph node, bone, cardiac, or other), biochemical activity, and prior or ongoing systemic therapies. These may include somatostatin analogs, targeted therapies, peptide receptor radionuclide therapy, chemotherapy, and surgical resection of the primary tumor or metastases. Temporal relationships between oncological diagnosis, onset of carcinoid syndrome, and detection of cardiac involvement will be analyzed when data permit.

Cardiac management strategies will be recorded in detail. This includes medical therapy for heart failure, timing and type of surgical valve interventions, and the use of transcatheter approaches. For patients evaluated for transcatheter procedures, anatomical considerations, procedural planning parameters, and heart team decisions will be documented where available. Procedural outcomes, in-hospital course, and short-term follow-up data will be collected in accordance with local documentation standards.

The primary objective of the registry is descriptive: to define the clinical, echocardiographic, and oncological profile of patients with moderate to severe carcinoid heart disease in a contemporary, multicenter cohort. Secondary objectives include identification of clinical and imaging features associated with advanced right ventricular dysfunction, exploration of factors associated with referral for surgical versus transcatheter intervention, and assessment of early clinical outcomes following different management strategies.

Where longitudinal data are available, follow-up analyses will evaluate survival, heart failure progression, need for repeat interventions, and changes in functional status. A predefined subgroup analysis will focus on patients undergoing transcatheter valve therapies to assess feasibility, safety, and short- to mid-term effectiveness in this specific population.

Data will be anonymized at the site level before central aggregation. Each participating center will obtain appropriate approval from its institutional ethics or bioethics committee in accordance with national regulations. Given the retrospective and observational nature of the registry, no study-specific interventions are performed, and patient management remains entirely at the discretion of the treating physicians.

By systematically collecting and analyzing real-world data from multiple centers, this registry aims to enhance understanding of carcinoid heart disease, improve risk stratification, and support evidence-based decision-making regarding timing and type of valvular intervention. The results are expected to inform future prospective studies and contribute to the development of interdisciplinary care pathways integrating cardiology and oncology expertise in the management of this complex condition.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Piotr N Rudziński, MD, PhD; Phone Number: +48608499737; Email: piotr.rudzinski@ikard.pl

Study Locations

• Poland
  • Warsaw, Poland, 04-628
    • National Institute of Cardiology in Warsaw
    • Contact: Piotr N Rudziński, MD, PhD; Phone Number: +48608499737; Email: piotr.rudzinski@ikard.pl
    • Contact: Malwina Gonet, MD, MS; Phone Number: +48223434342; Email: malwina.gonet@ikard.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients with carcinoid heart disease who are evaluated and treated at multiple tertiary cardiology and oncology centers across Poland, including the National Institute of Cardiology. Patients included in this registry represent a real-world, multicenter cohort of individuals with neuroendocrine tumors complicated by moderate to severe valvular heart disease. Data are collected retrospectively from consecutive patients meeting eligibility criteria, reflecting standard clinical practice and management of cardiac and oncologic care. The population includes both patients managed conservatively and those considered for surgical or transcatheter valve interventions.

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Confirmed diagnosis of a neuroendocrine tumor consistent with carcinoid heart disease.
• Echocardiographic evidence of at least moderate valvular disease associated with endocardial fibrosis.
• Elevated NT-proBNP levels (>260 ng/L) consistent with cardiac dysfunction.
• Availability of relevant clinical, echocardiographic, and laboratory data.
• For patients who underwent cardiac surgery, histopathological confirmation of carcinoid-related cardiac tissue (if available).
• Ability to provide informed consent for participation in the registry (or waiver as per local ethics approval for retrospective data).

Exclusion Criteria:

• Patients with insufficient clinical or imaging data to confirm carcinoid heart disease.
• Presence of other primary cardiac conditions causing significant valvular disease unrelated to carcinoid syndrome (e.g., rheumatic heart disease, congenital valve disease)
• Active participation in interventional clinical trials that would conflict with registry data collection
• Patients younger than 18 years

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of patients with carcinoid heart disease	Characterization of patients with carcinoid heart disease defined as: presence of neuroendocrine tumor with hepatic metastases, echocardiographic evidence of right-sided valvular disease (tricuspid and/or pulmonary valve involvement), and biochemical evidence of serotonin excess (elevated urinary 5-HIAA or serum serotonin)	At baseline (time of registry enrollment or most recent echocardiogram)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of patients eligible for transcatheter valve interventions	Identification of candidates for transcatheter tricuspid or pulmonary valve replacement/repair among patients with carcinoid heart disease, assessed by echocardiography, CT-based anatomical evaluation and multidisciplinary Heart Team decision	Baseline
Assessment of clinical factors associated with advanced valvular dysfunction	Identification of clinical factors associated with advanced valvular dysfunction in carcinoid heart disease, assessed by urinary 5-HIAA level (µmol/24h), NT-proBNP (pg/mL) and NYHA functional class	Baseline
Assessment of echocardiographic factors associated with advanced valvular dysfunction	Identification of echocardiographic factors associated with advanced valvular dysfunction in carcinoid heart disease, assessed by tricuspid regurgitation grade and pulmonary valve function on transthoracic echocardiography	Baseline

Collaborators and Investigators

• Sponsor: National Institute of Cardiology, Warsaw, Poland

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Observational Study; Valvular Heart Disease; Neuroendocrine Tumor; Carcinoid Syndrome; Right-Sided Heart Failure; Carcinoid Heart Disease; Transcatheter Tricuspid Valve Intervention; Multicenter Registry
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Neoplasms; Heart Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Chemically-Induced Disorders; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Drug-Related Side Effects and Adverse Reactions; Malignant Carcinoid Syndrome; Carcinoid Tumor; Heart Failure; Neuroendocrine Tumors; Heart Valve Diseases; Carcinoid Heart Disease; Serotonin Syndrome
• Other Study ID Numbers: 1C.8/I/26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) will be entered into a secure electronic case report form (eCRF) provided by the scientific platform of the Polish Cardiac Society (Polskie Towarzystwo Kardiologiczne). All patient data will be fully anonymized before entry to protect privacy. The eCRF will be accessible to all participating centers. De-identified datasets may be shared with qualified researchers upon reasonable request, following approval by the registry steering committee and local ethics boards, in compliance with applicable national and institutional regulations.
• IPD Sharing Time Frame: June 2026 - June 2027
• IPD Sharing Access Criteria: Access to de-identified individual participant data (IPD) and supporting information (study protocol and statistical analysis plan) will be granted to qualified researchers upon reasonable request. Requests will be reviewed and approved by the registry steering committee and relevant local ethics boards. Approved researchers will have access to anonymized clinical, echocardiographic, laboratory, and treatment data through secure transfer or controlled access via the eCRF platform provided by the scientific platform of the Polish Cardiac Society. Data use will be governed by a data use agreement specifying conditions for confidentiality, publication, and compliance with applicable national and institutional regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No