What is the clinical presentation, diagnosis, management, and prognosis of carcinoid heart disease?

Carcinoid Heart Disease: Clinical Presentation, Diagnosis, Management, and Prognosis

Carcinoid heart disease (CHD) dramatically worsens prognosis in patients with neuroendocrine tumors, with 3-year survival of only 31% compared to 68% in patients without CHD. 1 Early diagnosis and appropriate management are crucial to improve outcomes.

Clinical Presentation

Symptoms and Signs

• Right heart failure symptoms predominate due to right-sided valve involvement:
  • Peripheral edema
  • Ascites
  • Pulsatile hepatomegaly
  • Fatigue and reduced exercise tolerance

Physical Examination

• Murmurs may be difficult to detect due to low velocities in the right heart 1
• Clinical examination alone is not an accurate predictor of tricuspid regurgitation 1
• Signs of right-sided heart failure develop as disease progresses

Epidemiology

• Prevalence has decreased from 50-70% to about 20% of carcinoid syndrome patients due to improved treatments 1, 2
• Up to 20% of patients with carcinoid syndrome present with CHD at diagnosis 1
• Most commonly affects right-sided heart valves (tricuspid more than pulmonary) 1, 2
• Left-sided lesions occur in up to 15% of patients with carcinoid syndrome, but in 47% of patients with CHD 1
• Left-sided CHD almost invariably involves patent foramen ovale 1

Diagnosis

Biomarkers

• NT-proBNP is highly recommended (cut-off level of 260 pg/ml) to rule out CHD morbidity 1, 2
• Urinary 5-HIAA has high sensitivity (100%) but low specificity for CHD 1, 2
• Patients with 5-HIAA levels ≥300 μmol/24h and ≥3 flushing episodes daily have higher risk of CHD 2

Electrocardiography

• ECG changes are non-specific 1
• Important for detecting arrhythmias 1

Imaging

1. Echocardiography:

   • Mainstay diagnostic tool 1, 2
   • Pathognomonic features include:
     • Thickening and retraction of valve leaflets/cusps
     • Reduced mobility of valves
     • Involvement of subvalvular apparatus
     • Combination of valvular regurgitation and stenosis
     • Right heart chamber enlargement 1

2. Contrast Echocardiography:

   • Should be performed to detect intracardiac shunts and patent foramen ovale
   • Multiple views of each valve needed for optimal evaluation 1
   • Transoesophageal echocardiography when necessary 1

3. Cardiac MRI and CT:

   • Useful for evaluating pulmonary valve function
   • Helpful for detecting cardiac metastases 1, 3
   • Adds valuable information in multivalvular disease 3

Management

Medical Management

1. Somatostatin Analogs (SSAs):

   • First-line therapy for carcinoid syndrome 2
   • Long-acting formulations:
     • Octreotide LAR 20-30 mg IM every 4 weeks
     • Lanreotide 120 mg deep SC every 4 weeks 2
   • Short-acting octreotide (150-250 μg SC three times daily) for breakthrough symptoms 2
   • May reduce circulating vasoactive substances, but no evidence yet that this stabilizes CHD 1

2. Heart Failure Management:

   • Diuretic therapy to relieve symptoms of right heart failure 1, 4
   • Limited efficacy for pure right heart failure 1

Surgical Management

1. Valve Replacement Surgery:

   • Offers definitive therapy for symptoms 1
   • Marked symptomatic improvement of at least one New York Heart Association class 1
   • Median survival of 6 years compared to medically treated patients 1
   • Bioprosthetic valves preferred over mechanical valves due to decreased need for anticoagulation and likelihood of future non-cardiac surgeries 5, 3

2. Surgical Considerations:

   • Should be performed by skilled operators in specialized centers with experience in NETs 2
   • Intraoperative pulmonary valve inspection recommended as echocardiography can underestimate stenosis 5
   • Preservation of tricuspid subvalvular apparatus to prevent right heart failure 5
   • Right ventricular geometry should be respected 5

3. Perioperative Management:

   • Prophylaxis against carcinoid crisis using IV octreotide (preoperative bolus of 100-200 μg followed by continuous infusion of 50 μg/h) 2
   • Accurate echocardiographic evaluation before surgical procedures 2

Multidisciplinary Approach

• All patients should be discussed and managed by a multidisciplinary team 1
• Collaboration between oncology, cardiology, cardiovascular surgeons, anesthesiologists, and other specialists is essential 3, 6, 4
• Referral to specialized cardiology centers for evaluation and possible cardiac surgery 2

Prognosis

• CHD significantly worsens prognosis: 3-year survival of 31% with CHD vs 68% without CHD 1, 2
• Without treatment and for patients with advanced heart failure, prognosis can be less than a year 6
• Valve replacement surgery improves survival compared to medical management alone 1
• Early surgical intervention may improve outcomes 3
• Optimized standardized protocols for CHD management have shown excellent results with low perioperative mortality 5

Key Pitfalls and Caveats

1. Pulmonary valve stenosis can be underestimated by echocardiography; intraoperative inspection is recommended 5
2. Perioperative mortality for valve surgery has historically been high (~17%) but can be significantly reduced with standardized protocols 5
3. Left-sided CHD is rare but should be suspected in patients with patent foramen ovale 1
4. Cytotoxic chemotherapy has been associated with elevated risk of progressive heart disease 1
5. Early screening upon recognition of carcinoid syndrome is crucial, as no existing therapies can reverse the fibrotic damage once it occurs 4