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The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus.

We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director.

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Patient Summary

A woman in her mid 60s with history of neuroendocrine tumor (NET) presented to the cardio-oncology clinic with chronic progressive SOB and fatigue. She was diagnosed with NET after presenting with a small bowel obstruction (SBO) several years prior. At the time, she was found to have liver and pulmonary metastasis with MR enterography showing thickening of the terminal ileum. Ileocecetomy and biopsy of the liver lesions confirmed metastatic NET. Despite treatment with octreotide and everolimus, follow up CT showed progression of liver lesions and she was eventually started on telotristat and enrolled in a clinical trial. On presentation, she was not tachycardiac, hypotensive or requiring oxygen supplementation (KD: Correct?). On exam, she demonstrated elevated JVP with a positive hepato-jugular reflex and a 3/6 holosytolic murmur loudest at the LLSB that increased with inspiration. Lab work revealed urinary 5-HIAA was 212 (nl < 6mg/24 hours). TTE showed moderately dilated RV and severely dilated RA. Furthermore, there was a thickened, calcified and retracted TV with severe TR which was consistent with carcinoid heart disease. She was treated with diuretics and was continued on systemic therapies to help achieve control of her NET before surgical intervention for her valvular disease was considered.  

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Case Media

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Episode Schematics & Teaching

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The CardioNerds 5! – 5 major takeaways from the #CNCR case

1. The patient had an NET history and presented with shortness of breath. Under what circumstances do patients with NETs present with cardiac symptoms? 
   1. Amongst patients with neuroendocrine tumors (NETs), carcinoid tumors refer classically to gastrointestinal NETs. Around 30 to 40% of these patients will presents with features of carcinoid syndrome, including vasomotor symptoms (e.g., flushing), diarrhea, and bronchospasm. The majority of patients with carcinoid syndrome have metastases to the liver and the vasoactive substances (e.g., 5-hydroxytryptamine [5-HT]) reach the systemic circulation via the hepatic vein bypassing degradation in the liver.  
   2. Similarly, cardiac involvement occurs after metastasis to the liver and exposure of the heart to vasoactive substances. Generally, symptoms are limited to the right heart as the lungs clear carcinoid-related substances. Left-sided involvement may occur, however, in a patient with carcinoid heart disease and an intracardiac right to left shunt is present.  
   3. In addition to the symptoms of carcinoid syndrome, patients with carcinoid heart disease including severe dyspnea, fatigue, and signs and symptoms of right heart failure (e.g., ascites, peripheral edema).  

2.  The patient was diagnosed with carcinoid heart disease. What are the typical echocardiographic findings of carcinoid heart disease?   
   1. The echocardiographic findings of carcinoid heart disease are heterogeneous from mild thickening of a single valve leaflet to advanced disease with significant thickening and retraction of multiple valves. The vasoactive substances of carcinoid can specifically cause valvular thickening (5-HT receptors being most prevalent on heart valves) and restricted leaflet motion that can result in a “club-like” appearance of the leaflets. This occurs on the right-sided heart valves (unless an intracardiac shunt exists), with TV involvement being most common.  
   2. Specifically, in mild cases, the normal concave curvature of the tricuspid leaflets is reduced and the leaflets straighten, This affects its motion during diastole leading to valve dysfunction. Eventually there is progressive thickening of the valve leaflets, chordae and papillary muscle leading to significant leaflet retraction and reduced leaflet motion. When carcinoid heart disease becomes severe, the leaflets can be fixed and fail to coapt leading to severe tricuspid regurgitation, tricuspid stenosis, and signs and symptoms of right heart failure.  
   3. As with the tricuspid valve, carcinoid heart disease can also affect the pulmonary valve leading to diffuse thickening and the formation of typical “carcinoid plaques.” This similarly can result in retraction of the valve cusps and mixed pulmonic regurgitation and pulmonic stenosis. Note pulmonic stenosis secondary to carcinoid has an extremely poor prognosis (with median survival typically less than 2 years) and is often not responsive to balloon vavuloplasty.  

3 . What is the typical diagnostic evaluation of carcinoid heart disease in patients with NET? 

• In patients with NET and subsequently carcinoid syndrome, there should be monitoring for the development of heart failure, right-sided symptoms and new murmurs. Nonetheless, high index of suspicion is necessary as up to 57% of patients with moderate to severe TR can be asymptomatic or have mild symptoms and one-third of patients can lack a cardiac murmur.  
• NT-proBNP is a useful biomarker of carcinoid heart disease, and a cutoff level of 260 pg/ml (31 pmol/l) and has been used as a screening tool for carcinoid heart disease (sensitivity 60-92%, specificity 80-91%). Furthermore, plasma and urinary levels of 5-HIAA are significantly higher in patients with carcinoid heart disease compared with those without cardiac involvement. 5-HIAA levels >300 mmol/24 h conferred a 2- to 3-fold increased risk for developing or progression of carcinoid heart disease  
• TTE is the imaging modality of choice for patients with signs and/or symptoms of carcinoid heart disease, in patients with elevated NT-proBNP , and any patient undergoing surgical liver or abdominal intervention. The findings of carcinoid heart disease are on a spectrum, but there are some characteristic findings as outlined above. TEE can be an additional test to fully characterize valvular involvement and/or for surgical planning. Furthermore, cardiac CT and CMR may be valuable as adjuncts 

4. How do you manage carcinoid heart disease? 

• The only definitive and effective therapy for carcinoid heart disease is valve intervention. Diuretics and aldosterone antagonists can be helpful to relieve symptoms, but typically only have temporary effectiveness. Telotristat ethyl, an oral tryptophan hydroxylase inhibitor used in combination with a somatostatin analog for management of diarrhea associated with carcinoid syndrome, has been used to try to prevent the development and progression of carcinoid heart disease.  
• Surgical valve intervention should be considered in patients with severe valvular disease and/or signs of right heart failure, with at least 12 months of anticipated post-operative survival fromt heir NET disease.  
• Symptomatic management primarily involves loops diuretics and aldosterone antagonists for relieving symptoms associated with RHF. Digoxin, vasodilators, and ACEi have no proven efficacy in this population. Bioprosthetic valves may be preferred over mechanical valves due to the inherent increased risk of bleeding in patients with advanced liver disease and hepatic dysfunction from carcinoid disease. However, bioprosthetic valves may be more prone to premature dysfunction and degeneration due to the underlying carcinoid process and thrombosis formation. A careful multi-disciplinary team and approach is needed to individualize valve choice for each patient.  
• Transcatheter valve replacement has been undertaken for pulmonic valve involvement, but transcatheter tricuspid valve replacement is not common.  

5. What is the overall prognosis of patients with carcinoid heart disease with and without surgical management?  

• Carcinoid heart disease with NYHA III or IV symptoms have a poor prognosis and median survival is only 11 months. In carcinoid patients with cardiac symptoms and controlled systemic disease, cardiac valve replacement surgery alleviates otherwise intractable symptoms and appears to improve survival. 

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References

• JACC 2017 – Carcinoid Heart Disease 
• JACC 2017 – Carcinoid Heart Disease – ACC Review 
• https://www.uptodate.com/contents/carcinoid-heart-disease#H14 

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CardioNerds Case Reports: Recruitment Edition Series Production Team

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