Heart in the Crossfire: Interatrial Septal Carcinoid Metastasis

Christian Bayingana, MD MPH MBA, Pasquale Marotta DO, Sanjeev Francis, MD
Cardiovascular Service Line, Maine Medical Center¹, Portland, ME, USA

Clinical History

A 69-year-old male was referred to our cardio-oncology program for evaluation of cardiomyopathy and possible cardiac metastasis in the setting of carcinoid. The patient reported a progressive history of intermittent exercise-induced lightheadedness and flushing for almost 10 years. Patient had previously undergone exercise stress transthoracic echocardiogram (TTE), which had not shown any evidence of ischemia.

The patient had a history of chronic retroperitoneal lymphadenopathy on prior imaging, with noted increased fluorodeoxyglucose (FDG) uptake on positron emission tomography computed tomography (PET CT) the prior year. He had recently been diagnosed with well differentiated neuroendocrine tumor (Ki-67 3%) involving the jejunum/head of pancreas with metastatic liver disease and was initiated on monthly Lanreotide.

TTE prior to initial cardio-oncology consultation showed mild left ventricular (LV) systolic dysfunction with an ejection fraction (EF) of 53%, no significant valvular abnormalities, and abnormal global longitudinal strain -13%. A Dotatate PET CT scan showed intense and focal uptake in the area of the interatrial septum (Figure 1). Further review of his recent TTE also demonstrated thickening of the interatrial septum (Figure 2).

Figure 1. Dotatate PET CT scan in the axial (A), coronal and sagittal (B) planes showing intense and focal uptake in the area of the interatrial septum (see arrow).

Figure 2. Transthoracic echocardiography apical 4 chamber still frame at end-diastole showing inter-atrial thickening (see arrow) without discrete mass.

CMR Findings

Cardiovascular magnetic resonance (CMR) was performed on a Ingenia 1.5 T scanner (Philips Healthcare, Best, Netherlands) using a dedicated cardiac phased-array coil. Imaging sequences included cine balanced steady state free precession (bSSFP), T1- and T2-weighted fast spin echo, T2 fat-suppressed imaging, and first-pass perfusion following intravenous gadolinium-based contrast agent (gadobutrol 0.1 mmol/kg). The study was terminated early due to a moderate allergic reaction (pruritus, hives, and cough) that resolved following intravenous diphenhydramine.

CMR showed a 1.9 x 1.4 x 0.7 cm mass involving the interatrial septum as seen on 4-chamber bSSFP sequence (Figure 3, Movie 1). The mass is hyper-intense on T2 weighted images (Figure 4) and did not change in signal intensity with fat saturation, excluding lipomatous composition.  It was isointense (relative to the myocardium) on T1 weighted images. First pass perfusion imaging performed with gadolinium (Figure 5, Movie 2) demonstrated focal enhancement consistent with a vascular lesion. Late gadolinium enhancement images were unavailable in the setting of early scan termination due to allergic reaction. LV function at that time was noted to be normal (EF 61%) with normal chamber volume (left ventricular end-diastolic volume index (LVEDVI) 74 mL/m²). Right ventricular function was also preserved (EF 56%) with normal chamber volume (right ventricular end-diastolic volume index (RVEDVi) 82 mL/m²). Valvular assessment showed no evidence of significant tricuspid or mitral regurgitation or stenosis.

Figure 3. Four chamber cine bSSFP at end-diastole showing a 1.9 x 1.4 x 0.7 cm mass involving the interatrial septum (arrow).

Movie 1. Cine bSSFP 4 chamber sequence stack shows an inter-atrial mass.

Figure 4. T2 weighted with fat saturation axial plane shows an inter-atrial mass appearing hyper-intense (arrow).

Figure 5. First pass perfusion imaging performed with gadolinium in axial plane showing uptake illustrating vascular enhancement (arrows).

Movie 2. First pass perfusion cine sequence with focused view of the inter-atrial septum with uptake within the mass.

Conclusion

The patient’s CMR findings combined with PET CT scan findings were consistent with a metastasis from known pancreatic/jejunal carcinoid tumor. In follow-up, the patient did not have any embolic phenomena symptoms such a transient ischemic attach (TIA). Patient subsequently achieved 10 METS during follow-up exercise nuclear myocardial perfusion imaging, with an EF of 68%. Patient was subsequently started on chemotherapy with Everolimus (Afinitor), and did not have cardiac symptoms. Subsequent TTE showed an EF of 54%. Follow-up Dotatate PET CT scan 7 months later showed a stable appearance of metastatic disease as described earlier. The patient notably did not have any symptoms of valvulopathy or volume overload.

Perspective

Cardiac carcinoid metastasis is an extremely rare clinical occurrence, with an incidence of about 1.75% – 4.3% of cases, with 53% located in the LV, and 47% in the atria and interventricular septum. Only single-digit cases are reported in the literature.[1] Most of these are typically asymptomatic, and are often seen in patients with advanced carcinoid syndrome and extensive carcinoid metastatic disease.[2,3]

CMR in this case was utilized to further assess the interatrial septum lesion identified on prior Dotatate PET CT scan. Dotatate is 89%-95% specific for neuroendocrine tumors due to its ability to target somatostatin receptors, which are overexpressed in neuroendocrine tumor cells found in carcinoid tumors. In our patient, intense and focal Dotatate uptake was noted in the interatrial septum. Cardiac carcinoid metastases have a particularly high degree of Dotatate uptake compared with focal myocardial inflammation, such as in myocarditis or sarcoid.[4]

In our patient, the interatrial septum lesion had not been fully characterized on echocardiography. In the absence of histologic confirmation, the differential diagnosis included lipomatous hypertrophy of the interatrial septum, atrial lipoma, primary and metastatic cardiac tumors. The lesion’s intermediate T1 signal, hyperintensity on T2-weighted imaging without signal suppression on fat-saturated sequences, and focal Dotatate uptake all argue against benign lipomatous hypertrophy. Lack of symmetric ‘dumbbell’ morphology through the fossa ovalis and absence of the characteristic high T1 fat signal further exclude lipoma or hypertrophy. The focal first-pass perfusion enhancement pattern supports vascularized primary vs. metastatic disease.

As a point of consideration, in the absence of known Dotatate PET CT findings and the context of patient’s known systemic neuroendocrine malignancy, the subtle interatrial mass on CMR paired with aforementioned tissue characterization strongly suggested cardiac metastasis, prompting oncologic correlation. Nonetheless, the high specificity of somatostatin receptor imaging made PET CT the virtually diagnostic modality in this case. Carcinoid heart disease arises secondary to chronic exposure to vasoactive mediators (notably serotonin and tachykinins) leading to endocardial plaque deposition and primarily right-sided valvulopathy in the absence of primary pulmonary carcinoid or intra-cardiac shunt. In contrast, carcinoid metastasis to the heart represents direct tumor deposit, which may occur even in the absence of systemic serotonin toxicity. As illustrated by our case, the absence of clinical carcinoid syndrome, right sided valvular thickening, regurgitation, or volume overload in the setting of intracardiac metastasis is exceedingly rare and is not well understood.[5,6]

CMR superior spatial resolution, ability to assess tissue properties, and functional evaluation capabilities was an essential complement to achieve a comprehensive diagnostic approach. CMR accurately differentiates localized masses seen on other modalities such as Dotatate PET CT from any pericardial or epicardial lesions, thereby improving diagnostic precision.[7] CMR is crucial in guiding decision making for medical vs surgical management of cardiac carcinoid metastasis.[8] Notably, the interatrial septum lesion noted on Dotatate PET CT scan and CMR was not seen on subsequent non-gated chest CT, underscoring the selection of appropriate modalities for imaging diagnosis of intra-cardiac carcinoid metastasis.

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References

1. Shotwell MK, Alyami BA, Sankaramangalam K, Alharbi A, Patel B. Cardiac Metastasis of Neuroendocrine Tumor Without Cardiovascular Symptoms. JACC Case Rep. 2022 Oct 19;4(20):1357-1359.
2. Bonsen LR, Aalbersberg EA, Tesselaar M, Stokkel MP. Cardiac neuroendocrine tumour metastases: case reports and review of the literature. Nucl Med Commun. 2016 May;37(5):461-5.
3. El Ghannudi S, Ouvrard E, Mikail N, Leroy Freschini B, Schindler TH, Imperiale A. Cutting-Edge Imaging of Cardiac Metastases from Neuroendocrine Tumors: Lesson from a Case Series. Diagnostics (Basel). 2022 May 9;12(5):1182.
4. Lee H, Alhamshari AS, Patel V, Bhattaru A, Rojulpote C, Vidula MK, Pryma DA, Bravo PE. Cardiac Neuroendocrine Tumor Metastases on 68Ga-DOTATATE PET/CT: Identification and Prognostic Significance. J Nucl Med. 2024 Nov 1;65(11):1745-1753.
5. Collins N, Bellamy G, Hayes P. Intrapericardial carcinoid metastasis. J Am Soc Echocardiogr. 2004 Jun;17(6):675-6.
6. Yan AT, Gupta P, Deva D, Choi R, Kirpalani A. An unusual case of metastatic carcinoid tumour in the interventricular septum. J Cardiovasc Med (Hagerstown). 2016 Dec;17 Suppl 2:e126-e128.
7. Arnfield EG, Tam L, Pattison DA, Younger J, Chikatamarla VA, Wyld D, Burge M, McCormack L, Ladwa R, Ramsay S. Cardiac metastases from neuroendocrine neoplasms: complementary role of SSTR PET/CT and cardiac MRI. J Nucl Cardiol. 2023 Dec;30(6):2676-2691.
8. Barnebee D, Morse B, Strosberg JR, Pejic M, Jeong D. Cardiac Magnetic Resonance for Diagnosis of Neuroendocrine Tumor Metastases to the Right and Left Ventricles with Carcinoid Heart Disease. Case Rep Cardiol. 2019 Dec 5;2019:8746413.

Case prepared by:
Jason N. Johnson, MD MHS
Editor-in-Chief, Cases of SCMR
Le Bonheur Children’s Hospital, The University of Tennessee Health Science Center, St. Jude Children’s Research Hospital