Development of severe intrapulmonary shunting in a patient with carcinoid heart disease after closure of a persistent foramen ovale: a case report

Background Neuroendocrine tumors (NETs) can affect the cardiopulmonary system causing carcinoid heart disease and valve destruction. Persistent foramen ovale (PFO) occlusion is indicated in patients with carcinoid heart disease and shunt-related left-heart valve involvement. Case Summary We report the case of a 54-year-old female patient with metastatic NET originating from the small bowel. The patient was on medication with octreotide and telotristat. One year after diagnosis, cardiac involvement of carcinoid developed with regurgitation of right-sided and, due to PFO, left-sided heart valves. Closure of PFO was performed (Occlutech 16/18 mm). One year later she presented with recurrent severe dyspnoea. The PFO-occluder was in situ without residual shunt. Valvular heart disease, including left-sided disease, and metastatic spread of NET were stable. Blood gas analysis revealed arterial hypoxemia (pO2 = 44 mmHg/5.87 kPa), which was related to extensive intrapulmonary shunting (31% shunt fraction) confirmed using contrast-enhanced echocardiography. The patient was prescribed long-term oxygen supplementation as symptomatic therapy and anti-tumoral therapy was intensified with selective internal radiotherapy of the liver metastases in order to improve biochemical control of the carcinoid syndrome. Discussion An echocardiographic assessment of the presence of a PFO is recommended in patients with NET as PFO closure minimizes the risk of left-sided carcinoid valve disease. Deterioration of symptomatic status in metastasized NET might also be due to a hepatopulmonary-like physiology with intrapulmonary shunting and arterial desaturation thought to be caused by vasoactive substances secreted by the tumor. This is a rare case describing the development of this syndrome after PFO closure.

Progression of Carcinoid Heart Disease in the Modern Management Era

Background The development of carcinoid heart disease (CaHD) is still relatively unclear. It is difficult to define an optimal follow‐up for patients without any cardiac involvement at baseline. The aim of this study was to assess the prevalence and natural history of CaHD by annual echocardiographic examinations. Methods and Results We studied 137 consecutive patients (61±12 years, 53% men) with proven digestive endocrine tumor and carcinoid syndrome between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right‐sided and left‐sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CaHD. An increase of 25% of the score was considered to be significant. Mean follow‐up was 54±45 months. Prevalence of CaHD was 27% at baseline and 32% at 5‐year follow‐up. Disease progression was reported in 28% of patients with initial CaHD followed up for >2 years (n=25). In patients without any cardiac involvement at baseline, occurrence of disease was 21%. CaHD occurred >5 years from the initial echocardiographic examination in 42% of our cases, especially in patients presenting with new recurrence of a digestive endocrine tumor. An increase of urinary 5‐hydroxyindoleacetic acid by 25% during follow‐up was identified as an independent predictor of CaHD occurrence during follow‐up (hazard ratio [HR], 5.81; 95% CI, 1.19–28.38; P =0.03), as well as a maximum value of urinary 5‐hydroxyindoleacetic acid >205 mg/24 h during follow‐up (HR, 8.41; 95% CI, 1.64–43.07; P =0.01). Conclusions Our study demonstrates that in patients without initial CaHD, cardiac involvement may occur late and is related to serotonin. Our data emphasize the need for cardiologic follow‐up in patients with recurrence of the tumor process.

Heidinger syndrome - Carcinoid syndrome

Carcinoid heart disease was first described in 1954. It develops in over 70% of carcinoid syndrome patients. Up to 20% of patients with carcinoid syndrome have pronounced carcinoid heart disease at diagnosis. Cardiac involvement is usually well tolerated by patients. Symptoms are associated with secretion of serotonin, tachykinin and other vasoactive substances in the systemic circulation. Deposition of fibrous tissue along the tricuspid annulus leads to ring constriction and is the basis of tricuspid stenosis. Primary insular carcinoid tumor of the ovary is a very rare tumor that accounts for less than 1% of all carcinoid cases. We present a case of a 62-year-old woman, demonstrating shortness of breath and fatigue, diarrhea, redness and progressive swelling on both lower legs. After single-photon emission computed tomography we found pathologically increased somatostatin expression in a tumor formation in the pelvis. After removal of the primary focus, the patient received a prosthetic tricuspid valve with good clinical results.

Role of Cardiac Biomarkers in Cancer Patients

In patients with cancer—and especially some specific subtypes—the heart can be pathologically affected due to the direct action of the tumor or its secretion products or due to the toxicity of some oncological treatments. Cardiac biomarkers have been investigated as inexpensive and easily accessible tools for prediction, early diagnosis, monitoring, or prognosis of various forms of cancer-related cardiac diseases. However, their clinical usefulness was not always clearly demonstrated in every area of cardioncology. For the identification of anthracycline related cardiotoxicity in the very early stages troponins proved to be more efficient detectors than imaging methods. Nevertheless, the lack of a standardized dosage methodology and of cardiotoxicity specific thresholds, do not yet allow to outline the precise way to employ them in clinical routine and to incorporate them into appropriate diagnostic or managing algorithms. Cardiac biomarkers proved also effective in patients with primary cardiac amyloidosis, in which both troponins and natriuretic peptides were able to predict adverse outcome, and carcinoid heart disease, where a precise diagnostic cut-off for N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was identified to screen patients with valvular involvement. Likewise, NT-proBNP proved to be an excellent predictor of postoperative atrial fibrillation (POAF). On the contrary, evidence is still not sufficient to promote the routine use of cardiac biomarkers to early diagnose myocarditis due to immune check points inhibitors (ICIs), radiotherapy induced cardiotoxicity and cardiac complications related to androgenetic deprivation. In this review we present all the evidence gathered so far regarding the usefulness and limitations of these relatively inexpensive diagnostic tools in the field of cardio-oncology.