Improving outcomes in carcinoid heart disease - learning from a single centre.

INTRODUCTION: A significant proportion of patients with carcinoid syndrome develop carcinoid heart disease (CHD). Valve degeneration can lead to right heart failure, and worsening prognosis. Replacement of affected valves is an effective therapy. We reviewed patients treated with valve replacement to assess prognostic factors. METHODS: CHD patients records who underwent valve replacement from 2003-2019 were reviewed. RESULTS: Twenty-six patients underwent valve replacement. Mean (SD) age was 61 (11) years, 54% female. Eleven tumours were grade G1, with the remaining G2. NYHA pre-surgery mean (SD) 2.0 (0.7); post-surgery mean 1.2; follow-up mean (SD) 1.6 (0.8). Mean NYHA score difference from pre- to post-surgery -0.71 ( P  = 0.002). 88.5% two (PR & TR), 3.9% one, 3.9% three and 3.9% four valves replaced. 13 patients received Lu177 oxodotreotide; 27% completed four cycles. Mortality at 1 and 5 years follow up was 42% and 50% respectively. Cox proportional hazards model of survival from surgery, adjusting for age [hazard ratio (HR) 0.96 (0.89-1.03) ( P  = 0.25)], four cycles of Lu177 oxodotreotide demonstrated HR 0.087 (0.0079-0.95) ( P  = 0.045) indicating improved survival. DISCUSSION: Surgical patients were often NYHA grade II, and symptoms improved post-surgery. Four cycles of Lu177 oxodotreotide improved survival, although the confidence interval was wide. Further studies should be performed to assess Lu177 oxodotreotide in CHD.

Patent foramen ovale in carcinoid heart disease: The potential role for and risks of percutaneous closure prior to cardiothoracic surgery.

Neuroendocrine tumours (NETs) are rare but once metastasised, can lead to the release of vasoactive substances into the systemic circulation, and the classical features of carcinoid syndrome (CS) such as flushing and diarrhoea. A consequence of CS is carcinoid heart disease (CHD) which primarily affects the right-sided heart valves and can eventually lead to right heart failure. In this cohort, tricuspid and/or pulmonary valve replacement provides symptomatic relief. A patent foramen ovale (PFO) in patients with CHD can lead to the shunting of oxygen deficient blood to the systemic circulation causing hypoxaemia and reduced exercise tolerance. Additionally, the haemodynamic changes caused by regurgitant right-sided heart valves can increase the patency of a PFO allowing the passage of vasoactive substances to the systemic circulation thereby affecting the left-sided heart valves. We present data on the incidence of PFO in patients referred for surgery at our centre, in which the standard approach is to close the defect at time of cardiothoracic surgery. In addition, we present a series of four cases that highlight how the option of percutaneous PFO closure prior to open valve surgery may reduce haemodynamic instability and open a window of opportunity to enhance preoperative status. Percutaneous PFO closure then acts as a bridge to definitive cardiothoracic surgery, although there are risks in such an approach.

The prevalence, operations, and outcomes of carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) is a sequela of carcinoid liver metastases (LM). The true prevalence of CHD is unknown due to infrequent screening by transthoracic echocardiography (TTE). Octreotide is believed to protect against new and recurrent CHD, but supporting data are scant. This study determined CHD prevalence and outcomes in patients screened by TTE and treated with octreotide. METHODS: Records of carcinoid patients from 2001 to 2021 were reviewed. Survival was estimated by Kaplan-Meyer curves and compared by log-rank. RESULTS: Among 282 patients screened by TTE, overall survival was lower in CHD (n = 40) versus non-CHD (n = 242) patients (p < 0.001). Despite octreotide therapy, 21 patients developed CHD. Among patients with inoperable LM, survival was lower in CHD patients without valve replacement (VR) (p < 0.001), but similar between CHD patients with VR and non-CHD patients. CHD patients with VR and hepatic cytoreduction had survival similar to CHD patients without VR. CONCLUSION: VR improves survival in CHD patients with inoperable LM. Hepatic cytoreduction after VR should be reserved for carefully selected cases. Our data do not support a protective effect of octreotide.

Ablation of typical atrial flutter as therapeutic component in carcinoid heart disease: a case report.

BACKGROUND: Carcinoid heart disease is the cardiac manifestation of carcinoid syndrome. There is limited research on rhythm management in patients with carcinoid heart disease. The association of typical atrial flutter and carcinoid heart disease in particular is poorly described. CASE PRESENTATION: Here we present a case of a 77-year-old German woman with carcinoid heart disease and recurrent typical atrial flutter complicating the postoperative course after tricuspid valve replacement and its successful long-term rhythm control by ablation therapy. CONCLUSION: There is limited evidence on rhythm management in patients with the rare diagnosis of carcinoid heart disease. Typical atrial flutter repeatedly complicated the postoperative course of our patient with carcinoid heart disease and could finally be treated curatively by ablation. Radiofrequency ablation should be considered as a valuable therapeutic component in the challenging therapy of this disease.

Transcatheter Pulmonary Valve Implantation in Carcinoid Heart Disease.

Carcinoid heart disease is a rare condition affecting mostly tricuspid and pulmonary valves causing right-sided heart failure. Surgical valve replacement is the mainstay of treatment when patients become symptomatic and/or in the presence of right heart remodeling. We present a case of severe pulmonary valve regurgitation secondary to carcinoid heart disease occurring 4 years after a surgical tricuspid replacement, successfully treated with direct transcatheter pulmonary valve implantation without pre-stenting.

Hedinger Syndrome with Intraoperative Carcinoid Crisis - Understanding the Pathophysiology for a Successful Management.

Carcinoid tumors can be a cause for right heart valve disease, also known as Hedinger syndrome or carcinoid heart disease. Proper understanding of the pathophysiology is of the uttermost importance for adequate treatment of these patients, especially during heart surgery.

A 33-year follow-up after valvular surgery for carcinoid heart disease.

AIMS: Valvular surgery has improved long-term prognosis in severe carcinoid heart disease (CaHD). Experience is limited and uncertainty remains about predictors for survival and strategy regarding single vs. double-valve surgery. The aim was to review survival and echocardiographic findings after valvular surgery for CaHD at our institution. METHODS AND RESULTS: Between 1986 and 2019, 60 consecutive patients, median age 64 years, underwent valve surgery for severe CaHD. Operations involved combined tricuspid valve replacement (TVR) and pulmonary valve replacement (PVR) in 42 cases, and TVR-only or TVR with pulmonary valvotomy (no PVR) in 18 patients. All implanted valves were bioprosthetic. Preoperative echocardiography, creatinine, NT-pro-brain natriuretic peptide (NT-pro-BNP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) were obtained. 30-Day mortality was 12% (n=7), and 8% for the most recent decade 2010-2019. Median survival was 2.2 years and maximum survival 21 years. Patients undergoing combined TVR and PVR had significantly higher survival compared with operations without PVR (median 3.0 vs. 0.9 years, P = 0.02). Preoperative levels of NT-pro-BNP and 5-HIAA in the top quartile predicted poor survival. On preoperative echocardiograms, pulmonary regurgitation was severe in 51% and indeterminate in 17%. Postoperative echocardiography confirmed relatively good durability of bioprostheses, relative to the patients' limited oncological life expectancy. CONCLUSION: Valvular surgery in CaHD has an acceptable perioperative risk. Survival for combined TVR and PVR was significantly higher compared with operations without PVR. Bioprosthetic valve replacement appears to have adequate durability. Preoperative echocardiography may underestimate pulmonary pathology. Combined TVR and PVR should be considered in most patients.

Outcomes and periprocedural management of cardiac implantable electronic devices in patients with carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) is a rare complication of hormonally active neuroendocrine tumors that often requires surgical intervention. Data on cardiac implantable electronic device (CIED) implantation in patients with CHD are limited. OBJECTIVE: The purpose of this study was to evaluate the experience of CIED implantation in patients with CHD. METHODS: Patients with a diagnosis of CHD and a CIED procedure from January 1, 1995, through June 1, 2020, were identified using a Mayo Clinic proprietary data retrieval tool. Retrospective review was performed to extract relevant data, which included indications for implant, procedural details, complications, and mortality. RESULTS: A total of 27 patients (55.6% male; mean age at device implant 65.6 ± 8.8 years) with cumulative follow-up of 75 patient-years (median 1.1 years; interquartile range 0.4-4.6 years) were included for analysis. The majority of implanted devices were dual-chamber permanent pacemakers (63%). Among all CHD patients who underwent any cardiac surgery, the incidence of CIED implantation was 12%. The most common indication for implantation was high-grade heart block (66.7%). Device implant complication rates were modest (14.8%). No patient suffered carcinoid crisis during implantation, and there was no periimplant mortality. Median time from implant to death was 2.5 years, with 1-year mortality of 15%. CONCLUSION: CHD is a morbid condition, and surgical valve intervention carries associated risks, particularly a high requirement for postoperative pacing needs. Our data suggest that CIED implantation can be performed relatively safely. Clinicians must be aware of the relevant carcinoid physiology and take appropriate precautions to mitigate risks.

Outcomes of surgical treatment for carcinoid heart disease: A systematic review and meta-analysis.

BACKGROUND: Carcinoid heart disease (CaHD) develops from vasoactive substances released by neuroendocrine tumors, which can cause significant patient morbidity and mortality without surgical intervention. We performed a systematic review and meta-analysis to elucidate granular perioperative details and long-term outcomes in these patients. METHODS: Electronic search of Ovid, Scopus, Cumulative Index of Nursing and Allied Health Literature, and Cochrane Controlled Trials Register was performed to examine surgical treatment of carcinoid disease. Nine articles comprising 416 patients were selected. Study-level data were extracted and pooled for meta-analysis. RESULTS: Mean patient age was 63 years (95% confidence interval, 57-70) with 53% (95% confidence interval, 46-61) of patients being male. In addition, 75% (95% confidence interval, 54-96) of neuroendocrine tumors originated from the small bowel or colon and 98% (95% confidence interval, 93-100) had liver metastases. Right heart failure was present in 48% (95% confidence interval, 14-81). Moderate or severe regurgitation was present in 97% (95% confidence interval, 95-99) of tricuspid and 72% (95% confidence interval, 58-83) of pulmonary valves. In addition, 99% (95% confidence interval, 98-100) of tricuspid and 59% (95% confidence interval, 38-79) of pulmonary valves were replaced. Bioprosthetic valves were used in 80% (95% confidence interval, 68-93) of tricuspid positions. Mean hospital duration of stay was 16 days (95% confidence interval, 7-25). Thirty-day mortality was 9% (95% confidence interval, 6-12). Mean follow-up was 25 months (95% confidence interval, 11-39). Median survival was 3 years (95% confidence interval, 2.5-3.5). CONCLUSION: For patients >18 years of age, surgical treatment of carcinoid heart disease can be performed with a reasonable safety profile. However, overall survival appears to have ongoing effects of the primary disease.

Cardiac Imaging in Carcinoid Heart Disease.

Carcinoid disease is caused by neuroendocrine tumors, most often located in the gut, and leads in approximately 20% of cases to specific, severe heart disease, most prominently affecting right-sided valves. If cardiac disease occurs, it determines the patient's prognosis more than local growth of the tumor. Surgical treatment of carcinoid-induced valve disease has been found to improve survival in observational studies. Cardiac imaging is crucial for both diagnosis and management of carcinoid heart disease; in the past, imaging was accomplished largely by echocardiography, but more recently, imaging for carcinoid heart disease has increasingly become multimodal and warrants awareness of the particular diagnostic challenges of this disease. This paper reviews the pathophysiology and manifestations of carcinoid heart disease in light of the different imaging modalities.

Features of carcinoid heart disease identified by cardiac computed tomography.

BACKGROUND: Carcinoid heart disease (HD) is a rare form of valvular heart disease, the features of which have not been fully described by cardiac computed tomography (CT). METHODS: All patients with carcinoid HD that underwent cardiac CT, either preoperatively or for assessment of coronary arteries, between Apr-2006 and Dec-2019 at the Royal Free Hospital, UK, were reviewed. RESULTS: Of 32 patients with carcinoid HD, 29 (91%) had heart valve involvement. Abnormalities of the tricuspid and pulmonary valves were present in all patients, affecting all three leaflets in 23/26 (89%) unoperated patients for both valves. The aortic valve was affected in 4/29 (14%) patients and the mitral valve in 5/29 (17%). Left heart valves were affected in 6/29 (21%) patients. One patient (1/29; 3%) had all four valves affected. Severe changes with significant valvular regurgitation were seen in ≥75% of patients with tricuspid, pulmonary, and aortic valve abnormalities. Three patients had carcinoid myocardial metastases (3/32; 9%) and one patient had constrictive pericarditis (1/32; 3%). Ten patients had surgery of whom four (40%) had invasive coronary angiography preoperatively. Ten patients had a patent foramen ovale. Cardiac CT allowed an accurate assessment of damage to different leaflets/cusps, particularly of the pulmonary valve, where visualization with echocardiography was often (3/8; 38%) incomplete. CONCLUSION: Cardiac CT is a powerful tool for assessment of cardiac valve abnormalities, coronary arteries and the spatial relationship of coronary arteries with myocardial metastasis in patients with carcinoid HD, and should form part of multimodal imaging of this complex pathology.

Surgical aspects of valve replacement in carcinoid heart disease.

Tricuspid and pulmonary valve replacement in patients with advanced carcinoid heart disease (CaHD) reduces right heart failure and improves prognosis. The surgical literature is limited concerning description of technical aspects of valve replacement in CaHD. Although a dedicated multidisciplinary care is required for these frail patients, optimization of surgical technique is important and may lead to better postoperative outcomes.