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.

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review.

BACKGROUND: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality. METHODS: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. RESULTS: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3-65% and 3-42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266-1,381 versus 67.5-575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791-2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). CONCLUSIONS: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients.

Early Outcomes of Surgery for Carcinoid Heart Disease.

BACKGROUND: The prognosis of patients with metastatic neuroendocrine neoplasms (NEN) continues to improve with modern oncological therapy. In the subgroup of patients with carcinoid syndrome, the development of carcinoid heart disease (CaHD) severely impacts long term survival. Valve surgery has been demonstrated to improve survival and symptoms in patients with CaHD. We sought to assess the outcomes of surgery for CaHD from a single Neuroendocrine Service. METHODS: We retrospectively reviewed outcomes of patients with CaHD and metastatic NEN who underwent valvular surgery over a 4-year period (2012-2016). RESULTS: Twenty (20) patients (mean age 64 years, range 29-77 years), all with metastatic small intestinal NEN treated with somatostatin analogues, underwent surgery. Tumour grade was: G1 (n=8), G2 (n=9), and unknown (n=3). Preoperative New York Heart Association (NYHA) class was III/IV in 15 patients (75%). The valves affected were: tricuspid (n=20; 19 replace, 1 repair), pulmonary (n=14; 14 replace), mitral (n=2; two replace) and aortic valve (n=2; two replace). Concomitant procedures included patent foramen ovale closure (n=9), right ventricular outflow tract (RVOT) (n=4) augmentation and coronary artery bypass grafting (n=3). There were two operative deaths (10%) due to right heart and liver failure. At 6 weeks, all surviving patients had symptom improvement (NYHA I/II). Median follow-up was 2±1.5 years (<1 month to 5 years). One asymptomatic patient developed RVOT obstruction after pulmonary replacement. Two patients had valvular recurrence. One and 2-year survival were 74% and 48% respectively. Of 13 late deaths, 12 were cancer-related (two with uncorrected progressive pulmonary regurgitation). CONCLUSIONS: Surgery for CaHD can be performed with satisfactory early results, leading to an improvement of cardiac symptoms, survival and enabling subsequent oncologic treatment. Further studies are required to improve longer term outcomes in these complex patients with CaHD.

Serotonin levels and 1-year mortality in patients with neuroendocrine tumors: a systematic review and meta-analysis.

Aim: Elevated serotonin in patients with neuroendocrine tumors (NETs) may impact heart failure incidence but a quantitative relationship has not been established. Materials & methods: Systematic review and meta-analysis of studies assessing 24-h urinary 5-hydroxyindoleacetic acid (u5-HIAA) and mortality in patients with NETs (2007-2017) with a primary outcome of 1-year mortality risk and 24-h u5-HIAA. Results: We identified 1715 records of which 12 studies including 755 patients (3442 person-years with 376 deaths) were eligible for meta-analysis. Mean u5-HIAA was 149.2 mg/24 h (standard deviation: 96.6) and mortality was 13.0%. The meta-regression equation showed an 11.8% (95% CI: 8.9-17.0%; I2  = 93.0%) increase in 1-year mortality for every ten-unit increase in u5-HIAA. Conclusion: Serotonin measured by its metabolite u5-HIAA is predictive of 1-year all-cause mortality in patients with NETs.

The path to surgery in carcinoid heart disease: a retrospective study and a multidisciplinary proposal of a new algorithm.

Background: Development of carcinoid heart disease (CHD) is the major negative prognostic factor in patients with the carcinoid syndrome. The only effective treatment is valve replacement. However, the selection of candidates and determination of optimal timing remain unclear. Considerable variability in local screening and treatment strategies exist. Methods: In this single-centre study, we retrospectively analysed the diagnostic process and outcome of all CHD patients who underwent valve surgery between 2000 and 2016. We propose a new CHD screening and management algorithm. Results: All patients (n = 15), mean age 64 ± 7, underwent tricuspid valve surgery. In 14 of them (93%) an additional valve was replaced. In only a minority of patients (27%) CHD diagnosis was established by screening. Survival after 1, 3, 12 and 24 months was 93%, 80%, 53% and 33%, respectively. Causes of death included infections and critical illness immediately postoperatively, and tumour progression and right heart failure in the longer term. There was a trend (p = .099) towards better preoperative right ventricular function in the patients who survived more than 12 months postoperatively (TAPSE 20 mm ± 4) compared to those who died between 3 to 12 months after surgery (TAPSE 16 mm ± 1). The former group had a shorter mean interval from diagnosis of the carcinoid syndrome to cardiac diagnosis than the latter (13 vs. 105 months, p = .014). Conclusion: Mortality after valve replacement for CHD remains high. A probably underestimated cause is late referral for cardiac surgery. We propose a systematic, multidisciplinary approach to all carcinoid syndrome patients.

Improving outcome of valve replacement for carcinoid heart disease.

OBJECTIVE: Carcinoid heart disease is characterized by tricuspid valve regurgitation and varying degrees of pulmonary valve regurgitation or stenosis. Valve replacement procedures may be complicated by systemic effects of carcinoid syndrome, as well as hepatic dysfunction and right heart failure. This study was performed to identify factors that might be associated with improving early mortality rates and late outcomes. METHODS: Between November 1985 and January 2018, 240 adult patients underwent surgery for carcinoid heart disease at the Mayo Clinic. We analyzed the association of multiple clinical and echocardiographic variables on early mortality and late survival. RESULTS: The median (interquartile range) age of patients was 63 years (55-69), and 117 patients (49%) were male. Before operation, 157 patients (70%) had New York Heart Association class III or IV limitation. Somatostatin analogs were used in 221 patients (92%), and long-acting somatostatins were used in 130 patients (54%). Loop diuretic therapy was used preoperatively in 125 patients (52%). Early mortality rate was 29% (9/22) between 1985 and 1994, but decreased to 7% (6/81) during 1995 to 2004, and to 5% (7/128) from 2005 onward. Overall survival estimates at 1, 3, and 5 years were 69%, 48%, and 34%, respectively. Older age, advanced New York Heart Association class, and a nonlinear effect of creatinine were independently associated with overall mortality. CONCLUSIONS: Valve replacement for carcinoid heart disease has acceptable short-term mortality, and early risk has decreased in the current era. Earlier intervention may improve overall survival.

Cardiac Surgery for Carcinoid Heart Disease: A Weapon Not to Be Misused.

Carcinoid heart disease (CHD) complicates approximately 25% of patients with a carcinoid tumor and carcinoid syndrome and leads to heart valve degeneration with mixed-stenotic and regurgitation pathology and consequent heart failure (HF) leading to significant morbidity and mortality. Cardiac surgery in symptomatic, severe CHD leads to significantly better functional capacity and prolonged survival when compared to medical treatment alone. Recent studies have shown improvement in postoperative outcomes of patients undergoing surgery for CHD over the last decades. The trend for early diagnosis and application of surgery prior to the manifestation of HF symptoms, which tended to develop during the previous years, does not seem justifiable based on the findings of recent studies. Therefore, the optimal timing of intervention in CHD and the type of valve that should preferably be used remain issues of controversy. This review comprehensively examines the existing literature on the treatment options for patients with CHD, with a special focus on short- and long-term survival after cardiac surgery, and discusses the selection of the exact patient profile and intervention timing that are more likely to optimize the benefit-to-risk ratio for surgical intervention.

Results of Contemporary Valve Surgery in Patients with Carcinoid Heart Disease.

BACKGROUND: Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating from enterochromaffin cells and secreting mainly serotonin. The diagnosis is based on clinical symptoms, hormone blood levels, radiological and nuclear imaging, and histological confirmation. However, most patients have metastases at the time of diagnosis because the clinical signs often remain unnoticed or are attributed to other abdominal conditions. In up to 50% of patients the endocardium is affected due to a hormonally active tumor profile. The study aim was to report the outcome of surgical treatment in patients with carcinoid heart disease, including the data of radiological and nuclear imaging, histological diagnosis, and follow up information. METHODS: Between 2008 and 2014, a total of 39 consecutive patients (28 males, 11 females; mean age 66 years; range: 28-84 years) with carcinoid heart syndrome were operated on at the authors' institution. Valvular heart disease was diagnosed with two-dimensional echocardiography. The study population included 26 patients (67%) with severe metastatic disease, who underwent radiotherapy preoperatively, and 13 patients (33%) who were metastasis-free and did not receive preoperative systemic therapy. Follow up was available for all hospital survivors, all of whom underwent serial echocardiographic follow up postoperatively. Adverse cardiac events were defined as cardiac-related death, a need for valvular reintervention, the occurrence of valve prosthesis-related complications, or echocardiographic evidence of new, high-degree valvular dysfunction during follow up. RESULTS: The majority of patients (n = 34; 87%) underwent isolated tricuspid valve replacement, while simultaneous pulmonary valve replacement was performed in five patients (13%). Postoperative complications included reoperation for bleeding in five patients (13%) and new heart block requiring pacemaker implantation in 10 (25%). The in-hospital mortality was 5% (n = 2). The overall survival was 43% at six years postoperatively. At the latest follow up, 12 of the 17 survivors were in NYHA class I, and five in NYHA class II. The adverse cardiac event rate was 71%. Echocardiographically, 46% of patients (6/13) showed at least stationary or mild improvement in the right ventricular ejection fraction at follow up, with no evidence of paravalvular leak, infective endocarditis, or progressive other native valvular carcinoid affection. Postoperatively, the right atrial dimensions were preserved as normal in 23 patients (59%), mildly dilated in six (15%), moderately dilated in three (8%), and severely dilated in seven (18%). Valve-in-valve transcatheter aortic valve implantation was performed in two patients (12%) due to structural degeneration of the valve bioprosthesis and native valve disease progression. CONCLUSIONS: Despite advanced systemic disease, the surgical treatment of patients with carcinoid heart syndrome is associated with an acceptable perioperative risk and satisfactory mid-term survival. Those patients who survived valve surgery benefited from a significant improvement in their functional capacity. Percutaneous procedures may represent a useful tool to reduce the risk of late valvular reinterventions.

Valve Replacement in Patients with Carcinoid Heart Disease: Choosing the Right Valve at the Right Time.

BACKGROUND AND AIM OF THE STUDY: The prosthetic valve of choice in patients with carcinoid valve disease (CVD) remains controversial due to the limited life expectancy of patients with advanced-stage neuroendocrine tumors (NETs) on the one hand, and concerns regarding structural valve deterioration (SVD) on the other hand. METHODS: The records of 17 patients (11 females, seven males; mean age 65 ± 11 years; undergoing 18 operations) with primarily right heart failure due to CVD were reviewed. All patients received somatostatin analogs perioperatively. Hospital and follow up data (acquired via direct patient contact and echocardiography) collected included baseline characteristics, procedural details, and clinical outcomes. RESULTS: The primary NET site was the ileum (n = 11), lungs (n = 2) and stomach, colon and appendix (n = 1 each). In one patient the primary tumor location could not be identified. Preoperative urinary levels of 5-hydroxyindole acetic acid (5-HIAA; 61 ± 36 mg/24 h) and serum levels of chromogranin A (2926 ± 4057 ng/ml) were 10- and 50-fold greater than normal, respectively. A total of 23 valves was implanted: five tricuspid valve replacements (TVR; four tissue and one mechanical), TVR and pulmonary valve replacements (PVR; three tissue and one mechanical), and TVR and mitral valve replacements (MVR; one tissue and two mechanical). The 30-day mortality was 11% (n = 2). No patient experienced a carcinoid crisis. The mean follow up was 24 ± 21 months (range: 4-85 months). Four patients (receiving seven valves) developed SVD at 12, 14, 15, and 20 months after surgery, and all of these patients died. The actuarial four-year survival and freedom from SVD were 23 ± 14% and 43 ± 15%, respectively. CONCLUSIONS: The data acquired suggested that the main advantage of tissue valve prostheses, namely to avoid lifelong, intense anticoagulation, might be offset by accelerated SVD. The use of mechanical valves should be considered in CVD patients with a large primary tumor mass and persistent high urinary levels of 5-HIAA, and who are unresponsive to therapy.

Serial surveillance of carcinoid heart disease: factors associated with echocardiographic progression and mortality.

BACKGROUND: Carcinoid heart disease is a complication of metastatic neuroendocrine tumours (NETs). We sought to identify factors associated with echocardiographic progression of carcinoid heart disease and death in patients with metastatic NETs. METHODS: Patients with advanced non-pancreatic NETs and documented liver metastases and/or carcinoid syndrome underwent prospective serial clinical, biochemical, echocardiographic and radiological assessment. Patients were categorised as carcinoid heart disease progressors, non-progressors or deceased. Multinomial regression was used to assess the univariate association between variables and carcinoid heart disease progression. RESULTS: One hundred and thirty-seven patients were included. Thirteen patients (9%) were progressors, 95 (69%) non-progressors and 29 (21%) patients deceased. Baseline median levels of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in the progressors. Every 100 nmol l(-1) increase in 5-HIAA yielded a 5% greater odds of disease progression (OR 1.05, 95% CI: 1.01, 1.09; P=0.012) and a 7% greater odds of death (OR 1.07, 95% CI: 1.03, 1.10; P=0.001). A 100 ng l(-1) increase in NT-proBNP did not increase the risk of progression, but did increase the risk of death by 11%. CONCLUSIONS: The biochemical burden of disease, in particular baseline plasma 5-HIAA concentration, is independently associated with carcinoid heart disease progression and death. Clinical and radiological factors are less useful prognostic indicators of carcinoid heart disease progression and/or death.

Prognosis of patients with carcinoid heart disease after valvular surgery.

A best evidence topic in cardiac surgery was written according to a structured protocol. We addressed the following question: in patients who are diagnosed with carcinoid heart disease (CHD), do valvular surgeries improve their prognosis? Fifty percent of the patients with clinically diagnosed carcinoid syndrome had cardiac involvement which was present either as valvular dysfunction or as cardiac metastases. These patients often require surgery due to their heightened risk of cardiac disease. Altogether 217 relevant papers were identified as a result of the below-mentioned search, of which 10 papers represented the best evidence to answer the question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. Of the patients who were identified to have carcinoid heart disease in different studies, 193 patients had valve procedure, mainly replacements at tricuspid, mitral and aortic valve positions and either valvuloplasty or replacement at pulmonary valve. Tricuspid and pulmonary valves represented the majority of the excised valves among patients undergoing valvular surgery for CHD. The pathology of carcinoid valve was attributed to the presence of plaque, causing thickening and retraction. Pure regurgitation was the most common finding in all the valves except pulmonary valve which had both stenosis and insufficiency. Thirty-day mortality was 17% (range 1-63%) and long-term survivors were reported to be alive at an average of 58 months (28-80 months) after the valve surgery. The evidence demonstrates that surgical intervention can lead to improved prognosis and reduce the symptoms of heart failure. Postoperative mortality was mainly due to the carcinoid disease itself and not as a complication of the surgery. Therefore, surgery could be considered for symptomatic palliation in carefully selected individuals.

The clinical presentation and management of carcinoid heart disease.

Carcinoid heart disease is a major cause of morbidity and mortality in patients with metastatic neuroendocrine tumours (NETs). Although cases of carcinoid syndrome and severe carcinoid heart disease requiring urgent intervention are well described, many patients with significant carcinoid heart disease may have insidious symptoms or even be asymptomatic. As haemodynamically significant carcinoid heart disease may be clinically silent, specific and individualised considerations must be made as to the most appropriate clinical criteria and time point at which surgical valve replacement should be undertaken in patients with carcinoid heart disease.

Cardiac surgery for carcinoid heart disease in 12 cases.

PURPOSE: Cardiac involvement is now a major source of morbidity and mortality in patients with carcinoid tumors. We reviewed patients with carcinoid heart disease who underwent valvular surgery in our center. METHODS: Twelve patients with carcinoid heart diseases underwent cardiac surgery between 2000 and 2008. Patients were divided into two groups: group A (n = 6) comprised patients who survived more than 6 months after cardiac surgery, and group D (n = 6) comprised those who died within 6 months. Preoperative factors were compared between the groups. RESULTS: All the 12 patients with carcinoid heart disease underwent tricuspid valve surgery (3 had tricuspid repair and 9 had tricuspid replacement with a bioprosthetic valve). Postoperative 30-day mortality was 16.7% and 2-year actuarial survival was 50.0%. Median survival after the first diagnosis of carcinoid disease was 4.4 years that from first diagnosis of carcinoid heart disease was 2.7 years. Preoperative median left ventricular ejection fraction in group D (52.5%) was significantly lower than that in group A (67.2%, P < 0.05). There were no statistically significant differences between the groups in other parameters. CONCLUSION: Postoperative prognosis may be worse when preoperative left ventricular ejection fraction is borderline, even if it is within the normal limits. Cardiac evaluation is needed in all patients with carcinoid disease from the earliest time of medical and oncological therapy to improve patient outcome.

Hepatic resection for the carcinoid syndrome in patients with severe carcinoid heart disease: does valve replacement permit safe hepatic resection?

BACKGROUND: Hepatic resection of metastatic carcinoid cancer can prolong survival and control symptomatic endocrinopathy. Decompensated carcinoid heart disease (CHD) can develop in some patients with metastatic carcinoid cancers, which can preclude operation for resectable hepatic metastases. We hypothesized that outcomes after hepatic resection for patients with the carcinoid syndrome after valve replacement for CHD would be similar to carcinoid patients without CHD. STUDY DESIGN: We compared the survival and symptom control after hepatic resection for patients undergoing valve replacement for CHD to carcinoid patients without CHD matched for age, sex, and extent of hepatectomy. RESULTS: Fourteen patients with earlier valve replacement for CHD were compared with 28 carcinoid patients without CHD. All patients had hepatic resection for metastatic carcinoid disease and carcinoid syndrome. Mean age, sex distribution, and extent of hepatectomy (major hepatectomy, 78%) was similar between groups. Mean interval from valve replacement to hepatectomy was 101 days. There was no operative mortality. Major operative morbidity, inclusive of operative blood loss and cardiorespiratory events, occurred in 28.5% and 14.2% for CHD and non-CHD groups, respectively (p = 0.16). Symptom-free survival for CHD and non-CHD groups was 69% and 81% at 1 year (p = 0.22) and 61% and 44% (p = 0.17) at 5 years, respectively. Octreotide-free survival after hepatectomy 69% and 84% (p = 0.15) at 1 year and 62% and 52% (p = 0.29) 5 years, respectively. Overall survival CHD and non-CHD groups 100% at 1 year and 100% and 70% (p = 0.002) 5 years. CONCLUSIONS: Valve replacement for severe CHD is safe and hepatic resection is associated with similar outcomes as patients without CHD undergoing hepatic resection for carcinoid syndrome. Identifying resectable hepatic metastases from carcinoids in patients with severe CHD should prompt valve replacement and interval hepatic resection.

Comparison of prognostic value of tissue Doppler imaging in carcinoid heart disease versus the value in patients with the carcinoid syndrome but without carcinoid heart disease.

The aim of this study was to evaluate the prognostic value of tissue Doppler imaging (TDI) in carcinoid heart disease (CHD). We prospectively enrolled 56 consecutive patients with proved digestive endocrine tumor and carcinoid syndrome. All patients underwent serial conventional, contrast, and TDI echocardiographic studies. The end point was all-cause mortality. Mean follow-up was 34 +/- 21 months. At the end of follow-up, 30 patients (54%) presented right CHD and 13 patients (23%) left CHD. A progression of CHD was documented in 23 patients (41%). Twenty-two patients (39%) died during follow-up. According to mortality receiver operating characteristic curves, ratio of early transmitral flow velocity to early diastolic mitral annulus velocity (E/e' ratio) associated with an optimal sensitivity of 80% and specificity of 90% was 8. Mortality rate was significantly higher when the E/e' ratio was >or=8 (94% vs 10% when E/e' ratio was <8, p <0.0001). Using univariate analysis, the following factors were associated with death: left-sided CHD (p = 0.07) and E/e' ratio >or=8 (p <0.0001). The only independent marker of death detected by multivariate analysis was an E/e' ratio >or=8 (odds ratio 6.2, 95% confidence interval 1.95 to 19.7, p = 0.002). In conclusion, TDI used during routine transthoracic echocardiography can be helpful to identify high-risk patients with CHD.

Role of hepatic resection for patients with carcinoid heart disease.

OBJECTIVE: To evaluate the effects of resection of hepatic carcinoid metastases on progression and prognosis of carcinoid heart disease. PATIENTS AND METHODS: From our database of 265 consecutive patients diagnosed as having carcinoid heart disease from January 1, 1980, through December 31, 2005, we calculated survival from first diagnosis of cardiac involvement. Hepatic resection during follow-up was entered as a time-dependent covariable in a multivariable analysis. In patients with serial echocardiograms more than 1 year apart without intervening cardiac surgery, a previously validated cardiac severity score was calculated. A score increase that exceeded 25% was considered relevant progression. RESULTS: Hepatic resection was performed in 31 patients (12%) during follow-up. Five-year survival was significantly higher in these patients (86.5%; 95% confidence interval [CI], 73.5%-100.0%) than in patients without hepatic resection (29.0%; 95% CI, 23.3%-36.1%; univariable hazard ratio for hepatic resection, 0.25; 95% CI 0.12-0.53; P<.001). Hepatic resection remained strongly associated with improved prognosis in multivariable analysis (hazard ratio, 0.31; 95% CI, 0.14-0.66; P=.003). Among 77 patients (29%) with serial echocardiograms, 10 (13%) underwent hepatic resection during follow-up; resection was independently associated with decreased risk of cardiac progression (odds ratio, 0.29; 95% CI, 0.06-0.75; P=.03). CONCLUSION: Despite the limitations of this retrospective nonrandomized study, our data suggest that patients with carcinoid heart disease who undergo hepatic resection have decreased cardiac progression and improved prognosis. Eligible patients should be considered for hepatic surgery.

Intraoperative management of patients with carcinoid heart disease having valvular surgery: a review of one hundred consecutive cases.

BACKGROUND: Cardiac surgery for carcinoid heart disease is complicated by hemodynamic instability secondary to carcinoid crises, cardiovascular dysfunction, and blood loss. The safety of vasopressors and the benefit of aprotinin during concomitant octreotide administration are uncertain. METHODS: We reviewed the effects of vasopressors and aprotinin on octreotide administration and mortality by univariate analysis in 100 consecutive cases of cardiac surgery for carcinoid heart disease from 1985 to 2003. Because mortality declines were temporally related to the introduction of aprotinin, bivariate analyses were performed to identify other factors associated with mortality. RESULTS: Carcinoid symptoms and hypotension were treated with octreotide (n = 89) and/or vasopressors (n = 93). Vasopressors were not associated with increased octreotide administration. Patients requiring epinephrine had higher mortality but also had worse preoperative New York Heart Association class, higher urinary 5-hydroxyindoleacetic acid levels, and increased blood transfusion requirements. Aprotinin (n = 54) was associated with decreased blood transfusion requirements, increased octreotide administration, but not mortality. Overall mortality was 13%, declining from 28% between 1985 and 1994 to 6% between 1995 and 2003. Mortality was associated with greater blood transfusion requirements and longer duration of cardiopulmonary bypass. CONCLUSIONS: Vasopressors may be used in conjunction with octreotide in carcinoid patients. The increased mortality associated with epinephrine likely reflects selection bias rather than a primary adverse effect. The improved survival over time in carcinoid patients is multifactorial and unrelated to aprotinin administration, suggesting further inhibition of the kallikrein-kinin system has little added benefit for this outcome in the presence of octreotide.

Description of patients with midgut carcinoid tumours: clinical database from a Danish centre.

BACKGROUND: We have initiated a clinical database of patients with neuroendocrine tumours (n = 132). Data on patients with well-differentiated endocrine carcinoma (WHO classification) previous classified as midgut carcinoid patients, are presented. PATIENTS AND METHODS: Retrospectively, 56 patients with midgut carcinoid tumours were evaluated with respect to symptoms, primary tumour size, metastases, tumour markers, treatment and survival. RESULTS: Flushing was described in 29%, diarrhoea in 52%, abdominal pain in 34%, bronchial constriction in 2% and carcinoid heart disease in 4% of the patients. Fifty-two percent had liver metastases at referral. Twenty-seven percent were considered to have had radical surgery. Patients not considered for radical surgery and patients with liver metastases had significantly higher tumour marker levels (serum chromogranin A (CgA), serum serotonin and urinary 5-hydroxyindolic acid (5-HIAA)) compared to radically-operated patients and to patients without liver metastases (p<0.05, respectively). For all the midgut carcinoid tumour patients the overall 5-year survival rate was 72%. The radically-operated patients had a 5-year survival rate of 100% (other death causes excluded). The patients with normal CgA or <5 liver metastases at referral had a 100% 5-year survival rate. The patients with <5 liver metastases had a significantly better 5-year survival rate compared to patients with multiple liver metastases (100% vs. 50%, p<0.05). CONCLUSION: This group of patients exhibited the same characteristic clinical features with similar survival as reported from other specialised centres. Radical surgery, normal CgA level and <5 liver metastases indicated a good prognosis and patients with <5 liver metastases had a significantly better survival compared to patients with multiple liver metastases.