Synoptic reporting of echocardiography in carcinoid heart disease (ENETS Carcinoid Heart Disease Task Force).

BACKGROUND: This European Neuroendocrine Tumor Society (ENETS) Expert Consensus document aims to provide practical guidance and standardization for echocardiography in the screening and follow-up of carcinoid heart disease (CHD) in patients with a neuroendocrine tumour (NET) and carcinoid syndrome. METHODS: NET experts within the ENETS Carcinoid Heart Disease Task Force reviewed both general reporting guidelines and specialized scoring systems for transthoracic echocardiography (TTE) in CHD. Based on this review, a dedicated template report was designed by the multidisciplinary working group of cardiologists, oncologists, endocrinologists, gastroenterologists, surgeons and radiologists. RESULTS: We propose a Synoptic Reporting of Echocardiography in Carcinoid Heart Disease which represents an agreed peer reviewed proforma to capture information at the time of referral and enable a detailed outcome of CHD assessment. This includes a systematic and detailed list of structures to evaluate data to capture at the time of reporting of TTE. CONCLUSIONS: Adherence to these reporting guidelines aims to promote homogeneous and detailed evaluation of CHD to secure accurate assessment and allow comparison of studies performed intra- and inter-individually. These guidelines could also facilitate CHD assessment as part of prospective clinical trials to enable standardization of the findings seen in response to therapy.

Myopericarditis and thyroiditis: a case report.

BACKGROUND: Hyperthyroidism is commonly associated with adverse cardiovascular effects, including tachydysrhythmia, heart failure, and hypertension, although the association between hyperthyroidism and myopericarditis is restricted to a small number of case reports. CASE SUMMARY: A 45-year-old Caucasian male with no past medical history was admitted with chest pain. The electrocardiogram demonstrated diffuse ST-segment elevation, the troponin T rose, and he was diagnosed with myopericarditis. He was noted to have markedly deranged thyroid function tests and a diagnosis of hyperthyroidism secondary to Graves' disease was made. He was treated with Bisoprolol, Carbimazole, Prednisolone, Ibuprofen, and Colchicine, his symptoms resolved rapidly and he was discharged. Five weeks later he re-presented with similar symptoms and recurrent pericarditis was diagnosed. His symptoms settled with a repeat course of steroids. DISCUSSION: We hypothesize that there may be an underappreciated link between hyperthyroidism and myopericarditis. Potential pathophysiological mechanisms include viral infection, autoimmunity, or changes in myocardial fat metabolism. Suggested management consists of a combination of current guidelines for the treatment of hyperthyroidism and pericardial disease, with attention to certain disease-drug interactions. Further research is required to evaluate the true incidence of hyperthyroidism-associated myopericarditis, elucidate its pathophysiology and instruct management.

Carcinoid Heart Disease: a Review.

PURPOSE OF REVIEW: The development of carcinoid heart disease (CHD) is a fibrotic complication of neuroendocrine neoplasms (NEN) which is associated with a poor prognosis. This review aims to summarise the clinical features, investigations and management of this condition. RECENT FINDINGS: CHD can affect up to 50% of NET patients with carcinoid syndrome. However, it is often not screened for appropriately and recognised late when patients become symptomatic. A screening strategy with biomarkers and multimodality imaging is necessary for early recognition. Management by an experienced multidisciplinary team with appropriate medical therapeutic strategies and where indicated surgical intervention is needed to optimise clinical outcomes. CHD is a poor prognostic factor, but recently, outcomes have improved due to the multidisciplinary approach and centralised care of CHD-NET patients.

Cardiac Metastases in Patients with Neuroendocrine Tumours: Clinical Features, Therapy Outcomes, and Prognostic Implications.

BACKGROUND: Cardiac metastases (CM) from neuroendocrine tumours (NET) are rare; however, with the introduction of new molecular imaging modalities, such as 68Ga-DOTATATE PET-CT for NET diagnosis and re-staging, they are now identified more frequently. This study presents a single-institution experience on the NET CM characteristics, management, and prognostic implications. METHODS: Between January 1998 and January 2020, 25 NET patients with CM were treated in our unit. A retrospective review of electronic records was performed. Overall survival (OS) was assessed by the Kaplan-Meier method. Cox regression models were used to evaluate the association of various clinical variables with OS. RESULTS: The median age in the NET CM cohort was 64 years, with small intestine being the most common primary (84%). Nearly half of the patients suffered either from shortness of breath (48%) or had palpitations (12%). Peptide receptor radionuclide therapy (PRRT) was applied in more than half of the patients (64%), who had an improved trend for a longer median OS compared to those patients who did not receive PRRT (76.0 vs. 14.0 months, p = 0.196). The multivariate analysis demonstrated that concomitant skeletal or pancreatic metastases, as well as N-terminal pro-B-type natriuretic peptide (NT pro-BNP) >2 × upper limit of normal (ULN), were independent poor prognosticators. CONCLUSIONS: Clinical features of NET CM ranged from asymptomatic patients to heart failure. Concomitant bone or pancreatic metastases and NT pro-BNP levels >2 ULN predicted shorter survival time. PRRT serves as a feasible therapy with promising survival benefits; however, more data are needed.

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.

A workflow for patient-specific fluid-structure interaction analysis of the mitral valve: A proof of concept on a mitral regurgitation case.

The mechanics of the mitral valve (MV) are the result of the interaction of different anatomical structures complexly arranged within the left heart (LH), with the blood flow. MV structure abnormalities might cause valve regurgitation which in turn can lead to heart failure. Patient-specific computational models of the MV could provide a personalised understanding of MV mechanics, dysfunctions and possible interventions. In this study, we propose a semi-automatic pipeline for MV modelling based on the integration of state-of-the-art medical imaging, i.e. cardiac magnetic resonance (CMR) and 3D transoesophageal-echocardiogram (TOE) with fluid-structure interaction (FSI) simulations. An FSI model of a patient with MV regurgitation was implemented using the finite element (FE) method and smoothed particle hydrodynamics (SPH). Our study showed the feasibility of combining image information and computer simulations to reproduce patient-specific MV mechanics as seen on medical images, and the potential for efficient in-silico studies of MV disease, personalised treatments and device design.

Carcinoid Heart Disease: A Review.

Carcinoid heart disease remains a major cause of morbidity and mortality among patients with carcinoid syndrome and metastatic neuroendocrine tumors. Screening of all patients with N-terminal pro-B-type natriuretic peptide and transthoracic echocardiography is critical for early detection, as early symptoms and signs have low sensitivity for the disease. Cardiac surgery, in appropriate cases, is the only definitive therapy for advanced carcinoid heart disease, and it improves patient symptoms and survival. Management of carcinoid heart disease is complex, and multidisciplinary assessment of cardiac status, hormonal syndrome, and tumor burden is critical in guiding optimal timing of surgery.

Diagnosing and Managing Carcinoid Heart Disease in Patients With Neuroendocrine Tumors: An Expert Statement.

Carcinoid heart disease is a frequent occurrence in patients with carcinoid syndrome and is responsible for substantial morbidity and mortality. The pathophysiology of carcinoid heart disease is poorly understood; however, chronic exposure to excessive circulating serotonin is considered one of the most important contributing factors. Despite recognition, international consensus guidelines specifically addressing the diagnosis and management of carcinoid heart disease are lacking. Furthermore, there is considerable variation in multiple aspects of screening and management of the disease. The aim of these guidelines was to provide succinct, practical advice on the diagnosis and management of carcinoid heart disease as well as its surveillance. Recommendations and proposed algorithms for the investigation, screening, and management have been developed based on an evidence-based review of the published data and on the expert opinion of a multidisciplinary consensus panel consisting of neuroendocrine tumor experts, including oncologists, gastroenterologists, and endocrinologists, in conjunction with cardiologists and cardiothoracic surgeons.

Accuracy and Test-Retest Reproducibility of Two-Dimensional Knowledge-Based Volumetric Reconstruction of the Right Ventricle in Pulmonary Hypertension.

BACKGROUND: Right heart function is the key determinant of symptoms and prognosis in pulmonary hypertension (PH), but the right ventricle has a complex geometry that is challenging to quantify by two-dimensional (2D) echocardiography. A novel 2D echocardiographic technique for right ventricular (RV) quantitation involves knowledge-based reconstruction (KBR), a hybrid of 2D echocardiography-acquired coordinates localized in three-dimensional space and connected by reference to a disease-specific RV shape library. The aim of this study was to determine the accuracy of 2D KBR against cardiac magnetic resonance imaging in PH and the test-retest reproducibility of both conventional 2D echocardiographic RV fractional area change (FAC) and 2D KBR. METHODS: Twenty-eight patients with PH underwent same-day echocardiography and cardiac magnetic resonance imaging. Two operators performed serial RV FAC and 2D KBR acquisition and postprocessing to assess inter- and intraobserver test-retest reproducibility. RESULTS: Bland-Altman analysis (mean bias ± 95% limits of agreement) showed good agreement for end-diastolic volume (3.5 ± 25.0 mL), end-systolic volume (0.9 ± 19.9 mL), stroke volume (2.6 ± 23.1 mL), and ejection fraction (0.4 ± 10.2%) measured by 2D KBR and cardiac magnetic resonance imaging. There were no significant interobserver or intraobserver test-retest differences for 2D KBR RV metrics, with acceptable limits of agreement (interobserver end-diastolic volume, -0.9 ± 21.8 mL; end-systolic volume, -1.3 ± 25.8 mL; stroke volume, -0.2 ± 24.2 mL; ejection fraction, 0.7 ± 14.4%). Significant test-retest variability was observed for 2D echocardiographic RV areas and FAC. CONCLUSIONS: Two-dimensional KBR is an accurate, novel technique for RV volumetric quantification in PH, with superior test-retest reproducibility compared with conventional 2D echocardiographic RV FAC.

Accuracy and reproducibility of right ventricular quantification in patients with pressure and volume overload using single-beat three-dimensional echocardiography.

BACKGROUND: The right ventricle is a complex structure that is challenging to quantify by two-dimensional (2D) echocardiography. Unlike disk summation three-dimensional (3D) echocardiography (3DE), single-beat 3DE can acquire large volumes at high volume rates in one cardiac cycle, avoiding stitching artifacts or long breath-holds. The aim of this study was to assess the accuracy and test-retest reproducibility of single-beat 3DE for quantifying right ventricular (RV) volumes in adult populations of acquired RV pressure or volume overload, namely, pulmonary hypertension (PH) and carcinoid heart disease, respectively. Three-dimensional and 2D echocardiographic indices were also compared for identifying RV dysfunction in PH. METHODS: A prospective cross-sectional study was performed in 100 individuals who underwent 2D echocardiography, 3DE, and cardiac magnetic resonance imaging: 49 patients with PH, 20 with carcinoid heart disease, 11 with metastatic carcinoid tumors without cardiac involvement, and 20 healthy volunteers. Two operators performed test-retest acquisition and postprocessing for inter- and intraobserver reproducibility in 20 subjects. RESULTS: RV single-beat 3DE was attainable in 96% of cases, with mean volume rates of 32 to 45 volumes/sec. Bland-Altman analysis of all subjects (presented as mean bias ± 95% limits of agreement) revealed good agreement for end-diastolic volume (-2.3 ± 27.4 mL) and end-systolic volume (5.2 ± 19.0 mL) measured by 3DE and cardiac magnetic resonance imaging, with a tendency to underestimate stroke volume (-7.5 ± 23.6 mL) and ejection fraction (-4.6 ± 13.8%) by 3DE. Subgroup analysis demonstrated a greater bias for volumetric underestimation, particularly in healthy volunteers (end-diastolic volume, -11.9 ± 18.0 mL; stroke volume, -11.2 ± 20.2 mL). Receiver operating characteristic curve analysis showed that 3DE-derived ejection fraction was significantly superior to 2D echocardiographic parameters for identifying RV dysfunction in PH (sensitivity, 94%; specificity, 88%; area under the curve, 0.95; P = .031). There was significant interobserver test-retest bias for RV volume underestimation (end-diastolic volume, -12.5 ± 28.1 mL; stroke volume, -10.6 ± 23.2 mL). CONCLUSIONS: Single-beat 3DE is feasible and clinically applicable for volumetric quantification in acquired RV pressure or volume overload. It has improved limits of agreement compared with previous disk summation 3D echocardiographic studies and has incremental value over standard 2D echocardiographic measures for identifying RV dysfunction. Despite the ability to obtain and postprocess a full-volume 3D echocardiographic RV data set, the quality of the raw data did influence the accuracy of the data obtained. The technique performs better with dilated rather than nondilated RV cavities, with a learning curve that might affect the test-retest reproducibility for serial RV studies.

Myocardial Scar Detection by Standard CT Coronary Angiography.

We have described a myocardial infarct scar identified by a standard dual source CT coronary angiography (CTCA). We were able to detect the scar during the routine coronary assessment without contrast late enhancement and without additional radiation exposure. It is therefore feasible to assess chronic scar using a standard CTCA technique.

Circulating plasma and platelet 5-hydroxytryptamine in carcinoid heart disease: a pilot study.

BACKGROUND AND AIM OF THE STUDY: Carcinoid heart disease (CaHD) is a rare form of valvular heart disease in patients with carcinoid syndrome (CS). The role of 5-hydroxytryptamine (5-HT) in the pathogenesis of CaHD is unclear. The study aim was to evaluate the association between platelet 5-HT (5-HTplt) and plasma 5-HT (5-HTpls) and valvular dysfunction. METHODS: Twelve patients with CaHD, 18 with CS and 10 'normal' subjects were recruited. Patients with CaHD underwent cardiac catheterization and echocardiography. 5-HTplt and 5-HTpls was sampled in blood from the femoral vein, right and left ventricle, and left antecubital fossa vein. RESULTS: Levels of 5-HTpls and 5-HTplt were significantly higher in patients with CaHD (median 5-HTpls 325 nmol/l and 5-HTplt 18.9 nmol/10(9) platelets) and CS (median 5-HTpls 155 nmol/l and 5-HTplt 16.4 nmol/10(9) platelets) when compared to healthy controls (median 5-HTpls 9 nmol/l and 5-HTplt 3.7 nmol/10(9) platelets; p < 0.0001 and p = 0.003, respectively). There was a significant increase in 5-HTplt and 5-HTpls between the femoral vein and right heart (p = 0.007 and p = 0.0002, respectively). There was no significant difference in 5-HTplt or 5-HTpls between the right and left side of the heart, irrespective of the presence of a patent foramen ovale or of left-sided CaHD. CONCLUSION: Plasma and platelet 5-HT levels are elevated in patients with CaHD. Despite exposure to similar levels of intracardiac plasma and platelet 5-HT, the development of valve dysfunction is heterogeneous. This suggests that individual heart valves have a susceptibility to the development of valvular dysfunction which is not related solely to plasma or platelet 5-HT levels.

Can non-invasive measurements aid clinical assessment of volume in patients with cirrhosis?

AIM: To evaluate the non-invasive assessments of volume status in patients with cirrhosis. METHODS: Echocardiography and multifrequency bioimpedance analysis measurements and short synacthen tests were made in 20 stable and 25 acutely decompensated patients with cirrhosis. RESULTS: Both groups had similar clinical assessments, cortisol response and total body water (TBW), however the ratio of extracellular water (ECW)/TBW was significantly greater in the trunk (0.420 ± 0.004 vs 0.404 ± 0.005), and limbs (R leg 0.41 ± 0.003 vs 0.398 ± 0.003, P < 0.05, and L leg 0.412 ± 0.003 vs 0.399 ± 0.003) with decompensated cirrhosis compared to stable cirrhotics, P < 0.05). Echocardiogram derived right atrial and ventricular filling and end diastolic pressures and presence of increased left ventricular end diastolic volume and diastolic dysfunction were similar in both groups. The decompensated group had lower systemic blood pressure, mean systolic 101.8 ± 4.3 vs 122.4 ± 5.3 and diastolic 58.4 ± 4.1 mmHg vs 68.8 ± 3.1 mmHg respectively, P < 0.01, and serum albumin 30 (27-33) vs 32 (31-40.5) g/L, P < 0.01. CONCLUSION: Decompensated cirrhotics had greater leg and truncal ECW expansion with lower serum albumin levels consistent with intravascular volume depletion and increased vascular permeability.

Risk factors for the development and progression of carcinoid heart disease.

The development of valvular heart disease in patients with carcinoid syndrome is thought to be related to the secretion of vasoactive substances by a tumor. We sought to identify modifiable risk factors for the development of carcinoid heart disease because this may help define strategies to attenuate the disease process. Two hundred fifty-two patients with carcinoid syndrome were prospectively followed with serial echocardiograms at 6-month intervals. Clinical characteristics, biochemical markers, and radiologic markers were measured at set intervals. An echocardiographic scoring system was applied. Patients were defined as having progression of carcinoid heart disease if the echocardiographic score increased by ≥25%. After a median follow-up of 29 months, 44 patients developed carcinoid heart disease or had progression of existing valvular dysfunction. At time of progression of carcinoid heart disease compared to the previous 6 months, there was a significant increase in median levels of 5-hydroxyindoleacetic acid (5-HIAA; 791 vs 460.5 µmol/24 hours) and flushing episodes (4.5 vs 2 episodes per day). Independent predictors of the development or progression of carcinoid heart disease were a 5-HIAA level ≥ 300 µmol/24 hours and ≥ 3 episodes of flushing per day. 5-HIAA levels of ≥ 300 to 599, 600 to 899, and > 900 µmol/24 hours conferred 2.74, 3.16, and 3.40 times the risk of progression of carcinoid heart disease, respectively. In conclusion, a 5-HIAA level ≥ 300 µmol/24 hours and ≥ 3 flushing episodes per day are predictors of the development or progression of carcinoid heart disease.

Outcomes, risks and complications of cardiac surgery for carcinoid heart disease.

OBJECTIVE: The development of carcinoid heart disease causes significant valvular dysfunction, eventually leading to symptomatic right heart failure and impaired survival. Data regarding cardiovascular surgery are limited. We sought to identify outcomes, risks and complications of valve surgery for carcinoid heart disease. METHODS: Twenty-two patients with carcinoid heart disease underwent cardiac valve surgery between 2006 and 2010. Patients were considered for surgery if (1) they had stable carcinoid tumour, (2) they had severe valvular dysfunction and (3) were symptomatic and (4) they had no other significant co-morbidities. Three patients underwent tricuspid valve replacement alone, 15 patients underwent tricuspid and pulmonary valve replacement, two patients underwent tricuspid, pulmonary and mitral valve replacement and two patients underwent quadruple valve replacement. RESULTS: Overall 30-day mortality was 18%. Causes of death were right ventricular dysfunction (two patients), carcinoid crises (one patient) and pneumonia (one patient). Four patients required permanent pacemaker for complete heart block. Of those that survived initial surgery, median follow-up was 26 months (interquartile range 8-42); 1- and 2-year survival rates were 56% and 44%, respectively. There was no significant difference in survival between those patients in the New York Heart Association (NYHA) class I/II, mild/moderate right ventricular dilatation or N-terminal brain natriuretic peptide (NT-proBNP) <1245 pg ml(-1) compared with those in NYHA class III/IV, severe right ventricular enlargement or NT-proBNP > 1245 pg ml(-1), respectively. Long-term causes of death were related to advanced metastatic carcinoid tumour. No patient required re-operation for bioprosthetic degeneration. CONCLUSION: Valve surgery for carcinoid heart disease is of higher risk compared with most other forms of valvular surgery. However, in those that survive the operation significant improvement in functional class occurs. Most long-term complications were related to the tumour itself rather than cardiac complications.

Utility of 3D transoesophageal echocardiography for the assessment of tricuspid and pulmonary valves in carcinoid heart disease.

We report on the case of a 45-year-old lady with metastatic carcinoid tumour and carcinoid syndrome who develops severe valvulopathy involving the tricuspid and pulmonary valve. The use of three-dimensional transoesophageal echocardiography allowed more detailed morphological assessment of tricuspid and pulmonary valve pathology, sub-valvular apparatus and improved delineation of the relationship between these structures and surrounding cardiac chambers.

Surgery for carcinoid heart disease: current outcomes, concerns and controversies.

Cardiac involvement in patients with carcinoid disease is a well-recognized pathology. Early reports described right-sided heart involvement. More recently, both right- and left-sided heart disease have been reported. Progress of the treatment of carcinoid disease is leading to an increase in the number of patients presenting for surgery to treat valvular dysfunction. owing to improvements in the prognosis of the basic disease, valve replacement surgery is now a reasonable option in patients with severe valvular dysfunction. This article provides an overview of carcinoid heart disease with an emphasis on current outcomes, concerns and controversies associated with the surgical management of this disease.

Features of carcinoid heart disease identified by 2- and 3-dimensional echocardiography and cardiac MRI.

BACKGROUND: Carcinoid heart disease is a rare form of valvular heart disease. We sought describe the spectrum of carcinoid heart disease identified by echocardiography and cardiac MRI. METHOD AND RESULTS: Two hundred fifty-two patients with carcinoid syndrome underwent a range of investigations including 2D transthoracic echocardiography, 3D transthoracic echocardiography and transesophageal echocardiography, and cardiac MRI. Fifty-two patients had evidence of carcinoid heart disease. Involvement of the tricuspid, pulmonary, mitral, and aortic valves were found in 47 (90%), 36 (69%), 15 (29%), and 14 (27%), respectively. Myocardial metastases were found in 2 (3.8%) patients. Several patterns of disease were identified depending on the extent and severity to which each leaflet and its associated subvalvular apparatus was affected. Thirteen of 15 (87%) patients with left-sided carcinoid involvement had a patent foramen ovale. Three patients with severe degree of shunting had severe valvular regurgitation. Patients with mild/moderate degree of shunting had mild or moderate valvular regurgitation. Three-dimensional transthoracic echocardiography/transesophageal echocardiography provided detailed anatomic information particularly for the tricuspid and pulmonary valves. Cardiac MRI allowed complementary assessment of valvular heart disease and delineation of myocardial metastases. Gallium-68 octreotide positron emission tomography identified neuroendocrine metastases. CONCLUSIONS: Carcinoid heart disease is a heterogeneous disease with a wide spectrum of echocardiographic findings. A multimodality approach is needed in patients with this complex pathology.

Drug-induced fibrotic valvular heart disease.

The initial association between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s. Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists pergolide and cabergoline, and more recently, the recreational drug ecstasy (3,4 methylenedioxymethamphetamine; MDMA) have been implicated. Results from clinical trials show that drug dose and treatment duration affect both the risk of developing the disease and its severity. The natural history of the disease remains unclear, although regression of valvular lesions after the end of treatment has been reported. Interference with serotonin metabolism and its associated receptors and transporter gene seems a likely mechanism for development of the drug-induced valvular heart disease. Physicians need to balance the benefits of continued therapy with these drugs against possible risks. Further investigation is needed to assist with treatment decisions. Continued vigilance is necessary because several commonly prescribed treatments interact with serotonergic pathways.