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Received: 21 September 2021    Accepted: 30 October 2021

DOI: 10.1111/jne.13060

S TA N D A R D S

Synoptic reporting of echocardiography in carcinoid heart

disease (ENETS Carcinoid Heart Disease Task Force)

Johannes Hofland1  | Angela Lamarca2,3 | Richard Steeds4 | Christos Toumpanakis5 |

Rajaventhan Srirajaskanthan6 | Rachel Riechelmann7 | Francesco Panzuto8  |
Andrea Frilling9 | Timm Denecke10 | Emanuel Christ11 | Simona Grozinsky-­Glasberg12 |
Joseph Davar13 | the ENETS Carcinoid Heart Disease Task Force
1
Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus MC and Erasmus Cancer Institute, Rotterdam, The
Netherlands
2
Department of Medical Oncology, The Christie NHS Foundation, Manchester, UK
3
Division of Cancer Sciences, University of Manchester, Manchester, UK
4
Department of Cardiology, University Hospitals Birmingham NHS Foundation Trust and Institute of Cardiovascular Sciences, University of Birmingham,
Birmingham, UK
5
Centre for Gastroenterology, Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK
6
Department of Gastroenterology, Neuroendocrine Tumour Unit, Kings College hospital, London, UK
7
Department of Clinical Oncology, AC Camargo Cancer Center, São Paulo, Brazil
8
Digestive Disease Unit, Sant' Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
9
Department of Surgery and Cancer, Imperial College London, London, UK
10
Department of Diagnostic and Interventional Radiology, Leipzig University Medical Center, Leipzig, Germany
11
Division of Endocrinology, Diabetology and Metabolism, ENETS Centre of Excellence, University Hospital Basel, Basel, Switzerland
12
Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology and Metabolism, Hadassah Medical Center and Faculty of Medicine,
Hebrew University of Jerusalem, Jerusalem, Israel
13
Royal Free Hospital & University College London, London, UK

Correspondence
Joseph Davar, Department of Cardiology, Abstract
Royal Free Hospital & University College Background: This European Neuroendocrine Tumor Society (ENETS) Expert
London, Pond Street, NW3 2QG, UK.
Email: [email protected] 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 re-
viewed both general reporting guidelines and specialized scoring systems for tran-
sthoracic echocardiography (TTE) in CHD. Based on this review, a dedicated template
report was designed by the multidisciplinary working group of cardiologists, oncolo-
gists, 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 informa-
tion at the time of referral and enable a detailed outcome of CHD assessment. This

This is an open access article under the terms of the Creative Commons Attribution-­NonCommercial-­NoDerivs License, which permits use and distribution in
any medium, provided the original work is properly cited, the use is non-­commercial and no modifications or adaptations are made.
© 2021 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

Journal of Neuroendocrinology. 2022;34:e13060.  wileyonlinelibrary.com/journal/jne |

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https://doi.org/10.1111/jne.13060
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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 facili-
tate CHD assessment as part of prospective clinical trials to enable standardization of
the findings seen in response to therapy.

KEYWORDS

carcinoid heart disease, echocardiography, neuroendocrine neoplasia, synoptic reporting

1 |  I NTRO D U C TI O N of right-­sided heart valve lesions based on such findings lacks sen-
sitivity. The development of severe CHD and onset of symptoms is
Carcinoid heart disease (CHD) is a severe complication of the car- highly variable and can be rapid, occurring in some over a matter of
cinoid syndrome, which is the most prevalent hormonal syndrome months.3 All patients with carcinoid syndrome should be screened
in patients with neuroendocrine tumours (NETs), particularly those for CHD because this has major prognostic implications evidenced
of small intestinal origin. It was first described in the 1950s as right-­ by the limited 3-­year survival of approximately 30% in patients with
sided valvular disease in a series of patients with small bowel NETs untreated CHD.3 Following the diagnosis of CHD, initiation of med-
1,2
and extensive abdominal metastases. Current data estimate the ical management of symptomatic patients is generally associated
prevalence of CHD in 20%–­50% of patients with carcinoid syn- with an improvement in clinical condition, whereas the impact on
drome,3 which in itself is observed in approximately 20% of pa- prognosis remains unclear. Of utmost importance, the diagnosis of
tients with a gastrointestinal or pulmonary NET.4 The importance CHD of any grade in individual patients should prompt discussion
of screening and identification of CHD relies on this being a well-­ within an expert multidisciplinary team of the indications and timing
recognized independent negative prognostic indicator for survival of valve replacement relative to medical management.
from historic case series.5,6
CHD is characterized most frequently by tricuspid valve (TV) and
pulmonary valve (PV) regurgitation and stenosis.7 At a histological 1.1 | Screening and diagnosis of CHD
level, there is increased deposition of fibrous tissue on the cardiac
valves, endocardium and rarely the intima of the major vessels, lead- Screening of CHD should be considered in all patients with carcinoid
8
ing to the formation of plaque-­like structures. The affected heart syndrome and/or elevated levels of 5-­HIAA,3 especially in patients
valves undergo a progressive process of thickening, retraction and at higher risk of development of CHD, including patients with liver
fixation, ultimately contributing to impaired function. The endocrine metastases or with uncontrolled or refractory carcinoid syndrome.
release of bioactive peptides and amines most often by liver me- Patients with primary ovarian or lung NETs or patients with retrop-
tastases of NETs are considered major drivers to the development eritoneal metastases are at high risk of CHD even in the absence of
of CHD. Circulating serotonin (or 5-­hydroxytryptamine) is consid- liver metastases. Furthermore, patients with fibrosis around mesen-
ered the predominant causative factor in CHD development through teric metastases seem to have a higher risk of developing CHD in
stimulation of the serotonin receptor subtype 2B on endocardial fi- the future.9
broblasts and smooth muscle cells and release of paracrine profi- A variety of screening techniques for CHD have been explored
brotic factors, although confirmation of this process is pending. In over the years. Transthoracic echocardiography (TTE) constitutes
approximately one-­third of cases, CHD can also affect the left-­sided the key modality in the evaluation of CHD and in the assessment
valves (aortic valve in 29%, and mitral valve in 27%), not only in pa- of its disease severity. In those patients in whom TTE is technically
tients with co-­existing patent foramen ovale (PFO), but also in those difficult or where images are too poor quality to exclude CHD, trans-­
with bronchial NET with a high level of serotonin production.7 oesophageal echocardiography may be a useful but semi-­invasive
Patients suffering from CHD can be asymptomatic, but even- tool. Alternatives such as cardiac magnetic resonance imaging may
tually develop progressive symptoms of (exertional) dyspnoea and be an option7 and can offer advantages in accurate quantification
fatigue, together with common signs of right-­sided heart failure, of ventricular structure and function in response to CHD, thereby
including elevated jugular venous pressure, hepatomegaly and pe- enabling a more comprehensive assessment.10 Likewise, cardiac
ripheral oedema. Findings on auscultation of the heart depend on computed tomography (CT) can be useful for valve assessment in
the valves involved but it is important to note that clinical detection suspected CHD, particularly of the PV (which is difficult to assess
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with TTE), and offers further advantages, including imaging of the 2.2 | Drafting of the standardized
coronary arteries and of cardiac metastases. Cardiac CT is especially reporting template
useful in patients who are considered for surgical intervention.11
This document follows the European Neuroendocrine Tumor The validity and clinical applicability of the available echocardiog-
Society (ENETS) consensus guidelines for the standard of care for raphy scoring systems was discussed among a dedicated working
12
echocardiography, published in 2009. Participants of the multidis- group within the CHD Task Force of the ENETS Advisory Board. A
ciplinary CHD Task Force within the ENETS Advisory Board devel- template for a standardized report was drafted based on the expert
oped the present standardized reporting form of echocardiography consensus document on adult TTE reporting from the European
for assessment and follow-­up of CHD. This synoptic reporting guide- Association of Cardiovascular Imaging14 and on the Royal Free
line aims to homogenize practice in CHD assessment by TTE and Carcinoid Heart Disease Score.15 The initial draft was discussed
reporting between individual operators and different institutions, a among the expert working group, comprised of cardiologists, on-
clear unmet need in NET practice.13 cologists, endocrinologists, gastroenterologists, surgeons and radi-
ologists. Important aspects for the standardized echocardiography
report included its use in both neuroendocrine neoplasm and non-­
2 | M E TH O DS referral centres, for screening as well as follow-­up of documented
CHD and following valve replacement. A majority consensus was
2.1 | Literature review reached for each data element by iterative discussions of the syn-
optic reporting draft. The pre-­f inal template was circulated for
A systematic review was undertaken to mine the literature for echo- feedback to the complete CHD Task Force and adopted according
cardiography reporting in CHD. Embase and Medline databases to provided suggestions.
were searched from inception until 19–­05–­2021 with the follow-
ing search strings: (‘carcinoid syndrome'/de OR ((carcinoid NEXT/1
(syndrome* OR heart OR cardiac OR flush)) OR carcinoidosis OR 3 | R E S U LT S
carcinoidoses):Ab,ti) AND (echocardiography/exp OR echography/
de OR ‘Doppler ultrasonography'/de OR (echocardiogra* OR ech- The Synoptic Carcinoid Echocardiography Report is available in
ogra* OR ultraso* OR tte OR Doppler*):Ab,ti) AND (‘scoring system'/ Table 1.
de OR ‘reporting and data system'/de OR ‘diagnostic accuracy'/de
OR ‘diagnostic test accuracy study'/de OR ‘disease severity'/de OR
‘disease severity assessment'/de OR quantification/de OR predic- 3.1 | Transthoracic echocardiography: basic
tion/de OR (((scoring OR reporting OR grading) NEAR/3 (system* principles for CHD assessment
OR assessment*)) OR (diagnostic NEAR/3 accura*) OR severit*
OR quantif* OR predict* OR (echocardiogra* NEAR/3 (feature* When performing TTE, evaluation of the thickening, mobility and
OR spectrum* OR characteristic*))):ab,ti) NOT (‘case report'/de retraction of leaflets/cusps of valves is of crucial importance. CHD
OR case-­report*:ti) AND [english]/lim NOT [conference abstract]/ is a heterogeneous disease, with a wide spectrum of echocardio-
lim NOT ([animals]/lim NOT [humans]/lim) for Embase, (Malignant graphic findings. Findings may vary from mild, isolated thickening
Carcinoid Syndrome/ OR ((carcinoid ADJ (syndrome* OR heart OR of a single valve leaflet/cusp with no significant reduction in leaf-
cardiac OR flush)) OR carcinoidosis OR carcinoidoses).ab,ti.) AND let/cusp mobility, to advanced thickening, retraction and immobil-
(exp Echocardiography/ OR Ultrasonography/ OR Ultrasonography, ity of multiple leaflets/cusps with associated severe valve disease.7
Doppler/ OR (echocardiogra* OR echogra* OR ultraso* OR tte OR For assessment of the leaflet thickness, the most affected leaflet/
Doppler*).ab,ti.) AND (Clinical Decision Rules/ OR Severity of Illness cusp should be assessed in zoomed views in a frame without valve
Index/ OR Forecasting/ OR (((scoring OR reporting OR grading) motion, with leaflets/cusps whenever possible perpendicular to the
ADJ3 (system* OR assessment*)) OR (diagnostic ADJ3 accura*) OR echocardiographic beam, taking advantage of the axial resolution.
severit* OR quantif* OR predict* OR (echocardiogra* ADJ3 (feature* Measurements should be taken three times and averaged.16,17
OR spectrum* OR characteristic*))).ab,ti.) NOT (case reports/ OR
case-­report*.ti.) AND english.la. NOT (exp animals/ NOT humans/)
for Medline. 3.2 | Tricuspid valve assessment
In total, 124 records were retrieved from the two databases.
After the removal of duplicates, 88 publications were left for as- The most frequently affected valve in CHD is the TV with involve-
sessment of eligibility. After screening title and abstract for clini- ment in 90% of cases.7 It is the largest and most apically posi-
cal reports on echocardiography reporting in CHD, 17 publications tioned valve and consists of the fibrous annulus with the three
contained relevant information for the current consensus guideline. leaflets (anterior, posterior and septal), the papillary muscles and
After evaluation of the full-­text articles, six publications with original chordae.18–­20 The three TV leaflets vary in both circumferential
CHD scoring systems remained. (annular) and radial size. The anterior leaflet is the longest radial
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4 of 11       HOFLAND et al.

TA B L E 1   Synoptic Carcinoid Echocardiography Report

Clinical details (to be filled in at time of TTE by the requesting clinical team)
Patient details Date of birth: __/__/_____
Patient ID: _____________
Gender Female
Male
Indication for TTE Screening (suspected CHD)
Follow-­up (known CHD)
Referring physician __________________________
Assessment at time of TTE
Date of TTE Date: __/__/_____
Time of TTE __:__ am/pm
Study Location ___________________________
Performed by _____________________
Previous cardiac surgery Yes which __________
No
If valve surgery in the past Biological valve
Metallic valve
Size of valve replacement _____________
Type of valve replacement _____________
Blood pressure ___/____ mmHg
Heart rate ___ bpm
Heart rhythm Sinus rhythm
Other which ______
Height _____ cm
Weight _____ kg
BSA _____ m2
Technique
Quality of cardiac images Good
Fair
Poor
Right-­sided valvular assessment
Tricuspid valve
Valve apparatus description: ________________
Regurgitation, vena contracta width with Nyquist limit ___mm Score CHD score
50–­70 cm/sec: Normal 0
< 3 mm: Mild 1
3–­6 mm: Moderate 2
> 6 mm: Severe 3
Stenosis, mean pressure gradient: ___ mmHg
Normal 0
< 5 mmHg: Mild 1
5–­8 mmHg: Moderate 2
>8 mmHg: Severe 3
Leaflet description (describe the most severely affected
leaflet):
Leaflet thickening (mm) Normal 0
≥ 3 to < 4: Mild 1
≥ 4 to < 5: Moderate 2
≥ 5: Severe 3

(Continues)
HOFLAND et al. |
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TA B L E 1   (Continued)

Leaflet excursion Normal 0

> 50 to ≤ 75% of normal:Mild 1
> 25 to ≤ 50% of normal:Moderate 2
≤ 25% of normal of fixed:Severe 3
Leaflet retraction Normal 0
Mild 1
Moderate 2
Severe 3
Pulmonary valve
Valve apparatus description: ________________
Regurgitation, vena contracta width with Nyquist limit ___ mm
50–­70 cm/sec ___ ms
Regurgitation, pressure half time of PR jet: ___ CHD Score
Regurgitation, PR index#
Normal 0
< 3 mm: Mild 1
3–­6 mm: Moderate 2
> 7 mm: Severe 3
Stenosis, Vmax ___ m/s
Normal 0
<3 m/s: Mild 1
3–­4 m/s: Moderate 2
> 4 m/s: Severe 3
Leaflet description (describe the most severely affected
cusp):
Cusp thickening (mm) Normal 0
≥ 3 to < 4: Mild 1
≥ 4 to < 5: Moderate 2
≥ 5: Severe 3
Cusp excursion Normal 0
> 50 to ≤ 75% of normal: Mild 1
> 25 to ≤ 50% of normal: Moderate 2
≤ 25% of normal of fixed:Severe 3
Cusp retraction Normal 0
Mild 1
Moderate 2
Severe 3
Right ventricular/atrial assessment
Findings ________________
Right atrial area ___ cm2
Right ventricular basal diameter (25–­41 mm) ___ mm CHD score
RV mid diameter (normal 19–­35 mm) ___ mm
RV < 2/3 of LV size: Normal 0
RV = LV size Mild dilatation 1
Larger than LV size Moderate dilatation 2
Much larger than LV Severe dilatation 3
Right ventricular function
TAPSE (normal > 17 mm) _____

(Continues)
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6 of 11       HOFLAND et al.

TA B L E 1   (Continued)

RV area change (normal > 35%) _____%

Visual assessment _____ CHD score
Integrated RV assessment Normal 0
Mild impairment 1
Moderate impairment 2
Severe impairment 3
Left-­sided valvular assessment
Mitral valve
Valve apparatus description: ________________
Regurgitation, vena contracta width ___ mm CHD score
Normal 0
< 3 mm: Mild 1
3–­6 mm: Moderate 2
≥ 7 mm: Severe 3
Stenosis, mean pressure gradient: ___ mmHg
Stenosis, mitral valve area: ___ cm
Normal 0
< 5 mmHg or > 1.5cm:Mild 1
6–­10 mmHg or 1–­1.5 cm: Moderate 2
> 10 mmHg or < 1.0 cm: Severe 3
Leaflet description (describe the most severely affected
leaflet):
Leaflet thickening (mm) Normal 0
≥ 3 to < 4: Mild 1
≥ 4 to < 5: Moderate 2
≥ 5: Severe 3
Leaflet excursion Normal 0
> 50 to ≤ 75% of normal: Mild 1
> 25 to ≤ 50% of normal: Moderate 2
≤ 25% of normal of fixed: Severe 3
Leaflet retraction Normal 0
Mild 1
Moderate 2
Severe 3
Aortic valve
Valve apparatus description: _______________
Regurgitation, vena contracta width ___ mm
Normal 0
< 3 mm: Mild 1
3–­6 mm: Moderate 2
> 6 mm: Severe 3
Stenosis, Vmax ___ m/s
Stenosis, mean pressure gradient ___ mmHg
Normal 0
< 3 m/s or < 20 mmHg: Mild 1
3–­4 m/s or 20–­39 mmHg:Moderate 2
> 4 m/s or > 40 mmHg:Severe 3

(Continues)
HOFLAND et al. |
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TA B L E 1   (Continued)

Cusp description (describe the most severely affected cusp):

Cusp thickening (mm) Normal 0
≥ 3 to < 4: Mild 1
≥ 4 to < 5: Moderate 2
≥ 5: Severe 3
Cusp excursion Normal 0
> 50 to ≤ 75% of normal: Mild 1
> 25 to ≤ 50% of normal: Moderate 2
≤ 25% of normal of fixed: Severe 3
Cusp retraction Normal 0
Mild 1
Moderate 2
Severe 3
Carcinoid heart disease score
Score tricuspid valve ___
Score pulmonary valve ___
Score mitral valve ___
Score aortic valve ___
Score right ventricle ___
Total carcinoid heart disease score ___
Left ventricular/atrial assessment
Findings ________________
Left atrial Volume ___ml
LV size
EDD ___mm
ESD ___mm
EDV ___ml
ESV ___ml
LVEF ____ %
Structural abnormalities ________________
Patent foramen ovale Present
Present
Not assessed
Other relevant findings Free text:
Conclusions Free text:

Abbreviations: AR, aortic regurgitation; AS, aortic stenosis; bpm, beats per minute; BSA, body surface area; CHD, carcinoid heart disease; cm,
centimetre; EDD, end diastolic diameter; EDV, end diastolic volume; ESD, end systolic diameter; ESV, end systolic volume; ID, identification number;
kg, kilogram; LVEF, left ventricular ejection fraction; m, metres; mmHg, millimetres of mercury; MR, mitral regurgitation; MS, mitral stenosis;
PHT, pressure half-­time; PR, pulmonary regurgitation; PS, pulmonary stenosis; TAPSE, Tricuspid annular plane systolic excursion; TR, tricuspid
regurgitation; TS, tricuspid stenosis; TTE, transthoracic echocardiography.
#PR index: Duration of the PR signal divided by the total duration of diastole

leaflet with the largest area and the greatest motion. The septal always possible on 2D imaging to identify individual leaflets with a
leaflet is the shortest in the radial direction and the least mo- sufficient degree of accuracy. The four-­chamber view (A4C), par-
bile. The posterior leaflet is the shortest circumferentially. 21 The asternal long axis (PLAX) view of right ventricular inflow and par-
complex anatomy of TV makes it difficult to visualize all three asternal short axis (PSAX) views are mandatory. 21 Subcostal views
leaflets in one 2D view; hence, multiple views, extensively de- can also be useful but it should be noted that, in patients with
scribed in the guidelines of the American and British Societies of CHD with large liver metastases, subcostal views are frequently
Echocardiography, 22–­24 should be utilized. Despite this, it is not unobtainable. Inflow velocities are affected by respiration; hence,
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8 of 11       HOFLAND et al.

all measurements taken must be averaged throughout the respira- 3.5 | Assessment of left-­sided heart and
tory cycle or recorded at end-­expiratory apnoea. In patients with foramen ovale
atrial fibrillation, measurements from a minimum of five cardiac
cycles should be averaged. Whenever possible, it is best to as- Because left-­sided CHD can be present in a minority of patients and
sess the severity of the disease (especially severity of tricuspid left-­sided valvular or ventricular disorders are more often the result
stenosis) at heart rate less than 100 bpm and preferably between of degenerative, structural or ischaemic diseases, a dedicated de-
70 and 80 bpm. scription of the mitral and aortic valves as well as left ventricular and
atrial size and function should be included in CHD echocardiography
reporting.
3.3 | Pulmonary valve assessment Agitated saline contrast echocardiography should be per-
formed to detect PFO in patients with confirmed CHD. 27 To this
The PV is the second most affected valve in CHD with a prevalence end, a 20-­ to 22-­g auge Abbocath is placed into the antecubital
of 69%.7 The PV consists of three cusps and is supported by the vein and connected to a three-­way tap. Two Luer lock 10-­m L sy-
pulmonary root, which is part of the right ventricular outflow tract ringes are attached to the three-­way tap. One of the syringes is
(RVOT). There are three pulmonary sinuses of Valsalva, formed by filled with 8.5 mL of saline, 1.0 mL of blood is withdrawn from the
the semilunar attachments of the valve leaflets proximally and the vein into the syringe and 0.5  mL of air is added to the ‘mixture’.
sinotubular junction distally. 25 The pulmonary valve sinuses are la- Saline, blood and 0.5 mL of air are mixed between 2 Luer lock sy-
belled in relation to the aortic sinuses; the three sinuses can be ringes attached to the three-­way tap on the arm of the patient.
anterior, right and left posterior sinuses. 26 The infundibulum places Then a 3–­5-­m L bolus of the agitated mixture is injected as a bolus
the pulmonary valve above the ventricular septum, in a superior into the vein under ultrasound control and with continuous re-
position that offers a unique advantage for resection of the pulmo- cording of images. The injection should be repeated under cough
nary valve leaflets during surgery. The PV is imaged by TTE from and Valsalva manoeuvre (release phase). A PFO is considered pres-
the PLAX view of RVOT and pulmonary artery, the PSAX view of ent when there is a transfer of microbubbles from the right atrium
bifurcation of pulmonary artery and the PSAX view of basal right to the left atrium within three to five cardiac cycles. The size shunt
ventricle. The subcostal short axis view of basal right ventricle can can be defined as small (< 5 bubbles), moderate (6–­25 bubbles),
be explored as well but, as mentioned above, subcostal views for or severe (>  25 bubbles). Assessment of PFO is of particular im-
patients with CHD are rarely obtainable. Echocardiographic visuali- portance in all patients being considered for surgery because any
zation of the PV is more difficult than for other valves, and usually PFO should be closed at operation to prevent later recurrence of
only one or two cusps will be visualized simultaneously. 22 Overall, CHD in the left-­sided valves. Performance of agitated saline test-
PV involvement may be underappreciated with echocardiography ing should follow current guideline recommendations. 28
and careful, comprehensive investigations using 2D, 3D, colour-­ Myocardial metastases have been reported in 4% of neuroendo-
flow and spectral Doppler imaging are needed to provide a thor- crine neoplasm patients with echocardiography and are likely more
68
ough assessment. often visualized with contemporary Ga-­labelled somatostatin
receptor-­t argeted positron emission tomography imaging, 29 as well
as cardiac CT or magnetic resonance imaging because the sensitivity
3.4 | Right atrium and ventricle assessment to identify them with TTE is low.

The assessment of right-­sided structures was the topic of spe-

cific guidelines of ASE endorsed by the European and Canadian 3.6 | Validated CHD scoring systems
Societies. 22 In accordance with current guidelines, assessment of
right atrial and right ventricular (RV) structure and function should be Following our literature review, six different scoring systems
performed from a modified A4C view, in which the maximum basal for the presence of CHD were identified,15,30–­3 4 which are sum-
22
dimension of the Right Ventricle is seen. The Right Ventricle is usu- marized in Table  2. The feasibility and diagnostic capability of all
ally smaller than the Left Ventricle in a standard A4C view and, if the available scoring systems were evaluated in a single prospective
apex of the heart is shared or occupied by the Right Ventricle, this trial of 100  NET patients with liver metastases and/or carcinoid
is an indication of volume overloading and dilatation. In advanced syndrome. 34 In this study, 21% of patients were found to have
CHD with severe TV and/or PV regurgitation, the RV ventricle may CHD on echocardiography and all had New York Heart Association
measure within the normal reference limits but appears larger than Class I–­II. Overall, there were no major differences between the
the small, underfilled left ventricle. The basal RV diameter is defined different scoring systems in feasibility, sensitivity/specificity or
as the maximal short-­axis dimension in the basal one-­third of the correlation with biochemical markers of CHD or carcinoid syn-
right ventricle seen on the four-­chamber view. In the normal right drome, although the Royal Free Hospital CHD Score had the best
ventricle, the maximal short-­axis dimension is located in the basal correlation with N-­terminal pro B-­t ype natriuretic peptide and
one-­third of the ventricular cavity. plasma 5-­hydroxyindoleacetic acid combined with area under the
HOFLAND et al. |
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TA B L E 2   Summary of Carcinoid Heart Disease Scoring systems

Denney Westberg Moller Bhattacharyya Mansencal Dobson

et al. (1998)30 et al. (2001)33 et al. (2003)32 et al. (2008)35 et al. (2010)31 et al. (2014)34

Patients screened/ 23/13 (57%) 52/40 (77%) 71/50 (70%) 200/39 (20%) 80/42 (53%) 100/21 (21%)
with CHD (%)
Study design Prospective Retrospective Retrospective Prospective Prospective Prospective
Items scored
Thickening TV TV TV, PV TV, PV, MV, AV TV, PV, MV, AV TV, PV
Mobility TV TV, PV TV, PV, MV, AV TV, PV, MV, AV TV, PV
Retraction TV TV, PV TV, PV, MV, AV
Stenosis PV TV, PV, MV, AV TV, PV TV, PV
Regurgitation TV, PV TV TV, PV TV, PV, MV, AV TV, PV, MV, AV TV, PV
Right ventricle Size, function, Size, function Size Size, function
aberrant flow
Right atrium Size
Maximum score 14 8 20 66 30 33

Note: Carcinoid heart disease (CHD) scoring systems for transthoracic echocardiography were collected from literature following a systematic review.
The different studies used to design the scoring systems are listed in the columns.
Abbreviations: AV, aortic valve; MV, mitral valve; PVV, pulmonary valve; TV, tricuspid valve.

curve for a diagnosis of CHD of 0.988. 34 Given our intention of a to identify patients at higher risk of CHD for whom echocardiog-
standardized report for purposes of both screening and long-­term raphy is indicated. However, performance and reporting of TTE in
follow-­up and functionality for deciding on the indication for val- patients with suspected CHD varies between institutions.13 The
vular surgery, the working group based this synopsis on the Royal present Synoptic Reporting of Echocardiography in Carcinoid Heart
Free Hospital CHD score, comprising most comprehensive scoring Disease aims to provide a guide for homogeneous assessment of
system and incorporating all structures relevant to the CHD pro- CHD at time of TTE performance. The use of synoptic over narra-
cess. This 22-­item score was developed within a prospective trial tive reporting can lead to several improvements in the screening
in 200  NET patients, 20% of which had a diagnosis of CHD, and and surveillance of CHD, including unity, consistency, comprehen-
had an overall excellent agreement between expert echocardiog- siveness and quantification.
raphers, with a κ value of 0.89.15 Following an integrated approach The proposed Synoptic Reporting of Echocardiography includes
of visual assessment of structure and function, as well as of semi-­ details on the information required at the time of TTE request to
quantitative and quantitative parameters, the individual items of provide a holistic clinical overview of the patient's status and ratio-
valvular and right ventricular abnormalities within the CHD score nale for testing, as well as the specific details on structures that must
should be classified into three grades. Recommendations for calcu- be evaluated during the TTE.
lation of CHD score items are provided in Table 1. It is important The clinical fields to be filled in at time of TTE being requested
to emphasize that the purpose of the CHD score is to provide a by the clinical team are focused on providing detailed information
baseline assessment and identify progression/worsening of valve on the rationale for such investigation being performed, including
disease. It does not define cut-­offs for different grades of valve dis- the presence or absence of CHD symptoms, or values on biomarkers
ease but instead identifies worsening of valve disease. Progression at the time of referral. In addition, data on the indication for TTE
of CHD can be defined if the CHD score is increased by 25% from is further specified, with clear discrepancy between screening and
previous examinations, whereas new-­onset CHD can be diagnosed follow-­up after diagnosis of CHD. This information aims to support
if newly detected features of CHD were not present on previous further CHD assessment by providing a well-­defined clinical history
echocardiograms. of each individual patient.
The proposed items of information to be collected at the time of
TTE performance aim to provide a systematic assessment of CHD
4 | D I S CU S S I O N with evaluation of all relevant structures. This detailed evaluation
aims to facilitate a thorough assessment of CHD, attempting to re-
Accurate assessment of CHD is crucial for patients with advanced duce the chances of missing incipient indicators of CHD that may be
NETs as a result of its impact on morbidity and mortality. TTE is otherwise under-­reported. By doing so, early identification of CHD
the current gold standard for assessment of CHD. Its role as a di- (progression) and selection of patients for valve replacement may
agnostic tool is usually preceded by screening biomarker testing be achieved.
 |
10 of 11       HOFLAND et al.

Current CHD assessment and reporting varies significantly be- from Ipsen and Triple A and has received research grant support from
tween institutions. This is one of the main reasons why the incidence Ipsen and Novartis. Dr Christos Toumpanakis reports speaker and
and progression of CHD varies between studies. On top of this, the advisory board honoraria from Novartis, IPSEN, AAA and Lexicon
lack of standardized TTE reporting is also one of the main challenges and has received education grants for the NET Unit from Novartis,
for prospective studies in this setting, for which a central review of IPSEN, AAA and Lexicon. The other authors declare that they have
all TTE examinations may be required to overcome such a problem. no conflicts of interest.
The utilization of our synoptic report could facilitate homogeneous
assessment of CHD between institutions, which would allow inter-­ AU T H O R C O N T R I B U T I O N S
institutional comparisons of CHD prevalence, severity and outcome Johannes Hofland: Data curation; Formal analysis; Methodology;
data. In addition, it could also facilitate the delivery of prospective Writing –­ original draft. Angela Lamarca: Data curation; Methodology;
studies in which CHD may be one of the clinical endpoints. Validation; Writing –­ original draft. Rick Steeds: Conceptualization;
In summary, our proposed Synoptic Reporting of Data curation; Methodology; Supervision; Validation;
Echocardiography in Carcinoid Heart Disease aims to provide an Writing  –­  original draft. C. Toumpanakis: Conceptualization; Data
agreed peer-­reviewed proforma to capture information at the time curation; Methodology; Supervision; Writing  –­  review & edit-
of referral and enable a detailed outcome of CHD assessment to ing. Rajaventhan Srirajaskanthan: Methodology; Validation;
provide a detailed holistic assessment of a relevant complication for Writing  –­  review & editing. Rachel Riechelmann: Methodology;
patients with advanced NETs. Its use aims to enhance systematic as- Writing  –­  review & editing. Francesco Panzuto: Methodology;
sessment during the screening and surveillance of all relevant struc- Writing  –­  review & editing. A Frilling: Methodology; Writing  –­  re-
tures and also facilitate inter-­institutional comparison of outcomes. view & editing. Timm Denecke: Methodology; Writing  –­  review &
This article is part of a special issue on standised (synoptic) re- editing. Emanuel Christ: Methodology; Writing  –­  review & edit-
porting of neuroendocrine tumours (see editorial36 and articles37-­40). ing. Simona Grozinsky-­Glasberg: Conceptualization; Investigation;
Methodology; Supervision; Writing  –­  review & editing. Joseph
AC K N OW L E D G E M E N T S Davar: Conceptualization; Investigation; Methodology; Supervision;
Dr Angela Lamarca is part funded by The Christie Charity. We thank Validation; Writing –­ original draft; Writing –­ review & editing.
Dr Wichor Bramer from the Erasmus MC Medical Library for de-
veloping and updating the search strategies. Other members of the PEER REVIEW
ENETS Carcinoid Heart Disease Task Force include: Ashley K Clift, The peer review history for this article is available at https://publo​
Department of Endocrine Surgery, Imperial College London, London, ns.com/publo​n/10.1111/jne.13060.
United Kingdom; Wanda Geilvoet, Department of Internal Medicine,
Section of Endocrinology, ENETS Center of Excellence, Erasmus MC DATA AVA I L A B I L I T Y
and Erasmus Cancer Institute, Rotterdam, The Netherlands; Enrique This guideline does not have original data and therefore has no data
Grande, Medical Oncology Department, MD Anderson Cancer storage/availability.
Center Madrid, Madrid. Spain. Louis de Mestier, Gastroenterology
and Pancreatology, Hopital Beaujon, Clichy, France; Ulrich-­Frank ORCID
Pape, Department of Internal Medicine and Gastroenterology, Johannes Hofland  https://orcid.org/0000-0003-0679-6209
Asklepios Kliniken, Hamburg, Germany; Vikas Prasad, Department Francesco Panzuto  https://orcid.org/0000-0003-2789-4289
of Nuclear Medicine, University Hospital Ulm, Ulm, Germany; Marie-­
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