Culshaw et al.

Echo Research & Practice (2025) 12:15 Echo Research & Practice
https://doi.org/10.1186/s44156-025-00078-z

GUIDELINE Open Access

British Society of Echocardiography

guideline for the transthoracic
echocardiographic assessment of adult patients
with obstructive hypertrophic cardiomyopathy
receiving myosin‑inhibitor therapy
Clare M. Culshaw1*, Daniel Augustine2,3, Caroline J. Coats4, Ivo Andrade5, Keith Pearce5, Antonis Pantazis6,
William Bradlow7, Lauren Turvey7, William Moody8, Lynne Williams9, Rachel Bastianen10, Jane Draper10,
David L. Oxborough11 and Robert M. Cooper1,11*

Keywords Mavacamten, Myosin-inhibitor, Obstructive HCM, Surveillance Echocardiogram

Introduction Seminal studies of Mavacamten highlighted potential

Hypertrophic cardiomyopathy (HCM) is a disease char- risk of heart failure due to left ventricular (LV) systolic
acterised by myocardial hypertrophy. This is linked to dysfunction in a small percentage of oHCM patients. Due
dysfunction of the cardiac sarcomere that results in exces- to this risk, safety monitoring is required when integrat-
sive cardiac myosin–actin cross-bridging and increased ing this therapy into clinical practice [1]. Echocardiogra-
sensitivity to calcium. Mavacamten is a selective, revers- phy is a key diagnostic imaging tool when diagnosing and
ible myosin-inhibitor licensed in the United Kingdom as managing oHCM and is part of the surveillance for those
an oral therapy to treat symptomatic obstructive Hyper- patients being treated with Mavacamten. This guideline
trophic Cardiomyopathy (oHCM) [1, 2]. from the British Society of Echocardiography outlines
a protocol for minimum standards for surveillance of
patients undergoing treatment using Mavacamten.

*Correspondence: Background
Clare M. Culshaw Hypertrophic Cardiomyopathy is a disease of cardiac
Clare.Culshaw@lhch.nhs.uk
Robert M. Cooper myocytes characterised by left ventricular hypertrophy
Rob.Cooper@lhch.nhs.uk (LVH) in the absence of abnormal loading conditions.
1
2
Liverpool Heart and Chest Hospital, Thomas Drive, Liverpool L14 3PE, UK Most commonly observed pathogenic genetic variants in
Royal United Hospitals Bath NHS Foundation Trust, Bath, Bath, UK
3
University of Bath, Bath, UK those with HCM include changes in myosin heavy chain
4
Queen Elizabeth University Hospital, Glasgow, UK 7 (MYH7) and myosin binding protein C3 (MYBPC3)
5
6
Manchester University NHS Foundation Trust, Manchester, UK genes. These variants contribute to the excessive myosin-
Royal Brompton and Harefield Hospital, London, UK
7
University Hospital Birmingham, Birmingham, UK actin cross bridging that underpins the clinical features of
8
Queen Elizabeth Hospital Birmingham, Birmingham, UK the disease [3]. Half of individuals carrying a pathogenic
9
10
Royal Papworth Hospital, London, UK variant express the disease by the third decade of life [3].
Guys and St Thomas Hospital, London, UK
11
Sports and Exercise Sciences, Liverpool John Moores University, Additional core pathophysiological features include dias-
Liverpool, UK tolic dysfunction, myocardial fibrosis and microvascular
Full list of author information is available at the end of the article

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 2 of 15

ischaemia. The classic form of LVH affects the basal ven- blockers as a second line therapy if betablockers are
tricular septum although other segments of the left ven- either ineffective, poorly tolerated, or contraindicated.
tricle can also be affected. The next management step includes either Disopyramide
The prevalence of HCM is estimated at 1:500 [4], with or Mavacamten [2]. Septal reduction therapy with either
UK Biobank data suggesting a general population preva- alcohol septal ablation or surgical myectomy is reserved
lence of LVH ≥ 15 mm in 0.11% in previously undiag- for patients with significant symptomatic LVOT obstruc-
nosed individuals [5]. With the improved diagnostic yield tion refractory to medical therapy [11].
of tests, family screening and the availability of genetic Mavacamten is a selective and reversible cardiac myo-
testing the genetic prevalence is expected to be as high sin ATPase inhibitor. It reduces the number of myosin
as 1:250 [6, 7]. These disease-causing genetic alterations heads in an active state. This shifts the overall myosin
affect the structure and function of sarcomeric proteins population towards an energy sparing, super-relaxed
resulting in molecular changes that cause excessive car- state, moving away from excessive cardiac myosin–actin
diac myosin–actin cross-bridging. This leads to a rise in cross-bridging. Mavacamten is reported to significantly
force generation and subsequent myocardial hypercon- reduce LVOT gradients, improve patients’ symptoms,
tractility [8]. A third of patients diagnosed with HCM improve exercise capacity, and reduce serum levels of
have evidence of LV outflow tract (LVOT) obstruction at N-terminal pro-type natriuretic peptide (NT pro BNP)
rest by the third and fourth decades of life [3]. Another and high sensitivity troponins [12, 13].
third develop evidence of LVOT obstruction with exer- Whilst Mavacamten has been shown to improve symp-
cise [9]. This is a result of the combination of the hyper- toms in study populations along with reduction in LVOT
trophied basal ventricular septum encroaching the obstruction, data from EXPLORER-HCM and VALOR-
LVOT, myocardial hypercontractility, and systolic ante- HCM have shown that for up to 5% of patients there will
rior motion of the mitral valve into the LVOT. be a reduction of LV ejection fraction (LVEF) to < 50%
Patients predominantly present with symptoms of [12, 13]. Follow up data suggested that the drop in LVEF
shortness of breath, although exertional chest pain, dizzi- resolved with the cessation or dose reduction of Mava-
ness and/or syncope are also reported. An abnormal rest- camten [12]. The MAVA-LTE study reported long term
ing LVOT pressure gradient is defined at > 30 mmHg [2], outcome up to 3 years showing sustained improvements
however, a LVOT peak pressure gradient of > 50 mmHg in gradients and symptoms, with low volume of transient,
is used as threshold for initiating treatment with Mava- reversible reduction in EF [14].
camten or alternative invasive options such as alcohol Due to the potential risk of heart failure linked to drop
septal ablation or surgical myectomy [2]. The presence in LVEF, recent National Institute for Clinical Excellence
and magnitude of the LVOT obstruction is a predic- (NICE) guidance recommends a minimal level of safety
tor of disease progression to heart failure and mortality monitoring that should be implemented where Mavaca-
[10] and therefore an important indicator in this patient mten is used in clinical practice [1]. Echocardiography
population. has been recommended as the diagnostic tool for the
Treatment is primarily aimed at improving quality safety monitoring for patients prescribed Mavacamten.
of life in those with restricting symptoms. Treating cli- NICE guidance recommends surveillance echocardiog-
nicians should ensure that phenocopies of HCM that raphy as per the summary of product characteristics of
required alternative treatment modalities are ruled out the medication at weeks 4, 8 and 12 post initiation of
[2]. Historically management of patients with symp- Mavacamten followed by 24 weekly echocardiograms
tomatic LVOT obstruction includes lifestyle advice, long term. Echocardiography is also mandated 4 weeks
medications with negative inotropic effect and/or inva- after any dose change (see Figs. 1, 2). All echocardiogra-
sive septal reduction therapy. Lifestyle changes include phy data will be taken in to account at a clinical review
weight reduction, avoidance of dehydration and avoid- in combination with symptoms when considering dose
ance of excessive alcohol consumption. The European alterations.
Society of Cardiology recommends betablockers as first Due to the high frequency of surveillance echocardio-
line therapy, with non- dihydropyridine calcium channel grams stipulated by NICE this document by the BSE aims
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 3 of 15

Fig. 1 Recommended algorithm for patients who are normal and rapid CYP metabolisers. *Interrupt treatment at any point if LVEF <50%

to standardise echocardiographic practice in this domain should be undertaken before initiation of treatment with
and support services in using clinically targeted echocar- Mavacamten. This should be performed with the patient
diograms to satisfy the requirements and allow safe mon- on standard medical treatment and will inform the next
itoring for patients using Mavacamten. Mavacamten is stage of treatment. In addition to a baseline echocardio-
currently the only licensed myosin inhibitor medication gram, it is recommended that patients undergo pharma-
in the UK. There is the potential for other myosin inhibi- cogenomic testing in order to assess metabolic activity
tor medications to reach the clinical space in the future. linked to removal of Mavacamten. (see Appendix 1 for
This document focusses on the use of Mavacamten as pharmacogenomic guidance).
this was the focus of NICE technology appraisal guid- Several practical considerations are important when
ance [1]. However, elements of this BSE protocol could evaluating echocardiographic protocols for those on
be used or adapted to other myosin inhibitors if their use myosin inhibitors:
requires monitoring in a similar manner to Mavacamten.
• The standardisation of manoeuvres used in the
The role of echocardiography and recommended baseline assessment of level of LVOT obstruction
Mavacamten protocol detected.
A full comprehensive echocardiographic assessment in • The increase in volume of echocardiograms due to
accordance with the British Society of Echocardiogra- the high frequency of surveillance scans (see Figs. 1,
phy Hypertrophic Cardiomyopathy guideline [15, 16] 2, 3 and 4).
• The standardisation of monitoring scans.
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 4 of 15

Fig. 2 Recommended algorithm for patients who are slow/poor CYP metabolisers or while CYP status is pending. *Interrupt treatment at any point
if LVEF <50%

with the direction of forward flow and guided by colour

The detection of LVOT obstruction can be achieved flow Doppler [15, 16]. It can be helpful to sweep the angle
with provocation manoeuvres when not obvious at rest, of interrogation between the LVOT and left atrium (LA)
aiming to alter the loading conditions and mimic the to allow for improved discrimination of LVOT gradients
physiological circumstances under which LVOT obstruc- from mitral regurgitation Doppler profiles.
tion is maximised. LVOT gradients should be assessed Whilst the baseline echocardiography study is
at rest and with Valsalva manoeuvre in the left lateral expected to adhere to the full BSE protocol for Hyper-
recumbent position. The CW doppler should be aligned trophic Cardiomyopathy [15, 16], the surveillance scans
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 5 of 15

LVEF <50%(See igure 4) See figure 4

Current Dose (treatment not paused) Week 12

LVEF 50-55% regardless of

valsalva LVOT gradient or LVEF Maintain on current dose and
>55% and valsalva LVOT gradient
and every 24 weeks

follow up in 24 weeks
<30mmHg

1. up-titration to next higher daily

(mg) dose level:2.5mg to 5mg: 5mg
to 10mg :10 to 15mg.
2. Recheck clinical status, Valsalva
LVOT Gradient and LVEF at week
4 after dose increase and maintain
current dose for the next 8 weeks
unless EF <55%.
LVEF >55% and valsalva LVOT 3. Further up-titration is allowed
gradient > 30mmHg after 12 weeks of treatment on the
current dose, if LVEF >55%.
Recheck at week 4
4. Maximum daily dose 15mg.
For CYP2C19 poor metabolisers
phenotype- maximum dose is 5mg.
If titrating from 2.5mg to 5mg:
follow-up 4 and 8 weeks later.

Fig. 3 Maintenance assessment algorithm. Echocardiography should be performed every 24 weeks unless a dose titration is needed or LVEF drops
to < 50%

recommended by NICE guidance supports the concept and reported. The minimum dataset for a surveillance
of targeted echocardiography studies. For the purpose echocardiogram should include the licensing require-
of consistency, the protocol of surveillance echocardi- ments for Mavacamten as they are described in NICE
ography should be reproducible, accurately recorded Guidance [1]. There are also some echocardiographic
parameters that can optionally be acquired depending on
specific local departmental requirements.
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 6 of 15

Fig. 4 Actions if LVEF drops to < 50%. If at any visit the patient’s LVEF is < 50%, the treatment should be interrupted for at least 4 weeks
and only restarted if LVEF ≥ 50%

Minimum dataset
Transthoracic echocardiography‑ for treatment using cardiac myosin inhibitor for treatment of obstructive hypertrophic
cardiomyopathy

Measurement View Modality Explanation Image

Visual assess- PLAX 2D Parasternal long axis (PLAX) is optimised to dem-

ment view onstrate the best image available [15, 16]

Visual assess- plax 2D and CF Optimise colour flow doppler (CFD) settings.
ment of MR view doppler Adjust the lateral CFD region of interest (ROI)
to include 1 cm of the LV on the left lateral border
and the roof of the LA on the right lateral border
[15, 16]
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 7 of 15

Measurement View Modality Explanation Image

Visual assess- PLAX 2D Place M-Mode cursor through the MV leaflet tips,
ment of SAM view and M-Mode ensuring image is on axis. Involves MV leaflets
and/or chordae [15, 16]

Visual assess- PSAX 2D Parasternal short axis window (PSAX) to demon-

ment of SAM view strate best image available [15, 16]

MR secondary A4C 2D CF/CW MR Quantification may be limited as the PISA

to SAM A3C Doppler dome may merge with turbulent flow. MR second-
ary to SAM is predominantly posteriorly directed
and originates more medial in the apical 4
chamber view. If quantification assessment of MR
is precluded by LVOTO, other indicators of MR
severity should be considered [17]. For example,
an E velocity of < 1.3 m/s and an E/A ratio < 1 are
strongly suggestive of non- severe MR [15, 16]. CW
Doppler velocity from MR jet facilitates differentia-
tion of LVOT flow from MR in A5C
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 8 of 15

Measurement View Modality Explanation Image

LV Simpson’s A4C, 2D LV volumes should be obtained using 2D imaging
Biplane vol- A2C Units: from A4C and A2C [18]. Trace the endocardial
umes EDV mL border. LV length is defined as the distance
ESV mL between the midpoint of the mitral valve level
line and the most distal point of the LV apex.
Take care to ensure the LV is not foreshort-
ened. Papillary muscles and trabeculations are
excluded from the volumes and considered
part of the chamber. Measure at end-diastole
and end-systole. Measurement is indexed to BSA.
Consider LV opacification for improved endocar-
dial definition. 3D assessment of the LV is a highly
feasible and reproducible parameter of LV systolic
function. Given the superiority over 2D estimates,
3D assessment of LV volumes and LVEF is recom-
mended in cases were image quality permits
accurate measurement. Given the additional
time involved this is not mandated where accu-
rate LVEF can be provided by Simpson’s biplane
assessment. A numerical value for LVEF should
be included in all echo reports. A visual estimate
should be provided only when image quality
is suboptimal Simpson’s biplane estimate [18]
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 9 of 15

Measurement View Modality Explanation Image

LVOT gradients A5C CW Doppler For the mechanics of performing a Valsalva
at rest/Valsalva A3C manoeuvre, please refer to the BSE HCM protocol
manoeuvre [15]
Assess LVOT obstruction gradients at rest,
with Valsalva manoeuvre. Align CW Doppler
through entire turbulent colour flow for peak
obstruction velocity [15, 16]. Peak velocity
recorded on A5C or A3C should be recorded
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 10 of 15

Optional measurements

Measurement View Modality Explanation Image

LV GLS Measurement A4C LV GLS Optimal ECG signal with minimal

A3C heart rate variability should be pre-
A2C sent across the three cardiac cycles.
Heart rate variability will limit
the circulation of GLS values, which
can be problematic in patients
with atrial fibrillation. High -quality
acquisition, maintaining a frame
rate of 40–90 frames/sat a normal
heart rate is key [18]

Clear endocardial and epicardial

definition is required to ensure
adequate segmental tracking
throughout the cardiac cycle.
Markers are placed in each
of the respective basal and apical
regions, using automatic tracking
where possible to maintain repro-
ducible results. Automatic tracking
should be combined with visual
assessment of tracking in each
view across the whole ROI, includ-
ing the endocardial and epicardial
border. If more than two seg-
ments in more than one view are
not adequately tracked, the calcula-
tion of GLS should be avoided [18]
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 11 of 15

Measurement View Modality Explanation Image

LA strain A4C LA Strain When acquiring images for LA
A2C strain analysis, dedicated atrial
windows should be acquired
to maximum LA volume. LA strain
analysis in views that are optimised
for the LV therefore forshorten-
ing leads to overestimation of LA
values [19]

TDI velocities A4C PW TDI Place sample volume (5-10 mm)

Septal at or within 1 cm of the inser-
and lateral tion of the mitral valve leaflets.
walls Measure at the end of expiration.
Units: cm/s Scale and sweep speed optimised
(100 mm/s) [18].
e’: Peak velocity at the leading
edge of spectral wave form in early
diastole (after T wave). If possible
average both septum and lateral
wall measurements
S’: Peak systolic Velocity
Limitation: this measure assumes
that the function of these two
segments represents longitudinal
function of the entire ventricle, this
is unlikely in conditions that result
in regional wall motion abnormali-
ties [18].

Place sample volume (1–3 mm)

at level of the MV leaflet tips in dias-
tole. Use of CFD can help to align
the centre of trans-mitral flow.
Measure at end expiration. Emax:
peak velocity in early diastole.
Amax: peak velocity in late diastole
(after P wave). DT: Flow decelera-
tion time from peak E wave to end
of E wave signal [18].
PW doppler mitral A4C MV EV max AV Obtain RV focussed view. From
inflow (PWD) max E/A A4C view slide and/or angu-
ratio DT late the tail of the transducer
along the horizontal plane to place
the RV in the centre of the image
(instead of the conventional
left heart-centred image) whilst
ensuring that the LV outflow tract
does not come into view. This
allows the RV free wall to be clearly
seen. Next, rotate the transducer
to obtain the maximum diameter
[18]
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 12 of 15

Measurement View Modality Explanation Image

RV focussed view A4C RV/RA Visual Perform CW Doppler and colour
(2D) assessment quantification for TR in all views
where the TV is visualised. See BSE
pulmonary hypertension guidelines
for estimating probability of pulmo-
nary hypertension [20]

A4C TR Vmax,
extent of TR

A4C Lat TV/ TAPSE Align the M-mode cursor

MV annulus along the direction of the lat-
(MM) eral tricuspid or mitral annulus
to maximise longitudinal motion
of the annulus. Measurement
accuracy is improved by zooming
on the TV annulus and selecting
a high sweep speed. Measure
total excursion of the tricuspid
annulus [20]. Limitation: This
is an angle dependent measure-
ment and is therefore underesti-
mated when M-mode alignment
is not parallel [21]. TAPSE is further
limited due to the assumption
that the longitudinal motion of this
single region of the annulus rep-
resents the function of the entire
RV, this is unlikely in cases of RV
regional wall motion abnormali-
ties [21]
A4C RV RV S′ PW tissue Doppler S wave measure-
(TDI) ment taken at the lateral tricuspid
annulus in systole. It is important
to ensure the basal RV free wall
segment and the lateral tricuspid
annulus are aligned with the Dop-
pler cursor to avoid velocity under-
estimation [22]. As well as Doppler
alignment limitations, the accuracy
of this measurement is further lim-
ited by the assumption that overall
function of the RV is reflected
by basal RV contraction. Accuracy
of this measure is therefore limited
by conditions such as RV infarction
and prior cardiac surgery [23]
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 13 of 15

Measurement View Modality Explanation Image

LVOT gradients A5C CW doppler Assess LVOT obstruction gradi-
when standing A3C ents when standing. Also assess
when standing with Valsalva
manoeuvre to maximise veloc-
ity observed. Align CW Doppler
through entire turbulent colour
flow for peak obstruction velocity
[15, 16]. Peak velocity recorded
on A5C or A3C should be recorded

Minimum dataset for TTE for patients with obstructive

hypertrophic cardiomyopathy receiving cardiac myosin
inhibitor treatment

View Parameters

PLAX 2D
Colour Doppler for MV, LVOT and AV
M-Mode of MV leaflets for SAM
PSAX 2D MV Level
AP4C 2D and focused for Biplane
Simpsons and for GLS (GLS
is optional)
2D and focused LA for LA strain assessment is essential during surveillance of patients
(optional) being treated with Mavacamten, when values obtained
Colour Flow Doppler of MV fall on boundaries this may influence treatment deci-
CW Doppler for MR sions. The BSE recommend that contrast is used when
PW Doppler for Mitral inflow/TDI two or more segments cannot be visualised [24]. LV vol-
velocities at LV septal/lateral regions
(Optional) umes in both systole and diastole are greater when meas-
AP5C 2D ured using contrast agents than without as tracing of the
Colour Doppler for LVOT LV borders more reliably leads to inclusion of trabecula-
CW Doppler for LVOT resting/Val- tion within the cavity. Minimal detectable difference for
salva 2D contrast LVEF has been noted to be in the order of 4%
AP2C 2D and focused for Biplane in comparison to 9–11% for non-contrast 2D LVEF [25].
Simpsons and for GLS (GLS optional) The use of contrast can have unpredictable effects on 2D
2D and focused LA for LA strain
(optional) speckle tracking, therefore it is recommended the use of
Colour Doppler for MR contrast is given after strain acquisition [26]. If a contrast
Optional RV assessment recom- agent is required, it is recommended the BSE contrast
mended at week 12- 2D, CW Echocardiography: Practical guideline is adhered to [24].
doppler of TV, TR CW doppler, TAPSE,
TDI, PASP
Stress echocardiography
AP3C Valsalva with CW for LVOT
Exercise stress echocardiography may be required as
Colour Doppler for MR
part of standard of care for those symptomatic patients
Colour Doppler for LVOT, 2D for GLS
(Optional)
without obvious gradients at rest or with Valsalva (gra-
dients < 50 mmHg). Stress Echocardiography using a
treadmill or bike is recommended in patients with HCM,
Contrast echocardiography/ultrasound enhancing agents dobutamine infusion is not used as this is known to pro-
Suboptimal endocardial border definition can lead to duce increased outflow Doppler velocities in normal
errors in LV volume and LVEF estimation. Accurate LVEF hearts. If exercise stress echo is required please refer to
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 14 of 15

the stress protocol within the BSE Hypertrophic Cardio- Declarations

myopathy guidelines [15, 16]. Stress echocardiography
Ethics approval and consent to participate
is not recommended as part of routine surveillance for Not applicable.
Mavacamten therapy.
Consent for publication
Not applicable.
Conclusion
Mavacamten is the first licensed cardiac myosin-inhibi- Competing interests
tor. Due to the potential for excessive reduction in LVEF The authors declare no competing interests.

[12, 13] surveillance of LV function is mandatory [1]. Author details

Echocardiography is a key imaging modality in the ini- 1
Liverpool Heart and Chest Hospital, Thomas Drive, Liverpool L14 3PE, UK.
2
tial assessment and subsequent monitoring of patients Royal United Hospitals Bath NHS Foundation Trust, Bath, Bath, UK. 3 Uni-
versity of Bath, Bath, UK. 4 Queen Elizabeth University Hospital, Glasgow,
treated with Mavacamten. High quality LVEF assessment UK. 5 Manchester University NHS Foundation Trust, Manchester, UK. 6 Royal
is vital along with accurate LVOT gradient acquisition, Brompton and Harefield Hospital, London, UK. 7 University Hospital Birming-
including assessment with Valsalva manoeuvre. These ham, Birmingham, UK. 8 Queen Elizabeth Hospital Birmingham, Birmingham,
UK. 9 Royal Papworth Hospital, London, UK. 10 Guys and St Thomas Hospital,
assessments are essential and are key when optimising London, UK. 11 Sports and Exercise Sciences, Liverpool John Moores University,
and monitoring safety in patients treated with Mavaca- Liverpool, UK.
mten. Additional key echocardiographic indices can also
Received: 18 November 2024 Accepted: 29 April 2025
be assessed at Mavacamten surveillance echocardiogra-
phy according to local capacity, and routine standard of
care echocardiograms adhering to BSE guidelines [15, 16]
should continue in parallel with a full data set collected. References
1. NICE. Mavacamten for treating symptomatic obstructive hypertrophic
cardiomyopathy. 2023. https://​www.​nice.​org.​uk/​guida​nce/​ta913
2. Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C,
Appendix 1 Bezzina CR, Biagini E, Blom NA, de Boer RA, De Winter T, Elliott PM, Flather
Prior to initiation of Mavacamten, it is recommended M, Garcia-Pavia P, Haugaa KH, Ingles J, Jurcut RO, Klaassen S, Limongelli G,
that patients undergo pharmacogenomic testing in order Loeys B, Mogensen J, Olivotto I, Pantazis A, Sharma S, Peter Van Tintelen
J, Ware JS, Kaski JP, ESC Scientific Document Group. 2023 ESC guidelines
to assess metabolic activity linked to removal of Mava- for the management of cardiomyopathies: developed by the task force
camten. As Mavacamten is metabolised through the on the management of cardiomyopathies of the European society of
hepatic enzymes CYP2C19 (74%), CYP3A4 (18%) and cardiology (ESC). Eur Heart J. 2023;44(37):3503–626. https://​doi.​org/​10.​
1093/​eurhe​artj/​ehad1​94.
CYP2C9 (7.65%) genotyping of CYP2C19 is required to 3. Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics,
guide Mavacamten therapy and dosing. Depending on pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res.
results, patients will be characterised as rapid, normal, 2017;121(7):749–70.
4. Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL,
intermediate or poor (slow) metabolisers. Those patients Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS,
who are “poor” metabolisers have the risk being exposed Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P. 2020 AHA/ACC
to higher than intended doses of Mavacamten (due to guideline for the diagnosis and treatment of patients with hypertrophic
cardiomyopathy: a report of the American college of cardiology/Ameri-
reduced clearance) therefore adjustments need to be can heart association joint committee on clinical practice guidelines.
made during dose titration [27]. In the situation where Circulation. 2020;142(25):e558–631. https://​doi.​org/​10.​1161/​CIR.​00000​
there may be a delay gaining access to CYP status patients 00000​000937.
5. Lopes LR, Aung N, van Duijvenboden S, Munroe PB, Elliott PM, Petersen
may be initiated at a low dose of 2.5 mg until CYP status SE. Prevalence of hypertrophic cardiomyopathy in the UK Biobank popu-
is known. lation. JAMA Cardiol. 2021;6(7):852–4. https://​doi.​org/​10.​1001/​jamac​ardio.​
2021.​0689.
6. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Preva-
Author contributions lence of hypertrophic cardiomyopathy in a general population of young
CM.C. is the primary author of this manuscript, RM.C provided expert over- adults. Echocardiographic analysis of 4111 subjects in the CARDIA
sight and guidance. RM.C, D.A., CJ.C., I.A., K.P., A.P., W.B., L.T., W.M., L.W., R.B., study. Coronary artery risk development in (Young) adults. Circulation.
J.D. and DL.O, all subsequently reviewed the manuscript and after revising it 1995;92(4):785–9.
critically, were involved in re-drafting the manuscript, before giving it their 7. Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on
final approval for its submission. There has been no funding received for this the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol.
manuscript. 2015;65(12):1249–54.
8. Marian AJ. Molecular genetic basis of hypertrophic cardiomyopathy. Circ
Funding Res. 2021;128(10):1533–53.
This work did not receive any specific grant from any funding agency in the 9. Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT, et al.
public, commercial or not-for-profit sector. Hypertrophic cardiomyopathy is predominantly a disease of the left
ventricular outflow tract obstruction. Circulation. 2006;114(19):2232–9.
Data availability 10. Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, et al. Effect
No datasets were generated or analysed during the current study. of left ventricular outflow tract obstruction on clinical outcome in hyper-
trophic cardiomyopathy. N Engl J Med. 2003;348(4):2232–9.
Culshaw et al. Echo Research & Practice (2025) 12:15 Page 15 of 15

11. Nishimura RA, Seggewiss H, Schaff HV. Hypertrophic obstructive Lyon AR, Augustine DX. British society for echocardiography and british
cardiomyopathy: surgical myectomy and septal ablation. Circ Res. cardio-oncology society guideline for transthoracic echocardiographic
2017;121(7):771–83. assessment of adult cancer patients receiving anthracyclines and/or
12. Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, trastuzumab. Echo Res Pract. 2021;8(1):G1–18. https://​doi.​org/​10.​1530/​
et al. Mavacamten for treatment of symptomatic obstructive hyper- ERP-​21-​0001.
trophic Cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, 27. Chiang M, Sychterz C, Perera V, Merali S, Palmisano M, Templeton IE,
placecebo-controlled, phase 3 trail. Lancet. 2020;396(10253):759–69. Gaohua L. Physiologically Based pharmacokinetic modeling and simula-
13. Desai M, Owens A, Geske J, et al. Myosin inhibition in patients with tion of mavacamten exposure with drug-drug interactions from CYP
obstructive hypertrophic cardiomyopathy referred for septal reduction inducers and inhibitors by CYP2C19 phenotype. Clin Pharmacol Ther.
therapy. JACC. 2022;80(2):95–108. https://​doi.​org/​10.​1016/j.​jacc.​2022.​04.​ 2023;114(4):922–32. https://​doi.​org/​10.​1002/​cpt.​3005.
048.
14. Garcia-Pavia P, Oręziak A, Masri A, Barriales-Villa R, Abraham TP, Owens
AT, Jensen MK, Wojakowski W, Seidler T, Hagege A, Lakdawala NK, Wang Publisher’s Note
A, Wheeler MT, Choudhury L, Balaratnam G, Shah A, Fox S, Hegde SM, Springer Nature remains neutral with regard to jurisdictional claims in pub-
Olivotto I. Long-term effect of mavacamten in obstructive hypertrophic lished maps and institutional affiliations.
cardiomyopathy. Eur Heart J. 2024;45(47):5071–83. https://​doi.​org/​10.​
1093/​eurhe​artj/​ehae5​79.
15. Turvey L, Augustine DX, Robinson S, et al. Transthoracic echocardiogra-
phy of hypertrophic cardiomyopathy in adults: a practical guideline from
the British Society of Echocardiography. Echo Res Pract. 2021;8:G61–86.
https://​doi.​org/​10.​1530/​ERP-​20-​0042.
16. Nagueh SF, Phelan D, Abraham T, Armour A, Desai MY, Dragulescu A, Gil-
liland Y, Lester SJ, Maldonado Y, Mohiddin S, Nieman K, Sperry BW, Woo A.
Recommendations for multimodality cardiovascular imaging of patients
with hypertrophic cardiomyopathy: an update from the American
Society of Echocardiography, in collaboration with the American society
of nuclear cardiology, the society for cardiovascular magnetic resonance,
and the society of cardiovascular computed tomography. J Am Soc
Echocardiogr. 2022;35(6):533–69. https://​doi.​org/​10.​1016/j.​echo.​2022.​03.​
012.
17. Robinson S, Ring L, Augustine DX, et al. The assessment of mitral valve
disease: a guideline from the British Society of Echocardiography. Echo
Res Pract. 2021;8:G87–136. https://​doi.​org/​10.​1530/​ERP-​20-​0034.
18. Robinson S, Rana B, Oxborough D, et al. A practical guideline for per-
forming a comprehensive transthoracic echocardiogram in adults: the
British Society of Echocardiography minimum dataset. Echo Res Pract.
2020;7:G59–93. https://​doi.​org/​10.​1530/​ERP-​20-​0026.
19. Robinson S, Ring L, Oxborough D, et al. The assessment of left ventricular
diastolic function: guidance and recommendations from the British
Society of Echocardiography. Echo Res Pract. 2024;11:16. https://​doi.​org/​
10.​1186/​s44156-​024-​00051-2.
20. Augustine DX, Coates-Bradshaw LD, Willis J, et al. Echocardiographic
assessment of pulmonary hypertension: a guideline protocol from the
British Society of Echocardiography. Echo Res Pract. 2018;5:G11–24.
https://​doi.​org/​10.​1530/​ERP-​17-​0071.
21. Zaidi A, Knight DS, Augustine DX, et al. Echocardiographic assessment
of the right heart in adults: a practical guideline from the British Society
of Echocardiography. Echo Res Pract. 2020;7:G19–41. https://​doi.​org/​10.​
1530/​ERP-​19-​0051.
22. Zagzebski JA. Essentials of ultrasound physics. St Louis: Mosby Inc; 1996.
23. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran
K, Solomon SD, Louie EK, Schiller NB. Guidelines for the echocardio-
graphic assessment of the right heart in adults: a report from the Ameri-
can Society of Echocardiography endorsed by the European Association
of Echocardiography, a registered branch of the European Society of
Cardiology, and the Canadian Society of Echocardiography. J Am Soc
Echocardiogr. 2010;23:685–713.
24. Senior R, Becher H, Monaghan M, Agati L, Zamorano J, Vanoverschelde
JL, Nihoyannopoulos P, Edvardsen T, Lancellotti P, EACVI Scientific Docu-
ments Committee for 2014–16 and 2016–18; EACVI Scientific Docu-
ments Committee for 2014–16 and 2016–18. Clinical practice of contrast
echocardiography: recommendation by the European Association of
Cardiovascular Imaging (EACVI) 2017. Eur Heart J Cardiovasc Imaging.
2017;18(11):1205–1205. https://​doi.​org/​10.​1093/​ehjci/​jex182.
25. Suwatanaviroj T, He W, Pituskin E, Paterson I, Choy J, Becher H. What is the
minimum change in left ventricular ejection fraction, which can be meas-
ured with contrast echocardiography? Echo Res Pract. 2018;5(2):71–7.
https://​doi.​org/​10.​1530/​ERP-​18-​0003.
26. Dobson R, Ghosh AK, Ky B, Marwick T, Stout M, Harkness A, Steeds R,
Robinson S, Oxborough D, Adlam D, Stanway S, Rana B, Ingram T, Ring
L, Rosen S, Plummer C, Manisty C, Harbinson M, Sharma V, Pearce K,