2025 BSE指南：接受肌球蛋白抑制剂治疗的成人梗阻性肥厚型心肌病患者的经胸超声心动图评估

British Society ofEchocardiography guideline forthetransthoracic echocardiographic assessment ofadult patients withobstructive hypertrophic cardiomyopathy receiving myosin‑inhibitor therapy

ClareM.Culshaw 1\* , DanielAugustine 2,3 , CarolineJ.Coats 4 , IvoAndrade 5 , KeithPearce 5 , AntonisPantazis 6 , WilliamBradlow 7 , LaurenTurvey 7 , WilliamMoody 8 , LynneWilliams 9 , RachelBastianen 10 , JaneDraper 10 , DavidL.Oxborough 11 and RobertM.Cooper 1,11\*

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

Introduction

Hypertrophic cardiomyopathy (HCM) is a disease characterised by myocardial hypertrophy. This is linked to dysfunction of the cardiac sarcomere that results in excessive cardiac myosin–actin cross-bridging and increased sensitivity to calcium. Mavacamten is a selective, reversible myosin-inhibitor licensed in the United Kingdom as an oral therapy to treat symptomatic obstructive Hypertrophic Cardiomyopathy (oHCM) [ 1 , 2 ].

Seminal studies of Mavacamten highlighted potential risk of heart failure due to left ventricular (LV) systolic dysfunction in a small percentage of oHCM patients. Due to this risk, safety monitoring is required when integrating this therapy into clinical practice [ 1 ]. Echocardiography is a key diagnostic imaging tool when diagnosing and managing oHCM and is part of the surveillance for those patients being treated with Mavacamten. This guideline from the British Society of Echocardiography outlines a protocol for minimum standards for surveillance of patients undergoing treatment using Mavacamten.

Background

Hypertrophic Cardiomyopathy is a disease of cardiac myocytes characterised by left ventricular hypertrophy (LVH) in the absence of abnormal loading conditions. Most commonly observed pathogenic genetic variants in those with HCM include changes in myosin heavy chain 7 (MYH7) and myosin binding protein C3 (MYBPC3) genes. These variants contribute to the excessive myosinactin cross bridging that underpins the clinical features of the disease [ 3 ]. Half of individuals carrying a pathogenic variant express the disease by the third decade of life [ 3 ]. Additional core pathophysiological features include diastolic dysfunction, myocardial fibrosis and microvascular

ischaemia. The classic form of LVH affects the basal ventricular septum although other segments of the left ventricle can also be affected.

The prevalence of HCM is estimated at 1:500 [ 4 ], with UK Biobank data suggesting a general population prevalence of $\mathrm{LVH}\!\ge\!15\,\mathrm{\mm}$ in $0.11\%$ in previously undiagnosed individuals [ 5 ]. With the improved diagnostic yield of tests, family screening and the availability of genetic testing the genetic prevalence is expected to be as high as 1:250 [ 6 , 7 ]. These disease-causing genetic alterations affect the structure and function of sarcomeric proteins resulting in molecular changes that cause excessive cardiac myosin–actin cross-bridging. This leads to a rise in force generation and subsequent myocardial hypercontractility [ 8 ]. A third of patients diagnosed with HCM have evidence of LV outflow tract (LVOT) obstruction at rest by the third and fourth decades of life [ 3 ]. Another third develop evidence of LVOT obstruction with exercise [ 9 ]. This is a result of the combination of the hypertrophied basal ventricular septum encroaching the LVOT, myocardial hypercontractility, and systolic anterior motion of the mitral valve into the LVOT.

Patients predominantly present with symptoms of shortness of breath, although exertional chest pain, dizziness and/or syncope are also reported. An abnormal resting LVOT pressure gradient is defined ${\sf a t}\!>\!30~\mathrm{mmHg}$ [ 2 ], however, a LVOT peak pressure gradient $\mathrm{of}\,{>}\,50\ \mathrm{mmHg}$ is used as threshold for initiating treatment with Mavacamten or alternative invasive options such as alcohol septal ablation or surgical myectomy [ 2 ]. The presence and magnitude of the LVOT obstruction is a predictor of disease progression to heart failure and mortality [ 10 ] and therefore an important indicator in this patient population.

Treatment is primarily aimed at improving quality of life in those with restricting symptoms. Treating clinicians should ensure that phenocopies of HCM that required alternative treatment modalities are ruled out [ 2 ]. Historically management of patients with symptomatic LVOT obstruction includes lifestyle advice, medications with negative inotropic effect and/or invasive septal reduction therapy. Lifestyle changes include weight reduction, avoidance of dehydration and avoidance of excessive alcohol consumption. The European Society of Cardiology recommends betablockers as first line therapy, with non- dihydropyridine calcium channel

blockers as a second line therapy if betablockers are either ineffective, poorly tolerated, or contraindicated. The next management step includes either Disopyramide or Mavacamten [ 2 ]. Septal reduction therapy with either alcohol septal ablation or surgical myectomy is reserved for patients with significant symptomatic LVOT obstruction refractory to medical therapy [ 11 ].

Mavacamten is a selective and reversible cardiac myosin ATPase inhibitor. It reduces the number of myosin heads in an active state. This shifts the overall myosin population towards an energy sparing, super-relaxed state, moving away from excessive cardiac myosin–actin cross-bridging. Mavacamten is reported to significantly reduce LVOT gradients, improve patients’ symptoms, improve exercise capacity, and reduce serum levels of N-terminal pro-type natriuretic peptide (NT pro BNP) and high sensitivity troponins [ 12 , 13 ].

Whilst Mavacamten has been shown to improve symptoms in study populations along with reduction in LVOT obstruction, data from EXPLORER-HCM and VALORHCM have shown that for up to $5\%$ of patients there will be a reduction of LV ejection fraction (LVEF) to $<50\%$ [ 12 , 13 ]. Follow up data suggested that the drop in LVEF resolved with the cessation or dose reduction of Mavacamten [ 12 ]. The MAVA-LTE study reported long term outcome up to 3years showing sustained improvements in gradients and symptoms, with low volume of transient, reversible reduction in EF [ 14 ].

Due to the potential risk of heart failure linked to drop in LVEF, recent National Institute for Clinical Excellence (NICE) guidance recommends a minimal level of safety monitoring that should be implemented where Mavacamten is used in clinical practice [ 1 ]. Echocardiography has been recommended as the diagnostic tool for the safety monitoring for patients prescribed Mavacamten. NICE guidance recommends surveillance echocardiography as per the summary of product characteristics of the medication at weeks 4, 8 and 12 post initiation of Mavacamten followed by 24 weekly echocardiograms long term. Echocardiography is also mandated 4 weeks after any dose change (see Figs. 1 , 2 ). All echocardiography data will be taken in to account at a clinical review in combination with symptoms when considering dose alterations.

Due to the high frequency of surveillance echocardiograms stipulated by NICE this document by the BSE aims

 Recommended algorithm forpatients who are normal andrapid CYP metabolisers. \*Interrupt treatment atany point ifLVEF

Fig.1

to standardise echocardiographic practice in this domain and support services in using clinically targeted echocardiograms to satisfy the requirements and allow safe monitoring for patients using Mavacamten. Mavacamten is currently the only licensed myosin inhibitor medication in the UK. There is the potential for other myosin inhibitor medications to reach the clinical space in the future. This document focusses on the use of Mavacamten as this was the focus of NICE technology appraisal guidance [ 1 ]. However, elements of this BSE protocol could be used or adapted to other myosin inhibitors if their use requires monitoring in a similar manner to Mavacamten.

## The role ofechocardiography andrecommended Mavacamten protocol

A full comprehensive echocardiographic assessment in accordance with the British Society of Echocardiography Hypertrophic Cardiomyopathy guideline [ 15 , 16 ]

should be undertaken before initiation of treatment with Mavacamten. This should be performed with the patient on standard medical treatment and will inform the next stage of treatment. In addition to a baseline echocardiogram, it is recommended that patients undergo pharmacogenomic testing in order to assess metabolic activity linked to removal of Mavacamten. (see Appendix 1 for pharmacogenomic guidance).

Several practical considerations are important when evaluating echocardiographic protocols for those on myosin inhibitors:

• The standardisation of manoeuvres used in the baseline assessment of level of LVOT obstruction detected. • The increase in volume of echocardiograms due to the high frequency of surveillance scans (see Figs. 1 , 2 , 3 and 4 ). • The standardisation of monitoring scans.

 Fig.2 Recommended algorithm forpatients who are slow/poor CYP metabolisers orwhileCYP status ispending. \*Interrupt treatment atany point ifLVEF $\scriptstyle<50\%$

The detection of LVOT obstruction can be achieved with provocation manoeuvres when not obvious at rest, aiming to alter the loading conditions and mimic the physiological circumstances under which LVOT obstruction is maximised. LVOT gradients should be assessed at rest and with Valsalva manoeuvre in the left lateral recumbent position. The CW doppler should be aligned

with the direction of forward flow and guided by colour flow Doppler [ 15 , 16 ]. It can be helpful to sweep the angle of interrogation between the LVOT and left atrium (LA) to allow for improved discrimination of LVOT gradients from mitral regurgitation Doppler profiles.

Whilst the baseline echocardiography study is expected to adhere to the full BSE protocol for Hypertrophic Cardiomyopathy [ 15 , 16 ], the surveillance scans

 Fig.3 Maintenance assessment algorithm. Echocardiography should be performed every 24weeks unless adose titration isneeded orLVEF drops $\dag{0}<\d50\%$

recommended by NICE guidance supports the concept of targeted echocardiography studies. For the purpose of consistency, the protocol of surveillance echocardiography should be reproducible, accurately recorded

and reported. The minimum dataset for a surveillance echocardiogram should include the licensing requirements for Mavacamten as they are described in NICE Guidance [ 1 ]. There are also some echocardiographic parameters that can optionally be acquired depending on specific local departmental requirements.

 Fig.4 Actions ifLVEF drops to $<50\%$ . If atany visit thepatient’s LVEF $\mathsf{i s c}_{}{<50\%}_{}$ , thetreatment should be interrupted foratleast 4weeks andonlyrestarted ifLVEF $\geq50\%$

Minimum dataset

Transthoracic echocardiography‑ fortreatment using cardiac myosin inhibitor fortreatment ofobstructive hypertrophic cardiomyopathy

![Measurement Measurement View View Modality Modality Explanation Explanation Image Image Visual assess- Visual assess- PLAX PLAX 2D 2D Parasternal long axis (PLAx) is optimised to dem- Parasternal long axis (PLAX) isoptimised todemment ment view view onstrate the best image available [15, 16] onstrate thebest image available [ 15 , 16 ] Visual assess- Visual assess- plax plax 2D and CF 2D andCF Optimise colour flow doppler (CFD) settings. Optimise colour flow doppler (CFD) settings. ment of MR ment ofMR view view doppler doppler Adjust thelateral CFD region ofinterest (ROI) Adjust the lateral CFD region of interest (ROl) to include 1 cm of the LV on the left lateral border toinclude 1cm oftheLV ontheleft lateral border and theroof of the LA on theright lateral border andtheroof oftheLA ontheright lateral border [15, 16] [ 15 , 16 ] ](https://venus-trag-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-06-20/41bb62a2-287b-42a5-a122-e5d7e6ce9888/41bb62a2-287b-42a5-a122-e5d7e6ce9888.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1750421767%3B1750425367&q-key-time=1750421767%3B1750425367&q-header-list=host&q-url-param-list=&q-signature=e3f24360a9cf10c162a74222a5c134196381587d) ![Measurement Measurement View View Modality Modality Explanation Explanation Image Image Visual assess- Visual assess- PLAX PLAX 2D 2D Place M-Mode cursor through the MV leaflet tips, Place M-Mode cursor throughtheMV leaflet tips, ment of SAM ment ofSAM view view and M-Mode andM-Mode ensuring image is on axis. Involves MV leaflets ensuring image isonaxis. Involves MV leaflets and/or chordae [15, 16] and/orchordae [ 15 , 16 ] Visual assess- Visual assess- PSAX PSAX 2D 2D Parasternal short axis window (PSAX) to demon- Parasternal shortaxis window (PSAX) todemonment ofSAM ment ofSAM view view strate best image available [15, 16] strate best image available [ 15 , 16 ] MR secondary MR secondary A4C A4C 2D CF/CW 2D CF/CW MR Quantification may be limited as the PISA MR Quantification may be limited asthePISA to SAM toSAM A3C A3C Doppler Doppler dome may merge with turbulent flow. MR second- dome may merge withturbulent flow. MR secondary to SAM is predominantly posteriorly directed ary toSAM ispredominantly posteriorly directed and originates more medial in the apical 4 andoriginates more medial intheapical 4 chamber view. If quantification assessment of MR chamber view. If quantification assessment ofMR is precluded by LVOTO, other indicators of MR isprecluded byLVOTO, other indicators ofMR severity should be considered [17]. For example, severity should be considered [ 17 ]. Forexample, an E velocity of<1.3 m/s and an E/A ratio<1 are anE velocity andanE/A ratio are strongly suggestive of non- severe MR [15, 16]. CW strongly suggestive ofnon- severe MR [ 15 , 16 ]. CW Doppler velocity from MR jet facilitates differentia- Doppler velocity fromMR jet facilitates differentiation of LVOT flow from MR in A5C tion ofLVOT flow fromMR inA5C ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-06-20/6f88b9eb-714e-4719-8773-4c3eeadca9b8/6f88b9eb-714e-4719-8773-4c3eeadca9b8.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1750421767%3B1750425367&q-key-time=1750421767%3B1750425367&q-header-list=host&q-url-param-list=&q-signature=d9019fc07d8f63e8c27e2134a8c7a54ceabca3d6) ![Measurement Measurement View View Modality Modality Explanation Explanation Image Image LV Simpson's LV Simpson’s A4C, A4C, 2D 2D LV volumes should be obtained using 2D imaging LV volumes should be obtained using 2D imaging Biplane vol- Biplane vol- A2C A2C Units: Units: from A4C and A2C [18]. Trace the endocardial fromA4C andA2C [ 18 ]. Trace theendocardial umes umes EDV mL EDV mL border. LV length is defined as the distance border. LV length isdefined asthedistance ESV mL ESV mL between the midpoint of the mitral valve level betweenthemidpoint ofthemitral valve level line and the most distal point of the LV apex. line andthemost distal point oftheLV apex. Take care to ensure the LV is not foreshort- Take care toensure theLV isnotforeshortened. Papillary muscles and trabeculations are ened. Papillary muscles andtrabeculations are excluded from the volumes and considered excluded fromthevolumes andconsidered part of the chamber.Measure at end-diastole part ofthechamber. Measure atend-diastole and end-systole.Measurementisindexed to BSA. andend-systole. Measurement isindexed toBSA. Consider LV opacification forimproved endocar- Consider LV opacification for improved endocar-dial definition. 3D assessment of the LV is a highly dial definition. 3D assessment oftheLV isahighly feasible and reproducible parameter of LV systolic feasible andreproducible parameter ofLV systolic function. Given the superiority over 2D estimates, function. Given thesuperiority over2D estimates, 3D assessment of LV volumes and LVEF is recom- 3D assessment ofLV volumes andLVEF isrecommended in cases were image quality permits mended incases were image quality permits accurate measurement. Given the additional accurate measurement. Given theadditional time involved this is not mandated where accu- time involved this isnotmandated whereaccurate LVEF can be provided by Simpson's biplane rate LVEF can be provided bySimpson’s biplane assessment. A numerical value for LVEF should assessment. Anumerical value forLVEF should be included in all echo reports. A visual estimate be included inall echo reports. Avisual estimate should be provided only when image quality should be provided onlywhenimage quality is suboptimal Simpson's biplane estimate [18] issuboptimal Simpson’s biplane estimate [ 18 ] ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-06-20/f456eef0-5b51-4f06-bba5-9d7f61f85450/f456eef0-5b51-4f06-bba5-9d7f61f85450.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1750421767%3B1750425367&q-key-time=1750421767%3B1750425367&q-header-list=host&q-url-param-list=&q-signature=d457b143a14da0fd845fd079d1d6fddd77318faf) ![Measurement Measurement View View Modality Modality Explanation Explanation Image Image LVOT gradients LVOT gradients A5C A5C CW Doppler CW Doppler For the mechanics ofperforming a Valsalva For themechanics ofperforming aValsalva 4.86m/s atrest/Valsalva atrest/Valsalva A3C A3C manoeuvre, please refer to the BSE HCM protocol manoeuvre, please refer totheBSE HCM protocol p94.59mmHg manoeuvre manoeuvre [15] [ 15 ] Assess LVOT obstruction gradients at rest, Assess LVOT obstruction gradients atrest, with Valsalva manoeuvre. Align CW Doppler withValsalva manoeuvre. Align CW Doppler through entire turbulent colour flow for peak throughentire turbulent colour flow forpeak obstruction velocity [15, 16]. Peak velocity obstruction velocity [ 15 , 16 ]. Peak velocity recordedonA5CorA3Cshouldberecorded recorded onA5C orA3C should be recorded 5.94m/s 141.14 mmHg ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-06-20/c2c00c18-6b52-47ff-8ca7-6c07773a02f0/c2c00c18-6b52-47ff-8ca7-6c07773a02f0.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1750421767%3B1750425367&q-key-time=1750421767%3B1750425367&q-header-list=host&q-url-param-list=&q-signature=5f7d41218671062c10f941a9ee205ae805d84f06) Optional measurements

![Measurement Measurement View View Modality Modality Explanation Explanation Image Image LV GLS Measurement LV GLS Measurement A4C A4C LV GLS LV GLS Optimal ECG signal withminimal Optimal ECG signal with minimal A3C A3C heart rate variability should be pre- heart rate variability should be preA2C A2C sent across the three cardiac cycles. sent acrossthethree cardiac cycles. Heart rate variability will limit Heart rate variability will limit the circulation of GLS values, which thecirculation ofGLS values, which can be problematic inpatients can be problematic in patients with atrial fibrillation. High -quality withatrial fibrillation. High -quality acquisition, maintaining a frame acquisition, maintaining aframe rate of 40-90 frames/sat a normal rate of40–90 frames/sat anormal heart rate is key [18] heart rate iskey [ 18 ] Clear endocardial and epicardial Clear endocardial andepicardial definition is required to ensure definition isrequired toensure adequate segmental tracking adequate segmental tracking throughout the cardiac cycle. throughoutthecardiac cycle. Markers are placed in each Markers are placed ineach of the respective basal and apical oftherespective basal andapical regions, using automatic tracking regions, using automatic tracking where possible to maintain repro- wherepossible tomaintain reproducible results. Automatic tracking ducible results. Automatic tracking should be combined withvisual should be combined with visual assessment of tracking in each assessment oftracking ineach view across the whole ROl, includ- view acrossthewhole ROI, including the endocardial and epicardial ingtheendocardial andepicardial border. If more than two seg- border. If more thantwo segments in more than one view are ments inmore thanone view are not adequately tracked, the calcula- notadequately tracked, thecalculation of GLS should be avoided [18] tion ofGLS should be avoided [ 18 ] GS=-18.5% GS=-18.5% ANTSE SE ANT 1 INF _AT ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-06-20/e4be7964-ff54-4e0f-8bd5-8c6c28f1e7ac/e4be7964-ff54-4e0f-8bd5-8c6c28f1e7ac.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1750421767%3B1750425367&q-key-time=1750421767%3B1750425367&q-header-list=host&q-url-param-list=&q-signature=c249f286634af47f47dc030727c1e9e255923751) ![Measurement Measurement View View Modality Modality Explanation Explanation Image Image LA strain LA strain A4C A4C LA Strain LA Strain When acquiring images for LA When acquiring images forLA A2C A2C strain analysis, dedicated atrial strain analysis, dedicated atrial windows should be acquired windows should be acquired to maximum LA volume. LA strain tomaximum LA volume. LA strain analysis in views that are optimised analysis inviews thatare optimised for the LV therefore forshorten- fortheLV therefore forshortening leads to overestimation of LA ing leads tooverestimation ofLA values [19] values [ 19 ] TDI velocities TDI velocities A4C A4C PW TDI PW TDI Place sample volume (5-10 mm) Place sample volume (5-10mm) Septal Septal at or within 1 cm of the inser- atorwithin 1cm oftheinser- E'Sept0.05m/s and lateral andlateral tion of the mitral valve leaflets. tion ofthemitral valve leaflets. walls walls Measure at the end of expiration. Measure attheend ofexpiration. Units: cm/s Units: cm/s Scale and sweep speed optimised Scale andsweep speed optimised (100 mm/s) [18]. ( [ 18 ]. e': Peak velocity at the leading e’: Peak velocity attheleading edge of spectral wave form in early edge ofspectral wave form inearly diastole (after T wave).If possible diastole (after T wave). If possible average both septum and lateral average bothseptum andlateral wall measurements wall measurements S': Peak systolic Velocity S’: Peak systolic Velocity Limitation: this measure assumes Limitation: this measure assumes that the function of these two thatthefunction ofthese two segments represents longitudinal segments represents longitudinal function of the entire ventricle, this function oftheentire ventricle, this is unlikely in conditions that result isunlikely inconditions thatresult in regional wall motion abnormali- inregional wall motion abnormalities [18]. ties [ 18 ]. Place sample volume (1-3 mm) Place sample volume (1–3mm) at level of the MV leaflet tips in dias- atlevel oftheMV leaflet tips indiastole. Use of CFD can help to align tole. Use ofCFD can help toalign the centre of trans-mitral flow. thecentre oftrans-mitral flow. Measure at end expiration. Emax: Measure atend expiration. Emax: peak velocity in early diastole. peak velocity inearly diastole. Amax: peak velocity inlate diastole Amax: peak velocity in late diastole (after P wave). DT: Flow decelera- (after P wave). DT: Flow deceleration time from peak E wave to end tion time frompeak E wave toend of E wave signal [18]. ofE wave signal [ 18 ]. PW doppler mitral PW doppler mitral A4C MV A4C MV EV max AV EV max AV Obtain RV focussed view.From Obtain RV focussed view. From inflow inflow (PWD) (PWD) max E/A max E/A A4C view slide and/or angu- A4C view slide and/oranguratio DT ratio DT late thetail ofthetransducer late the tail of the transducer along the horizontal plane to place alongthehorizontal plane toplace the RV in the centre of the image theRV inthecentre oftheimage (instead oftheconventional (instead of the conventional left heart-centred image) whilst left heart-centred image) whilst ensuring that the LV outflow tract ensuring thattheLV outflow tract does not come into view. This does notcomeinto view. This allows the RV free wall to be clearly allows theRV free wall tobe clearly seen. Next, rotate the transducer seen. Next, rotate thetransducer to obtain the maximum diameter toobtain themaximum diameter [18] [ 18 ] ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-06-20/65d0ef2b-1009-4fd0-9c07-e81c40cfb670/65d0ef2b-1009-4fd0-9c07-e81c40cfb670.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1750421767%3B1750425367&q-key-time=1750421767%3B1750425367&q-header-list=host&q-url-param-list=&q-signature=47ddca5c7acbe3445b5cfd30bd955d4046844a49) |eral tricuspid or mitral annulus ||| |---|---|---| | to maximise longitudinal motion | to maximise longitudinal motion || | of the annulus. Measurement ||| |||| | ment taken at the lateral tricuspid||| |||| |||| |||| | by conditions such as RV infarction|||

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

Minimum dataset forTTE forpatients withobstructive 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| |AP4C| Simpsons and for GLS (GLS is optional) | |AP4C|| |AP4C| 2D and focused LA for LA strain (optional) | |AP4C|Colour Flow Doppler of MV| || CW Doppler for MR PW Doppler for Mitral inflow/TDI velocities at LV septal/lateral regions (Optional) | ||| |AP5C|2D| |AP5C|| |AP5C|Colour Doppler for LVOT| || CW Doppler for LVOT resting/Val- salva | |AP2C|2D and focused for Biplane| |AP2C|Simpsons and for GLS (GLS optional)| |AP2C| 2D and focused LA for LA strain (optional) | |AP2C| Colour Doppler for MR Optional RV assessment recom- mended at week 12- 2D, CW doppler ofTV, TR CW doppler, TAPSE, | |AP2C| Colour Doppler for MR Optional RV assessment recom- mended at week 12- 2D, CW doppler ofTV, TR CW doppler, TAPSE, | |AP3C|| |AP3C|Valsalva with CW for LVOT| |AP3C|Colour Doppler for MR| |AP3C| Colour Doppler for LVOT, 2D for GLS (Optional) | |AP3C||

Contrast echocardiography/ultrasound enhancing agents

Suboptimal endocardial border definition can lead to errors in LV volume and LVEF estimation. Accurate LVEF

assessment is essential during surveillance of patients being treated with Mavacamten, when values obtained fall on boundaries this may influence treatment decisions. The BSE recommend that contrast is used when two or more segments cannot be visualised [ 24 ]. LV volumes in both systole and diastole are greater when measured using contrast agents than without as tracing of the LV borders more reliably leads to inclusion of trabeculation within the cavity. Minimal detectable difference for 2D contrast LVEF has been noted to be in the order of $4\%$ in comparison to $9–11\%$ for non-contrast 2D LVEF [ 25 ]. The use of contrast can have unpredictable effects on 2D speckle tracking, therefore it is recommended the use of contrast is given after strain acquisition [ 26 ]. If a contrast agent is required, it is recommended the BSE contrast Echocardiography: Practical guideline is adhered to [ 24 ].

Stress echocardiography

Exercise stress echocardiography may be required as part of standard of care for those symptomatic patients without obvious gradients at rest or with Valsalva (gradients $<50~\mathrm{\mmHg}$ ). Stress Echocardiography using a treadmill or bike is recommended in patients with HCM, dobutamine infusion is not used as this is known to produce increased outflow Doppler velocities in normal hearts. If exercise stress echo is required please refer to

the stress protocol within the BSE Hypertrophic Cardiomyopathy guidelines [ 15 , 16 ]. Stress echocardiography is not recommended as part of routine surveillance for Mavacamten therapy.

Conclusion

Mavacamten is the first licensed cardiac myosin-inhibitor. Due to the potential for excessive reduction in LVEF [ 12 , 13 ] surveillance of LV function is mandatory [ 1 ]. Echocardiography is a key imaging modality in the initial assessment and subsequent monitoring of patients treated with Mavacamten. High quality LVEF assessment is vital along with accurate LVOT gradient acquisition, including assessment with Valsalva manoeuvre. These assessments are essential and are key when optimising and monitoring safety in patients treated with Mavacamten. Additional key echocardiographic indices can also be assessed at Mavacamten surveillance echocardiography 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.

Appendix1

Prior to initiation of Mavacamten, it is recommended that patients undergo pharmacogenomic testing in order to assess metabolic activity linked to removal of Mavacamten. As Mavacamten is metabolised through the hepatic enzymes CYP2C19 $(74\%)$ , CYP3A4 $(18\%)$ and CYP2C9 $(7.65\%)$ genotyping of CYP2C19 is required to guide Mavacamten therapy and dosing. Depending on results, patients will be characterised as rapid, normal, intermediate or poor (slow) metabolisers. Those patients who are “poor” metabolisers have the risk being exposed to higher than intended doses of Mavacamten (due to reduced clearance) therefore adjustments need to be made during dose titration [ 27 ]. In the situation where there may be a delay gaining access to CYP status patients may be initiated at a low dose of $2.5\;\mathrm{mg}$ until CYP status is known.

Author contributions

CM.C. is the primary author of this manuscript, RM.C provided expert oversight and guidance. RM.C, D.A., CJ.C., I.A., K.P., A.P., W.B., L.T., W.M., L.W., R.B., J.D. and DL.O, all subsequently reviewed the manuscript and after revising it critically, were involved in re-drafting the manuscript, before giving it their final approval for its submission. There has been no funding received for this manuscript.

Funding

This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate Not applicable.

Consent for publication Not applicable.

Competing interests

The authors declare no competing interests.

Author details

1Liverpool Heart andChest Hospital, Thomas Drive, LiverpoolL14 3PE, UK. 2Royal United Hospitals Bath NHS Foundation Trust, Bath, Bath, UK. 3Uni-versity ofBath, Bath, UK. 4Queen Elizabeth University Hospital, Glasgow, UK. 5Manchester University NHS Foundation Trust, Manchester, UK. 6Royal Brompton andHarefield Hospital, London, UK. 7University Hospital Birming-ham, Birmingham, UK. 8Queen Elizabeth Hospital Birmingham, Birmingham, UK. 9Royal Papworth Hospital, London, UK. 10Guys andSt Thomas Hospital, London, UK. 11Sports andExercise Sciences, Liverpool John Moores University, Liverpool, UK.

Received: 18 November 2024 Accepted: 29 April 2025

References

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