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Case of biventricular hypertrophy and biventricular failure. Hypertrophy often indicates some degree of diastolic dysfunction with altered filling properties and compliance of the ventricles. As such, these patients are susceptible to increased heart rate, during which the filling time is impaired.
NH-TNE Teaching on Cardiac Hypertrophy
NH-TNE Teaching on Cardiac Hypertrophy
May 6, 2025
Case of a newborn with biventricular hypertrophy and biventricular dysfunction (systolic)
Case of a newborn with biventricular hypertrophy and biventricular dysfunction (systolic)
Sweep in parasternal long axis outlining that the aortic and pulmonary valve are opening and closing (no atresia - anatomical or functional)
Parasternal short axis outlining the biventricular hypertrophy. The RV seems to be "rocking" and with poor systolic contraction. The septum is dyskinetic with paradoxical movements. The LV free wall also appears to have areas of regional dysfunction.
Case of LV hypertrophy
Case of LV hypertrophy
In this patient, there is systolic anterior motion of the mitral valve - an indicator of LV hypertrophy. There is intra-cavitary acceleration of flow by colour. There is mitral regurgitation. The estimated peak LV pressure in systole is up to 84 mmHg by CW-Doppler.
LV hypertrophy in parasternal long axis with septal hypertrophy
Some degree of systolic anterior motion of the mitral valve. Septal hypertrophy.
Some dynamic obstruction secondary to the septal hypertrophy
Intra-cavitary acceleration with mitral insufficiency.
CW-Doppler estimating the peak systolic LV pressure by mitral insufficiency and capturing some of the intra-cavitary acceleration.
Mitral insufficiency - possibly secondary to the distortion of the mitral apparatus due to the LV hypertrophy. One may also appreciate some degree of RV hypertrophy.
Still frames in the context of significant hypertrophy
Still frames in the context of significant hypertrophy
LV inflow CW-Doppler with some Dagger-Shaped negative signal obtained from the ejection phase towards the LVOT, outlining intra-cavitary acceleration and dynamic obstruction.
Biventricular hypertrophy appreciated in diastole.
E/A (two measurements) outlining impaired relaxation from the hypertrophy where A is much higher than the E velocity.
Hypertrophy at mid-papillary muscle level in PSAX. We can appreciate that the pillar are hypertrophied, as well as there is circumferential hypertrophy. We can appreciate in diastole and systole.
Below - still frames of the flow into the LV cavity showcasing the acceleration from inflow to outflow tract. However, we can appreciate that there is flow from below the LVOT feeding post-aortic valve the ascending aorta.
M-Mode showcasing hypertrophy in the PLAX. We can also appreciate some SAM in systole.
PLAX zoom in the LVOT - flow accelerated just below the aortic valve but passing through the LVOT. This is because of dynamic obstruction within the cavity during contraction.
Case of a newborn on high dose dexamethasone who developed biventricular hypertrophy
Case of a newborn on high dose dexamethasone who developed biventricular hypertrophy
Short axis with significant circumferential hypertrophy of the LV, as well as some hypertrophy of the papillary muscles
Parasternal long axis outlining LV hypertrophy and septal hypertrophy.
3D volumes showing circumferential hypertrophy
Acceleration in the LV outflow tract (dynamic sub-aortic acceleration from the septal hypertrophy). There is pseudo (incomplete) systolic anterior motion of the mitral valve. There is also some degree of RV hypertrophy.
Tilted 4 chamber view to evaluate the LVOT with a posterior sweep showing that the papillary muscles are hypertrophied.
Nyquist (velocity filter) at 148 cm/s. Less aliasing but still some subjective acceleration at the LVOT. The LVOT is narrowed from the dynamic contraction of the septum and some degree of pseudo-SAM (systolic anterior motion of mitral valve).
Focus and zoom on the LVOT
LVOT view. Filling seems preserved in diastole.
Intracavitary acceleration at a Nyquist of 92.4 cm/s.
Intra-cavitary acceleration with some degree of mild mitral insufficiency.
The RV hypertrophy is appreciated in this tilted 4 chamber view with some RV focus.
Parasternal long axis. One with a zoom on the LVOT / Aortic valve. The other one with colour showing some mitral regurgitation.
Parasternal long axis. One with a zoom on the LVOT / Aortic valve. The other one with colour showing some mitral regurgitation. One may also appreciate some degree of RVOT free wall hypertrophy.
Some images below (frozen) showing some pseudo-systolic anterior motion of the mitral valve, associated with mitral regurgitation and some acceleration in the left ventricular outflow tract.
Case of severe hypertrophic cardiomyopathy
Case of severe hypertrophic cardiomyopathy
Significant hypertrophy appreciated from the parasternal long axis view. The hypertrophy is septal and at the level of the LV free wall. The LV cavity is almost completely obliterated.
Colour clips indicating acceleration of flow in the out flow tract.
Seep in the parasternal long axis with colour. The RV may be seen with some degree of hypertrophy and filling by colour.
Parasternal short axis view outlining the significant hypertrophy.
Another sweep in the parasternal short axis view. The Aortic valve may be seen. It seems to open and close and be tri-leaflet.
Significant hypertrophy observed in the apical 4 chamber view. There is "kissing" ventricular walls.
There is mitral insufficiency by colour flow.
Acceleration of flow at the level of the LV outflow tract. There is filling of the aorta with flow that seems to originate from below the valve (not retrograde from the ductus)
There is some degree of RV hypertrophy with some tricuspid insufficiency and intra-cavitary acceleration by colour (although the Nyquist is at 61 cm/s)
This view outlines well the biventricular hypertrophy with the significant septal hypertrophy.
Subcostal view.
Subcostal short axis view. Outlining the RVOT with flow through the pulmonary valve.
Flow may be seen in the descending aorta.
Inflow PW-Doppler.
M-Mode in the parasternal long axis view outlining the significant hypertrophy of the septum and the posterior wall.
LV Intra-cavitary peak gradient of at least 81 mmHg estimated by CW-Doppler
RV Intra-cavitary peak gradient of at least 33 mmHg estimated by CW-Doppler. The “Dagger-Shaped” Doppler Signal.
The “Dagger-Shaped” Doppler Signal: A Marker of Dynamic Muscular Obstruction
The “Dagger-Shaped” Doppler Signal: A Marker of Dynamic Muscular Obstruction
On spectral Doppler echocardiography, a distinctive dagger-shaped waveform is a hallmark of dynamic muscular obstruction, typically seen in the ventricular outflow tracts.
This curved, late-peaking Doppler envelope reflects a progressive acceleration of blood flow due to dynamic narrowing during systole, most commonly observed in:
Left ventricular outflow tract (LVOT) obstruction in hypertrophic cardiomyopathy (HCM), where systolic anterior motion of the mitral valve and septal hypertrophy produce a characteristic dagger-shaped spectral profile.
Right ventricular outflow tract (RVOT) obstruction, particularly in infants with unrepaired Tetralogy of Fallot (TOF). Here, continuous-wave Doppler may reveal:
A curved dagger-like contour, indicating dynamic muscular obstruction.
A triangular contour, typically reflecting fixed obstruction at the pulmonary valve level.
Recognizing this spectral morphology is essential, as it helps differentiate dynamic intramyocardial obstruction from fixed anatomical stenosis and can guide clinical interpretation in both congenital and acquired cardiac conditions.
Dagger-Shaped in the LV cavity CW-Doppler.
TR of 37 by CW-Doppler
Measurement of the septum by 2D (B-mode) Echocardiography
Case of septal hypertrophy in the context of infant of diabetic mother
Case of septal hypertrophy in the context of infant of diabetic mother
Parasternal long axis outlining the biventricular hypertrophy, with some septal hypertrophy.
Parasternal short axis outlining the biventricular hypertrophy, with some septal hypertrophy. There is flattening of the interventricular septum at the peak of systole.
Apical 4 chamber view. There is subjective paradoxical movement of the septum, although this view is not the most optimal to appreciate that.
Colour box outlines the tricuspid regurgitant jet. There is also flow going through the LVOT to the aorta.
5 chamber view (tilted)
The patent ductus arteriosus is bidirectional, right to left in systole.
Inter-atrial communications that are mainly left to right.
Subcostal view. one may appreciate that the blood flow is going through the aortic valve to the ascending aorta, at the level of the LVOT.
Right Ventricular Hypertrophy
Right Ventricular Hypertrophy
Systolic Anterior Motion of the Mitral Valve
Systolic Anterior Motion of the Mitral Valve
See more in Example case of hypertrophic cardiomyopathy (HOCM)
SAM in dynamic left ventricular outflow tract (LVOT) obstruction results from a combination of the Venturi effect (upper right) and drag forces (lower right). In hypertrophic cardiomyopathy, the mitral valve leaflets are elongated and abnormally anteriorly displaced (increased α angle), making drag forces the dominant mechanism driving leaflet motion toward the septum. Inspired from reference: Geske, Jeffrey B., et al. "Septal reduction therapies in hypertrophic cardiomyopathy: comparison of surgical septal myectomy and alcohol septal ablation." Interventional cardiology 6.2 (2014): 199.
Presentation of DrsJuliana Quintero Salazar & Pasinee Kanaprach on management of IDM-related hypertrophy
Presentation of DrsJuliana Quintero Salazar & Pasinee Kanaprach on management of IDM-related hypertrophy
HOCM 2.pdfManagement of Neonatal Shock Secondary to Hypertrophic Obstructive Cardiomyopathy
Management of Neonatal Shock Secondary to Hypertrophic Obstructive Cardiomyopathy
Below, we address strategies regarding newborns who develop a low–cardiac output state driven by dynamic left ventricular outflow tract (LVOT) obstruction in the setting of poor left ventricular filling due to significant cardiac hypertrophy, leading to systemic hypoperfusion. The content emphasizes physiologic stabilization, careful preload optimization, avoidance of inotropic strategies that exacerbate obstruction, heart-rate control, afterload support, and the role of targeted neonatal echocardiography to guide real-time decision-making and monitor response to therapy. Of course, these concepts must be individualized to the clinical context and integrated into a holistic evaluation and management approach, ideally within a multidisciplinary team. Management requires frequent reassessment and continuous evaluation of the physiologic response, with particular attention to avoiding polypharmacy and potentially detrimental side effects. The judicious use of any medication or strategy should always be guided by careful bedside assessment, grounded in a clear understanding of the underlying physiology and the infant’s dynamic response to the treatment plan.
Managing a newborn with Hypertrophic Obstructive Cardiomyopathy (HOCM) and hemodynamic instability is a high-stakes balancing act. Unlike typical neonatal shock, the goal here is not to increase contractility, but rather to reduce obstruction and optimize diastolic filling, leading to improved systemic output. In HOCM, one of the issues is Systolic Anterior Motion (SAM) of the mitral valve, where the valve is sucked into the narrowed Left Ventricular Outflow Tract (LVOT) during systole, causing a dynamic obstruction. Another concern is the decreased left ventricular compliance, leading to raised LV end-diastolic pressure and possibly post-capillary pulmonary hypertension (this can present with significant pulmonary edema, and left to right restrictive inter-atrial shunting - depending on presence/size of the defect). These patients may present with pulmonary venous congestion.
Strategies
Preload Management
Goal: Keep the ventricle "full" to stent the LVOT open.
Purpose: Increasing the end-diastolic volume physically pushes the septum and mitral valve apart, reducing the degree of obstruction.
Advantage: Most "physiologic" way to reduce the gradient without using drugs.
Watch for: Over-distension leading to pulmonary edema, though these patients usually require higher-than-normal filling pressures (CVP 8–12 mmHg).
Judicious use of fluid bolus and maintenance fluid. While it is reasonable to avoid dehydration, excessive fluid administration can be detrimental as well. Some of these infants are infants of diabetic mother and are already on a supra-physiological total fluid intake due to the high glucose intake required to maintain normoglycemia.
Vasopressors (Increasing Systemic Afterload)
Agents: Phenylephrine, Vasopressin (sometimes norepinephrine = although it may have the undesirable side effect of increasing chronotropy and, as such, less favoured)
Purpose: To increase Systemic Vascular Resistance (SVR). A higher afterload "back-pressures" the LVOT, helping to keep it open. It also delays LVOT opening which allows to increase modestly the filling time.
Advantage: Phenylephrine is a pure alpha-agonist; it slows the heart rate (reflexively) and increases afterload without increasing contractility. Vasopressin is excellent for hypotension without affecting the heart rate or inotropy. Vasopressin may increase the risk of hyponatremia (theoretically), that can be present especially in infants of diabetic mother exposed to high total fluid intake due to glucose issues.
Watch for: Excessive vasoconstriction leading to decreased organ perfusion or gut ischemia.
Theoretical/physiological concepts related to increasing SVR in HOCM with hemodynamic instability:
Neonates with HOCM have markedly hypertrophied, poorly compliant ventricles that can “over‑empty” when systemic pressure is low, worsening LVOT obstruction.
If LV end‑systolic pressure exceeds aortic root pressure, the ventricle may nearly empty, pulling the septum/anterior leaflet into the LVOT and increasing the gradient.
Raising systemic vascular resistance (SVR) and aortic pressure with vasoconstrictors (phenylephrine, vasopressin) increases LV afterload, increases end‑systolic volume, and can reduce the dynamic component of LVOT obstruction—an established principle from adult HOCM applied to neonates.
In reported neonatal series, vasopressin increased systolic/mean/diastolic BP, reduced heart rate and oxygen requirement, and echocardiography showed reduced LVOT gradient after afterload augmentation.
Increasing systemic vascular resistance (SVR) raises arterial blood pressure, which may reduce sympathetic drive through baroreceptor-mediated feedback, leading to a decrease in heart rate. The resulting prolongation of diastole can enhance left ventricular filling.
Effects on pulmonary and ductal flow
Some infants with HOCM often have high pulmonary vascular resistance and a large ductus with right‑to‑left shunt, limiting LV preload.
Increasing SVR raises the SVR:PVR ratio, augmenting the transductal pressure gradient, promoting left‑to‑right ductal flow, higher pulmonary blood flow, and better left‑atrial filling, which further improves LV filling and can lessen obstruction.
Neonatal tolerance of higher afterload
Because the hypertrophied neonatal LV has increased muscle mass, it may tolerate or even benefit from higher afterload, unlike the normal immature myocardium where high afterload often depresses output.
In a hypertrophied ventricle, increased wall thickness reduces wall stress for a given pressure: Wall stress ∝ (Pressure × Radius) / (2 × Wall thickness). With greater wall thickness, the LV can generate higher pressure with less myocardial stress per fiber. This makes the ventricle more efficient at handling increased afterload.
References:
Boyd SM, Riley KL, Giesinger R, McNamara P. Use of vasopressin in neonatal hypertrophic obstructive cardiomyopathy: case series. J Perinatol. 2020 Sep 19;40(12):1815–22.
Loomba R, Flores S, Bronicki RA. Vasopressin in neonatal hypertrophic cardiomyopathy: do perceived benefits translate to clinical outcome? J Perinatol. 2021 Feb 18;41(5):1243–5.
Hiroyama M, Wang S, Aoyagi T, Oikawa R, Sanbe A, Takeo S, et al. Vasopressin promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor in neonatal mice. Eur J Pharmacol. 2007 Mar 22;559(2–3):151–9.
Giesinger R, Boyd SM, Rios D, McNamara P. Towards optimization of cardiovascular stability in neonates with hypertrophic cardiomyopathy: uniqueness of the neonatal cardiovascular system. J Perinatol. 2021 Jan 28;41(5):1246–8.
Nakamura Y, Haneda T, Osaki J, Miyata S, Kikuchi K. Hypertrophic growth of cultured neonatal rat heart cells mediated by vasopressin V1A receptor. Eur J Pharmacol. 2000 Mar 10;395(3):263–9.
Beta-Blockers
Agents: Esmolol (acute/titratable), Propranolol (maintenance).
Purpose: To decrease heart rate (increasing diastolic filling time). However, they may have some inherent negative inotropy properties. While this can reduce the "venturi effect" that causes SAM, it can also lead to altered ventricular function (especially if there is concomittant RV dysfunction in the context of high PVR status).
Advantage: Esmolol is short-acting and can be turned off quickly if the baby decompensates.
Watch for: Bradycardia and hypotension. Beta-blockers are contraindicated if there is overt low-output heart failure without significant LVOT obstruction. It is also agents that can induce bronchospasm.
Ventilation and Sedation
Purpose: To reduce the work of breathing and metabolic demand.
Strategy: Maintain high-normal CO2 to avoid tachycardia. Positive Pressure Ventilation (PPV) should be used carefully, as high mean airway pressures can decrease preload (venous return), which worsens HOCM.
Sedation and analgesia (especially with agents like dexmedetomidine) should be considered to reduce metabolic demand and heart rate, avoid increase adrenergic stimulation such as with crying. Release of catecholamines will increase contractility, worsening the obstruction, and increase heart rate (decreases filling time)
What to Avoid: Inotropes
Agents: Epinephrine, Dobutamine, Dopamine (and even Norepinephrine if you have access to other vasopressors without chronotropic effect).
The Rationale: These should generally be avoided or used with extreme caution because of their increasing heart rate capacity.
The Danger: Increasing contractility (positive inotropy) or heart rate (positive chronotropy) worsens the LVOT obstruction and SAM, creating a "spiral" where the harder the heart pumps, the less blood actually leaves the ventricle.
Norepinephrine: While it has alpha effects, its beta-1 activity can worsen the gradient. Only use if SVR is dangerously low and phenylephrine/vasopressin is insufficient.
Milrinone:
In the context of severe HOCM with hemodynamic instability, milrinone is generally avoided and should be approached with caution. Milrinone is an "inodilator"—it increases contractility (inotropy) and decreases systemic vascular resistance (vasodilation). In a HOCM patient, both of these actions are less desirable. Strengthening the ventricular squeeze increases the velocity of blood through the narrow LVOT. This creates a stronger Venturi effect, which pulls the mitral valve into the septum (SAM), worsening the obstruction. Dropping the systemic blood pressure by reduction of SVR and LV afterload can reduce the "back-pressure" that helps keep the LVOT open (and make the LVOT open earlier limiting filling time). A lower afterload allows the ventricle to empty more forcefully and completely, which makes the obstruction more severe.
Milrinone is also a lusitropic agent that improves relaxation - which is the only potential benefit in this physiology. However, this benefit is almost always outweighed by the risks of increased SAM and hypotension. Despite the risks, Milrinone is sometimes considered in very specific, complex neonatal cases (such as an infant of a diabetic mother with HOCM and concurrent PPHN). If used, it is almost always paired with a Beta-blocker (like Esmolol) to counteract the increased contractility and heart rate, as well as with a vasopressor (vasopressin or phenylephrine) while still getting the benefits of relaxation (diastolic lusitropy).
PGE
In the context of severe HOCM, Prostaglandin E1 (PGE1) is not typically a first-line therapy because HOCM is an intramyocardial structural disease, not a classic "ductal-dependent" lesion. However, in a newborn with hemodynamic collapse, its role is nuanced and depends entirely on the secondary consequences of the hypertrophied muscle. If the hypertrophy is so massive that it causes Critical Left Ventricular Outflow Tract (LVOT) Obstruction, the baby may present exactly like a "Left-Sided Obstructive Lesion" (e.g., Critical Aortic Stenosis). PGE1 can be used to maintain systemic perfusion via the Ductus Arteriosus (Right-to-Left shunting). If the LV cannot pump blood past the obstruction to the body, a patent ductus allows the Right Ventricle (RV) to take over systemic circulation.
The "RV Pop-off": In cases where HOCM is associated with severe Pulmonary Hypertension (PPHN), keeping the ductus open acts as a "pressure-relief valve" for the RV, preventing right-sided heart failure.
If the LVOT is significantly obstructed by the septum and SAM, the baby will die of cardiogenic shock without a ductus to provide systemic blood flow.
As such, it can buy time to start Esmolol, vasopressor therapy and/or volume resuscitation.
The Risks: Vasodilation - PGE1 is a potent systemic vasodilator. As discussed with Milrinone, dropping SVR is not desirable in HOCM. If the ductus is open but the SVR drops too low, it can worsen the LVOT obstruction and "steal" blood away from the coronary arteries. Like all neonates on PGE1, there is a high risk of apnea requiring intubation. You can also get hypotension from the drug's direct effect, which then triggers tachycardia—and tachycardia is the enemy of HOCM filling
Pulmonary Vasodilators (iNO)
Use with extreme caution, or not at all.
Purpose: To treat concomittant pulmonary hypertension.
The Risk: Inhaled Nitric Oxide (iNO) reduces Right Ventricular (RV) afterload. This can increase venous return to the left atrium, which is good, but it can also decrease the "splinting" effect the RV has on the septum, potentially worsening LVOT obstruction. It will promote left to right shunting at the ductal level, while many of these patients need some degree of right to left shunting if there is insufficient systemic flow due to the dynamic LVOT obstruction and reduction in LVO.
Verdict: Generally avoided unless there is documented, severe PPHN that is the primary driver of instability. If the PFO is left to right, it informs that the LA pressure is higher than the RA pressure, and as such iNO should be avoided.
ECMO (The Last Resort)
Purpose: To provide total circulatory support when medical management fails to relieve the LVOT gradient or maintain perfusion.
VA-ECMO Unloads the heart and ensures end-organ perfusion.
Hypertrophic Cardiomyopathy: Persistent and Genetic Forms
Hypertrophic Cardiomyopathy: Persistent and Genetic Forms
Transient myocardial hypertrophy can occur in infants exposed to maternal diabetes or corticosteroids and in recipient twins affected by twin–twin transfusion syndrome. Hypertrophy associated with systemic hypertension represents a response to increased ventricular loading and should be distinguished from primary hypertrophic cardiomyopathy (HCM).
Persistent hypertrophy warrants investigation for sarcomeric disease, RASopathies such as Noonan syndrome, Costello syndrome, and Noonan syndrome with multiple lentigines (formerly LEOPARD syndrome), as well as metabolic and mitochondrial disorders. The underlying diagnosis influences prognosis and treatment; metabolic disease should not automatically be considered irreversible.
Treatment is guided by symptoms, ventricular function, and the presence of left ventricular outflow tract (LVOT) obstruction. Conventional medications primarily relieve symptoms and improve hemodynamics. Symptom control does not replace assessment of sudden cardiac death risk.
Beta-blockers
Nonvasodilating beta-blockers are first-line therapy for symptoms attributable to LVOT obstruction. Options include propranolol, atenolol, and metoprolol, depending on age and clinical circumstances. Monitor heart rate, blood pressure, fatigue, and treatment tolerance. Cardioselectivity is not required; avoiding vasodilating agents is the relevant distinction in obstructive physiology.
Verapamil
Verapamil may be considered when beta-blockers are ineffective or not tolerated. Its negative chronotropic and inotropic effects may improve filling and symptoms.
Verapamil is potentially harmful in infants younger than 6 weeks and in patients with hypotension, severe dyspnea at rest, or very high resting LVOT gradients, such as >100 mmHg. It should not be described as routinely safe in neonates.
Disopyramide
Disopyramide is a class Ia antiarrhythmic with substantial negative inotropic effects. It may be added to an atrioventricular nodal blocking agent for persistent symptoms associated with LVOT obstruction. Pediatric evidence is mainly observational.
In a retrospective cohort of 51 children, 33 of 38 previously symptomatic patients reported improvement at 6 months, and 12 became asymptomatic. The maximal LVOT gradient did not change significantly. Seven of the 33 initial responders subsequently underwent septal myectomy during follow-up. These findings support potential symptomatic benefit but do not establish prevention of disease progression or a consistent reduction in obstruction.
An accompanying beta-blocker or appropriate nondihydropyridine calcium channel blocker limits the risk of rapid atrioventricular conduction during atrial arrhythmias. ECG surveillance is required because disopyramide can prolong QTc.
Ivabradine
Ivabradine inhibits the sinoatrial I_f current, lowering heart rate without a direct negative inotropic effect. It has no established role in treating pediatric or neonatal obstructive HCM and should not be presented as an alternative to disopyramide for reducing LVOT obstruction.
Its US pediatric indication is stable symptomatic heart failure due to dilated cardiomyopathy in children aged ≥6 months who are in sinus rhythm with an elevated heart rate. This indication should be kept separate from HCM management.
Surgical septal myectomy
Septal myectomy is an established treatment for symptomatic obstructive HCM despite appropriate medical therapy. Selected children and young adults with very high resting gradients may merit earlier intervention. Decisions and procedures should involve an experienced multidisciplinary HCM center.
Cardiac Myosin Inhibitors
Cardiac myosin inhibitors reduce the number of force-generating actin–myosin interactions, decreasing myocardial hypercontractility and dynamic LVOT obstruction. Their clinical benefits must be balanced against the risk of excessive reduction in systolic function.
Mavacamten (Camzyos)
Mavacamten is an oral, selective, reversible cardiac myosin inhibitor. US approval: Initially approved for adults in 2022. On September 30, 2026, the FDA expanded the indication to adults and pediatric patients weighing ≥30 kg with symptomatic obstructive HCM, to improve functional capacity and symptoms. The pediatric evidence includes SCOUT-HCM, which enrolled 44 adolescents aged 12 to <18 years. Safety and effectiveness have not been established in pediatric patients weighing <30 kg. Pivotal adult evidence: In EXPLORER-HCM, 251 adults were randomized to mavacamten or placebo. At 30 weeks, 37% versus 17% met the composite exercise-capacity and functional-class endpoint. Mavacamten also improved symptoms and reduced the post-exercise LVOT gradient, with a between-group difference of approximately 36 mmHg. This is an absolute pressure difference, not a percentage reduction.
Dosing and safety:
Use the current prescribing algorithm, including its separate adult and pediatric instructions. Dose selection depends on echocardiographic findings and interacting medications.
Echocardiographic assessment is required before and during treatment. Initiation with LVEF <55% is not recommended; interrupt treatment if LVEF falls below 50% or clinical status worsens.
Strong CYP2C19 inhibitors and moderate-to-strong CYP2C19 or CYP3A4 inducers are contraindicated. Other interacting drugs may require dose adjustment and additional monitoring.
Additive negative inotropic effects require careful review of concomitant medications.
Mavacamten carries a boxed warning for heart failure and is supplied through a REMS program in the United States.
Embryofetal toxicity and contraceptive counseling are relevant considerations for patients of reproductive potential.
Aficamten (Myqorzo)
Aficamten is an oral, selective, reversible cardiac myosin inhibitor. Its shorter half-life relative to mavacamten supports comparatively rapid dose adjustment, but clinically important drug interactions remain relevant. US approval: Approved on December 19, 2025, for adults with symptomatic obstructive HCM to improve functional capacity and symptoms.
Pivotal evidence:
SEQUOIA-HCM: Among 282 adults, aficamten improved peak oxygen uptake at 24 weeks compared with placebo, with a between-group difference of 1.7 mL/kg/min. Symptoms, health status, and LVOT obstruction also improved. The primary report was published in the New England Journal of Medicine in 2024.
MAPLE-HCM: Among 175 adults, peak oxygen uptake increased by 1.1 mL/kg/min with aficamten and decreased by 1.2 mL/kg/min with metoprolol at 24 weeks. The between-group difference was 2.3 mL/kg/min. Aficamten also improved symptoms and several hemodynamic measures. These adult findings should not be extrapolated directly to infants or children.
ACACIA-HCM: Among 517 adults with symptomatic nonobstructive HCM, aficamten improved exercise capacity and patient-reported health status at 36 weeks. The between-group differences were 0.67 mL/kg/min for peak oxygen uptake and 3.0 points for KCCQ-CSS. Reversible LVEF reductions below 50% occurred in 10.5% receiving aficamten versus 0.8% receiving placebo. These findings concern a different population from its established obstructive-HCM indication.
Dosing and safety:
The US adult starting dose is 5 mg once daily, with subsequent dosing individualized to echocardiographic findings and clinical status.
Aficamten carries a boxed warning for systolic dysfunction and heart failure and requires serial echocardiography and participation in a US REMS program.
Initiation with LVEF <55% is not recommended. Its dose-reduction and interruption thresholds differ from those for mavacamten; follow the aficamten-specific prescribing algorithm.
Clinically important interactions include drugs that inhibit multiple elimination pathways, strong CYP2C9 inhibitors, and changes involving CYP3A inducers. Rifampin is contraindicated.
Pediatric safety and effectiveness have not been established.
Guidelines and Pediatric Application
The 2023 ESC and 2024 AHA/ACC recommendations introduced myosin inhibition as an option for adults with persistent symptomatic LVOT obstruction despite conventional therapy. These guideline publications predate the September 2026 pediatric expansion of mavacamten’s US indication. Regulatory approval and guideline recommendations should therefore be described separately. For neonates and smaller infants, the evidence supporting myosin inhibitors remains insufficient for routine treatment. Management centers on identifying the underlying cause, characterizing the hemodynamic consequences, and selecting therapy with pediatric cardiology expertise. US approval statements and REMS requirements above should not be interpreted as describing Canadian authorization or access.
Echocardiography_2021_Anwar.pdffped-09-708732.pdfs41390-025-03819-2.pdfNature_Rev_Disease_Primer_2025_Argiro.pdf1-s2.0-S2213177923002366-main.pdfReferences for inherited cardiomyopathies
References for inherited cardiomyopathies
FDA Orange Book. FDA Orange Book. 2026.
2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2024. Ommen SR, Ho CY, Asif IM, et al.Guideline
Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy. The New England Journal of Medicine. 2025. Garcia-Pavia P, Maron MS, Masri A, et al.Clinical Trial
CAMZYOS. FDA Drug Label. Food and Drug Administration. Updated date: 2025-04-17
Mavacamten for Treatment of Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM): Health Status Analysis of a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet. 2021. Spertus JA, Fine JT, Elliott P, et al.
Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks. Circulation. 2023. Desai MY, Owens A, Geske JB, et al.
Hypertrophic Cardiomyopathy. The New England Journal of Medicine. 2025. Braunwald E.Review
Hypertrophic cardiomyopathy. Nature Reviews. Disease Primers. 2025. Argirò A, Parikh V, Jurcut R, et al.Review
Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. Journal of the American College of Cardiology. 2022. Maron BJ, Desai MY, Nishimura RA, et al.SR
Targeting the Cause of Obstructive Hypertrophic Cardiomyopathy. The Journal of the American Medical Association. 2022. Larkin HD.
Evolving strategies in obstructive hypertrophic cardiomyopathy: myosin inhibitors as monotherapy compared with beta-blockers. Heart Failure Reviews. 2026. Grupper A, Sverdlov AL, Cheema BS, Nasrollahizadeh A, Hosseini K.RecentReview
Cardiac Myosin Inhibitors for Managing Obstructive Hypertrophic Cardiomyopathy: JACC: Heart Failure State-of-the-Art Review. JACC. Heart Failure. 2023. Ostrominski JW, Guo R, Elliott PM, Ho CY.Review
Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology. 2021. Hegde SM, Lester SJ, Solomon SD, et al.RCT
Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology. 2023. Maron MS, Masri A, Choudhury L, et al.RCT
Aficamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: 48-Week Results From FOREST-HCM. JACC. Heart Failure. 2025. Saberi S, Abraham TP, Choudhury L, et al.RCT
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