Mavacamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy During Active Chemotherapy

Abstract

Background

The role of cardiac myosin inhibitors in patients with obstructive hypertrophic cardiomyopathy (oHCM) and active malignancy remains unexplored.

Case Summary

A 68-year-old woman with colon cancer presented with worsening dyspnea. Echocardiography showed severe asymmetric septal hypertrophy, systolic anterior motion of the mitral valve, and a peak left ventricular outflow tract gradient of 115 mm Hg. Beta-blocker therapy failed to control symptoms. After multidisciplinary cardio-oncology evaluation, mavacamten therapy was initiated. Within 4 weeks, the patient's left ventricular outflow tract gradient decreased to 10 mm Hg, her NYHA functional class improved to I, and her NT-proBNP levels dropped markedly. Chemotherapy continued without interruption. Nine months later, her oncologic disease progressed, and palliative care was adopted.

Discussion

This case highlights mavacamten as a safe and effective therapy for oHCM in a patient actively receiving chemotherapy. It underscores the potential value of cardiac myosin inhibition in complex comorbid scenarios.

Take-Home Message

Mavacamten can substantially improve quality of life in oHCM, even in patients with active malignancy.

Graphical Abstract

History of Presentation

A 68-year-old woman presented to the cardio-oncology clinic with worsening exertional dyspnea (NYHA functional class III). She denied chest pain, palpitations, or syncope. On examination, her blood pressure was 130/80 mm Hg and her heart rate was 82 beats/min. A systolic murmur, accentuated by Valsalva maneuver, was audible at the left sternal border. Lung auscultation was clear, and there were no peripheral edema or stigmata of heart failure.

Take-Home Messages

• •Even in the context of active malignancy, cardiac myosin inhibitors may provide meaningful improvements in quality of life for patients with obstructive hypertrophic cardiomyopathy.
• •Multidisciplinary cardio-oncology teams are essential to integrate novel cardiovascular therapies without interrupting cancer treatment.

Past Medical History

The patient was being evaluated for left-sided colon adenocarcinoma with unresectable hepatic metastases, diagnosed 1 year prior. Tumor genotyping was RAS/BRAF wild-type and microsatellite stable, guiding therapy with FOLFOX chemotherapy plus panitumumab. She did not have hypertension or other cardiovascular risk factors, nor did she have a known family history of cardiac disease or sudden cardiac death.

Differential Diagnosis

The differential diagnosis for this patient's exertional dyspnea in the context of metastatic cancer was broad, including both cardiac and noncardiac etiologies. We considered anemia and pulmonary etiologies such as pulmonary embolism or pulmonary metastases/pleural effusion. Cardiac causes included cancer therapy–related cardiac toxicity (both left ventricular dysfunction and ischemic heart disease), heart failure with preserved ejection fraction, heart valve disease including aortic stenosis (AS), and cardiomyopathies such as hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract (LVOT) obstruction.

Investigations

Initial electrocardiogram (Figure 1) showed sinus rhythm and was suggestive of left ventricular hypertrophy, with increased QRS voltages (deep S waves in V₁-V₂ and tall R waves in V₅-V₆) and associated repolarization abnormalities (ST-segment depression and T-wave inversion in the lateral leads). The patient's N-terminal pro–B-type natriuretic peptide was elevated (2,236 pg/mL), reflecting increased intracardiac pressures and wall stress. Transthoracic echocardiography showed severe asymmetric septal hypertrophy, as well as systolic anterior motion of the anterior mitral leaflet contacting the septum in midsystole, resulting in severe dynamic LVOT obstruction with a peak pressure gradient of 115 mm Hg (Figure 2, Video 1). The left ventricular ejection fraction (LVEF) was hyperdynamic at 70%, with cavity obliteration in systole. Importantly, the aortic valve was normal, and there was no significant AS to account for the murmur. Cardiac magnetic resonance imaging demonstrated features consistent with HCM, with asymmetric septal hypertrophy and a maximal septal thickness of 19 mm, systolic flow acceleration across the LVOT, and the absence of late gadolinium enhancement, suggesting no replacement fibrosis. However, increased extracellular volume (30.5%) was observed in the basal to mid septum, reflecting diffuse fibrosis at that location (Figure 3).

Figure 1.

Initial Electrocardiogram

The patient's electrocardiogram at the initial cardio-oncology clinic.

Figure 2.

Initial Echocardiographic Assessment

(A) Parasternal long-axis and (C) apical 4-chamber views showing asymmetric septal hypertrophy with systolic anterior motion of the mitral valve (white arrows). (B) M-mode tracing demonstrates septal contact (orange arrow). (D) Continuous-wave Doppler across the LVOT shows a resting peak gradient of 115 mm Hg. LVOT = left ventricular outflow tract.

Figure 3.

Cardiac Magnetic Resonance Imaging

(A and B) Still cine images in a telediastolic frame depicting asymmetric septal hypertrophy. (C) Midsystolic frame of a 3-chamber view, where a black signal void (yellow asterisk) suggests the presence of significant outflow tract obstruction. (D and E) Late gadolinium enhancement was absent, ruling out significant replacement fibrosis, although an increased extracellular volume could be detected in the basal and mid septum, reflecting diffuse involvement. (F) Postcontrast T1 map, short-axis view.

Management

Transient factors such as mild hypovolemia related to chemotherapy-induced anorexia, gastrointestinal losses, or general dehydration could have contributed to unmasking dynamic LVOT obstruction and precipitating symptom onset by reducing left ventricular preload in this patient with latent HCM. Initial management focused on medical therapy in line with guideline-directed first-line treatments. Bisoprolol was initiated and titrated up to 10 mg per day. However, she remained symptomatic and with dyspnea with low-grade activity, and peak provoked gradients with the Valsalva maneuver were still in the ∼60 mm Hg range. After multidisciplinary discussion in the cardio-oncology clinic, additional pharmacological treatment for LVOT obstruction was pursued, and mavacamten was started at a dose of 5 mg per day.

The patient's response was excellent. Her dyspnea improved to NYHA functional class I, and she reported being able to perform activities of daily living and moderate exercise (such as walking 1 km on flat ground) without significant breathlessness, which was a marked improvement. Chemotherapy was continued without interruption, and echocardiographic monitoring was performed after 4 weeks of cardiac myosin inhibition treatment. At that point, her resting LVOT gradient fell to 9 mm Hg and the provoked gradient to 15 mm Hg (Figure 4, Video 2). Her LVEF was 60% (a decrease from hyperdynamic 70%, but still well within normal). According to standard recommendations, the mavacamten dosage was reduced to 2.5 mg per day, and echocardiography at months 2 and 3 showed similar findings. Importantly, she felt well enough to continue and complete several cycles of chemotherapy without interruptions, as her cardiovascular symptoms were no longer a limiting factor. In addition, N-terminal pro–B-type natriuretic peptide levels fell to 350 pg/mL, reflecting reduced wall stress and filling pressures.

Figure 4.

Echocardiographic Assessment After 4 Weeks of Mavacamten

(A) Parasternal long-axis and (B) apical 4-chamber views showing resolution of systolic anterior motion of the mitral valve. (C) Continuous-wave Doppler across the LVOT demonstrates marked reduction of the resting peak gradient compared with baseline. LVOT = left ventricular outflow tract.

Approximately 9 months after initiating mavacamten, her metastatic cancer began to progress (with enlargement of liver lesions and onset of cancer-related cachexia). Given her declining condition and lack of further oncologic treatment options, a palliative approach was adopted, and she ultimately passed away.

Discussion

Obstructive hypertrophic cardiomyopathy (oHCM) is traditionally managed with a stepwise approach. Beta-blockers (or non-dihydropyridine calcium-channel blockers such as verapamil) are the first-line therapy to alleviate symptoms by reducing heart rate and contractility.¹ If symptoms persist, guidelines suggest adding disopyramide (a Class IA antiarrhythmic with negative inotropic effects). Disopyramide remains a suitable option for rapidly reducing LVOT gradients, particularly in inpatient settings, and is reasonable for patients with normal baseline QT intervals. The QT interval should be closely monitored and not exceed 500 ms or increase by more than 25% during therapy. However, given our patient's concurrent chemotherapy and potential for electrolyte disturbances, we considered the risk of QT prolongation and anticholinergic side effects unacceptable. With her unique situation (metastatic cancer with limited lifespan and higher procedural risk), proceeding to an invasive septal reduction therapy was not considered appropriate either.

Mavacamten allosterically inhibits cardiac myosin ATPase, reducing excessive myosin-actin cross-bridging. The result is decreased hypercontractility and improved diastolic compliance, which directly targets the pathophysiology of oHCM. Clinical trials have demonstrated that mavacamten can reduce LVOT gradients, improve symptoms, and enhance exercise capacity in patients with oHCM.² Importantly, guideline acceptance of mavacamten has rapidly followed evidence. The 2024 American Heart Association/American College of Cardiology updated HCM guidelines give a Class I recommendation for use of a cardiac myosin inhibitor in patients with symptomatic oHCM who are not adequately relieved by first-line therapies. This elevates mavacamten as a standard option before resorting to invasive septal reduction in appropriate patients. In practice, it permits clinicians to avoid or delay septal myectomy or alcohol septal ablation.¹ The VALOR-HCM trial exemplified this by studying patients who were candidates for septal reduction; after 16 weeks of mavacamten, the majority no longer met the criteria for invasive therapy.³

Since its approval, mavacamten has been applied in various complex HCM scenarios. Malhi et al⁴ reported an unusual case of HCM with predominant right ventricular outflow tract obstruction, where mavacamten therapy effectively relieved the right ventricular outflow tract gradient.⁴ Another case report by Vanhaecke et al⁵ described the challenging combination of severe AS coexisting with oHCM. They used mavacamten to reduce the HCM-related subaortic gradient, allowing clearer assessment of the true AS severity; after 1 month of mavacamten, the LVOT obstruction resolved, and the AS gradient unmasked as moderate.⁵ These reports, alongside our case, indicate that mavacamten can provide meaningful hemodynamic improvements in diverse and challenging conditions.

To our knowledge, the current case is the first to report mavacamten use in a patient actively undergoing chemotherapy for malignancy. This raises important considerations regarding safety and tolerability. In our patient, mavacamten was well tolerated, with no drug-drug interactions or overlapping toxicities with her chemotherapy.⁶ There was initial concern that overlapping side effects (eg, fatigue) might occur, but in fact her overall fatigue improved as her cardiac output obstruction was relieved. Mavacamten does require regular echocardiographic monitoring to ensure the LVEF remains ≥50%. In long-term extension studies, about 5% of patients had transient LVEF drops below 50%, all of which reversed on dose reduction. Our patient's ejection fraction remained safely above this threshold during follow-up. This close monitoring may pose a logistical challenge, but coordination between cardiology and oncology allowed these to be done alongside chemotherapy visits, minimizing patient burden.

The advent of cardiac myosin inhibitors marks a shift toward disease-specific medical therapy for oHCM. They offer a nonsurgical option that can be especially valuable in older patients or those with comorbidities. This case demonstrates that patients with active malignancy should not be categorically excluded from disease-specific therapies such as myosin inhibition, as meaningful symptomatic improvement may represent the most important therapeutic goal and can substantially enhance quality of life, even in the context of limited life expectancy.

Conclusions

This report illustrates mavacamten therapy as an effective bridge to better quality of life for our patient. By relieving obstruction, it addressed the key driver of her cardiopulmonary symptoms, allowing her remaining time to be as active and comfortable as possible. The case adds to the accumulating evidence that myosin inhibitor therapy can be successfully integrated into real-world patient management, including in those with complex concurrent illnesses.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Video 1

PLAX view in baseline echocardiography showing severe SAM of the anterior mitral leaflet.

Video 2

PLAX color view after treatment with mavacamten showing disappearance of SAM and absence of LVOTO.